Posted by on May 20, 2020 6:02 am
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HYDROXYCHLOROQUINE


Research Bibliography & Digest

 

The Economic Standard is gathering medical research about hydroxychloroquine as a treatment for COVID-19, alone or in combination with other drugs, published (or about to be published) in academic journals. Have a study? Submit citations with brief summaries, ideally from the text itself, via the submissions box below the Current Studies section or on the homepage. We are also logging ongoing research studies. Please note, this is NOT a general news or opinion page. Please also note that many recent articles are from preprint servers and have not been peer reviewed.  Thanks! — Ed.  P.S. Retracted papers are being removed from this list.

 

 

Research highlights:

 

From abstract: “We compared outcomes between treated and untreated patients using propensity-score caliper matching. Results Of 2,307 patients in the dataset, 679 were excluded. Of the remaining 1,645 patients, 263 (16%) died and 311 (18.9%) died or were intubated. Except for hydroxychloroquine and prednisone, patients that were treated with any of the medications were more likely to go through an outcome of death or intubation at baseline. After propensity matching we found an association between treatment with hydroxychloroquine and prednisone and better outcomes (hazard ratios with 95% CI of 0.83 +- 0.06 and 0.85 +- 0.03).”

 

 

Bibliography: Hydroxychloroquine or Chloroquine vs. COVID-19

 

  • Arshad, Samia et al. “Treatment with Hydroxychloroquine, Azithromycin, and Combination in Patients Hospitalized with COVID-19.” International Journal of Infectious Diseases, July 1, 2020. DOI: https://doi.org/10.1016/j.ijid.2020.06.099

From text:  “According to a protocol-based treatment algorithm, among hospitalized patients, use of hydroxychloroquine alone and in combination with azithromycin was associated with a significant reduction in-hospital mortality compared to not receiving hydroxychloroquine… Of 2,541 patients, with a median total hospitalization time of 6 days (IQR: 4-10 days), median age was 64 years (IQR:53-76 years), 51% male, 56% African American, with median time to follow-up of 28.5 days (IQR:3-53). Overall in-hospital mortality was 18.1% (95% CI:16.6%-19.7%); by treatment: hydroxychloroquine + azithromycin, 157/783 (20.1% [95% CI: 17.3%-23.0%]), hydroxychloroquine alone, 162/1202 (13.5% [95% CI: 11.6%-15.5%]), azithromycin alone, 33/147 (22.4% [95% CI: 16.0%-30.1%]), and neither drug, 108/409 (26.4% [95% CI: 22.2%-31.0%])​. Primary cause of mortality was respiratory failure (88%); no patient had documented torsades de pointes… Hydroxychloroquine provided a 66% hazard ratio reduction, and hydroxychloroquine + azithromycin 71% compared to neither treatment (p < 0.001).”

 

From abstract: “We compared outcomes between treated and untreated patients using propensity-score caliper matching. Results Of 2,307 patients in the dataset, 679 were excluded. Of the remaining 1,645 patients, 263 (16%) died and 311 (18.9%) died or were intubated. Except for hydroxychloroquine and prednisone, patients that were treated with any of the medications were more likely to go through an outcome of death or intubation at baseline. After propensity matching we found an association between treatment with hydroxychloroquine and prednisone and better outcomes (hazard ratios with 95% CI of 0.83 +- 0.06 and 0.85 +- 0.03).”

 

  • Bo Yu, et al. “Low Dose of Hydroxychloroquine Reduces Fatality of Critically Ill Patients With COVID-19.” Sci China Life Sci, 2020 May 15; 1-7.
     Doi: 10.1007/s11427-020-1732-2  

From abstract: “In this retrospective study, we included 550 critically ill COVID-19 patients who need mechanical ventilation in Tongji Hospital, Wuhan, from February 1, 2020 to April 4, 2020. All 550 patients received comparable basic treatments including antiviral drugs and antibiotics, and 48 of them were treated with oral HCQ treatment (200 mg twice a day for 7-10 days) in addition to the basic treatments… We found that fatalities are 18.8% (9/48) in HCQ group, which is significantly lower than 47.4% (238/502) in the NHCQ group (P<0.001).”

 

  • Brufsky, Adam.Distinct Viral Clades of SARS‐CoV‐2: Implications for Modeling of Viral Spread.” Journal of Medical Virology. April 20, 2020. https://doi.org/10.1002/jmv.25902

From abstract: “Distinct viral clades have a likely impact on COVID‐19 pathogenesis and spread. Sequence analysis from 2310 viral isolates from Nexstrain reveals that residue at 614 of the viral spike protein is changed from a putative ancestral aspartic acid (D) to a glycine (G) between two viral clades. The G strain is predominantly on the East Coast of the United States, and the D strain is predominantly on the West Coast. This mutation of the SARS‐CoV‐2 S protein spike is conserved in coronaviruses. Point mutations in a murine coronavirus spike protein can result in increased virulence through instability of the viral machinery and altered viral to cell membrane fusion. This observation may partially explain the discrepancy in predicted deaths from COVID‐19 between the East Coast and West Coast, and possibly explain that other factors aside from social distance, such as competition between two strains of differing virulence, may be at play.”

 

  • Brufsky, Adam. “Hyperglycemia, hydroxychloroquine, and the COVID‐19 pandemic.” Journal of Medical Virology. April 15, 2020. https://doi.org/10.1002/jmv.25887.

From abstract: “Coronavirus disease‐2019 (COVID‐19) infection and its severity can be explained by the concentration of glycosylated severe acute respiratory syndrome‐coronavirus 2 (SARS‐CoV‐2) viral particles in the lung epithelium, the concentration of glycosylated angiotensin‐converting enzyme receptor 2 (ACE2) in the lung epithelium, and the degree and control of the pulmonary immune response to the SARS‐CoV‐2 spike protein at approximately day 8 to 10 after symptom onset, which may be related to both. Binding of ACE2 by SARS‐CoV‐2 in COVID‐19 also suggests that prolonged uncontrolled hyperglycemia, and not just a history of diabetes mellitus, may be important in the pathogenesis of the disease. It is tempting to consider that the same mechanism acts in COVID‐19 as in SARS, where an overactive macrophage M1 inflammatory response, as neutralizing antibodies to the SARS‐CoV‐2 spike protein form at day 7 to 10, results in acute respiratory distress syndrome (ARDS) in susceptible patients. It also allows consideration of agents, such as hydroxychloroquine, which may interfere with this overly brisk macrophage inflammatory response and perhaps influence the course of the disease, in particular, those that blunt but do not completely abrogate the M1 to M2 balance in macrophage polarization, as well as viral load, which in SARS appears to be temporally related to the onset of ARDS.”

 

  • Brufsky, Adam, and Michael T. Lotze. “DC/L-SIGNs of Hope in the COVID19 Pandemic.” Journal of Medical Virology, May 6, 2020. Doi: https://doi.org/10.1002/jmv.25980.

From abstract: “A stable mutation in the SARS-CoV-2 spike protein found in one report is predicted to bind ACE2 less tightly, predicting a decrease in virulence. SARS-CoV-2 strains with various mutations in the viral spike can vary as much as 270fold in virulence in Vero E6 culture. Viral evolutionary theory suggests that one option for a viral strain introduced to a novel host is to maintain fitness through reduction in virulence, and these various glycosylation mutations in the spike protein can plausibly provide one such mechanism for attenuation.

 

  • Carlucci, Philip M., et al. “Hydroxychloroquine and azithromycin plus zinc vs hydroxychloroquine and azithromycin alone: outcomes in hospitalized COVID-19 patient.” medRxiv, May 8, 2020. Doi: https://doi.org/10.1101/2020.05.02.20080036.

From abstract: “In univariate analyses, zinc sulfate increased the frequency of patients being discharged home, and decreased the need for ventilation, admission to the ICU, and mortality or transfer to hospice for patients who were never admitted to the ICU… This study provides the first in vivo evidence that zinc sulfate in combination with hydroxychloroquine may play a role in therapeutic management for COVID-19.”

 

  • Chatterjee, Pranab, et al. “Healthcare workers & SARS-CoV-2 infection in India: A case-control investigation in the time of COVID-19.” Indian J Med Res, May 28, 2020. Doi: 10.4103/ijmr.IJMR_2234_20.

From abstract: “Consumption of four or more maintenance doses of HCQ was associated with a significant decline in the odds of getting infected (AOR: 0.44; 95% CI: 0.22-0.88); a dose-response relationship existed between frequency of exposure to HCQ and such reductions (χ2 for trend=48.88; P<0.001).

 

From abstract: “… for TTCR, the body temperature recovery time and the cough remission time were significantly shortened in the HCQ treatment group. Besides, a larger proportion of patients with improved pneumonia in the HCQ treatment group (80.6%, 25 of 32) compared with the control group (54.8%, 17 of 32)… However, there were 2 patients with mild adverse reactions in the HCQ treatment group.” 

 

  • Davido, Benjamin, et al. “Hydroxychloroquine plus azithromycin: a potential interest in reducing in-hospital morbidity due to COVID-19 pneumonia (HI-ZY-COVID)?” medRxiv, May 11, 2020. Doi: https://doi.org/10.1101/2020.05.05.20088757

From abstract: “Monocentric retrospective study conducted from 2th March to 17th April 2020…  Among 132 patients admitted for COVID-19 in the medicine ward, 45 received HCQ/azithromycin ≥ 48 hours, with a favorable outcome in 91.1% of cases (OR=6.2, p=0.002) versus others regimen (n=87). Groups were comparable at the baseline in terms of age, sex, comorbidities, extend in thoracic imaging, and severity. Among patients that required to be transferred to ICU (n=27) (for mechanical ventilation), median delay for transfer was 2 days (IQR 1-3). We report only 1 patient that presented an adverse event (a prolonged QT interval on EKG) that required to discontinue HCQ. Conclusion: The present study suggests a potential interest of the combination therapy using HCQ/azithromycin for the treatment of COVID-19 in in-hospital patients.”

 

From abstract: “Here we discuss the possible mechanisms of chloroquine interference with the SARS-CoV-2 replication cycle.”

 

  • Fan Jianhong, et al. “Connecting hydroxychloroquine in vitro antiviral activity to in vivo concentration for prediction of antiviral effect: a critical step in treating COVID-19 patients.” Clinical Infectious Diseases, ciaa623, May 21, 2020. Doi: https://doi.org/10.1093/cid/ciaa623

From abstract: “In vitro EC50/EC90 values for hydroxychloroquine should be compared to the in vivo free extracellular tissue concentration, which is similar to the free plasma hydroxychloroquine concentration.”

 

  • Ferraira, Antonio, et al. “Chronic treatment with hydroxychloroquine and SARS-CoV-2 infection.” Journal of Medical Virology, July 9, 2020. Doi: 10.1002/jmv.26286

From abstract: Out of 26,815 SARS-CoV-2 positive patients, 77 (0.29%) were chronically treated with HCQ, while 1,215 (0.36%) out of 333,489 negative patients were receiving it chronically (P=0.04). After adjustment for age, sex, and chronic treatment with corticosteroids and/or immunosuppressants, the odds ratio of SARS-CoV-2 infection for chronic treatment with HCQ has been 0.51 (0.37-0.70). Conclusions: Our data suggest that chronic treatment with HCQ confer protection against SARS-CoV-2 infection.

 

  • Freedberg, Daniel, et al. “Famotidine Use is Associated with Improved Clinical Outcomes in Hospitalized COVID-19 Patients: A Propensity Score Matched Retrospective Cohort Study.” medRxiv, May 8, 2020. Doi: https://doi.org/10.1101/2020.05.01.20086694.

From text: 1,620 hospitalized patients with COVID-19 were identified including 84 (5.1%) who received famotidine within 24 hours of hospital admission. 340 (21%) patients met the study composite outcome of death or intubation. Use of famotidine was associated with reduced risk for death or intubation (adjusted hazard ratio (aHR) 0.42, 95% CI 0.21-0.85) and also with reduced risk for death alone (aHR 0.30, 95% CI 0.11-0.80)… Use of hydroxychloroquine became common in the hospital during the study period…

 

From abstract: “… we cloned, tagged and expressed 26 of the 29 SARS-CoV-2 proteins in human cells and identified the human proteins physically associated with each using affinity-purification mass spectrometry (AP-MS), identifying 332 high-confidence SARS-CoV-2-human protein-protein interactions (PPIs). Among these, we identify 66 druggable human proteins or host factors targeted by 69 compounds (29 FDA-approved drugs, 12 drugs in clinical trials, and 28 preclinical compounds). Screening a subset of these in multiple viral assays identified two sets of pharmacological agents that displayed antiviral activity: inhibitors of mRNA translation and predicted regulators of the Sigma1 and Sigma2 receptors.”

 

  • Holland, LaRinda, et al. “An 81 nucleotide deletion in SARS-CoV-2 ORF7a identified from sentinel surveillance in Arizona (Jan-Mar 2020).” Journal of Virology, May 1, 2020Doi: 10.1128/JVI.00711-20.

From letter to the editor: “Like SARS-CoV, the SARS-CoV-2 genome encodes multiple open reading frames in the 3′ region. We found that the SARS-CoV-2 AZ-ASU2923 genome has an 81 nucleotide deletion in the ORF7a gene resulting in a 27 amino-acid in-frame deletion (Figure 2B). The SARS-CoV ORF7a ortholog is a viral antagonist of host restriction factor BST-2/Tetherin and induces apoptosis (11-14). Based on the SARS-CoV ORF7a structure (15), the 27-aa deletion in SARS-CoV-2 ORF7a maps to the putative signal peptide (partial) and first two beta strands. To validate the deletion, we performed RT-PCR using primers spanning the region and verified by Sanger sequencing the amplicons (Figure 2C). Similar deletions in SARS-CoV-2 genomes are emerging, notably in the ORF8 gene (16) that may potentially reduce virus fitness (17). Hence, further experiments are needed to determine the functional consequences of the ORF7a deletion.

 

  • Huang Mingxing, et al. “Preliminary evidence from a multicenter prospective observational study of the safety and efficacy of chloroquine for the treatment of COVID-19.” medRxiv Doi: https://doi.org/10.1101/2020.04.26.20081059

From results: ” A total of 197 patients completed chloroquine treatment, and 176 patients were included as historical controls. The median time to achieve an undetectable viral RNA was shorter in chloroquine than in non-chloroquine (absolute difference in medians -6.0 days; 95% CI -6.0 to -4.0). The duration of fever is shorter in chloroquine (geometric mean ratio 0.6; 95% CI 0.5 to 0.8). No serious adverse events were observed in the chloroquine group. Patients  treated with half dose experienced lower rate of adverse events than with full dose.”

 

From uncorrected proof: “By Day 14, the incidence rate of lung improvement based on CT imaging from the Chloroquine group was more than double that of the Lopinavar/Ritonavir group (rate ratio 2.21, 95% CI 0.81-6.62). These results suggest that patients treated with Chloroquine appear to recover better and regain their pulmonary function quicker than those treated with Lopinavir/Ritonavir.”

 

  • Klimke, A., et al.  “Hydroxychloroquine as an Aerosol Might Markedly Reduce and Even Prevent Severe Clinical Symptoms after SARS-CoV-2 Infection. Preprints 2020, 2020040090. Doi: 10.20944/preprints202004.0090.v1

“From abstract: “During the infection of alveolar epithelial cells of the lung, the ACE2 receptor has a central function. The antimalarial drugs chloroquine phosphate (CQ) and hydroxychloroquine (HCQ) impair in vitro the terminal glycosylation of ACE2 without significant change of cell-surface ACE2 and, therefore, might be potent inhibitors of SARS-CoV-2 infections. Starting inhibition at 0.1 µM, CQ completely prevented in vitro infections at 10 µM, suggesting a prophylactic effect and preventing the virus spread 5 hours after infection. In a first clinical trial, CQ was effective in inhibiting exacerbation of pneumonia, improving lung imaging findings, promotion of virus-negative conversion, and shortening the disease. In addition, HCQ, which is three times more potent than CQ in SARS-CoV-2 infected cells (EC50 0.72 µM), was significantly associated with viral load reduction/disappearance in COVID-19 patients compared to controls.”

 

  • Membrillo, FJ, et al. “Early hydroxychloroquine is associated with an increase of survival in COVID-19 patients: an observational study.” Preprints 2020, 2020050057. Doi: 10.20944/preprints202005.0057.v1.

From methods and results: “We enrolled all 18-85 years old inpatients from Central Defense Hospital ‘Gómez Ulla’, Madrid, Spain, who were hospitalised for COVID-19 and had a definitive outcome (dead or discharged)… We analysed first 220 medical records. 166 patients met the inclusion criteria. 48,8 % of patients not treated with HCQ died, 22% of those treated with hydroxychloroquine (p=0,002). According to clinical picture at admission, hydroxychloroquine increased the mean cumulative survival in all groups from 1,4 to 1,8 times. This difference was statistically significant in the mild group.

 

From abstract: “Decreased risk of in-hospital mortality was associated with female sex (HR 0.84, CI 0.77–0.90), African American race (HR 0.78 CI 0.65–0.95), and hydroxychloroquine use (HR 0.53, CI 0.41–0.67).”

 

  • Min Seo Kim, et al. “Treatment Response to Hydroxychloroquine, Lopinavir/Ritonavir, and Antibiotics for Moderate COVID 19: A First Report on the Pharmacological Outcomes from South Korea.” medRxiv, May 18, 2020. Doi: https://doi.org/10.1101/2020.05.13.20094193.

From abstract: “A retrospective cohort study of the 358 laboratory-confirmed SARS CoV 2 or COVID 19 patients was conducted. Of these patients, 270 adult patients met inclusion criteria and were included in our analyses. The primary endpoints were time to viral clearance and clinical improvement. The mean duration to viral clearance and clinical improvements were displayed as bar-plots to visualize treatment responses. Results: Ninety-seven moderate COVID 19 patients were managed with hydroxychloroquine (HQ) plus antibiotics (n = 22), lopinavir/ritonavir (Lop/R) plus antibiotics (n = 35), or conservative treatment (n = 40). Time to viral clearance, as signified by negative conversion on PCR, after initiation of treatment was significantly shorter with HQ plus antibiotics compared to Lop/R plus antibiotics (hazard ratio [HR], 0.49; 95% confidence interval [95% CI], 0.28 to 0.87) or conservative treatments (HR, 0.44; 95% CI, 0.25 to 0.78). Hospital stay duration after treatment was also shortest for patients treated with HQ plus antibiotics compared to other treatment groups.”

 

  • Nabirotchkin, Sergeui, et al. “Focusing on the Unfolded Protein Response and Autophagy Related Pathways to Reposition Common Approved Drugs Against COVID-19.” Preprints 2020, 2020030302. Doi: 10.20944/preprints202003.0302.v1

From abstract: “We have identified 97 approved drugs that are known to modulate these four identified pathways, and which represent, therefore, interesting repositioning candidates.” 

 

  • Pastick, Katelyn A., et al. “Review: Hydroxychloroquine and Chloroquine for Treatment of SARS-CoV-2 (COVID-19).” Open Forum Infectious Diseases, ofaa130, April 15, 2020. Doi: https://doi.org/10.1093/ofid/ofaa130

From abstract: “Here, we perform a rapid narrative review and discuss the strengths and limitations of existing in vitro and clinical studies. We call for additional randomized controlled trial evidence prior to the widespread incorporation of hydroxychloroquine and chloroquine into national and international treatment guidelines.”

 

  • Raoult, Didier, Million, et al. “Early treatment of 1061 COVID-19 patients with hydroxychloroquine and azithromycin, Marseille, France.” Travel Medicine and Infectious Disease, May 5, 2020. Doi: https://doi.org/10.1016/j.tmaid.2020.101738.

From abstract:”A total of 1061 patients were included in this analysis (46.4% male, mean age 43.6 years – range 14–95 years). Good clinical outcome and virological cure were obtained in 973 patients within 10 days (91.7%). Prolonged viral carriage was observed in 47 patients (4.4%) and was associated to a higher viral load at diagnosis (p < .001) but viral culture was negative at day 10. All but one, were PCR-cleared at day 15. A poor clinical outcome (PClinO) was observed for 46 patients (4.3%) and 8 died (0.75%) (74–95 years old). All deaths resulted from respiratory failure and not from cardiac toxicity.”

 

From abstract: ” In 80 in-patients receiving a combination of hydroxychloroquine and azithromycin we noted a clinical improvement in all but one 86 year-old patient who died, and one 74 yearold patient still in intensive care unit. A rapid fall of nasopharyngeal viral load tested by qPCR was noted, with 83% negative at Day7, and 93% at Day8. Virus cultures from patient respiratory samples were negative in 97.5% patients at Day5.”

 

From results: “At low MOI, azithromycin or hydroxychloroquine alone had no or low impact on the viral production compared to the positive control. We observed only a moderate effect for hydroxychloroquine at 5 Mu M in 2 of the 3 replicates (Figure 2a). For the combination of azithromycin and hydroxychloroquine, we observed inhibition of viral replication for wells containing hydroxychloroquine at 5 Mu M in combination with 98 azithromycin at 10 and 5 Mu M.”

 

  • Raoult, Didier, Gautret, et al. “Hydroxychloroquine and azithromycin as a treatment of COVID‐19: results of an open‐label non‐randomized clinical trial.” International Journal of Antimicrobial Agents, March 17, 2020. Doi: https://doi.org/10.1016/j.ijantimicag.2020.105949

From abstract: “Twenty cases were treated in this study and showed a significant reduction of the viral carriage at D6-post inclusion compared to controls, and much lower average carrying duration than reported of untreated patients in the literature. Azithromycin added to hydroxychloroquine was significantly more efficient for virus elimination.”

 

  • Risch, Harvey A. “Early Outpatient Treatment of Symptomatic, High-Risk Covid-19 Patients that Should be Ramped-Up Immediately as Key to the Pandemic Crisis.” American Journal of Epidemiology, kwaa093, May 27, 2020. Doi: https://doi.org/10.1093/aje/kwaa093.

From text: “Hydroxychloroquine+azithromycin has been widely misrepresented in both clinical reports and public media, and outpatient trials results are not expected until September. Early outpatient illness is very different than later hospitalized florid disease and the treatments differ. Evidence about use of hydroxychloroquine alone, or of hydroxychloroquine+azithromycin in inpatients, is irrelevant concerning efficacy of the pair in early high-risk outpatient disease. Five studies, including two controlled clinical trials, have demonstrated significant major outpatient treatment efficacy. Hydroxychloroquine+azithromycin has been used as standard-of-care in more than 300,000 older adults with multicomorbidities, with estimated proportion diagnosed with cardiac arrhythmias attributable to the medications 47/100,000 users, of which estimated mortality is <20%, 9/100,000 users, compared to the 10,000 Americans now dying each week. These medications need to be widely available and promoted immediately for physicians to prescribe.”

 

  • Sandeep, Samarth and Kirk McGregor. “Energetics Based Modeling of Hydroxychloroquine and Azithromycin Binding to the SARS-CoV-2 Spike (S)Protein – ACE2 Complex.” ChemRxiv, March 2020.  Doi: 10.26434/chemrxiv.12015792

From results section: “… hydroxychloroquine by itself appears to be ineffective in directly inhibiting the SARS-CoV-2 spike-ACE2 interaction. Instead, it seems to serve to increase the acidity of the ACE2 system in the interaction between the ACE2 and SARS-CoV-2 spike that could in many cases result in the degradation of the spike, and potentially the discontinuation of the virus’ ability to spread further. On the other hand, azithromycin provides high binding affinity when adjusted for energetics and has a much better ability at directly targeting the binding interaction point between the SARS-CoV-2 spike and ACE2.”

 

  • Scholz, M., et al. “COVID-19 Outpatients – Early Risk-Stratified Treatment with Zinc Plus Low Dose Hydroxychloroquine and Azithromycin: A Retrospective Case Series Study.” Preprints 2020, 2020070025 (Doi: 10.20944/preprints202007.0025.v1).

From abstract: “4 of 141 treated patients (2.8%) were hospitalized, which was significantly less (p<0.001) compared with 58 of 377 untreated patients (15.4%) (odds ratio 0.16, 95% CI 0.06-0.5). Therefore, the odds of hospitalization of treated patients were 84% less than in the untreated group. One patient (0.7%) died in the treatment group versus 13 patients (3.5%) in the untreated group (odds ratio 0.2, 95% CI 0.03-1.5; p=0.16). There were no cardiac side effects.”

 

  • Skipper, Caleb, et al. “Hydroxychloroquine in Nonhospitalized Adults With Early COVID-19. A Randomized Trial.” Annals of Internal Medicine, July 16, 2020. Doi: https://doi.org/10.7326/M20-4207

From results: “With placebo, 10 hospitalizations occurred (2 non–COVID-19–related), including 1 hospitalized death. With hydroxychloroquine, 4 hospitalizations occurred plus 1 nonhospitalized death (P = 0.29).”

 

From abstract: “After a large COVID-19 exposure event in an LTCH in Korea, PEP using hydroxychloroquine (HCQ) was administered to 211 individuals, including 189 patients and 22 careworkers, whose baseline polymerase chain reaction (PCR) tests for COVID-19 were negative. PEP was completed in 184 (97.4%) patients and 21 (95.5%) careworkers without serious adverse events… Based on our experience, further clinical studies are recommended for COVID-19 PEP.”

 

  • Wang, M., et al. “Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro.” Cell Research 30269–271 (2020). Doi: https://doi.org/10.1038/s41422-020-0282-0

From Letter to the Editor: “Our time-of-addition assay demonstrated that chloroquine functioned at both entry, and at post-entry stages of the 2019-nCoV infection in Vero E6 cells (Fig. 1c, d). Besides its antiviral activity, chloroquine has an immune-modulating activity, which may synergistically enhance its antiviral effect in vivo.”

 

  • Yang, X., et al. “Breakthrough: Chloroquine phosphate has shown apparent efficacy in treatment of COVID-19 associated pneumonia in clinical studies.” BioScience Trends. 2020 Volume 14 Issue 1 Pages 72-73. Doi: https://doi.org/10.5582/bst.2020.01047

From abstract: “Chloroquine phosphate, an old drug for treatment of malaria, is shown to have apparent efficacy and acceptable safety against COVID-19 associated pneumonia in multicenter clinical trials conducted in China.”

 

  • Yao X., et al. “In Vitro Antiviral Activity and Projection of Optimized Dosing Design of Hydroxychloroquine for the Treatment of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2).” Clinical Infectious Diseases. 2020 Mar 9. pii: ciaa237. Doi: https://doi.org/10.1093/cid/ciaa237

From abstract: “We propose that the immunomodulatory effect of hydroxychloroquine also may be useful in controlling the cytokine storm that occurs late-phase in critically ill SARS-CoV-2 infected patients… Hydroxychloroquine was found to be more potent than chloroquine to inhibit SARS-CoV-2 in vitro.”

 

  • Zhang Yan, et al. “Effectiveness of Hydrochloroquine on the New Coronavirus (COVID-19).” [Study title?]” Published in Chinese. February 18, 2020.

News summary: “On February 18, Peng Xin News (www.thepaper.cn) learned from Wuhan University People’s Hospital that a clinical trial conducted by the hospital in a multi-disciplinary study proved that 20 patients with new coronary pneumonia (NCP) had symptoms [that] were significantly improved and disease progression did not occur. Based on this, experts suggest that in the absence of effective drugs, hydroxychloroquine can be considered in the clinical treatment of new coronary pneumonia.”

 

From abstract: “Chloroquine (CQ) exhibits a promising inhibitory effect. However, the clinical use of CQ can cause severe side effects. We propose that hydroxychloroquine (HCQ), which exhibits an antiviral effect highly similar to that of CQ, could serve as a better therapeutic approach. HCQ is likely to attenuate the severe progression of COVID-19, inhibiting the cytokine storm by suppressing T cell activation.”

 

 

Hydroxychloroquine counter-findings (studies suggesting no/limited benefit against COVID-19)

 

  • Borba, Mayla, et al. “Chloroquine diphosphate in two different dosages as adjunctive therapy of hospitalized patients with severe respiratory syndrome in the context of coronavirus (SARS-CoV-2) infection: Preliminary safety results of a randomized, double-blinded, phase IIb clinical trial (CloroCovid-19 Study).” medRxiv, April 11, 2020.  doi: https://doi.org/10.1101/2020.04.07.20056424

From Preprint abstract: “Our study aimed to comprehensively evaluate the safety and efficacy of two different CQ dosages in patients with established severe COVID-19… Eligible participants were allocated to receive orally or via nasogastric tube high dose CQ (600mg CQ twice daily for 10 days or total dose 12g); or low dose CQ (450mg for 5 days, twice daily only on the first day, or total dose 2.7g). In addition, all patients received ceftriaxone and azithromycin… 81 patients were enrolled. The high dose CQ arm presented more QTc>500ms (25%), and a trend toward higher lethality (17%) than the lower dosage. Fatality rate was 13.5% (95%CI=6.9-23.0%), overlapping with the CI of historical data from similar patients not using CQ (95%CI=14.5-19.2%). In 14 patients with paired samples, respiratory secretion at day 4 was negative in only one patient. Interpretation Preliminary findings suggest that the higher CQ dosage (10-day regimen) should not be recommended for COVID-19 treatment because of its potential safety hazards.”

 

From abstract: “We included eleven studies including, three randomized controlled trials and eight observational studies. Among these, 2354 patients received hydroxychloroquine alone or in combination, while 1952 did not. Mortality was reported at different points of time. The overall mortality was not significantly different among patients who received hydroxychloroquine compared to the control group (OR: 1.41, 95% CI: 0.76 to 2.62; p = 0.28). Clinical worsening or lack of symptomatic improvement did not differ between patients who received hydroxychloroquine compared to those who did not (OR 1.1, 95% CI: 0.6 to 2.02; p = 0.76). Viral clearance, assessed by RT-PCR, did not differ significantly between the hydroxychloroquine and the control groups (OR: 1.13, CI: 0.26 to 5.01; p = 0.87).”

 

  • Chen Jun, et al. “A pilot study of hydroxychloroquine in treatment of patients with common coronavirus disease-19 (COVID-19).” J Zhejiang Univ (Med Sci). 2020, Vol. 49, Issue (1): 0-0. Doi: 10.3785/j.issn.1008-9292.2020.03.03

From text: “We prospectively enrolled 30 treatment-naive patients with confirmed COVID-19 after informed consent at Shanghai Public Health Clinical Center. The patients were randomized 1:1 to HCQ group and the control group. Patients in HCQ group were given HCQ 400 mg per day for 5 days plus conventional treatments, while those in the control group were given conventional treatment only… Results: One patient in HCQ group developed to severe during the treatment. On day 7, COVID-19 nucleic acid of throat swabs was negative in 13 (86.7%) cases in the HCQ group and 14 (93.3%) cases in the control group (P>0.05)… The median duration from hospitalization to virus nucleic acid negative conservation was 4 (1-9) days in HCQ group, which is comparable to that in the control group[2 (1-4) days… The median time for body temperature normalization in HCQ group was 1 (0-2) after hospitalization, which was also comparable to that in the control group 1 (0-3).”

 

  • Geleris, Joshua, et al.Observational Study of Hydroxychloroquine in Hospitalized Patients with Covid-19.” New England Journal of Medicine, May 7, 2020. Doi: 10.1056/NEJMoa2012410

From text: ‘In this observational study involving patients with Covid-19 who had been admitted to the hospital, hydroxychloroquine administration was not associated with either a greatly lowered or an increased risk of the composite end point of intubation or death. Randomized, controlled trials of hydroxychloroquine in patients with Covid-19 are needed.”

 

  • Horby, Peter, et al. “Effect of Hydroxychloroquine in Hospitalized Patients with COVID-19: Preliminary results from a multi-centre, randomized, controlled trial.” medRxiv, July 15, 2020. Doi: https://doi.org/10.1101/2020.07.15.20151852 

From abstract: “Results: 1561 patients randomly allocated to receive hydroxychloroquine were compared with 3155 patients concurrently allocated to usual care. Overall, 418 (26.8%) patients allocated hydroxychloroquine and 788 (25.0%) patients allocated usual care died within 28 days (rate ratio 1.09; 95% confidence interval [CI] 0.96 to 1.23; P=0.18). Consistent results were seen in all pre-specified subgroups of patients. Patients allocated to hydroxychloroquine were less likely to be discharged from hospital alive within 28 days (60.3% vs. 62.8%; rate ratio 0.92; 95% CI 0.85-0.99) and those not on invasive mechanical ventilation at baseline were more likely to reach the composite endpoint of invasive mechanical ventilation or death (29.8% vs. 26.5%; risk ratio 1.12; 95% CI 1.01-1.25). There was no excess of new major cardiac arrhythmia. Conclusions: In patients hospitalized with COVID-19, hydroxychloroquine was not associated with reductions in 28-day mortality but was associated with an increased length of hospital stay and increased risk of progressing to invasive mechanical ventilation or death.”

 

  • Hulme, Oliver J., et al. “Reply to Gautret et al. 2020: A Bayesian reanalysis of the effects of hydroxychloroquine and azithromycin on viral carriage in patients with COVID-19.” medRxiv, March 31, 2020. Doi: https://doi.org/10.1101/2020.03.31.20048777

From the abstract: “To assess whether HCQ is more effective when combined with AZ, we performed the same tests, and found only anecdotal evidence for the positive effect model for the original data (BF ~2.8), and moderate evidence for all other variants of the data (BF ~5.6)… Our analyses only explore the effects of different assumptions about excluded and untested patients. These assumptions are not adequately reported, nor are they justified in the original paper, and we find that varying them causes substantive changes to the evidential support for the main claims of the original paper. This statistical uncertainty is exacerbated by the fact that the treatments were not randomised, and subject to several confounding variables including the patients’ consent to treatment, different care centres, and clinical decision-making.”

 

From abstract: “We performed a retrospective analysis of data from patients hospitalized with confirmed SARS-CoV-2 infection in all United States Veterans Health Administration medical centers until April 11, 2020. Patients were categorized based on their exposure to hydroxychloroquine alone (HC) or with azithromycin (HC+AZ) as treatments in addition to standard supportive management for Covid-19… Rates of death in the HC, HC+AZ, and no HC groups were 27.8%, 22.1%, 11.4%, respectively. Rates of ventilation in the HC, HC+AZ, and no HC groups were 13.3%, 6.9%, 14.1%, respectively. Compared to the no HC group, the risk of death from any cause was higher in the HC group (adjusted hazard ratio, 2.61; 95% CI, 1.10 to 6.17; P=0.03) but not in the HC+AZ group (adjusted hazard ratio, 1.14; 95% CI, 0.56 to 2.32; P=0.72).

 

  • Mahévas, Matthieu, et al. “Clinical efficacy of hydroxychloroquine in patients with covid-19 pneumonia who require oxygen: observational comparative study using routine care data.BMJ, May 14, 2020. Doi: https://doi.org/10.1136/bmj.m1844.

From results: “Overall survival at day 21 was 89% in the treatment group and 91% in the control group (1.2, 0.4 to 3.3). Survival without acute respiratory distress syndrome at day 21 was 69% in the treatment group compared with 74% in the control group (1.3, 0.7 to 2.6). At day 21, 82% of patients in the treatment group had been weaned from oxygen compared with 76% in the control group (weighted risk ratio 1.1, 95% confidence interval 0.9 to 1.3). Eight patients in the treatment group (10%) experienced electrocardiographic modifications that required discontinuation of treatment.”

 

  • Mitjà, Oriol, et al.Hydroxychloroquine for Early Treatment of Adults with Mild Covid-19: A Randomized-Controlled Trial.” Clinical Infectious Diseases, ciaa1009, July 16, 2020. Doi: https://doi.org/10.1093/cid/ciaa1009

From results: “A total of 293 patients were eligible for intention-to-treat analysis: 157 in the control arm and 136 in the intervention arm. The mean age was 41.6 years (SD 12.6), mean viral load at baseline was 7.90 (SD 1.82) Log10 copies/mL, and median time from symptom onset to randomization was 3 days. No significant differences were found in the mean reduction of viral load at day 3 (-1.41 vs. -1.41 Log10 copies/mL in the control and intervention arm, respectively; difference 0.01 [95% CI -0.28;0.29]) or at day 7 (-3.37 vs. -3.44; d –0.07 [-0.44;0.29]). This treatment regimen did not reduce risk of hospitalization (7.1%, control vs. 5.9%, intervention; RR 0.75 [0.32;1.77]) nor shortened the time to complete resolution of symptoms (12 days, control vs. 10 days, intervention; = 0.38). No relevant treatment-related AEs were reported.”

 

  • Molina, JM, et al. “No Evidence of Rapid Antiviral Clearance or Clinical Benefit with the Combination of Hydroxychloroquine and Azithromycin in Patients with Severe COVID-19 Infection.” Medecine et Maladies Infectieuses, March 30, 2020. Doi: https://doi.org/10.1016/j.medmal.2020.03.006

From text: “There were 7 men and 4 women with a mean age of 58.7 years (range: 20-77), 8 had significant comorbidities  associated  with  poor  outcomes  (obesity:  2;  solid  cancer:  3;  hematological cancer: 2; HIV-infection: 1)… At the time of treatment initiation, 10/11 had fever and received nasal oxygen therapy. Within 5 days, one patient died, two were transferred to the ICU.”

 

  • Rosenberg, Eli, et al. “Association of Treatment With Hydroxychloroquine or Azithromycin With In-Hospital Mortality in Patients With COVID-19 in New York State.” JAMA, May 11, 2020. Doi: 10.1001/jama.2020.8630

From abstract: “Overall in-hospital mortality was 20.3% (95% CI, 18.2%-22.4%). The probability of death for patients receiving hydroxychloroquine + azithromycin was 189/735 (25.7% [95% CI, 22.3%-28.9%]), hydroxychloroquine alone, 54/271 (19.9% [95% CI, 15.2%-24.7%]), azithromycin alone, 21/211 (10.0% [95% CI, 5.9%-14.0%]), and neither drug, 28/221 (12.7% [95% CI, 8.3%-17.1%]). In adjusted Cox proportional hazards models, compared with patients receiving neither drug, there were no significant differences in mortality for patients receiving hydroxychloroquine + azithromycin (HR, 1.35 [95% CI, 0.76-2.40]), hydroxychloroquine alone (HR, 1.08 [95% CI, 0.63-1.85]), or azithromycin alone (HR, 0.56 [95% CI, 0.26-1.21]).”

 

  • Wei Tang, et al. “Hydroxychloroquine in patients mainly with mild to moderate COVID-19: open-label, randomized, controlled trial.” BMJ, May 14, 2020; 369 Doi: https://doi.org/10.1136/bmj.m1849 

Setting 16 government-designated COVID-19 treatment centers in China through 11 to 29 in February 2020. Participants 150 patients hospitalized with laboratory-confirmed COVID-19 were included in the intention to treat analysis. 75 patients were assigned to HCQ plus SOC and 75 to SOC alone. Interventions HCQ was administrated with a loading dose of 1, 200 mg daily for three days followed by a maintained dose of 800 mg daily for the remaining days (total treatment duration: 2 or 3 weeks for mild/moderate or severe patients, respectively)… Results Among 150 patients, 148 were with mild to moderate disease and 2 were with severe disease. The mean days (±standard deviation, min to max) from symptoms onset to randomization was 16.6 (±10.5 days, 3 to 41 days). The negative conversion probability by 28 days in SOC plus HCQ group was 85.4% (95% confidence interval (CI) 73.8% to 93.8%), similar to that in the SOC group 81.3% (95%CI 71.2% to 89.6%). Between-group difference was 4.1% (95%CI -10.3% to 18.5%). 

 

 

Chloroquine/Hydroxychloroquine safety, side effects, COVID-19 background

 

  • ANSM. “Medicines used in patients with COVID-19: enhanced surveillance for adverse effects – Information point.” Assay summary, April 10, 2020.

From Summary (in French): “53 cases of cardiac adverse effects were thus analyzed, including 43 cases with hydroxychloroquine, alone or in combination (in particular with azithromycin). They are classified into three categories: 7 cases of sudden death, including 3 “recovered” by external electric shock, a dozen electrocardiographic rhythm disorders or cardiac symptoms evoking them as syncopes, and conduction disorders including prolongation of the QT interval, favorable evolution after stopping treatment. This initial assessment shows that the risks, in particular cardiovascular, associated with these treatments are very present and potentially increased in COVID-19 patients.”

 

  • Bosteels, Cedric, et al. Inflammatory Type 2 cDCs Acquire Features of cDC1s and Macrophages to Orchestrate Immunity to Respiratory Virus Infection.” Immunity 52, 1–18 June 16, 2020. Doi: https://doi.org/10.1016/j.immuni.2020.04.005

Summary: “Using single-cell technologies in models of respiratory viral infection, we found that lung cDC2s acquired expression of the Fc receptor CD64 shared with MCs and of IRF8 shared with cDC1s. These inflammatory cDC2s (inf-cDC2s) were superior in inducing CD4+ T helper (Th) cell polarization while simultaneously presenting antigen to CD8+ T cells. When carefully separated from inf-cDC2s, MCs lacked APC function. InfcDC2s matured in response to cell-intrinsic Toll-like receptor and type 1 interferon receptor signaling, upregulated an IRF8-dependent maturation module, and acquired antigens via convalescent serum and Fc receptors. Because hybrid inf-cDC2s are easily confused with monocyte-derived cells, their existence could explain why APC functions have been attributed to MCs.”

 

  • Brufsky, Adam, et al. “Infection of the Dendritic Cell through the ACE2/DC-SIGN/CD209 Complex and Measurement of Inflammatory Markers in Clinical Trials of COVID-19.” BMJ, May 14, 2020; 369. Doi: https://doi.org/10.1136/bmj.m1849 

From rapid respomse: “COVID-19 pathogenesis can be partially explained by infection of the dendritic cell and endothelial cells through ACE2/DC-SIGN/CD209 receptor complex on these cells as well as infection of the type II pneumocyte through its ACE2/L-SIGN/CD209 complex[5]. Hydroxychloroquine[6] and famotidine[7] are modulators of the dendritic cell. Such modulation could be expected to blunt the immune response and reduce levels of interleukin-6 (IL-6) C- reactive protein (CRP), and other inflammatory markers… The observational studies of hydroxychloroquine[2, 3] did not control for famotidine use. In the observational trial of famotidine as treatment for COVID-19 pneumonia, while the difference did not appear to be statistically significant, famotidine was associated with a HR of intubation or death of 0.55 (95% CI 0.18-1.75), while the combination of famotidine and hydroxychloroquine was associated with a HR of intubation of death of 0.35 (95% CI 0.14-0.85)[4].”

 

Abstract: “We report the change in the QT interval in 84 adult patients with SARS-CoV-2 infection treated with Hydroxychloroquine/Azithromycin combination. QTc prolonged maximally from baseline between days 3 and 4. in 30% of patients QTc increased by greater than 40ms. In 11% of patients QTc increased to >500 ms, representing high risk group for arrhythmia. The development of acute renal failure but not baseline QTc was a strong predictor of extreme QTc prolongation.”

 

  • Costedoat-Chalumeau, Nathalie, et al. “Hydroxychloroquine in systemic lupus erythematosus: results of a French multicentre controlled trial (PLUS Study).” Ann Rheum Dis 2013;72: 1786–92. Doi: 10.1136/annrheumdis-2012-202322

From abstract: “Overall, mean [HCQ] was 918±451 ng/ml. Active SLE was less prevalent in patients with higher [HCQ].”

 

  • Costedoat-Chalumeau, Nathalie, et al. “Heart conduction disorders related to antimalarials toxicity: an analysis of electrocardiograms in 85 patients treated with hydroxychloroquine for connective tissue diseases.” Rheumatology 2007; vol 46, issue 5: 808–810. Doi:10.1093/rheumatology/kel402

From abstract: “PR interval, QTc interval and heart rate were not different from normal values. The rate of heart conduction disorders was similar to what is expected in the general population, and contrasted with prior results in CQ-treated patients. Our results add further evidence on the safety of HCQ compared with CQ.”

 

  • Dan Liu, et al. “Chloroquine and Hydroxychloroquine Are Associated With Reduced Cardiovascular Risk: A Systematic Review and Meta-Analysis.” Drug Des Devel Ther. 2018 Jun 11;12:1685-1695.  Doi: 10.2147/DDDT.S166893

From abstract: “A total of 19 studies (7 case-control studies, 12 cohort studies, and no clinical trials) involving 19,679 participants were included in the meta-analysis. Pooled results for HRs or RRs showed that CQ/HCQ was associated with a significantly reduced risk of CVD (pooled RR 0.72, 95% CI 0.56-0.94, p=0.013)… Our results suggested that CQ/HCQ was associated with a reduced risk of CVD in patients with rheumatic diseases.”

 

  • De Spiegeleer, Anton, et al. “The effects of ARBs, ACEIs and statins on clinical outcomes of COVID-19 infection among nursing home residents.” medRxiv, May 15, 2020. Doi: https://doi.org/10.1101/2020.05.11.20096347

From abstract: “We found a statistically significant association between statin intake and the absence of symptoms during COVID-19 infection (unadjusted OR 2.91; CI 1.27-6.71; p=0.011), which remained statistically significant after adjusting for age, sex, functional status, diabetes mellitus and hypertension. The strength of this association was considerable and clinically important.”

 

  • Duarte, Elizabeth, et al. “Rapid fitness losses in mammalian RNA virus clones due to Muller’s ratchet.” Proc. Natl. Acad. Sci. USA Vol. 89, pp. 6015-6019, July 1992.

From abstract: “Muller’s ratchet is an important concept in population genetics. It predicts that when mutation rates are high and a significant proportion of mutations are deleterious, a kind of irreversible ratchet mechanism will gradually decrease the mean fitness of small populations of asexual organisms… Experimental support for Muller’s ratchet has previously been obtained in protozoa and in a tripartite RNA bacteriophage. We now show clear evidence that Muller’s ratchet can operate on a nonsegmented nonrecombining pathogenic RNA virus of animals and humans.”

 

  • Dunne, Michael, et al. “A Multicenter Study of Azithromycin, Alone and in Combination with Chloroquine, for the Treatment of Acute Uncomplicated Plasmodium falciparum Malaria in India.” Journal of Infectious Diseases, 2005; 191: 1582-8. Doi: 10.1086/429343

From results: “At day 28, 5 (33%) of 15 participants in the azithromycin-treated group had remained free of fever, compared with 4 (27%) of 15 in the chloroquine-treated group. All subsequently enrolled participants then received combination therapy with azithromycin and chloroquine. In 61 (97%) of 67 participants, resolution of fever and parasitemia had occurred by day 7, and, through day 28, no clinical or parasitologic relapse had occurred in them.”

 

  • Furst DE, et al. “Dose-loading with hydroxychloroquine improves the rate of response in early, active rheumatoid arthritis: A randomized, double-blind six-week trial with eighteen-week extension.” Arthritis & Rheumatism. 1999;42(2):357–65. Doi: 10.1002/1529-0131(199902)42:2<357::AID-ANR19>3.0.CO;2-J.

From abstract: “Based on the Paulus criteria, response during the 6-week double-blind portion of the study was 47.97%, 57.7%, and 63.6% in the 400 mg/day, 800 mg/day, and 1,200 mg/day groups, respectively (P = 0.052). Discontinuations for adverse events were dose related (3 in the 400 mg/day group, 5 in the 800 mg/day group, 6 in the 1,200 mg/day group). Most involved the gastrointestinal (GI) system, with the background naproxen treatment possibly contributing. Ocular abnormalities occurred in 17 of 212 patients (8%) but were not dose related.”

 

  • George, Mariam Mathew, et al. “Zinc Induces Dendritic Cell Tolerogenic Phenotype and Skews Regulatory T cell – Th17 Balance.” J Immunol. 2016 Sep 1; 197(5): 1864-76. Doi: 10.4049/jimmunol.1600410.

From abstract: ” In this study, we investigated the effect of Zn on DC phenotype and the generation of forkhead box P3 (FoxP3+) regulatory T cells (Tregs) using a model of Histoplasma capsulatum fungal infection. Exposure of bone marrow derived DCs to Zn in vitro induced a tolerogenic phenotype by diminishing surface major histocompatibility complex (MHC)II and promoting the tolerogenic markers, programmed death-ligand (PD-L)1, PD-L2 and the tryptophan degrading enzyme, indoleamine 2,3 dioxygenase (IDO). Zn triggered tryptophan degradation by IDO and kynurenine production by DCs and strongly suppressed the proinflammatory response to stimulation by toll like receptor (TLR) ligands. In vivo, Zn supplementation and subsequent H. capsulatum infection supressed MHCII on DCs, enhanced PD-L1 and PD-L2 expression on MHCIIlo DCs and skewed the Treg – Th17 balance in favour of FoxP3+ Tregs while decreasing Th17 cells. Thus, Zn shapes the tolerogenic potential of DCs in vitro and in vivo and promotes Tregs during fungal infection.”

 

  • Giudicessi JR, et al. “Urgent guidance for navigating and circumventing the QTc prolonging and torsadogenic potential of possible pharmacotherapies for COVID-19.” Mayo Clin Proc. April 7, 2020. Doi: https://doi.org/10.1016/j.mayocp.2020.03.024.

From guidance note: “… This document serves to help health care professionals mitigate the risk of drug-induced ventricular arrhythmias while minimizing risk of COVID-19 exposure to personnel and conserving the limited supply of personal protective equipment.”

 

  • Guo, Li, Jianwei Wang, et al. “Profiling Early Humoral Response to Diagnose Novel Coronavirus Disease (COVID-19).” Clinical Infectious Diseases, ciaa310, March 21, 2020. Doi: https://doi.org/10.1093/cid/ciaa310

From abstract: “Humoral response to SARS-CoV-2 can aid to the diagnosis of COVID-19, including subclinical cases.”

 

From abstract: “We report functional characterizations of 11 24 patient-derived viral isolates. We observed diverse mutations in these viral isolates, 25 including 6 different mutations in the spike glycoprotein (S protein), and 2 of which are 26 different SNVs that led to the same missense mutation. Importantly, these viral isolates 27 show significant variation in cytopathic effects and viral load, up to 270-fold differences, 28 when infecting Vero-E6 cells. Therefore, we provide direct evidence that the 29 SARS-CoV-2 has acquired mutations capable of substantially changing its pathogenicity.”

 

  • Huang Jing-Tao, et al. “Chronological Changes of Viral Shedding in Adult Inpatients with COVID- 19 in Wuhan, China.” Clinical Infectious Diseases, ciaa631, May 23, 2020. Doi: https://doi.org/10.1093/cid/ciaa631.

From results: “Viral load of SARS-CoV-2 peaked within the first few days (2-4 days) after admission, then decreased rapidly along with virus rebound under treatment. Critical patients had the highest viral loads, in contrast to the general patients showing the lowest viral loads. The viral loads were higher in sputum compared with nasal and pharyngeal swab (p=0.026). The positive rate of respiratory tract samples was significantly higher than that of gastrointestinal tract samples (p<0.001). The SARS-CoV-2 viral load was negatively correlated with portion parameters of blood routine and lymphocyte subsets, and was positively associated with laboratory features of cardiovascular system.”

 

  • Karasic, Thomas, et al. “Effect of Gemcitabine and nab-Paclitaxel With or Without Hydroxychloroquine on Patients With Advanced Pancreatic Cancer: A Phase 2 Randomized Clinical Trial.” JAMA Oncol. 2019 Jul 1;5(7):993-998. Doi: 10.1001/jamaoncol.2019.0684.

From abstract: “The addition of HCQ to block autophagy did not improve the primary end point of overall survival at 12 months. These data do not support the routine use of GA plus HCQ for metastatic pancreatic cancer in the absence of a biomarker. However, improvement seen in the overall response rate with HCQ may indicate a role for HCQ in the locally advanced setting, where tumor response may permit resection.”

 

  • Keyaerts, Els, Leen, Vijgen, et al. “In vitro inhibition of severe acute respiratory syndrome coronavirus by chloroquine.” Biochemical and Biophysical Research Communications 323 (2004) 264–268. Doi: https://doi.org/10.1016/j.bbrc.2004.08.085

From abstract: “Chloroquine, an old antimalarial drug, may be considered for immediate use in the prevention and treatment of SARS-CoV infections.”

 

From summary: “To date we have identified fourteen mutations in Spike that are accumulating. Mutations are considered in a broader phylogenetic context, geographically, and over time, to provide an early warning system to reveal mutations that may confer selective advantages in transmission or resistance to interventions. Each one is evaluated for evidence of positive selection, and the implications of the mutation are explored through structural modeling. The mutation Spike D614G is of urgent concern; it began spreading in Europe in early February, and when introduced to new regions it rapidly becomes the dominant form. Also, we present evidence of recombination between locally circulating strains, indicative of multiple strain infections.”

 

  • Lane, Jennifer CE, et al. “Safety of hydroxychloroquine, alone and in combination with azithromycin, in light of rapid wide-spread use for COVID-19: a multinational, network cohort and self-controlled case series study.” medRxiv April 10, 2020. Doi: https://doi.org/10.1101/2020.04.08.20054551

From Preprint abstract: Data comprised 14 sources of claims data or electronic medical records from Germany, Japan, Netherlands, Spain, UK, and USA…  Overall, 956,374 and 310,350 users of hydroxychloroquine and sulfasalazine, and 323,122 and 351,956 users of hydroxychloroquine-azithromycin and hydroxychloroquine-amoxicillin were included… No excess risk of SAEs was identified when 30-day hydroxychloroquine and sulfasalazine use were compared. SCCS confirmed these findings. However, when azithromycin was added to hydroxychloroquine, we observed an increased risk of 30-day cardiovascular mortality (CalHR2.19 [1.22-3.94]), chest pain/angina (CalHR 1.15 [95% CI 1.05-1.26]), and heart failure (CalHR 1.22 [95% CI 1.02-1.45]) Conclusions: Short-term hydroxychloroquine treatment is safe, but addition of azithromycin may induce heart failure and cardiovascular mortality, potentially due to synergistic effects on QT length. We call for caution if such combination is to be used in the management of Covid-19.” 

 

From conclusion: “… this study has identified three indicators (LDH, hs-CRP and lymphocytes), together with a clinical route… for COVID-19 prognostic prediction. We have developed an XGBoost machine learning-based model that can predict the mortality rates of patients more than 10 days in advance with more than 90% accuracy.”

 

  • Mercuro, Nicholas, et al. “Risk of QT Interval Prolongation Associated With Use of Hydroxychloroquine With or Without Concomitant Azithromycin Among Hospitalized Patients Testing Positive for Coronavirus Disease 2019 (COVID-19).” JAMA Cardiol. Published online May 1, 2020. Doi: 10.1001/jamacardio.2020.1834

From findings: ” In a cohort study of 90 hospitalized patients with coronavirus disease 2019, use of hydroxychloroquine with or without azithromycin for treatment of COVID-19 was associated with frequent QTc prolongation, and those taking hydroxychloroquine and azithromycin had greater QT prolongation than those taking hydroxychloroquine alone. One patient developed torsades de pointes.”

 

  • Morena, Valentina, et al. “Off-label use of tocilizumab for the treatment of SARS-CoV-2 pneumonia in Milan, Italy.” European Journal of Internal Medicine, May 2020. https://doi.org/10.1016/j.ejim.2020.05.011

From conclusion: “Tocilizumab exerts a rapidly beneficial effect on fever and inflammatory markers, although no significant impact on the clinical outcome can be inferred by our results. Critically ill patients seem to have a high risk of serious infections with this drug.”

 

  • Munster, Tino, et al. “Hydroxychloroquine Concentration–Response Relationships in Patients With Rheumatoid Arthritis.” Arthritis & Rheumatism, Vol. 46, No. 6, June 2002, pp. 1460-9. Doi: 10.1002/art.10307.

From abstract: “There is a weak, but predictable, relationship between blood DHCQ concentrations and efficacy of treatment with HCQ. In addition, there is an association between gastrointestinal adverse events and elevated blood HCQ concentrations. Further investigation of these relationships is warranted to see if DHCQ may be introduced as a new antirheumatic drug.”

 

From abstract: “A 29 nucleotide deletion in open reading frame 8 (ORF8) is the most obvious genetic change in severe acute respiratory syndrome coronavirus (SARS-CoV) during its emergence in humans. In spite of intense study, it remains unclear whether the deletion actually reflects adaptation to humans. Here we engineered full, partially deleted (−29 nt), and fully deleted ORF8 into a SARS-CoV infectious cDNA clone, strain Frankfurt-1. Replication of the resulting viruses was compared in primate cell cultures as well as Rhinolophus bat cells made permissive for SARS-CoV replication by lentiviral transduction of the human angiotensin-converting enzyme 2 receptor. Cells from cotton rat, goat, and sheep provided control scenarios that represent host systems in which SARS-CoV is neither endemic nor epidemic. Independent of the cell system, the truncation of ORF8 (29 nt deletion) decreased replication up to 23-fold. The effect was independent of the type I interferon response. The 29 nt deletion in SARS-CoV is a deleterious mutation acquired along the initial human-to-human transmission chain. The resulting loss of fitness may be due to a founder effect, which has rarely been documented in processes of viral emergence. These results have important implications for the retrospective assessment of the threat posed by SARS.”

 

From interpretation: “Although generally well tolerated by a healthy community population, chloroquine does not prevent infection with influenza.”

 

  • Quan Du, Sean, and Weiming Yuan. “Mathematical Modeling of Interaction between1 Innate and Adaptive Immune Responses in2 COVID-19 and Implications for Viral3 Pathogenesis.” Journal of Medical Virology, May 2020. https://doi.org/10.1002/jmv.25866

From abstract: “The interaction between host innate and adaptive immune responses was found to be a potential cause for the higher severity and mortality in COVID-19 patients. Specifically the timing mismatch between the two immune responses has a major impact on the disease progression. The adaptive immune response of the COVID-19 patients are more likely to come before the peak of viral load, while the opposite is true for influenza patients. This difference in timing causes delayed depletion of vulnerable epithelial cells in the lungs in COVID-19 patients while enhancing the viral clearance in influenza patients. Stronger adaptive immunity in COVID-19 patients can potentially lead to longer recovery time and more severe secondary complications.

 

From abstract: “Here we report the lethality of CQ or HCQ in combination with metformin as a warning of its potential serious clinical toxicity. We hope that our report will be helpful to stimulate pharmacovigilance and monitoring of adverse drug reactions with the use of CQ or HCQ, particularly in combination with metformin.”

 

From abstract: “Recently, zinc homeostasis has been demonstrated to affect dendritic cells, in particular the involvement of zinc transport proteins during lipopolysaccharide-induced upregulation of major histocompatibility complex proteins and co-stimulatory molecules. This adds to our understanding of the immunomodulatory potential of zinc and highlights its significance for immune function.”

 

  • Roques, Pierre, et al. “Paradoxical Effect of Chloroquine Treatment in Enhancing Chikungunya Virus Infection.” Viruses 2018, 10(5), 268. Doi: https://doi.org/10.3390/v10050268

From abstract: “Acute CHIKV infection was exacerbated in NHPs treated with prophylactic administration of chloroquine. These NHPs displayed a higher viremia and slower viral clearance.”

 

  • Saleh, Moussa, et al. “The Effect of Chloroquine, Hydroxychloroquine and Azithromycin on the Corrected QT Interval in Patients with SARS-CoV-2 Infection.” AHA Journals, April 29, 2020. Doi: https://doi.org/10.1161/CIRCEP.120.008662.

From results: “Two hundred one patients were treated for COVID-19 with chloroquine/hydroxychloroquine. Ten patients (5.0%) received chloroquine, 191 (95.0%) received hydroxychloroquine and 119 (59.2%) also received azithromycin. The primary outcome of TdP was not observed in the entire population. Baseline QTc intervals did not differ between patients treated with chloroquine/hydroxychloroquine (monotherapy group) vs. those treated with combination group (chloroquine/hydroxychloroquine and azithromycin) (440.6 ± 24.9 ms vs. 439.9 ± 24.7 ms, p =0.834). The maximum QTc during treatment was significantly longer in the combination group vs the monotherapy group (470.4 ± 45.0 ms vs. 453.3 ± 37.0 ms, p = 0.004). Seven patients (3.5%) required discontinuation of these medications due to QTc prolongation. No arrhythmogenic deaths were reported.”

 

  • Simpson, Timothy F., et al. ” Association of QT-Prolonging Medications With Risk of Autopsy-Defined Causes of Sudden Death.” JAMA Intern Med. 2020;180(5):698-706. Doi: 10.1001/jamainternmed.2020.0148 .

From abstract: “After autopsy adjudication, use of QTPMs was associated with increased risk of non-SAD… but not SAD in all exposure groups… These findings confirm the association between QTPMs and presumed SCD; however, after autopsy, this risk was specific for nonarrhythmic causes of sudden death. Studies using consensus SCD criteria may overestimate the association of QTPMs with the risk of SAD.”

 

  • Soeltoft, K., et al. “OP0191 All-cause mortality and cardiovascular death in hydroxychloroquine users in rheumatoid arthritis patients – a population based Danish cohort study.”

From research note: “We found a significant reduction in all-cause mortality and cardiovascular related death among HCQ initiators, with a hazard ratio of 0.83 (95% confidence interval [CI] 0.71–0.97) and 0.78 (95% CI: 0.61 to 0.99), respectively. We did not find any association between HCQ use and development of type II diabetes or specific ischaemic events (myocardial infarctions and ischaemic strokes).”

 

From results section: “A dose-dependent decrease in virus antigen-positive cells was observed starting at 0.1 μM chloroquine, and concentrations of 10 μM completely abolished SARS-CoV infection.”

 

From summary of findings: “Apart from halofantrine, antimalarial medicines that prolong the QT/QTc interval, such as quinine, chloroquine, artesunate-amodiaquine and dihydroartemisinin-piperaquine, have been associated with a low risk of cardiotoxicity.”

 

  • Yilmaz, Attila, et al. “HMG-CoA Reductase Inhibitors Suppress Maturation of Human Dendritic Cells: New Implications for Atherosclerosis.” Atherosclerosis, 2004 Jan;172(1):85-93. Doi: 10.1016/j.atherosclerosis.2003.10.002

From abstract: ” In the present study, we have shown that statins inhibit the maturation and antigen-presenting function of human myeloid dendritic cells, thus maybe contributing to their beneficial effects in atherosclerosis. Therefore, the use of statins as immunomodulators might also provide a new therapeutic approach to other immunological disorders.”

 

From abstract: “… we performed a retrospective, multi-centered study of 7,337 cases of COVID-19 in Hubei Province, China, among which 952 had pre-existing T2D. We found that subjects with T2D required more medical interventions and had a significantly higher mortality (7.8% versus 2.7%; adjusted hazard ratio [HR], 1.49) and multiple organ injury than the non-diabetic individuals. Further, we found that well-controlled BG (glycemic variability within 3.9 to 10.0 mmol/L) was associated with markedly lower mortality compared to individuals with poorly controlled BG (upper limit of glycemic variability exceeding 10.0 mmol/L) (adjusted HR, 0.14) during hospitalization. These findings provide clinical evidence correlating improved glycemic control with better outcomes in patients with COVID-19 and pre-existing T2D.”

 

“For virus infections of multicellular hosts, narrow genetic bottlenecks during transmission and within-host spread appear to be widespread. These bottlenecks will affect the maintenance of genetic variation in a virus population and the prevalence of mixed-strain infections, thereby ultimately determining the strength with which different random forces act during evolution. Here we consider different approaches for estimating bottleneck sizes and weigh their merits. We then review quantitative estimates of bottleneck size during cellular infection, within-host spread, horizontal transmission, and finally vertical transmission. In most cases we find that bottlenecks do regularly occur, although in many cases they appear to be virion-concentration dependent. Finally, we consider the evolutionary implications of genetic bottlenecks during virus infection. Although on average strong bottlenecks will lead to declines in fitness, we consider a number of scenarios in which bottlenecks could also be advantageous for viruses.”

 

 

Current Studies

 

United States, Canada & Mexico

 

  • “Randomized, Multi-arm Phase II Trial of Novel Agents for Treatment of High-risk COVID-19 Positive Patients.” Susanne Arnold. University of Kentucky. NCT04374019.

From brief summary: “This is a multi-arm, phase II trial for rapid efficacy and toxicity assessment of multiple therapies immediately after COVID19 positive testing in high-risk individuals. Therapies include stand-alone or combination treatment with hydroxychloroquine, azithromycin, ivermectin, or camostat mesilate. The hypothesis of this study is that the addition of agents that inhibit viral entry or replication of SARS-CoV-2 virus, through alternative mechanisms to hydroxychloroquine, will be devoid of additional moderate to severe toxicities, will prevent clinical deterioration, and will improve viral clearance in high risk individuals.”

Details: 240 participants, May 2020-May 2021.

 

  • “Early Short Course Corticosteroids in Hospitalized Patients With COVID-19.” Mayur Ramesh, principal investigator. Henry Ford Health System. NCT04374071.

From brief summary: “The investigators intend to study the role of early use of methylprednisolone in the hospitalized patients with a diagnosis of COVID-19 pneumonia.”

Details: 25o participants, March-April 2020. Patients with moderate or severe disease who presented to HFHS within the first week of the COVID epidemic in Detroit were initially treated with supportive care with or without a combination of lopinavir-ritonavir and ribavirin or hydroxychloroquine according an institutional guideline developed by Infectious Diseases Physicians and Pharmacists.

 

  • “RCT in Asymptomatic Volunteers With COVID-19 Comparing Azithromycin and Hydroxychloroquine vs. Hydroxychloroquine Alone vs Standard of Care Without Antibiotics.” Jeffrey L Carson, principal investigator. Rutgers, The State University of New Jersey. NCT04374552.

From ACT Trial brief summary: “This study will randomize those people who do not have symptoms into one of three treatment plans 1) Hydroxycholoquine and Azithromycin, or 2) no active medication (placebo). All participants will be followed for 2 months. The study will determine if there is any benefit to those who are asymptomatic to taking taking Hydroxychloroquine sulfate in combination with Azithromycin, or if there is no benefit from taking these medications.”

Details: 140 participants, May-November 2020. Experimental: Hydroxychloroquine & Azithromycin. Hydroxychloroquine sulfate 400 mg po BID for day one and then 400 mg QD for 4 days Azithromycin 500 mg po on day one, followed by 250 mg po QD X 4 days. Placebo Comparator: Placebo. Placebo for Hydroxychloroquine sulfate (2 pills bid day one and then 2 tablets QD for 4 days) Placebo for Azithromycin (2 pills on day one and followed by 1 pill po QD x 4 days)

 

  • “Trial of Early Therapies During Non-hospitalized Outpatient Window (TREAT NOW) for COVID-19.” Todd Rice, principal investigator. Vanderbilt University Medical Center. NCT04372628.

From TREAT NOW Trial detailed description: “We will conduct an investigator-initiated, multicenter, blinded, placebo-controlled, randomized clinical trial evaluating hydroxychloroquine vs. lopinavir/ritonavir vs placebo for early treatment of adults with COVID-19 in the outpatient setting prior to hospitalization. Patients, treating clinicians, and study personnel will all be blinded to study group assignment.”

Details: 900 participants, May-December 2020. Active Comparator: Group 1 – Hydroxychloroquine then Placebo. Hydroxychloroquine 400 mg orally twice daily for two doses (Day 1), then 200 mg twice daily for subsequent eight doses (Day 2-5), then placebo twice daily for subsequent eighteen doses (Days 6-14). Active Comparator: Group 2 – Lopinavir/ritonavir. Lopinavir/ritonavir 400 mg/100 mg orally twice daily for twenty-eight doses (Days 1-14).

 

  • “An Open-Label, Phase II of Antiviral Therapy Combined With Baricitinib in Moderate and Severe Patients With COVID-19.” Heinz-Josef Lenz, principal investigator. University of Southern California. NCT04373044.

From brief summary: “This phase II trial studies how well antiviral therapy works when given in combination with baricitinib for the treatment of moderate or severe coronavirus disease-2019 (COVID-19). Antiviral therapy such as hydroxychloroquine, lopinavir/ritonavir, and remdesivir may act against infections caused by the virus responsible for COVID-19. Baricitinib may reduce lung inflammation and help prevent the need for being placed on a ventilator should the disease worsen. Giving antiviral therapy in combination with baricitinib may reduce the risk of the disease from getting worse compared to antiviral therapy alone.”

Details: 59 participants, May 2020-April 2021. Patients receive baricitinib PO daily. Patients also receive an antiviral therapy regimen per the study investigator and treating physician: 1) hydroxychloroquine PO TID, 2) lopinavir/ritonavir PO BID, or 3) remdesivir. All treatment continues for 14 days in the absence of disease progression or unacceptable toxicity.

 

  • “A Randomized Study Evaluating the Safety and Efficacy of Hydroxychloroquine and Zinc in Combination With Either Azithromycin or Doxycycline for the Treatment of COVID-19 in the Outpatient Setting.” Avni Thakore, principal investigator. St. Francis Hospital, New York. NCT04370782.

From brief summary: “Zinc is a supplement with possible antiviral properties, having been shown to have effect in the common cold, many of which are due to coronavirus. In addition, elderly patients and patients with co-morbidities have high incidence of zinc deficiency. We are repleting zinc in all patients and studying its direct effect in combination with hydroxychloroquine, and an antibiotic, either azithromycin or doxycycline to see if there is enhanced treatment efficacy in early COVID-19 infection and assess the safety of these two regimen.”

Details: 750 participants, April-September 2020. Arm 1: Drug: Hydroxychloroquine. Hydroxychloroquine 400mg twice a day (BID) on day 1, followed by 200mg BID for days 2-5. Drug: Azithromycin. Azithromycin 500mg on day 1, followed by 250mg once daily for days 2-5. Drug: Zinc Sulfate. Zinc sulfate 220mg once daily for 5 days. Arm 2: Drug: Hydroxychloroquine. Hydroxychloroquine 400mg twice a day (BID) on day 1, followed by 200mg BID for days 2-5. Drug: Zinc Sulfate. Zinc sulfate 220mg once daily for 5 days. Drug: Doxycycline. Doxycycline 200 mg once daily for 5 days.

 

  • “Prophylactic Benefit of Hydroxychloroquine in COVID-19 Cases With Mild to Moderate Symptoms and in Healthcare Workers With High Exposure Risk (PREVENT).” Andrea Natale, principal investigator. Texas Cardiac Arrhythmia Research Foundation. NCT04371926.

From PREVENT trial detailed description: “This study is designed to evaluate the prophylactic efficacy of HCQ in COVID-19 cases with mild to moderate symptoms and in the hospital staff engaged in attending infected patients.”

Details: 64 participants, June 2020-June 2021. Active Comparator: HCQ arm. COVID-19 positive cases will receive receive hydroxychloroquine sulfate 400 mg twice daily on the day of enrollment, then 200 mg twice daily for the next 4 days for a 5 day total course. Staff randomized to this group will receive HCQ sulfate 400 mg/week for 4 weeks.

 

  • “Randomized, Double-Blind, Controlled Trial of Hydroxychloroquine vs Placebo as Post-Exposure Prophylaxis Against COVID-19 Infection.” Susan Hoover, study chair. Sanford Health. NCT04372017.

From brief summary: “This is a prospective, double-blind, randomized, placebo-controlled study in two distinct cohorts to evaluate the efficacy and safety of hydroxychloroquine in the prevention of COVID-19 infection.”

Details: 1,739 participants, April 2020-April 2022. Drug: Hydroxychloroquine. Participants randomized to hydroxychloroquine will take 800mg on day 1 followed by 400mg on days 2-5.

 

  • “Treating COVID-19 With Hydroxychloroquine: A Multicenter Randomized, Double-blind, Placebo-controlled Clinical Trial in Hospitalized Adults.” Mark Mulligan, principal investigator. NYU Langone Health, State University of New York – Downstate Medical Center. NCT04369742.

From TEACH Trial brief summary: “Our primary endpoint is a severe disease progression composite outcome (death, ICU admission, mechanical ventilation, ECMO, , and/or vasopressor requirement) at the 14-day post-treatment evaluation.  Notable secondary clinical outcomes include 30-day mortality, hospital length of stay, noninvasive ventilator support, and cytokine release syndrome (CRS) grading scale. Secondary exploratory objectives will examine SARS-CoV-2 viral eradication at the EOT, changes in COVID-19 putative prognostic markers and cytokine levels, and titers of anti-SARS-CoV-2 antibodies. This randomized trial will determine if HCQ is effective as treatment in hospitalized non-ICU patients with COVID-19.”

Details: 626 participants, April-June, 2020. Drug: Hydroxychloroquine (HCQ) HCQ 400mg (2 tab) by mouth BID (day 1), 200mg (1 tab) by mouth BID (days 2-5).

 

  • “Observational Study of COVID-19 Treatment Efficacy.” David Hall, responsible party. OSF Healthcare System, Illinois. NCT04369989.

From brief summary: “Provide the opportunity to compare the effectiveness of various treatments and treatment timelines provided to specific cohorts of patients that have the potential to impact future treatment plans for COVID-19 patients and/or future research hypotheses.”

Details: 1,000 participants, April 2020-April 2021. 

 

  • “A Multi-site, Randomized, Double-Blind, Multi-Arm Historical Control, Comparative Trial of the Safety and Efficacy of Hydroxychloroquine, and the Combination of HCQ and Famotidine for the Treatment of COVID-19.” Joseph Conigliaro, principal investigator. Northwell Health. NCT04370262.

From MATCH Trial brief summary: “The trial will statistically compare the clinical benefit afforded by the two treatment strategies to internal historical “standard of care” data from Northwell patents treated without benefit of either hydroxychloroquine or high-dose famotidine. We will compare clinical outcomes associated with hydroxychloroquine and the addition of high-dose intravascular famotidine. The trial is designed to enroll at least 600 COVID-19 patients hospitalized with moderate to severe disease into each of the two active treatment arms, with a total enrollment target of at least 1200 patients.”

Details: 1,170 participants, April-September 2020. Active Comparator: HCQ/Famotidine. Subjects in this study arm will receive a combination of oral hydroxychloroquine and intravenous famotidine. Famotidine Injection, 10mg/mL mixed with Normal Saline is given intravenously at 120mg (30% of 400 mg oral dose). The total daily dose proposed is 360mg/day famotidine IV for a maximum of 14 days, or hospital discharge, whichever comes first. Hydroxychloroquine sulfate 200mg tablets will be administered as per the current clinical protocol for COVID – 19; a loading dose of 400 mg BID on day 1, followed by 200 mg BID for 4 days, or a loading dose of 800 mg QD on day 1, followed by 400 mg QD for 4 days, as per site specific clinical protocol for COVID-19.”

 

  • “VA Remote and Equitable Access to COVID-19 Healthcare Delivery (VA-REACH TRIAL).” Salomeh Keyhani, principal investigator. San Francisco VA Health Care System. NCT04363203.

From the VA-REACH Trial detailed description: “When azithromycin and hydroxychloroquine are given together, they can cause cardiac side-effects that limit use in the outpatient setting. These drugs, however, have independent potential benefits against COVID-19 that require more rigorous study before either is considered standard of care. We propose a 3-arm RCT to determine the efficacy of hydroxychloroquine or azithromycin in treating mild to moderate COVID-19 among Veterans in the outpatient setting.”

Details: 600 participants, April 2020-March 2021. Active Comparator: Hydroxychloroquine: 2x200mg mg PO in the AM and 2x200mg PO in the PM on Day 1, followed by 200mg capsule in the AM and 200 mg in the PM on Days 2-5. Active Comparator: Azithromycin: 2x250mg by mouth (PO) in the AM followed by 250mg PO every day on days 2-5.

 

  • “Hydroxychloroquine as Primary Prophylaxis for COVID-19 in Healthcare Workers (HCQPreP).” Ann Chauffe, principal investigator. Louisiana State University Health Sciences Center in New Orleans. NCT04363450.

From HCQPreP Trial detailed description: “The study is a double blind placebo controlled at two hospitals in Lafayette, Louisiana aiming to enroll 1700 participants with a 1:1 randomization. The HCQ dose in 400mg twice on day 1, then 200mg twice weekly. The primary outcome variable is development of symptomatic COVID-19 infection. The secondary objectives are number of days absent from work due to symptomatic COVID-19 infection and rate of severe disease due to COVID-19 (hypoxia in setting of >50% lung involvement on chest imaging, respiratory failure, shock or end-organ damage). The study will enroll participants for four weeks with and plan to treat with hydroxychloroquine versus placebo for a total of 12 weeks.”

Details: 1,700 participants, May-July, 2020. Experimental: Hydroxychloroquine loading dose will be given as 400mg for two doses 12 hours apart. This will then be followed by maintenance dosing of 200mg twice weekly for the remainder of the trial.

 

  • “A Randomized-Control Pilot Study to Assess Hydroxychloroquine in Patients Infected With SARS-CoV-2 (COVID-19).” Marcel Curlin, principal investigator. Oregon Health and Science University. NCT04363866.

From brief summary: “This is a prospective, randomized, participant-blinded, placebo-controlled, pilot study to assess the preliminary efficacy and safety of hydroxychloroquine for the treatment of patients with lower respiratory tract SARS-CoV-2 infection.”

Details: 40 participants, May-December 2020. Experimental: Hydroxychloroquine. 400 mg bid (PO) Day 1, followed by 200 mg bid (PO) Day 2 through Day 5.

 

  • “Sarilumab for Patients With Moderate COVID-19 Disease: A Randomized Controlled Trial With a Play-The-Winner Design.” Westyn Branch-Elliman, principal investigator. VA Boston Healthcare System. NCT04359901.

From brief summary: “Hospitalized patients meeting clinical criteria for moderate disease and testing positive for coronavirus infection. Interventions: sarilumab, one subcutaneous treatment of 200 mg. Standard care is not pre-specified, may vary among patients, and may include agents with anti-viral activity, such as remdesivir or hydroxychloroquine, among others. Up to 120 patients, primary outcome intubation or death within 14 days. All data will be extracted remotely from the EHR.”

Details: 120 participants, April 2020-April 2022. Active Comparator: Standard of care plus subcutaneous sarilumab. Standard of care as directed by the treating clinicians, plus sarilumab 200 mg subcutaneous injection x 1.

 

  • “A Randomized, Placebo-Controlled, Double-Blind, Single Center, Efficacy and Safety Study of Allogeneic HB-adMSCs for the Treatment of COVID-19.” Rajiv Thakur, principal investigator. Hope Biosciences, Houston. NCT04362189.

From brief summary: “Hope Biosciences is conducting a research study of an investigational product called allogeneic adipose-derived mesenchymal stem cells (abbreviated as HB-adMSCs) as treatment for patients hospitalized with COVID-19. The study purpose is to evaluate the safety and efficacy of four IV infusions of either placebo or HB-adMSCs in subjects with or without hydroxychloroquine and azithromycin treatment for patients hospitalized with COVID-19.”

Details: 110 participants, May-October 2020. Experimental: HC+AZ+HB-adMSCs. Subjects assigned to this arm will receive 4 intravenous infusions of HB-adMSCs at 100 million cells/dose, in addition to prescribed treatment with hydroxychloroquine and azithromycin. HB-adMSC infusions will occur at day 0, 3, 7, and 10. Placebo Comparator: HC+AZ+Placebo. Subjects assigned to this arm will receive 4 intravenous infusions of placebo (saline solution), in addition to prescribed treatment with hydroxychloroquine and azithromycin. HB-adMSC infusions will occur at day 0, 3, 7, and 10.

 

  • “Evaluating the Efficacy of Hydroxychloroquine and Azithromycin to Prevent Hospitalization or Death in Persons With COVID-19.” Davey Smith, principal investigator. National Institute of Allergy and Infectious Diseases (NIAID) and Teva Pharmaceuticals Industries LTD. NCT04358068.

From detailed description: “This Phase IIB study will evaluate the efficacy of hydroxychloroquine (HCQ) and azithromycin (Azithro) to prevent hospitalization or death in symptomatic adult outpatients with COVID-19. Participants will be randomized 1:1 to receive active/placebo study treatment as follows: HCQ/Placebo 600 mg immediately followed by 200 mg three times a day for 7 days and Azithro/Placebo 500 mg on the first day, followed by 250 mg daily for 4 days.”

Details: 2,000 participants, May-October 2020. Stratification will be by “high” versus “low” risk of progression to severe COVID-19 disease, where “high risk” is defined as a person age ≥60 years or having at least one of several specified comorbidities.

 

  • “A Multi-center, Randomized, Double-blinded, Placebo-controlled Study to Evaluate the Safety and Efficacy of Hydroxychloroquine Monotherapy and in Combination With Azithromycin in Patients With Moderate and Severe COVID-19 Disease.” Novartis Pharmaceuticals. NCT04358081.

From brief summary: “Hydroxychloroquine treatment may inhibit viral nucleic acid-mediated activation of various innate immune pathways, as well as blockade of lysosomal functions in cell types relevant for viral entry and antigen presentation.”

Details: 444 participants, April-July 2020. Experimental: Arm 1: hydroxychloroquine + aithromycin placebo. Hydroxychloroquine 600mg o.d. as loading dose (Day 1) +followed by 200mg t.i.d to be initiated within 8-12 hours of the loading dose (not to exceed 12 hours) Azithromycin (AZI) placebo o.d. Experimental: Arm 2: hydroxychloroquine + azithromycin. Hydroxychloroquine 600 mg o.d. as a loading dose (Day 1) followed by 200 mg t.i.d. to be initiated within 8-12 hours of the loading dose (not to exceed 12 hours) Azithromycin: 500 mg as a loading dose (Day 1) followed by 250 mg o.d. Day 2 – Day 5. Placebo Comparator: Arm 3; hydroxychloroquine placebo + azithromycin placebo. Hydroxychloroquine placebo o.d. (day 1) followed by hydroxychloroquine placebo t.i.d Azythromycin placebo o.d.

 

  • “Efficacy of Novel Agents for Treatment of SARS-CoV-2 Infection Among High-Risk Outpatient Adults: An Adaptive Randomized Platform Trial.” Christine Johnston, principal investigator. University of Washington. NCT04354428.

From detailed description: “This is a randomized, multi-center, placebo-equivalent (ascorbic acid + folic acid)-controlled, blinded platform trial.Eligible participants will be enrolled and randomized in a 1:1:1 ratio to Hydrocychloroquine (HCQ) + placebo (folic acid), HCQ + azithromycin, or placebo (ascorbic acid + folic acid). Initially, this study will enroll up to 495 eligible adults ( with high risk for Lower respiratory tract infection (LRTI) progression at baseline who are PCR-confirmed SARS-CoV-2 infection (165 per arm). An additional cohort of 135 eligible adults without risk factors for LRTI progression at baseline who are PCR-confirmed SARS-CoV-2 infection will be enrolled for the co-primary virologic outcome.During the 28 study days, participants will take the medication, complete surveys, collect mid nasal swab for viral quantification, and assess symptoms for progression to LRT.”

Details: 630 participants, April-October 2020. Experimental: Hydroxychloroquine and Azithromycin. HCQ 400 mg orally twice on Day 1, followed by 200 mg orally twice daily for an additional 9 days (Days 2 to 10) + azithromycin 500 mg orally once on Day 1, followed by 250 mg orally once daily for an additional 4 days (Days 2 to 5). Experimental: Hydroxychloroquine and Folic Acid. HCQ 400 mg orally twice on Day 1, followed by 200 mg orally twice daily for an additional 9 days (Days 2 to 10) + placebo (folic acid 800 µg orally once on Day 1, followed by 400 µg orally once daily for an additional 4 days [Days 2 to 5]).

 

  • “Off Label Study to Evaluate the Efficacy of HCQ for Pre-exposure Prophylaxis (PrEP) to Prevent Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection Among Health Care Workers (HCWs) Who Are at High Risk of Occupational Exposure to SARS-CoV-2.” Michael Belmont, principal investigator. NYU Langone Health. NCT04354870.

From the detailed description: “Hydroxychloroquine (HCQ) is licensed for the chemoprophylaxis and treatment of malaria and as a disease modifying antirheumatic drug. It has a long history of being safe and well tolerated at typical doses. HCQ has antiviral activity in vitro against coronaviruses, and specifically Covid-19. This study is designed to evaluate the efficacy of hydroxychloroquine (HCQ) for pre exposure prophylaxis (PrEP) to prevent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among health care workers at high risk of occupational exposure to SARS-CoV-2 compared to the eligible cohort that declines treatment.”

Details: 350 participants, April-August 2020. Drug: Hydroxychloroquine (HCQ) Loading dose: 600 mg, oral, 1 day Maintenance dose: 200 mg, oral, daily, for 90 days.

 

  • “Protecting Health Care Workers From COVID-19 With Hydroxychloroquine Pre-exposure Prophylaxis: A Randomized, Placebo-controlled Trial.” Bradley A. Connor, principal investigator. GeoSentinel Foundation. NCT04352946.

From the HERO Trial detailed description: “This is a double-blinded, randomized placebo-controlled trial to determine if pre-exposure prophylaxis (PrEP) with 400mg hydroxychloroquine (HCQ), taken orally once daily, for health care workers in the hospital reduces symptomatic and asymptomatic COVID-19 disease during the pandemic.”

Details: 374 participants, April-August 2020. 

 

  • “A Randomized Phase 2/3 Trial of Hydroxychloroquine In Covid-19 Kinetics.” William O. Richards, principal investigator. University of South Alabama College of Medicine. NCT04353271.

From the THICK Trial brief summary: ” To test if the medication Hydroxychloroquine will decrease the amount of virus(as measured by PCR) , 7 days after initiation of therapy compared to control patients receiving placebo. The study design is a randomized (5 days of medication v. 5 days of placebo) clinical trial initiated immediately after diagnosis in ambulatory health care workers at University of South Alabama Health, or in ambulatory USA patients. At 7 days after enrollment another nasopharyngeal swab will be taken to measure if the virus is still present. At 10 weeks we will measure immunity from Covid-19 using a single blood sample. It is a phase 2/3 clinical trial.”

Details: 58 participants, April-July 2020.

 

  • “Hydroxychloroquine Treatment of Healthcare Workers With COVID19 Illness at Montefiore: a Review of Process Feasibility, Safety, and Clinical Outcomes.” Priya Nori, principal investigator. Montefiore Medical Center. NCT04350450.

From the arms and interventions: “Eligible participants will be offered the standard Montefiore HCQ dosing regimen of 400mg every 12 hours x 24 hours, then 400mg daily for remaining 4 days and complete a survey study. Participants who opt not to receive the study drug will also be invited to participate in the survey study assessing COVID19 symptoms.” 

Details: 100 participants, April-August 2020.

 

  • “High-dose Hydroxychloroquine for the Treatment of Ambulatory Patients With Mild COVID-19.” Reem Jan, principal investigator. University of Chicago. NCT04351620.

From the brief summary: “This is a single arm and single-center tolerability study of high dose HCQ therapy in outpatient adult participants with mild COVID-19. In vitro studies have shown antiviral effects of HCQ against SARS Cov-2, but the clinical outcomes in the disease have been variable. Our hypothesis is that targeting high risk patients earlier in the disease course and with a higher dose regimen are both required to see improvement in disease outcome measures in COVID-19. This study aims to prove the tolerability of high dose HCQ in this setting.”

Details: 20 participants, April-June 2020. 1200 mg hydroxychloroquine daily will be prescribed.

 

  • “The Fleming [FMTVDM] Directed CoVid-19 Treatment Protocol.” RM Fleming, principal investigator. The Camelot Foundation, Los Angeles. NCT04349410.

From the brief summary: “The purpose of this paper is to make clinicians and researchers aware of this proposed method for investigating the prevalence and severity of CVP – in addition to providing rapid determination of treatment response in each patient, directing treatment decisions; thereby reducing the loss of time, money, resources and patient lives.”

Details: 500 participants, April-November, 2020. Experimental: Treatment 1. Hydroxychloroquine 200 mg po q 8 hrs (600 mg qD) for a total of 10-days, and Azithromycin 500 mg IV on day 1, followed by 250 mg IV on days 2-5 (to prevent bacterial superinfection).

 

  • “Prophylactic Hydroxychloroquine vs Vitamin C in Healthcare Workers:RCT.” Adam Singer, principal investigator. Stony Brook University. NCT04347889.

From detailed description: “Healthcare workers (HCW) at risk of Covid-19 will have baseline serology for SARS-CoV-2 to see if they are already immune to Covid-19. HCW will get baseline assessment and if meeting inclusion criteria and no exclusion criteria they will be randomized in a 2:1 ratio to hydroxychloroquine or Vitamin C on a weekly basis for three months. Subjects will complete daily diary of symptoms and temperature, and will have repeat SARS-CoV-2 serology at 6 weeks and 3 months to determine seroconversion.”

Details: 1,212 participants, April-December 2020. Experimental: Hydroxychloroquine. Oral loading dose of 800 mg followed by once weekly oral hydroxychloroquine 400 mg for 3 months.

 

  • “Treatment in Patients With Suspected or Confirmed COVID-19 With Early Moderate or Severe Disease: A Randomized Clinical Trial.” Principal investigator: Meredith Clement. University Medical Center New Orleans. NCT04344444.

From brief summary: “Patients will be randomized to supportive care, OR hydroxychloroquine alone, OR hydroxychloroquine and azithromycin.” 

Details: 600 participants, April 2020-April 2021. Experimental: Arm B Hydroxychloroquine 400 mg po bid on Day 1 Hydroxychloroquine 200 mg po bid Days 2 through 5. Hydroxychloroquine as in Arm B AND Azithromycin 500 mg po on Day 1 Azithromycin 250 mg po days 2 through 5.

 

  • “An Open-Label, Single-Arm, Phase II Study to Evaluate the Efficacy and Safety of Oral Hydroxychloroquine, Indomethacin and Zithromax in Subjects Positive With SARS-CoV-2 With Mild Symptoms in Maricopa County.” Teresa Gaither, principal investigator. Perseverance Research Center, Arizona. NCT04344457.

From detailed description: “This study will measure the improvement of COVID-19 disease status as measured by time (days) required from initiation of treatment to improvement of clinical status from mild to symptom free on 14 days of a cocktail therapy of Hydroxychloroquine, Indomethacin and Zithromax.”

Details: 80 participants, April-September 2020. Drug: Hydroxychloroquine 200 mg PO BID 5 days. Drug: Indomethacin 50 mg PO TID 14 Days. Drug: Zithromax Oral Product 500 mg PO QD 3 Days.

 

  • “Feasibility, Safety and Early Efficacy Trial of Hydroxychloroquine as Primary Prevention of Corona Virus Disease 2019 in High Risk Health Care Providers.” Jawad Kirmani, principal investigator. Hackensack Meridian Health. NCT04345653.

From the brief summary: “The study proposes to conduct an open-label Phase II trial to evaluate the feasibility, safety and early efficacy of hydroxychloroquine (HCQ) administration in reduction of transmission of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and development of Corona Virus Disease 2019 (COVID-19) in high-risk, healthy acute care provider participants exposed, directly or indirectly, to COVID-19 patients.”

Details: 45 participants, April 2020-April 2021. Early data on use of HCQ for COVID treatment suggests anti-viral activity and immunomodulatory properties for reducing inflammation associated with COVID-19. Given the lack of data regarding use of HCQ for COVID-19 prevention in healthy participants in midst of pandemic crisis, this study proposes an expedited feasibility study focusing on safety and early efficacy.

 

  • A Randomized Controlled Clinical Trial: Hydroxychloroquine for the Treatment of COVID-19 in Hospitalized Patients (OAHU-COVID19).” Todd Seto, principal investigator. Queen’s Medical Centre, Oahu.  NCT04345692.  

From the brief summary: “This study is a randomized, open label clinical trial to evaluate the safety and efficacy of hydroxychloroquine (HCQ) plus usual care compared to usual care in approximately 350 hospitalized patients diagnosed with COVID-19. The study will be a 2-arm, non-blinded comparison between open label hydroxychloroquine and usual care. The course of treatment (HCQ) is five days. Participants will be followed to study day 28.”

Details: Experimental: 350 participants, March 2020-December 2021. Hydroxychloroquine. Hydroxychloroquine 400 mg 2x day by mouth on day 1, followed by 200 mg 2x day by mouth days 2-5.

 

  • “Military COVID-19 Hydroxychloroquine Pre-exposure and Post-exposure Prophylaxis Study.” Scott A. Wallace, United States Department of Defense. NCT04343677.

From outcome measures: “The primary aim of this study is to determine whether pre-exposure prophylaxis decreases the incidence of COVID-19 infections amongst personnel.”

Details: 1,450 participants, April-August 2020. The study will consist of 4 arms: A placebo control arm of 450 patients. A low dose prophylaxis arm of 450 patients treated with 200mg Hydroxychloroquine daily. A high dose prophylaxis arm of 450 patients treated with 400mg Hydroxychloroquine daily. A post-exposure arm of 100 patients treated with 400mg Hydroxychloroquine daily for 7 days.

 

  • Will Hydroxychloroquine Impede or Prevent COVID-19 (WHIP COVID-19).” O’Neill, William, principal investigator. Henry Ford Health System, Detroit COVID Consortium. NCT04341441.

From press release: “The study, titled WHIP COVID-19 Study, is a 3,000+ subject look at whether the drug prevents front-line workers from contracting the virus. Once they provide a blood sample, the study subjects will receive vials with unidentified, specific pills to take over the next eight weeks: a once-a-week dose of hydroxychloroquine, a once-a-day dose, or a placebo (a pill that looks like the medication, but does not contain any medication or other active ingredients).”

Details: Any hospital healthcare worker within the Metro Detroit area will be able to volunteer to participate. Participants will be provided with weekly dosing of hydroxychloroquine (HCQ) 400 mg po q weekly, daily dosing of HCQ 200 mg po q daily following a loading dose of 400 mg day 1, or placebo. 

 

  • “Pre-exposure Prophylaxis for SARS-Coronavirus-2: A Pragmatic Randomized Clinical Trial.” Radha Rajasingham, principal investigator. University of Minnesota. NCT04328467.

From detailed description: “Chloroquine or Hydroxychloroquine may have antiviral effects against SARS-COV2 which may prevent COVID-19 disease or reduce disease severity. It is not known at what dosing hydroxychloroquine may be effective for pre-exposure prophylaxis.”

Details: 3,500 participants, April-August 2020. Experimental: Intervention Once Weekly. 400 mg orally once, followed by 400mg 6 to 8 hours later, thereafter 400mg weekly for the duration of follow up, up to 12 weeks. Experimental: Intervention Twice Weekly. 400mg orally once, followed by 400mg 6 to 8 hours later, thereafter 400mg twice weekly for the duration of follow up, up to 12 weeks.

 

  • “Post-exposure Prophylaxis and Preemptive Therapy for SARS-Coronavirus-2: A Pragmatic Randomized Clinical Trial.” David Boulware, principal investigator. University of Minnesota, McGill University Health Centre/Research Institute of the McGill University Health Centre, University of Manitoba, University of Alberta. NCT04308668.

From the COVID-19 PEP Trial detailed description: “Hydroxychloroquine may have antiviral effects against SARS-COV2 which may prevent COVID-19 disease or early preemptive therapy may decrease disease severity. This trial will use a modification of standard malaria dosing of hydroxychloroquine to provide post-exposure prophylaxis to prevent disease or preemptive therapy for those with early symptoms.”

Details: 3,000 participants, March-May 2020. Drug: Hydroxychloroquine. 200mg tablet; 800 mg orally once, followed in 6 to 8 hours by 600 mg, then 600mg once a day for 4 consecutive days.

 

  • “Comparison Of Therapeutics for Hospitalized Patients Infected With SARS-CoV-2 In a Pragmatic aDaptive randoMizED Clinical Trial During the COVID-19 Pandemic (COVID MED Trial).” Daniel Freilich. Bassett Healthcare, New York State. NCT04328012.

From the COVID MED Trial brief summary: “This pragmatic adaptive trial compares outcome in COVID-19 patients treated with lopinavir/ritonavir, hydroxychloroquine, losartan, and placebo.”

Details: 4,000 participants, April 2020-January 2021. Group 1 standard care and lopinavir/ritonavir, Group 2 standard care and hydroxychloroquine, Group 3 standard care and losartan, or Group 4 standard care and placebo. Patients will be followed for up to 60 days.

 

  • “Randomized Study to Evaluate the Safety and Antiviral Efficacy of Hydroxychloroquine in Patients With Newly Diagnosed COVID-19 Compared to Standard of Care Treatment.” Brian Kendal, principal investigator. Providence Health & Services, Center for Outcomes Research and Education, Providence Cancer Center, Earle A. Chiles Research Institute. NCT04334967.

From detailed description: “This randomized control study will assess its potential as an off-label treatment in reducing the rates of hospitalization and subsequent mechanical ventilation from COVID-19 infection compared to standard of care treatment with Vitamin C.” 

Details: 1,250 participants. Experimental: Treatment Arm Patients in the treatment arm will receive 200 mg oral hydroxychloroquine. Day 1: 400 mg doses twice (800 mg total). Days 2-5: 200 mg dose twice (400 mg total daily).

 

  • “Outcomes Related to COVID-19 Treated With Hydroxychloroquine Among In-patients With Symptomatic Disease.” Boyd Taylor Thompson, principal investigator. Massachusetts General Hospital, National Heart, Lung, and Blood Institute (NHLBI). NCT04332991.

From ORCHID detailed description: “Study Aim: To compare the effect of hydroxychloroquine versus placebo on clinical outcomes, measured using the COVID Ordinal Outcomes Scale at Day 15, among adults with COVID-19 requiring hospitalization.”

Details: 510 participants, April 2020-April 2021. Participants assigned to the hydroxychloroquine arm will receive hydroxychloroquine sulfate 400 mg twice daily on the day of enrollment, then 200 mg twice daily for the next 4 days for a 5 day total course.

 

  • “Hydroxychloroquine Post Exposure Prophylaxis (PEP) for Household Contacts of COVID-19 Patients: A NYC Community-Based Randomized Clinical Trial.” Elizabeth Oelsner, principal investigator. Columbia University Irving Medical Center. NCT04318444.

From the detailed description: “This study will test if hydroxychloroquine may be used to prevent the development of COVID-19 symptoms in persons who live with an individual who has been diagnosed with COVID-19… This is a trial of hydroxychloroquine PEP among adult household contacts of COVID-19 patients in New York City (NYC). 

Details: 1,600 participants. March 2020-2021. Experimental: Hydroxychloroquine. Two tablets (400mg) twice daily on day 1; for days 2-5, they will be instructed to take one tablet (200mg) twice daily.

 

  • “Efficacy of Hydroxychloroquine for Post-exposure Prophylaxis (PEP) to Prevent Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection Among Adults Exposed to Coronavirus Disease (COVID-19): a Blinded, Randomized Study.” Ruanne V. Barnabas, principal investigator. University of Washington, NYU Langone Medical Center, Bill and Melinda Gates Foundation. NCT04328961.

From the detailed description: “This is a randomized, multi-center, placebo-equivalent (ascorbic acid) controlled, blinded study of Hydroxychloroquine (HCQ) post-exposure prophylaxis (PEP) for the prevention of SARS-CoV-2 infection in adults exposed to the virus.The overarching goal of this study is to assess the effectiveness of HCQ PEP… to inform public health control strategies.This study will enroll up to 2000 asymptomatic men and women 18 to 80 years of age (inclusive) at baseline who are close contacts of persons with PCR-confirmed SARS-CoV-2 or clinically suspected COVID-19 and a pending SARS-CoV-2 PCR test.”

Details: March-September 2020. Experimental: Hydroxychloroquine. Hydrochloroquine 400 mg orally daily for 3 days, then 200 mg orally daily for an additional 11 days.

 

  • “A Phase 1b, Randomized, Double-blinded, Placebo-controlled Study of Hydroxychloroquine in Outpatient Adults With COVID-19.” Sanofi Clinical Sciences & Operations, study director. Sanofi, Boston. NCT04333654.

From brief summary: “To assess the effect of hydroxychloroquine versus placebo on nasopharyngeal SARS-CoV-2 viral load in outpatient adults with COVID-19.”

Details: 210 participants. The duration of the study per participant will be around 18 days (1 or 2 days of screening followed by a 10-day treatment period and a 4 to 6 days follow-up period) May 2020.

 

  • “Randomized Comparison of Combination Azithromycin and Hydroxychloroquine vs. Hydroxychloroquine Alone for the Treatment of Confirmed COVID-19.” Sabiha Hussain, principal investigator. Rutgers, The State University of New Jersey. NCT04336332.

From the brief summary: “This is a three-arm randomized trial comparing the efficacy of single agent hydroxychloroquine to the combination of hydroxychloroquine and azithromycin, and to a delayed hydroxychloroquine regimen, which will serve as a contemporaneous Day 1-6 supportive care control, in eliminating detectable SARS-CoV-2 on day 6 following the initiation of treatment in order to determine which regimen is more effective.”

Details: 160 participants, April 2020-April 2021. Experimental: Arm A: Hydroxychloroquine Sulfate + Azithromycin. Hydroxychloroquine sulfate 200 mg taken by mouth three (3) times a day for 10 days. Azithromycin 500 mg taken by mouth on Day 1, followed by Azithromycin 250 mg taken by mouth once (1) time a day for four (4) days. Experimental: Arm B: Hydroxychloroquine Sulfate alone, Hydroxychloroquine sulfate 200 mg taken by mouth three (3) times a day for 10 days.

 

  • “An Open Label Phase II Pilot Study of Hydroxychloroquine, Vitamin C, Vitamin D, and Zinc for the Prevention of COVID-19 Infection.” Sabine Hazan, principal investigator. ProgenaBiome, Ventura, California. NCT04335084.

From the detailed description: “In this study, subjects will take a regimen of hydroxychloroquine, vitamin C, vitamin D, and Zinc to test if this combination can prevent infection with COVID-19. The study will last 24 weeks.”

Details: 600 participants, April 2020-April 2021.

 

  • “A Phase II Pilot Study of Quintuple Therapy to Treat COVID-19 Infection.” Sabine Hazan, principal investigator. ProgenaBiome, Ventura, California. NCT04334512.

From the HAZCpaC Trial brief summary: “This is a Phase II interventional study will test the efficacy of quintuple therapy (Hydroxychloroquine, Azithromycin, Vitamin C, Vitamin D, and Zinc) in the treatment of patients with COVID-19 infection).”

Details: 60 participants, April 2020-April 2021.

 

  • “A Prospective Clinical Study of Hydroxychloroquine in the Prevention of SARS- CoV-2 (COVID-19) Infection in Healthcare Workers After High-risk Exposures.” Peter A. McCullough, principal investigator. Baylor Healthcare System. NCT04333225.

From the brief summary: “In order to assess the efficacy of hydroxychloroquine treatment weekly for a total of 7 weeks in the prevention of COVID-19 infection, three hundred sixty (360) Healthcare workers with high risk exposure to patients infected with COVID-19 will be tested for COVID-19 infection via nasopharyngeal (NP) swab once weekly for 7 weeks. Of those, one hundred eighty (180) will receive weekly doses of hydroxychloroquine for the duration of the study. Subjects who opt not to receive the study drug will form the control group.”

Details: 360 participants. April-July 2020. 

 

  • “A Phase 2, International Multi-site, Bayesian Adaptive, Randomised, Double-blinded, Placebo-controlled Trial Assessing the Effectiveness of Varied Doses of Oral Chloroquine in Preventing or Reducing the Severity of COVID-19 Disease in Healthcare Workers.” Michael Avidan, principal investigator. Washington University School of Medicine. NCT04333732.

From the CROWN CORONATION brief summary: “Randomization will be stratified by age (<50 and ≥50) and study site. Participants will be healthcare workers at risk for contracting SARS-CoV-2. Participants will be randomized into one of four arms: Low-dose (300mg chloroquine base weekly); Medium-dose (300mg chloroquine base twice weekly); High-dose (150 mg chloroquine base daily); Placebo.”

Details: 55,000 projected participants. In certain countries (especially where malaria is not endemic), hydroxychloroquine is more readily available and will be used instead of chloroquine. 

 

  • “WU 352: Open-label, Randomized Controlled Trial of Hydroxychloroquine Alone or Hydroxychloroquine Plus Azithromycin or Chloroquine Alone or Chloroquine Plus Azithromycin in the Treatment of SARS CoV-2 Infection.” Jane O’Halloran, principal investigator. Washington University School of Medicine. NCT04341727.

From the detailed description: “This Phase III trial will utilize four treatment strategies in non-critically ill hospitalized participants (not requiring mechanical ventilation) with SARS CoV-2 infection… We are primarily interested in the time to recovery.”

Details: 500 participants, April 2020-April 2021. Arm 1: Hydroxychloroquine 400mg orally twice a day for one day, followed by 200mg twice a day for four consecutive days (Five days in total). The drug will be supplied in 200mg tablets. rm 2: Hydroxychloroquine 400mg orally twice a day for one day, followed by 200mg twice a day for four consecutive days (Five days in total). The drug will be supplied in 200mg tablets. AND Azithromycin 500mg orally once, followed by 250mg daily for four consecutive days (five days total). The drug will be supplied in 250mg tablets.

 

  • “PATCH 2 & 3: (Prevention and Treatment of COVID-19 With Hydroxychloroquine) An Open Label Multi-arm Randomized Trial of Hydroxychloroquine in the Prevention and Treatment of COVID-19.” Deneen Vojta, principal investigator. UnitedHealth Group. NCT04353037

From PATCH 2 & 3 Trial detailed description: “Sub-Study 1: COVID-19 patients in self-quarantine. Arm 1: Hydroxychloroquine 400 mg bid (two 200 mg tablets taken twice a day; totaling 800 mg per day) for two weeks; Arm 2: Placebo 2 pills bid for two weeks. Sub-Study 2: Asymptomatic health care worker prophylaxis. Arm 1: Hydroxychloroquine 600 mg qd (three 200 mg tablets taken once a day) for up to 2 months; Arm 2: Placebo 3 pills qd for up to 2 months; cross-over from placebo to HCQ 600 mg qd is allowed upon confirmatory diagnosis for COVID-19.”

Dertails: Drug: Group A HCQ Enrolled participants randomized in Group A receive the HCQ drug. Other Name: HCQ Arm Drug: Group B Control. Enrolled participants randomized in Group B will receive a placebo drug Other Name: Placebo Arm.

 

  • “Prevention and Treatment of COVID-19 with HCQ (PATCH).” Ravi K. Amaravadi, lead investigator. University of Pennsylvania Perelman School of Medicine. NCT04329923.

From the PATCH Trial website: “The PATCH trial tests hydroxychloroquine as a treatment in patients with COVID-19 and a preventative medication in health care workers at high risk of contracting COVID-19.” 

Details: Study Group 1: A double-blind placebo controlled trial of high dose hydroxychloroquine (HCQ) as a treatment for COVID-19 positive patients who are quarantined at home. Study Group 2: A randomized study testing different doses of HCQ in hospitalized COVID-19 patients. Study Group 3: A double-blind placebo controlled trial of HCQ as a preventative medicine in health care workers employed at the University of Pennsylvania.

 

  • “Preventing COVID-19 Infections: Healthcare Worker Exposure Response and Outcomes (HERO) Registry and Hydroxychloroquine (HERO-HCQ) Trial Program.” Adrian Hernandez, administrative principal investigator. Duke University School of Medicine Clinical Research Institute. For Patient-Centered Outcomes Research Institute. NCT04334148.

From the HERO Trial PCORI page: “… The second part of the program, a randomized clinical trial, will identify and seek consent from 15,000 HCWs from the registry who express interest in participating in the clinical trial. The trial will randomize participants to either one month of HCQ or placebo and will examine whether HCQ is effective in decreasing the rate of COVID-19 infection.”

Details: The $50 million program will engage the powerful PCORI-funded PCORnet®, the National Patient-Centered Clinical Research Network, which is an established health research network involving more than 850,000 clinicians and hundreds of health systems across the U.S. 

 

  • “Phase 2 Pragmatic Factorial Trial of Hydroxychloroquine, Azithromycin, or Both for Treatment of Severe SARS-CoV-2 Infection.” Jason Stout, principal investigator. Duke University Medical Center. NCT04335552.

From the brief summary: “This is a phase II, randomized, open-label, incomplete factorial with nested randomization clinical trial evaluating the efficacy and safety of two potential treatments for hospitalized patients with confirmed SARS-CoV-2 infection.” 

Details: 500 participants, April-August 2020. 1.Standard of care alone 2. Standard of care plus hydroxychloroquine. 3. Standard of care plus azithromycin. 4. Standard of care plus hydroxychloroquine plus azithromycin.

 

  • Pharmaceutical Products Development USDHHS Study.  Details currently unavailable.  News report: “The federal government has awarded Wilmington-based PPD $750,000 to research two antimalarial drugs being touted as a possible treatment for the novel coronavirus. According to federal contracting records, the contract research organization has until April 21 to develop an ‘expanded access treatment protocol for hydrochloroquine and chloroquine in patients with coronavirus disease (COVID-19), positive for SARS-COV-2 virus exposure, or pre-exposure and post-exposure prophylaxis.’ The U.S. Department of Health and Human Services awarded the contract on March 24.”

 

  • “Hydroxychloroquine vs. Azithromycin for Outpatients in Utah With COVID-19 (HyAzOUT): A Prospective Pragmatic Trial.” Brandon Webb, principal investigator. Intermountain Health Care, University of Utah, Utah DOH. NCT04334382.

From HyAzOUT brief summary: “This study will compare two drugs (hydroxychloroquine and azithromycin) to see if hydroxychloroquine is better than azithromycin in treating outpatients with suspected or confirmed COVID-19.”

Details: 1,550 participants. “Patients in the hydroxychloroquine arm will receive hydroxychloroquine 400mg po BID x 1 day, then 200mg po BID x 4 days (dose reductions for weight < 45kg). The drug dose (2.4 gm over 5 days) chosen falls at the lower end of doses proposed in various international trials, but it has proven in vitro efficacy, with a ratio of lung tissue trough concentrations to the EC50 (effective concentration to suppress 50% of viral activity) of >20. Patients in the azithromycin arm will receive azithromycin 500mg PO on day 1 plus 250mg PO daily on days 2-5.” April-December 2020.

 

  • “Hydroxychloroquine vs. Azithromycin for Hospitalized Patients With Suspected or Confirmed COVID-19 (HAHPS): A Prospective Pragmatic Trial.” Samuel Brown, principal investigator. Intermountain Health Care, University of Utah. NCT04329832.

From HAHPS Trial brief summary: “This study will compare two drugs (hydroxychloroquine and azithromycin) to see if hydroxychloroquine is better than azithromycin in treating hospitalized patients with suspected or confirmed COVID-19.”

Details: Patients in the hydroxychloroquine arm will receive hydroxychloroquine 400 mg by mouth twice daily for 1 day, then 200 mg by mouth twice daily for 4 days (dose reductions for weight < 45 kg or GFR (glomerular filtration rate)<50ml/min). Patients in the azithromycin arm will receive azithromycin 500 mg on day 1 plus 250 mg daily on days 2-5 (may be administered intravenously per clinician preference). If the patient has already received azithromycin prior to randomization, the prior doses will count toward the 5-day total.

 

  • “Protecting Frontline Health Care Workers From COVID-19 With Hydroxychloroquine Pre-exposure Prophylaxis: A Randomized, Placebo-controlled Multi-Site Trial in Toronto, Canada.” Megan Landes, principal investigator. University Health Network, Toronto. NCT04374942.

From HEROs Trial brief summary: “This study aims to evaluate whether hydroxychloroquine (HCQ), a well-tolerated drug typically used in the prevention of malaria transmission and rheumatic disease, taken before and during exposure to patients with COVID-19, is effective at reducing COVID-19 infections among ED health care workers.”

Details: 988 participants, April-August 2020. 50% of participants will be randomized to the study drug arm, and will take 400mg hydroxychloroquine orally once a day for three months (Day 1-90).

 

  • Hydroxychloroquine to Prevent COVID-19 Disease Amongst Healthcare Workers (PROVIDE): A Parallel Randomized Controlled Trial.” Waleed Al-Hazzani, principal investigator. St. Joseph’s Healthcare Hamilton. NCT04371523.

From the PROVIDE trial brief summary: 1. Determine if prophylactic once weekly hydroxychloroquine reduces the incidence of conversion from SARS-2-CoVnasopharyngeal swab negative to positive. 2. To determine if weekly prophylactic hydroxychloroquine reduced the severity of COVID-19 symptome. 3. To determine the safety of taking weekly prophylactic hydroxychloroquine.

Details: 1,100 participants, May-August, 2020. Drug: Apo-Hydroxychloroquine. Hydroxychloroquine sulfate 400mg PO BID on day one, then 400mg PO weekly, to be taken with meals for two months total.

 

  • “Randomized Trial Evaluating Effect of Outpatient Hydroxychloroquine on Reducing Hospital Admissions in Pregnant Women With SARS-CoV-2 Infection: HyPreC Trial.” Haim Abenhaim, contact. Sir Mortimer B. Davis Jewish General Hospital. NCT04354441.

From the HyPreC Trial detailed description: “To date, pregnant women have been systematically excluded from trials conducted in the general outpatient population. Thus, we will carry out a randomized, placebo-controlled, double blinded trial of HCQ (considered safe in pregnancy in pregnant women with early COVID-19 infection across Canada to evaluate its effect in reducing COVID-19-related hospitalizations.”

Details: 600 participants, May-November 2020. Drug: hydroxychloroquine sulfate 200 MG Hydroxychloroquine sulfate (Plaquenil) 2MG will be taken twice a day for 10 days. Participants will be couriered the medication upon giving consent and will start taking the medication immediately.

 

  • “IMPACT RAPPORT: IMPact of Antimalarials on Covid Infections: a Case Control sTudy of RAPPORT.” Stephanie O. Keeling, principal investigator. University of Alberta. NCT04347798.

From the IMPACT Trial brief summary: “This study aims to evaluate the experience of Alberta patients with inflammatory arthritis who participate in the the RAPPORT-ONTRAAC registry during the COVID-19 pandemic, specifically comparing the experience of those taking anti-malarial medications compared to those who do not. This registry includes approximately 2500 northern Alberta patients with inflammatory arthritis who receive highly complex therapies which may be associated with side effects. “

Details: 500 participants, April 2020-April 2021. 

 

  • “Treatment of Moderate to Severe Coronavirus Disease (COVID-19) in Hospitalized Patients.” Lisa Barrett, principal investigator. Nova Scotia Health Authority, Dalhousie University. NCT04321993.
From the brief summary: “Investigational medications adjunct to clinical standard of care treatment will be assessed to evaluate safety and effectiveness as an anti-COVID-19 treatment. All hospitalized persons with moderate to severe COVID-19 disease that meet eligibility criteria will be offered participation.”
Details: 1,000 participants, April 2020-February 2021. Lopinavir/ritonavir tablet 200mg/50mg 2 tables by mouth, every 12 hours for 10 days. Hydroxychloroquine sulfate sulfate tablet 200 mg 2 tablets by mouth, every 12 hours for 10 days. Baricitinib 2 mg po daily for 10 days. Sarilumab 200mg subcutaneous injection once.

 

  • Hydroxychloroquine Treatment for Severe COVID-19 Respiratory Disease: Randomised Clinical Trial (HYDRA Trial).” Carmen Hernandez-Cárdenas, principal investigator. National Institute of Respiratory Diseases, Mexico. NCT04315896.

From the HYDRA Trial detailed description: “Recruited patients with severe respiratory disease from COVID-19 will be randomized to an intervention group (400mg per day dose of hydroxychloroquine) and placebo. The investigators’ main outcome will be all cause hospital mortality. The investigators hypothesize that a 400mg per day dose of hydroxychloroquine for 10 days will reduce all-cause hospital mortality in patients with severe respiratory COVID-19 disease.”

Details: 500 participants, March-October 2020. Hydroxychloroquine tablet 200mg every 12 hours for 10 days.

 

  • “Chemoprophylaxis With Hydroxychloroquine in Healthcare Personnel in Contact With COVID-19 Patients: A Randomized Controlled Trial (PHYDRA Trial).” Jorge Rojas-Serrano, principal investigator. National Institute of Respiratory Diseases, Mexico. NCT04318015.

From the PHYDRA Trial brief summary: “Triple blinded, phase III randomized controlled trial with parallel groups (200mg of hydroxychloroquine per day vs. placebo) aiming to prove hydroxychloroquine’s security and efficacy as prophylaxis treatment for healthcare personnel exposed to COVID-19 patients.”

Details: 400 participants, April-December, 2020.Experimental: High-risk Treatment Hydroxychloroquine 200mg per day for 60 days.

 

  • “Treatment With Hydroxychloroquine vs Nitazoxanide + Hydroxychloroquine in Patients With COVID-19 With Risk Factors for Poor Outcome.” Hugo Mendieta Zeron, contact. José Meneses Calderón, principal investigator. Materno-Perinatal Hospital of the State of Mexico. NCT04341493.

From the brief summary: “NTZx has powerful antiviral effects through the phosphorylation of protein kinase activated by double-stranded RNA, which leads to an increase in phosphorylated factor 2-alpha, an intracellular protein with antiviral effects. The purpose of this study is to contrast the beneficial effect of NTZx vs NTZx plus hydroxychloroquine in patients Coronavirus Disease (COVID-19).”

Details: 86 participants, April-August 2020. Experimental: Nitazoxanide + hydroxychloroquine. Hydroxychloroquine 200 mg twice daily every 12 hours for 10 days plus Nitazoxanide 500 mg twice daily every 12 hours for 10 days. Active Comparator: Hydroxychloroquine. Hydroxychloroquine 200 mg twice daily every 12 hours for 10 days.

 

United Kingdom

 

  • “A Randomised Controlled Trial of Early Intervention in Patients HospItalised With COVID-19: Favipiravir Verses HydroxycholorquiNe & Azithromycin & Zinc vErsEs Standard CaRe.” Pallav Shah, principal investigator. Chelsea and Westminster NHS Foundation Trust. NCT04373733.

From PIONEER Trial detailed description: “A computer-based software will randomise participants 1:1:1 to either receive; hydroxychloroquine, azithromycin and zinc and standard medical care; favipiravir and standard medical care or standard medical care alone. The allocated medical regime will commence for 10 days.”

Details: 450 participants, May 2020-March 2021. Experimental: Favipiravir & Standard of Care. Favipiravir: Day 1 1800mg twice per day, Days 2-10 800mg twice per day. Experimental: Hydroxychloroquine, azithromycin, zinc & standard of Care. Hydroxychloroquine: Day 1 400mg twice per day, Days 2-10 200mg twice per day; Azithromycin: Day 1-3 250mg once per day; Zinc-sulfate: Days 1-10 125mg twice per day.

 

  • “ChemoPROphyLaxIs For covId-19 Infectious Disease (the PROLIFIC Trial).” Joseph Cheriyan, principal investigator. Cambridge University Hospitals NHS Foundation Trust. NCT04352933

From the PROLIFIC Trial detailed description: “This trial will be a double-blind, randomized, placebo-controlled trial in a cohort of frontline healthcare workers, who will potentially be exposed to SARS-CoV-2. Eligible participants will be frontline NHS workers aged 18 to 70 years who work in a healthcare setting with direct patient care. Participants will be randomised to one of 3 arms and receive either: (1) Hydroxychloroquine Daily (loading phase: 800mg for first 2 days; maintenance phase: 1 x 200mg tablet every day) + weekly placebo; (2) Hydroxychloroquine weekly (loading phase: 800mg for first 2 days; maintenance phase: 2 x 200mg tablets every 7th day/weekly) + daily placebo, or (3) placebo (daily and weekly).”

Details: 1,000 participants, April-October 2020. 

 

  • “A trial evaluating treatments for suspected coronavirus infection in people aged 50 years and above with pre-existing conditions and those aged 65 years and above.” UK registration. Prof. Christopher Butler, main contact. Royal College of General Practitioners, Research and Surveillance Center (Surrey), and Oxford University Nuffield Department of Primary Care Health Sciences, in partnership with EMIS Health.  Doi: https://doi.org/10.1186/ISRCTN86534580

From PRINCIPLE Trial [“Platform Randomised trial of INterventions against COVID-19 In older peopLE”] website: “We aim to find out whether selected treatments given to those at higher risk of becoming more ill when they are infected with COVID-19 can help reduce the need for hospitalisation and the length of stay required, helping people recover quicker and with fewer complications.”

Details: The trial is studying people aged 50 to 64 who have COVID-19 symptoms and a chronic health condition such as heart disease, asthma or cancer. It is currently unclear how many patients are taking part. Through March 2021.

 

  • “A randomised trial of treatments to prevent death in patients hospitalised with COVID-19 (coronavirus).” UK registration. Prof. Peter Horby (Chief Investigator, main contact). Oxford University Nuffield Department of Population Health. Doi: https://doi.org/10.1186/ISRCTN50189673

From RECOVERY Trial website: “The RECOVERY Trial [Randomised Evaluation of COV-id19 thERapY] will begin by testing some of these suggested treatments: Lopinavir-Ritonavir (commonly used to treat HIV); Low-dose Dexamethasone (a type of steroid, which is used in a range of conditions typically to reduce inflammation); Hydroxychloroquine (related to an anti-malarial drug); Inhaled interferon-beta1a (an antiviral drug; not currently in use in this trial).”

Details: Study protocol. Around 1,000 patients from 132 different hospitals recruited in first 15 days.

 

  • “A platform trial for severely ill patients with COVID-19.” International. NCT02735707.

From the REMAP-CAP website: “REMAP-CAP [A Randomised, Embedded, Multi-factorial, Adaptive Platform Trial for Community-Acquired Pneumonia] will study, on an open-label basis: Antiviral therapy (no antiviral, lopinavir/ritonavir (Kaletra), hydroxychloroquine being added); Corticosteroid strategy (no steroid, fixed 7 days, only while in septic shock); Immune modulation (no modulator, interferon-beta, anakinra, other agents being added).”

Details: Study protocol. The study is looking specifically at patients who develop community-acquired pneumonia (CAP) as a result of viral infections. Between 2,000 and 4,000 patients will be enrolled. REMAP-CAP is a trial format designed by clinicians who cared for patients and conducted research during the 2009 H1N1 pandemic, involving more than 50 research teams around the world working with local ICUs.

 

  • “Chloroquine/ Hydroxychloroquine Prevention of Coronavirus Disease (COVID-19) in the Healthcare Setting; a Randomised, Placebo-controlled Prophylaxis Study (COPCOV).” William Schilling, principal contact, co-lead investigator. University of Oxford, Mahidol Oxford Tropical Medicine Research Unit, Thailand. NCT04303507.

From the COPCOV brief summary: “The participant will be randomised to receive either chloroquinehydroxychloroquine or placebo (1:1 randomisation). A loading dose of 10mg base/kg, followed by 155 mg daily (250mg chloroquine phosphate salt or 200mg hydroxychloroquine sulphate) will be taken for 3 months.”  

Details: “… the investigator will recruit healthcare workers, or other individuals at significant risk who can be followed reliably for 5 months. 40,000 participants will be recruited and the investigator predict an average of 400-800 participants per site in 50-100 sites.” April 2020-April 2021.

 

Europe

 

  • “Efficacy of Azithromycin-associated Hydroxychloroquine Therapy Given in General Practice in Early-stage Disease in COVID-19 Patients: Randomized Controlled Trial: MG-COVID.” Julie Chastang, principal investigator. Assistance Publique – Hôpitaux de Paris. NCT04371406.

From MG-COVID trial brief summary: “We realize a randomized, controlled, open superiority trial, in 2 parallel groups (ratio 1:1).The main objective is to assess the efficacy of Hydroxychloroquine combined with azithromycin in COVID-19 patients in primary care, in add-on to standard of care, on unfavorable outcome defined by the onset of at least one of the following between D0 and D14: hospitalization, death or percutaneous O² saturation ≤ 92% in ambient air.”

Details: 2,770 participants, May-August, 2020. Drug: Hydroxychloroquine and Azithromycin Hydroxychloroquine sulfate (PLAQUENIL®), 200mg x 3 /d, for 10 days AND Azithromycin (ZITHROMAX®), 500mg on D1 and then 250mg/d for the next 4 days, in addition to standard of care.

 

  • “QT-Logs : a Clinical Study to Monitor Cardiac Safety, With Artificial Intelligence for QT Interval Analysis of ECG Data From Smartwatches, in Patients Receiving Hydroxychloroquine Treatment for COVID-19.” Jean Claude Deharo, contact. Assistance Publique Hopitaux De Marseille. NCT04371744.

From QT-Logs trial brief summary: “This observational pilot prospective study will evaluate a new method for remote monitoring of corrected QT measurement using an artificial intelligence (AI)-based solution and ECG data collected via smartwatches (AI-QTc), in patients ambulatory treated with the HC-AZ combination, at the early stage of COVID-19 infection, at a tertiary hospital center. Daily ECGs will be performed via the smartwatches. AI-QTc will be compared to standard manual QTc reviewed by cardiologist. Correlation and agreement between measures will be assessed.”

Details: 100 participants, April-May 2020.

 

  • “Efficacy of HYdroxychloroquine and DILtiazem-nIClosamide Combination for the Treatment of Non-severe Forms of SARS-CoV2 Infection in Patients With Co-morbidities: Multicenter, Randomized, Open-labeled Controlled Trial.” Karine Faure, principal investigator. University Hospital, Lille. NCT04372082.

From HYdILIC trial brief summary: “Participants will be randomized to receive SOC alone or SOC + hydroxychloroquine 200 mg three times a day during 10 days or SOC + association of niclosamide 2 g at J1 then 500 mg two times a day with diltiazem 60 mg three times a day during 10 days. Efficacy and tolerance of each treatments will be compared across the three treatment groups during the 28 days of follow-up.”

Details: 480 participants, May 2020-May 2023. 

 

  • “Efficacy Evaluation of Hydroxychloroquine Azithromycin in the Treatment of COVID-19 in Pregnant Women: an Open-label Randomized Clinical Trial.” Raoul RD Desbrier, principal investigator. Hospital St. Joseph, Marseille. NCT04365231.

From HASCOPT trial brief summary: “Pregnant women are systematically excluded from drug trials, and treatment options for this high-risk population remain untested. The aim of our study is to screen pregnant women presenting minor symptoms, for COVID-19 and to evaluate efficacy of hydroxychloroquine-azithromycin treatment in preventing aggravation of symptoms with development of hypoxemic respiratory failure and complications of pregnancy.”

Details: Experimental: Hydroxychloroquine and azithromycin treatment. hydroxychloroquine 10-day course of hydroxychloroquine 200 mg tablet three times a day. To be taken orally. – azithromycin 5-day course of azithromycin 250 mg tablet twice a day on the first day of treatment, then once a day the 4 following days.

 

 

  • “A Randomized Trial of Efficacy and Safety of an Early OUTpatient Treatment of COVID-19 in Patients With Risk Factor for Poor Outcome: a Strategy to Prevent Hospitalization.” Principal investigator: Jean-Marc Naccache, Groupe Hospitalier Paris Saint Joseph. NCT04365582.

From OUTCOV trial detailed description: “The investigators make the hypothesis that an early outpatient treatment of COVID among patient with respiratory symptoms and risk factors for poor outcome can improve the prognosis of these patient and decrease the need for hospital admission. Our study is an open label randomized clinical trial comparing 4 arms of treatment: Standards of Care (SoC) alone versus SoC + Azithromycine versus SoC + Hydroxychloroquine vs Soc + Lopinavir/Ritonavir.”

Details: 640 participants, April-July 2020. 

 

  • “Effect of Treatments in Patients Hospitalized for Severe COVID-19 Pneumonia: a Multicenter Cohort Study.” Study coordinator: Lee S Nguyen. Groupe Hospitalier Pitie-Salpetriere. NCT04365764.

From brief summary: “Several treatments have been used in during the Covid-19 pandemic of 2020. Using patients’ registries from several hospitals in Paris, we retrospectively analyzed associations between specific treatments, including but not limited to hydroxychloroquine, azithromycin, remdesivir, baricitinib, tocilizumab, sarilumab, lopinavir/ritonavir and oseltamivir; and clinical outcomes including, death and mechanical ventilation.”

Details: 400 participants, March-December 2020. 

 

  • “Factors Associated With Clinical Outcomes in Patients Hospitalized for Covid-19 in GHT-93 Est.” Principal investigator: Hélène Gros. Centre Hospitalier Intercommunal Robert Ballanger. NCT04366206.

From brief summary: “Healthcare centers treated several hundreds of patients with Covid-19 and prospectively gathered information in electronic format between March, 2020 to April, 2020. In the course of Covid-19 treatment, physicians employed several drugs, including hydroxychloroquine, azithromycin, lopinavir/ritonavir, tocilizumab, baricitinib, sarilumab, corticosteroids and systematic antibiotics (list is not exhaustive). This cohort study aims to assess factors associated with clinical outcomes in patients hospitalized for Covid-19, by analyzing associations between treatments and outcomes. All data are collected in electronical records during routine practice.”

Details: 143 participants, March-July 2020.

 

  • “Observational Cohort of COVID-19 Patients at Raymond-Poincare.” Simon Bessis, principal investigator. Raymond Poincaré Hospital. NCT04364698.

From COVID-RPC Trial detailed description: “Moreover, the question of how to manage these patients still raises many questions, particularly about the type of molecules to be introduced and at what point in the history of the disease. Some of these molecules, such as the Lopinavir/Ritonavir combinations and the Hydroxychloroquine/ Azithromycin combination, are not free of complications, particularly cardiac complications requiring close monitoring by ECGs and repeated dosing, the effectiveness of which has not yet been clearly demonstrated.”

Details: 500 participants, April-May, 2020.

 

  • “Efficacy Evaluation of Hydroxychloroquine Azithromycin in the Treatment of COVID-19 in Pregnant Women: an Open-label Randomized Clinical Trial.” Hospital St. Joseph, Marseille. NCT04365231.

From HASCOPT Trial brief summary: “Pregnant women are systematically excluded from drug trials, and treatment options for this high-risk population remain untested. The aim of our study is to screen pregnant women presenting minor symptoms, for COVID-19 and to evaluate efficacy of hydroxychloroquine-azithromycin treatment in preventing aggravation of symptoms with development of hypoxemic respiratory failure and complications of pregnancy.”

Details: 50 participants, April-June, 2020. “Drug: Hydroxychloroquine and azithromycin treatment: hydroxychloroquine 10-day course of hydroxychloroquine 200 mg tablet three times a day. To be taken orally. – azithromycin 5-day course of azithromycin 250 mg tablet twice a day on the first day of treatment, then once a day the 4 following days.”

 

  • “Factors Associated With Clinical Outcomes in Patients Hospitalized for Covid-19 in GHT-93 Est.” Dr. Hélène Gros, principal investigator. Centre Hospitalier Intercommunal Robert Ballanger. NCT04366206.

From brief summary: “This cohort study aims to assess factors associated with clinical outcomes in patients hospitalized for Covid-19, by analyzing associations between treatments and outcomes. All data are collected in electronical records during routine practice.”

Details: 143 participants, March-July 2020.

 

  • “Efficacy of Hydroxychloroquine, Telmisartan and Azithromycin on the Survival of Hospitalized Elderly Patients With COVID-19: a Randomized, Multicenter, Adaptative Study.” Frédéric Blanc, principal investigator. University Hospital, Strasbourg, France. NCT04359953.

From COVID-Aging Trial brief summary: “We therefore propose to carry out a therapeutic trial specific to the elderly with drugs at doses that are bearable for these patients. Using the WHO, clinicaltrial, pubmed and the Chinese CCDC/CHCTR websites to find the better drugs adapted to elderly people, we decided after concertation between infectiologists and geriatricians to do a four arms clinical trial during two weeks twice a day: Hydroxychloroquine 200mg, Telmisartan 40mg, Azithromycin 250mg and standard care. We therefore hypothesize that one or more of these treatments may have a beneficial effect in controlling COVID19, without major and repeated side effects in elderly patients.”

Details: 1,600 participants, April 2020-June 2021. Experimental: Hydroxychloroquine. Patient will take 200mg of Hydroxychloroquine twice a day during 14 days. Experimental: Azithromycin. Patient will take 250mg of Azithromycin twice a day during 14 days. Experimental: Telmisartan. Patient will take 40mg of Telmisartan twice a day during 14 days.

 

  • “Outpatient Treatment of Elderly People With Symptomatic SARS-CoV-2 Infection (COVID-19): a Multi-arm, Multi-stage (MAMS) Randomized Trial to Assess the Efficacy and Safety of Several Experimental Treatments to Decrease the Risk of Hospitalization or Death (COVERAGE Trial).” Denis Malvy, principal investigator. Bordeaux University Hospital. NCT04356495.

From COVERAGE Trial detailed description: “This is a randomized controlled, open-label, multi-arm multi-stage (MAMS) trial. Participants will be randomly allocated 1:1 to the following strategies: Arm 1: control arm. Arms 2. Experimental treatment At the time of trial initiation: People in the control arm will receive a complex of vitamins; people in the experimental arms will receive hydroxychloroquine, or favipiravir, or imatinib, or telmisartan.” 

Details: 1,057 participants, April-July, 2020. Experimental: Hydroxychloroquine Patients in this arm will receive Hydroxychloroquine (Plaquenil® 200 mg) during 10 days.

 

  • “Manifestations Related to Covid-19 in Patients With Systemic Lupus Erythematosus.” Christian Jorgensen, study director. University Hospital, Montpellier. NCT04355702.

From the detailed description: “The primary objective was to describe the prevalence and the severity of Covid-19 infection in patients wih systemic lupus erythematosus. The secondary objective was to compare these parameters in patients treated by hydroxychloroquine and those not treated by hydroxychloroquine.”

Details: 130 participants, March-May 2020.

 

  • “Randomized Trial Assessing Efficacy and Safety of Hydroxychloroquine Plus Azithromycin Versus Hydroxychloroquine for Hospitalized Adults With COVID-19 Pneumonia.” Jacques Reynes, principal investigator. University Hospital, Montpellier. NCT04345861.

From COVIDOC detailed description: “The multi-centre COVIDOC study will evaluate the efficacy and safety of the use of hydroxychloroquine (10 days) combined with azithromycin (5 days) compared to hydroxychloroquine (10 days) in the the clinical evolution by the ordinal scale of 7 points in adults hospitalized outside Intensive care unit with pneumonia caused by infection by the SARS-CoV2 virus in France.” 

Details: 150 participants, April 2020-April 2021. Active Comparator: monotherapy hydroxychloroquine. Hydroxychloroquine 800mg (Day 1), 600mg (from Day 2 to Day 10) + placebo from Day 1 to Day 5. Experimental: combination hydroxychloroquine + azithromycin. Hydroxychloroquine 800mg (Day 1), 600mg (from Day 2 to Day 10) and azithromycin 500mg (Day 1 ), 250 mg (from day 2 to Day 5).

 

  • “Evaluation of Azithromycin-Hydroxychloroquine Combination in Sars-CoV-2 Pneumonia.” Lois Kassegne, contact. University Hospital, Strasbourg, France. NCT04347512.

From: TEACHCOVID brief summary: “Hydroxychloroquine is an old chloroquine-derived drug, prescribed for auto-immune disorders. It has shown efficacy against Sars-CoV-2 in vitro. Some studies showed that Hydroxychloroquine might improve the clinical status of Sars-CoV-2 infected patients. Azithromycin is a macrolide antibiotic, with immunomodulatory properties. Adding Azithromycin to a hydroxychloroquine-based treatment showed an apparent accelerated viral clearance in infected patients.”

Details: 405 participants, May 2020-August 2021. Experimental: Hydroxychloroquine. Hydroxychloroquine is given for 5 days, with a loading dose of 400 mg qd at D1, and 200 mg qd for the next 4 days (D2-D5). Experimental: Hydroxychloroquine and Azithromycin. Hydroxychloroquine is given for 5 days, with a loading dose of 400 mg qd at D1, and 200 mg qd for the next 4 days (D2-D5). Azithromycin is given for 5 days, with a loading dose of 500 mg at D1, and 250 mg for the next 4 days.

 

  • “Dexamethasone Combined With Hydroxychloroquine Compared to Hydroxychloroquine Alone for Treatment of Severe Acute Respiratory Distress Syndrome Induced by Coronavirus Disease 19 (COVID-19): a Multicentre, Randomised Controlled Trial.” Francois Stephan, principal investigator. Centre Chirurgical Marie Lannelongue, France. NCT04347980.

From the DHYSCO Trial brief summary: “Single blind randomized clinical trial designed to evaluate the efficacy of the combination of hydroxychloroquine and dexamethasone as treatment for severe Acute Respiratory Distress Syndrome (ARDS) related to coronavirus disease 19 (COVID-19). We hypothesize that dexamethasone (20 mg for 5 days followed by 10 mg for 5 days) combined with 600 mg per day dose of hydroxychloroquine for 10 days will reduce the 28-day mortality compared to hydroxychloroquine alone in patients with severe ARDS related COVID-19.”

Details: 122 participants, April-August 2020.

 

  • “Randomized Multicenter Study Evaluating the Efficacy of Azithromycin and Hydroxychloroquine in the Prevention of SARS-CoV-2 Infection in the Hospital Population Exposed to Virus.” Jean Marc Treluyer, principal investigator. Assitance publique – Hôpitaux de Paris. NCT04344379.

From PREP-COVID Trial detailed description: “Randomized clinical trial with 3 arms : hydroxychloroquine group, 300 subjects/azithromycin group, 300 subjects/ placebo of hydroxychloroquine group, 300 subjects.”

Details: 900 participants, April-August 2020.

 

  • “Prevalence of COVID-19 Symptoms History in Patients With Systemic Lupus Erythematosus, Rheumatoid Arthritis, Sjogren’s Syndrome or Psoriatic Arthritis, With or Without Hydroxychloroquine Long-term Treatment.” Debellemaniere, Guillaume, principal investigator. Fondation Ophtalmologique Adolphe de Rothschild. NCT04345159. 

From the COVCALL brief summary: “This epidemiological, transversal, cohort study aims to determine the potential influence of an active long-term hydroxychloroquine intake over the prevalence of a history of symptoms evocative of a COVID-19 infection in patients with a history of systemic lupus erythematosus, rheumatoid arthritis, Sjogren’s syndrome or psoriatic arthritis, during the epidemic period in France. The information is gathered using a standardized questionnaire, by phone call.”

Details: 1,500 participants, April-October 2020. 

 

  • “Efficacy of Sarilumab + Azithromycin + Hydroxychloroquine, and Sarilumab Alone, for Adult Patients Hospitalized With Moderate to Severe COVID-19: a Multicenter Open-label 1:1 Randomized Controlled Trial.”  David Saadoun, contact. Assistance Publique – Hôpitaux de Paris. NCT04341870.

From the CORIMUNO-VIRO Trial brief summary: “The overall objective of the study is to determine the therapeutic effect and tolerance of Sarilumab in combination with Azithromycin and Hydroxychloroquine, compared to Sarilumab only, patients with moderate, severe pneumonia associated with Coronavirus disease 2019 (COVID-19).”

Details: 60 participants, April-July 2020. Sarilumab is a human IgG1 monoclonal antibody that binds specifically to both soluble and membrane-bound IL-6Rs (sIL-6Rα and mIL-6Rα) and has been shown to inhibit IL-6-mediated signaling through these receptors.

 

  • “COVID 19 – Epidemiology of SARS-CoV-2 and Mortality to Covid19 Disease Upon Hydroxychloroquine and Azithromycin Therapy in French Cancer Patients.” Lisa DeRosa, contact. Gustave Roussy, Cancer Campus, Grand Paris. NCT04341207.

From the ONCOVID brief summary: “To determine the prevalence and the 3-months incidence of SARS-CoV-2 in cancer patients (Part A). To evaluate the Covid-19 disease-specific mortality rate in cancer patients treated by hydroxychloroquine and azithromycin (Part B).”

Details: 1,000 participants, April 2020-April 2022. Drug: Hydroxychloroquine. Hydroxychloroquine 200 mg 3 times a day for 10 days. Drug: Azithromycin. Azithromycin 500 mg on day 1 followed by 250 mg/day for 4 days.

 

  • “Multi-centre, Adaptive, Randomized Trial of the Safety and Efficacy of Treatments of COVID-19 in Hospitalized Adults.” Florence Ader, study chair. Institut National de la Santé Et de la Recherche Médicale, France. NCT04315948.

From the DisCoVeRy Trial brief summary: “This study is a multi-centre, adaptive, randomized, open clinical trial of the safety and efficacy of treatments for COVID-19 in hospitalized adults. The study is a multi-centre/country trial that will be conducted in various sites in Europe with Inserm as sponsor… 4 treatment arms, each to be given in addition to the usual standard of care (SoC) in the participating hospital: SoC alone versus SoC + Remdesivir versus SoC + Lopinavir/Ritonavir versus SoC + Lopinavir/Ritonavir plus interferon ß-1a versus SoC + Hydroxychloroquine.”

Details: 3,100 participants, March 2020-March 2023. Hydroxychloroquine will be administered orally as a loading dose of 400 mg twice daily for one day followed by 400 mg once daily for 9 days. The loading dose of hydroxychloroquine through a nasogastric tube will be increased to 600 mg twice a day for one day, followed by a maintenance dose of 400 mg once a day for 9 days n=620.

 

  • “Hydroxychloroquine Versus Placebo in Patients Presenting COVID-19 Infection and at Risk of Secondary Complication: a Prospective, Multicentre, Randomised, Double-blind Study.” Vincent Dubee, principal investigator. University Hospital, Angers, France. NCT04325893.

From the HYCOVID brief summary: ” … hydroxychloroquine has immunomodulating and anti-inflammatory properties, which could theoretically prevent or limit secondary complications. The research hypothesis is that treatment with hydroxychloroquine improves prognosis and reduces the risk of death or using an invasive artificial ventilator on patients suffering from COVID-19.”

Details: 1,300 participants, April-September 2020. First dose of 400 mg will be taken immediately after inclusion at day 0, the second dose of 400 mg will be taken on the same evening and the treatment will then be continued for the following eight days at a rate of 200 mg in the morning and evening.

 

  • “Chemoprophylaxis of SARS-CoV-2 Infection (COVID-19) in Exposed Healthcare Workers : A Randomized Double-blind Placebo-controlled Clinical Trial.” Elisabeth Botelho-Nevers, principal investigator. Centre Hospitalier Universitaire de Saint Etienne, Institut Pasteur. NCT04328285.

From the COVIDAXIS Trial brief summary: “The COVIDAXIS trial evaluates a chemoprophylaxis of SARS-CoV-2 infection in Health Care Workers… COVIDAXIS 1 will study Hydroxychloroquine (HCQ) versus placebo; COVIDAXIS 2 will study Lopinavir/ritonavir (LPV/r) versus placebo.”

Details: 1,200 participants, March-November 2020. Group 1.1: HCQ 400 mg, 2 tablets twice daily at Day 1 and 200 mg, 1 tablet once daily afterwards. Group 1.2: Placebo of HCQ, 2 tablets twice daily at Day 1 and 1 tablet once daily afterwards). Group 2.1: LPV/r 400/100 mg, 2 tablets twice daily. Group 2.2: Placebo of LPV/r, 2 tablets twice daily.

 

  • “Randomized Controlled Trial of Hydroxychloroquine Versus Placebo in Early Ambulatory Diagnosis and Treatment of Elderly COVID19 Patients.” Michael Bitzer, contact. University Hospital Tuebingen. NCT04351516.

From COVID65plus Trial brief summary: “Patients over equal or older than 65 yearswill be treated with a hydroxychloroquine versus placebo reduced loading dose of 600mg on the first day followed with 400mg/day divided in 2x200mg for 6 more days resulting in a total duration of therapy of 7 days. Measurement of Hydroxychloroquine-levels will be performed on day 7, . A follow-up by video or telephone conference will be performed to observe drug intake and collect adverse events during treatment phase on a daily base on working days and once during the weekend (i.e. 6 out of 7 days). After treatment phase follow-up by telephone calls will be done on day 10, 30, 60 (+/- 2 days).” 

Details: 350 participants, May-December 2020. Drug: Hydroxychloroquine, dose of 600mg on the first day followed with 400mg/day divided in 2x200mg for 6 more days.

 

  • “Evaluation of the Efficacy and Safety of Camostat Mesilate + Hydroxychloroquine Combination Therapy in Hospitalized Patients With Moderate COVID-19 Infection.” Heinrich-Heine University, Duesseldorf, Germany. NCT04338906.

From the CLOCC Trial detailed description: “… the CLOCC trial will evaluate the efficacy and safety of a combination therapy consisting of hydroxychloroquine, which was used already as single agent with some effect, together with camostat mesylate in hospitalized patients with moderate COVID-19 infection. The rationale for this combination therapy stems from the observation that hydroxychloroquine interferes with viral entry and replication through several mechanisms including changes in endosomal pH and in glycosylation of the ACE2 receptor, which serves as entry receptor for SARS-CoV-2. Camostat acts as inhibitor of the host cell serine protease TMPRSS2, which is needed to prime the viral S protein for cell entry.”

Details: 334 participants, June 2020-December 2021. Experimental: Camostat + Hydroxychloroquine. Subjects will receive Camostat (400 mg tid) + hydroxychloroquine (400 mg bid day1, 200 mg bid d2-d7) Active Comparator: Placebo + Hydroxychloroquine. Subjects will receive placebo (tid) + hydroxychloroquine (400 mg bid day1, 200 mg bid d2-d7).

 

  • “Plasma Exchange in Patients With COVID-19 Disease and Invasive Mechanical Ventilation: a Randomized Controlled Trial.” Anna Cruceta. Fundacion Clinic per a la Recerca Biomédica. NCT04374539.

From REP-COVID Trial brief summary: “Plasma exchanges with 5% human albumin (2/3 of the exchanged plasma volume) and fresh frozen plasma (FFP: 1/3) in patients with quick <50% or only with 5% albumin in patients with quick of 50% or more. We will exchange between 1.2 and 1.5 plasma volumes, that will vary according to sex, weight, height and hematocrit.”

Details: 116 participants, April 2020-May 2021. Standard care, in both arms, includes Hydroxychloroquine sulfate 400 mg/12h the first day followed by 200 mg /12h 4 days.

 

  • “Phase I / II Multicentre, Randomized and Controlled Clinical Trial to Evaluate the Efficacy of Treatment With Hyperimmune Plasma Obtained From Convalescent Antibodies of COVID-19 Infection.” Ana Cardesa Gil, contact. Andalusian Network for Design and Translation of Advanced Therapies. NCT04366245.

From brief summary: “Phase I / II multicentre, randomized and controlled clinical trial to evaluate the efficacy of treatment with hyperimmune plasma obtained from convalescent antibodies of COVID-19 infection.”

Details: 72 participants, April 2020-December 2021. Drug:  Hidroxicloroquina + Azitromicina o Lopinavir/ritonavir + Interferon β-1b + Hidroxicloroquina.

 

  • “Prospective, Phase II, Randomized, Open-label, Parallel Group Study to Evaluate the Efficacy of Hydroxychloroquine Together With Baricitinib, Imatinib or Early Lopinavir / Ritonavir in Patients With SARS Cov2 Pneumonia.”  David Bernal, principal investigator. Hospital Universitario de Fuenlabrada. NCT04346147.

From Covid-19HUF Trial brief summary: “The study aims to compare lopinavir / ritonavir (200 /50), imatinib 400mg, baricitinib 4mg, in combination with hydroxychloroquine 200mg, administered for 7 days in the setting of SARS-CoV-2 pneumonia treatment.”

Details: 165 participants, April-September, 2020.

 

  • “Prevention of SARS-CoV-2 (COVID-19) Through Pre-Exposure Prophylaxis With Tenofovir Disoproxil Fumarate/Emtricitabine and Hydroxychloroquine in Healthcare Personnel: Randomized Clinical Trial Controlled With Placebo.” Rosa Polo, study chair. Plan Nacional sobre el Sida (PNS), Effice Servicios Para la Investigacion S.L., Hospital Universitario Ramón y Cajal. NCT04334928.

From EPICOS Trial brief summary: “This study aims to assess the efficacy of a daily single dose of tenofovir disoproxil fumarate (TDF) (245 mg)/ Emtricitabine (FTC) (200 mg), a daily single dose of hydroxychloroquine (HC) (200 mg), a daily single dose of TDF (245 mg)/FTC (200 mg) plus HC (200 mg) versus placebo, during 12 weeks in: (1) reducing the incidence of symptomatic disease and (2) reducing clinical severity COVID-19 among hospital healthcare workers aged 18 to 65 years in public and private hospitals in Spain.”

Details: 4,000 participants, April-June 2020. Existing recent and scarce literature shows that RNA synthesis nucleos(t)ide analogue inhibitors, acting as viral RNA chain terminators, like TDF, abacavir or lamivudine, amongst others, could have an effect against SARS-CoV-2 infection. 

 

  • “Randomized, Controlled, Double-blind Clinical Trial Comparing the Efficacy and Safety of Chemoprophylaxis With Hydroxychloroquine in Patients Under Biological Treatment and / or JAK Inhibitors in the Prevention of SARS-CoV-2 Infection.” Javier Crespo, contact. Instituto de Investigación Marqués de Valdecilla. NCT04330495.

From brief summary: “The investigators plan to evaluate a strategy of chemoprophylaxis with hydroxyloquine (HCQ) against COVID-19 infection in patients diagnosed with an immunomediated inflammatory disease who are following a treatment with biological agents and / or Jak inhibitors. The strategy will be carried out through a randomised double blind, placebo-controlled clinical trial and will assess comparative rates of infection (prevalence, incidence), severity including mortality, impact on clínical course of the primary diseases and toxicity.”

Details: 800 participants, April-November 2020. Experimental group. Chemoprophylaxis with hydroxychloroquine at a dose of 200 mg twice a day for 6 months.

 

  • “Pilot, Randomized, Multicenter, Open-label Clinical Trial of Combined Use of Hydroxychloroquine, Azithromycin, and Tocilizumab for the Treatment of SARS-CoV-2 Infection (COVID-19).” Pere Domingo, principal investigator. Fundació Institut de Recerca de l’Hospital de la Santa Creu i Sant Pau, Barcelona, Instituto de Salud Carlos III. NCT04332094.

From TOCOVID Trial brief summary: “This clinical trial is designed to evaluate the use of Tocilizumab in combination with hydroxychloroquine and azithromycin for the treatment of hospitalized adult patients with COVID-19.”

Details: 276 participants, April-September 2020. Experimental Arm. Drug: Tocilizumab 162 mg sc x 2 doses + tocilizumab 162mg sc x 2 doses at 12 hours (day 1). Drug: Hydroxychloroquine 400 mg / 12h v.o. day 1 followed by 200 mg / 12h v.o. for 6 days (7 days in total). Drug: Azithromycin 500 mg / day v.o. for 3 days. Control: Drug: Hydroxychloroquine 400 mg / 12h v.o. day 1 followed by 200 mg / 12h v.o. for 6 days (7 days in total). Drug: Azithromycin 500 mg / day v.o. for 3 days.

 

  • “Pre-Exposure Prophylaxis With Hydroxychloroquine for High-Risk Healthcare Workers During the COVID-19 Pandemic: A Unicentric, Double-Blinded Randomized Controlled Trial.” Jose Muñoz Gutiérrez, principal investigator. Barcelona Institute for Global Health. NCT04331834.

From the PrEP_COVID brief summary: “The investigators aim to evaluate the efficacy of pre-exposure prophylaxis with hydroxychloroquine in healthcare workers with high-risk of SARS-CoV-2 infection.”

Details: 440 participants, April-October, 2020. Experimental: Pre-exposure prophylaxis of SARS-CoV-2. Participants will receive hydroxychloroquine 400 mg daily during the first 4 days, followed by 400 mg weekly during 6 months.

 

  • “Treatment of Non-severe Confirmed Cases of COVID-19 and Chemoprophylaxis of Their Contacts as Prevention Strategy: a Cluster Randomized Clinical Trial (PEP CoV-2 Study).” Oriol Mitja, contact. Germans Trias i Pujol Hospital, Barcelona. NCT04304053.

From the PEP CoV-2 Study brief summary: “The investigators plan to evaluate the efficacy of the ‘test and treat’ strategy of infected patients and prophylactic chloroquine treatment to all contacts. The strategy entails decentralized COVID-19 testing and starting antiviral darunavir/cobicistat plus chloroquine treatment immediately in all who are found to be infected. “

Details: 3,040 participants. March-June 2020. Lopinavir/ritonavir, Darunavir (DRV)/Cobicistat, chloroquine.

 

  • “Oxygen-Ozone as Adjuvant Treatment in Early Control of COVID-19 Progression and Modulation of the Gut Microbial Flora (PROBIOZOVID).” Roberto Poscia, principal investigator. Azienda Policlinico Umberto I. NCT04366089.

From PROBIOZOVID trial brief description: “This is an interventional, non-pharmacological, open, randomized, prospective, non-profit study on the adjuvant use of oxygen ozone therapy plus probiotic supplementation in the early control of disease progression in patients with COVID-19… The main purpose of the study is to evaluate the effectiveness of an ozone therapy-based intervention (accompanied by supplementation with probiotics) in containing the progression of COVID-19 and in preventing the need for hospitalization in intensive care units.”

Details: Experimental: Oxygen-ozone and probiotic. Oxygen-ozone therapy, probiotic supplementation plus standard of care. Oxygen-ozone therapy: systemic autohemotherapy (twice a day). Probiotic supplementation: SivoMixx 200 billion (six sachets twice a day). Active Comparator: Standard of care Azithromycin 500mg 1 cp / day (alternatively lopinavir/ritonavir cps 200/50 mg, 2 cps x 2 / day or darunavir 800 mg 1 cp / day + ritonavir 100 mg 1 cp / day or darunavir/cobicistat 800/150 mg 1 cp / day), plus hydroxychloroquine cp 200 mg, 1 cp x 2 / day.

 

  • “Evaluation of the Impact of Bacteriotherapy in the Treatment of COVID-19.” Giancarlo Ceccarelli, principal investigator. University of Roma La Sapienza. NCT04368351.

From BACT-ovid Trial brief summary: “This is an observational, retrospective, non-profit study on the adjuvant use of bacteriotherapy in the early control of disease progression in patients affected by COVID-19 and treated with the current standard of care on the basis of the interim guidelines of the Italian Society of Infectious and Tropical Diseases.”

Details: 70 participants, March-June, 2020. SOC: Drug: Azithromycin. dose: 500mg 1 cp / day (alternatively lopinavir/ritonavir cps 200/50 mg, 2 cps x 2 / day or darunavir 800 mg 1 cp / day + ritonavir 100 mg 1 cp / day or darunavir/cobicistat 800/150 mg 1 cp / day). Drug: hydroxychloroquine dose: 200 mg, 1 cp x 2 / day.

 

  • “Oxygen-Ozone as Adjuvant Treatment in Early Control of Disease Progression in Patients With COVID-19 Associated With Modulation of the Gut Microbial Flora.” Roberto Poscia, principal investigator. Azienda Policlinico Umberto I. NCT04366089.

From PROBIOZOVID Trial brief summary: “This is an interventional, non-pharmacological, open, randomized, prospective, non-profit study on the adjuvant use of oxygen ozone therapy plus probiotic supplementation in the early control of disease progression in patients with COVID-19… Contextually, all patients are treated with the current standard of care on the basis of the interim guidelines of the Italian Society of Infectious and Tropical Diseases.”

Details: 152 participants, March-October 2020. Active Comparator: Standard of care. Azithromycin 500mg 1 cp / day (alternatively lopinavir/ritonavir cps 200/50 mg, 2 cps x 2 / day or darunavir 800 mg 1 cp / day + ritonavir 100 mg 1 cp / day or darunavir/cobicistat 800/150 mg 1 cp / day), plus hydroxychloroquine cp 200 mg, 1 cp x 2 / day.

 

  • “PROTECT: A Randomized Study With Hydroxychloroquine Versus Observational Support for Prevention or Early Phase Treatment of Coronavirus Disease (COVID-19).” Oriana Nanni, contact. Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori. NCT04363827.

From PROTECT Trial brief summary: “This is a Italian, superiority, open label cluster-randomised, interventional clinical trial aimed at assessing whether the treatment with Hydroxychloroquine can reduce the percentage of symptomatic subjects compared to observation only in household members/contacts of COVID-19 patients (Group 1) and if the treatment with Hydroxychloroquine could be introduced in early phase COVID-19 population (Group 2).”

Details: 2,300 participants, May-September 2020. Experimental: Group 1: Hydroxychloroquine. A loading dose Hydroxychloroquine 400 mg twice daily at day 1, followed by a weekly dose of Hydroxychloroquine 200 mg twice daily on days 8, 15 and 22, covering a total of 1 month of treatment. Experimental: Group 2: Hydroxycloroquine. A loading dose Hydroxychloroquine 400 mg twice daily at day 1 followed by 200 mg twice daily for a total of at least 5-7 days according to clinical evolution.

 

  • “An Open Label Cluster Randomized Controlled Trial of Chloroquine, Hydroxychloroquine or Only Supportive Care in Patients AdmItted With Moderate to Severe COVID-19.” Andy I.M. Hoepelman, responsible party. UMC Utrecht. NCT04362332.

From ARCHAIC Trial brief summary: “In the Dutch treatment protocol guideline (SWAB) designated treatment is supportive care with the option to add chloroquine base (CQ) or hydroxychloroquine (HCQ). CQ and HCQ are implemented because of their in vitro activity, results from small animal studies, and anecdotal patient’s data… Study design: Multicentre, cluster randomized cross-over, open label trial. Hospitals will be randomly allocated to one of 3 treatment arms in sequential periods of one week: chloroquine base versus hydroxychloroquine versus supportive care without any drug presumed active against SARS-COV-2. Patients will be treated based on the date of inclusion.”

Details: 950 participants, April 2020-April 2021. Active Comparator: chloroquine. Supportive care + chloroquine base arm: loading dose 600mg, followed by 300mg 12 hours later, followed by 300mg bid for 4 days; total treatment duration of 5 days. Active Comparator: hydroxychloroquine. Supportive care + hydroxychloroquine arm: loading dose 400mg bid, followed by 200mg bid for 4 days; total treatment duration of 5 days.

 

  • “Efficacy of Pragmatic Same-day COVID-19 Ring Prophylaxis for Adult Individuals Exposed to SARS-CoV-2 in Switzerland (COPEP).” Calmy Alexandra, principal investigator. University Hospital, Geneva. NCT04364022.

From COPEP Trial brief summary: “A study to assess, in a three-arm open-label cluster randomized clinical trial, the efficacy of a single-dose of HCQ treatment and of a 5-day course of LPV/r treatment in preventing COVID-19 in asymptomatic individuals exposed to a SARS-CoV-2 documented index patient, compared to surveillance alone.”

Details: 420 participants, April-October 2020. Drug: Hydroxychloroquine Sulfate 200 MG [Plaquenil]Drug: Lopinavir/ritonavir.

 

  • “A Multicenter, Randomized, Active Controlled, Open Label, Platform Trial on the Efficacy and Safety of Experimental Therapeutics for Patients With COVID-19 (Caused by Infection With Severe Acute Respiratory Syndrome Coronavirus-2).” Bernd Jilma, principal investigator. Medical University of Vienna. NCT04351724.

From the ACOVACT Trial brief summary: “… three substudies have been integrated. Currently, patients will be randomized to receive (hydroxy-)chloroquine, lopinavir/ritonavir or standard of care. Moreover, these patients are eligible for substudy A (randomized to rivaroxaban 5mg 1-0-1 vs. standard of care), substudy B (renin-angiotensin (RAS) blockade vs. no RAS blockade for patients with blood pressure >120/80mmHg), and substudy C (clazakizumab vs standard of care, for patients with respiratory deterioration and high inflammatory biomarkers).”

Details: 500 participants, April-December 2020. Experimental: (Hydroxy)Chloroquine. Due to limited availability of the experimental substances, this arm will include both chloroquine and hydroxychloroquine treatment. However, both substances are similar chemically and also with regards to the mechanism of action comparable. Dosage: Hydroxychloroquine 200mg 2-0-2 on day 1 followed by 200mg 1-0-1, or Chloroquine 250mg 2-0-2, as available.

 

  • “Use of Bromhexine and Hydroxychloroquine for Treatment of COVID-19 Pneumonia.” Miha Mežnar, contact. General and Teaching Hospital Celje, Slovenia. NCT04355026.

From brief summary: “Effective therapy that prevents the virus entrance should contain at least TMPRSS2 inhibitor or a competitive inhibitor of viral ACE 2 binding. The use of bromhexine at the dose adequate to selectively inhibit the TMPRSS2, resulting in preventing of viral entrance via TMPRSS2-specific pathway, coud be an effective treatment of Covid-19. In our study we would like to explore the therapeutic potential of bromhexin and hydroxychloroquine in Covid-19 patients.”

Details: 90 participants, April-July 2020. Experimental: hydroxychloroquine and bromhexine. Bromhexine 16 mg TID + hydroxychloroquine 200 mg BID. Active Comparator: hydroxychloroquine alone hydroxychloroquine 200 mg BID.

 

  • “Efficacy and Safety of Novel Treatment Options for Adults With COVID-19 Pneumonia. A Double-blinded, Randomized, Multi-stage, 6-armed Placebo-controlled Trial in the Framework of an Adaptive Trial Platform.” Thomas Benfield, principal investigator. Hvidovre Hospital, Denmark. NCT04345289.

From the brief summary: “Participants will be randomized 1:1:1:1:1:1 to parallel treatment arms: Convalescent plasma, sarilumab, hydroxychloroquine, baricitinib, intravenous and subcutaneous placebo, or oral placebo.”

Details: 1,500 participants, April 2020-June 2021. Hydroxychloroquine Tablets 600 mg/day for 7 days.

 

  • “Proactive Prophylaxis With Azithromycin and Chloroquine in Hospitalized Patients With COVID: A Randomized, Placebo-controlled Double-blinded Trial Evaluating Treatment With Azithromycin and Hydroxychloroquine to Patients With COVID-19.” Jens-Ulrik Stæhr Jensen, contact. Chronic Obstructive Pulmonary Disease Trial Network, Denmark. NCT04322396.

From the ProPAC-COVID detailed description: “This is a randomized, placebo-controlled, double-blinded multi-center trial evaluating the effect of azithromycin and hydroxychloroquine treatment in patients with COVID-19 during hospitalization. The aim of the study is to investigate whether the treatment can shorten hospitalization, reduce the risk of non-invasive ventilation, admittance to Intensive Care Units and death.”

Details: 226 participants. April-October 2020.

 

  • “Norwegian Coronavirus Disease 2019 Study: An Open Labeled Randomized Controlled Pragmatic Trial to Evaluate the Antiviral Effect of Chloroquine in Adult Patients With SARS-CoV-2 Infection.” Olav Dalgard, principal investigator. University Hospital, Akershus. NCT04316377.

From the NO-COVID brief summary: “In the current proposal, the investigators aim to investigate the virological and clinical effects of chloroquine treatment in patients with established COVID-19 in need of hospital admission. Patients will be randomized in a 1:1 fashion to standard of care or standard of care with the addition of therapy with chloroquine.”

Details: Two-arm, open label, pragmatic randomized controlled trial. April 2020-May 2025.

 

  • “The (Norwegian) NOR Solidarity Multicenter Trial on the Efficacy of Different Anti-viral Drugs in SARS-CoV-2 Infected Patients.” Andreas Barratt-Due, principal investigator. Oslo University Hospital. NCT04321616.

From the WHO NOR brief summary: “The (World Health Organization) WHO NOR- (Coronavirus infectious disease) COVID 19 study is a multi-centre, adaptive, randomized, open clinical trial to evaluate the safety and efficacy of hydroxychloroquine, remdesivir and standard of care in hospitalized adult patients diagnosed with COVID-19.” 

Details: 700 participants, March-August 2020. Drug: Remdesivir. Remdesivir will be given intravenously 100 mg daily for the duration of the hospitalization and up to 10 days total course. A loading dose of 200 mg at inclusion will be given. Hydroxychloroquine will be given orally (in the ICU in gastrointestinal tubes) with 800 mg x 2 loading dose followed by 400 mg x 2 every day for a total of 10 days.

 

  • “Chloroquine Phosphate Against Infection by the Novel Coronavirus SARS-CoV-2 (COVID-19): The HOPE Open-Label, Non Randomized Clinical Trial.” Helena Sambatakou, principal investigator. Uni-Pharma Kleon Tsetis Pharmaceutical Laboratories S.A., Greece. NCT04344951.

From the HOPE Trial brief summary: “This is an open label clinical study to evaluate the activity of chloroquine phosphate in patients with SARS-CoV-2 virus infection. The study aims to document possible prevention of pneumonia in patients staying at home and in improving the symptoms of SARS-CoV-2 pneumonia in patients who will be hospitalised.”

Details: 60 participants, April 2020-April 2021. Drug: UNIKINON (Chloroquine phosphate) 200mg tablets. Once a patient is considered eligible for the study, they will receive oral chloroquine phosphate. The total duration of treatment will be 7 days. The dosage will be 500mg every 12 hours. 

 

Russia

 

  • “An Open Randomized Study of the Effectiveness of the Drug Dalargin for the Prevention and Treatment of Symptoms of Pulmonary Complications in Patients With Coronavirus Infection (SARS-COVID-19).” Tatyana Astrelina, principal investigator. Burnasyan Federal Medical Biophysical Center. NCT04346693.

From brief summary: “The purpose of the study is to evaluate an effectiveness of the drug Dalargin for the prevention and treatment of severe pulmonary complications symptoms associated with severe and critical coronavirus infection cases (SARS COVID19, expanded as Severe acute respiratory syndrome Cоrona Virus Disease 2019).”

Details: 320 participants, April-December 2020.

 

  • “An Open Randomized Study of the Effectiveness of the Drug Mefloquine, Tablets 250 mg, Produced by FSUE SPC ‘Farmzashita’ of the Federal Medical Biological Agency, FMBA of Russia (Russia) for the Treatment of Patients With COVID19.” Tatyana Astrelina, principal investigator. Burnasyan Federal Medical Biophysical Center. NCT04347031.

From brief summary: “Study of the effectiveness and safety of the drug Mefloquine, tablets 250 mg, produced by FSUE “SPC” Farmzaschita ” FMBA of Russia (Russia), in comparison with the drug Hydroxychloroquine, tablets 200 mg, for the treatment of patients with coronavirus infection, in the “off-label” mode, to make a decision on the possibility of expanding the indications for use.”

Details: 320 participants, April-August, 2020.

 

Middle East & Africa 

 

  • “Multi-centre Randomised Controlled Trial of Chloroquine/Hydroxychloroquine Versus Standard of Care for Treatment of Mild Covid-19 in HIV-positive Outpatients in South Africa.” Sean Wasserman, principal investigator. University of Cape Town. NCT04360759.

From CQOTE Trial detailed description: “The trial objective is to compare chloroquine (or hydroxychloroquine) versus standard of care for the primary endpoint of hospitalisation or death at 28 days.”

Details: 560 participants, May 2020-May 2021. Experimental: Arm 1: Chloroquine or hydroxychloroquine. Loading dose of 4 tablets (150 mg chloroquine base per chloroquine salt tablet; 155 mg chloroquine base per hydroxychloroquine tablet) at time 0 and 6 hours, followed by a maintenance dose of 2 tablets at time 12 hours, and then twice daily for a total of 7 days.

 

  • “Clinical Trial Evaluating Safety and Efficacy of Hydroxychloroquine and Nitazoxanide Combination as Adjuvant Therapy in Covid-19 Newly Diagnosed Egyptian Patients: A Tanta University Hope.” Kamal Okasha, principal investigator. Tanta University, Cairo. NCT04361318.

From arms and interventions: “Both hydroxychloroquine & nitazoxanide will be administered orally to participating patients.”

Details: 100 participants, May-October 2020. Experimental: Hydroxychloroquine plus Nitazoxanide. 200 mg of Hydroxychloroquine orally three times daily for 10 days plus 500 mg of Nitazoxanide orally twice daily for 6 days.

 

  • “Isotretinoin in Treatment of COVID-19 (Randomized).” Lamia Elgarhy, principal investigator. Tanta University, Cairo, NCT04361422.

From brief summary: “Several potential mechanisms of action of Chloroquine/Hydroxychloroquine against SARS-CoV-2 have been postulated and they are actually used in treatment regimens for COVID-19.(7) It was reported that chloroquine increase the blood level of isotretinoin, so lower doses is required when combined. We assume to test the efficacy of isotretinoin in treatment of COVID-19 versus combined therapy with the standard treatment of COVID-19.”

Details: Group (1): 50 patients will receive isotretinoin 0.5 mg/kg/day for one month or until viral clearance.Group (2): 50 patients will receive standard therapy for COVID-19 (Paracetamol 500 mg /6h, Hydroxychloroquine 500 mg/ 12h, Oseltamivir 150 mg /12 h for 5 days, Azithromycin 1 gm first day then 500 mg/day for 1st line or Clarithromycin 500 mg/12 h for 7-14 days, Ascorbic acid 500 mg/12 h and Cyanocobalamin IV once daily plus Lopinavir 400mg/Ritonavir 100 mg caps 2 capsules twice daily in severe cases).Group (3): 50 patients will receive standard therapy for COVID-19 + isotretinoin 0.25 mg/kg/day for one month or until viral clearance.

 

  • “Hydroxychloroquine in Combination With Azithromycin or Sirolimus for Treating COVID-19 Patients: A Pilot, Multicenter Randomized Open-Label Trial.” Iyad Sultan, principal investigator. King Hussein Cancer Center, Jordan. NCT04374903.

From COVID-19 HOPE Trial brief summary: “The evidence for using sirolimus for influenza is emphasized by a RCT that showed reduction of mechanical ventilation time by 50% (7 days on sirolimus arm vs 15 days on oseltamivir/steroids arm). Safe administration in human subjects is illustrated by multiple phase I/II clinical trials, performed in patients with cancer. COVID19-HOPE trial will randomize patients to 2 arms: HCQ/AZ (Arm A) and HCQ/SIR (Arm B).”

Details:  Experimental: Study Arm A (HCQ & AZ) Subjects will receive HCQ 600mg PO X 10 days and AZ PO 250mg DAILY X 10 days. Experimental: Study Arm B (HCQ+SIR). Subjects will receive HCQ 600mg PO X 10 days and SIR 4mg PO X 1 day then 2mg PO DAILY X 9 days.

 

  • “A Multicenter, Open-label, Pilot Study on Using Hydroxychloroquine (HCQ) and Azithromycin (AZ) Prophylaxis for Healthcare Workers With a Potential Risk of Exposure to COVID-19 Patients.” Iyad Sultan, principal investigator. King Hussein Cancer Center, Jordan. NCT04354597.

From the MOPHYDA Trial brief summary: “In this study, we aim to study prophylactic efficacy of the combination (HCQ and AZ) among health care professionals in a 16 weeks period.”

Details: 200 participants, April-October 2020. Experimental: Study Arm A (HCQ & AZ) Subjects will receive weekly HCQ 400mg X 1 Day PO and AZ 500mg PO X 3 Days; weekly for 16 weeks.

 

  • “Assessment of Efficacy and Safety of HCQ and Antibiotics Administrated to Patients COVID19(+), in Tunisia.” Jalila Ben Khelil, principal investigator. Abderrahmane Mami Hospital, Tunisia. NCT04351919.

From the COVID+PA Trial brief summary: “The study will assess the number of patients who become asymptomatic from clinical signs of COVID19 and will assess the efficacy of Hydroxychloroquine (HCQ) and Azithromycine effects on paucisymptomatic patients with ou without co-morbidities.”

Details: 400 patients, April-July 2020. Drug: Hydroxychloroquine. 400mg per day during 10 days Drug: Azithromycin. 500 mg per day during 5 days.

 

  • “Assessment of the Efficacy and Safety of Hydroxychloroquine (HCQ) Administered as a Prophylaxis for Health Professionals Exposed to COVID19 and Working in Medical Intensive Care Units, in Tunisia. Multicentric Randomized Comparative Study.” Jalila Ben Khelil, principal investigator. Abderrahmane Mami Hospital, Tunisia. NCT04349228.

From COVID_2Pro Trial detailed description: “Interventional, Multicentric, Randomized Controlled Study in Two Parallel Groups of 530 Healthcare Professionals working in the Intensive Care Unit Exposed to Risk of COVID19 Infection Taking Hydroxychloroquine (HCQ) (200 mg/day) VS Placebo.”

Details: 530 participants, April-July 2020.

 

  • “Efficacy and Safety of Favipiravir in Management of COVID-19.” Hany Dabbous, principal investigator. Ain Shams University, Egypt. NCT04349241.

From FAV-001 Trial brief summary: “Randomized controlled interventional trial (Clinical Trial) phase 3 to assess the safety and efficacy of favipiravir versus the standard care therapy in the treatment of patients with COVID-19.”

Details: “Active Comparator: Standard of care therapy oseltamivir 75 mg 12 hourly for 5-10 days and hydroxychloroquine 400mg 12 hourly day -1 followed by 200mg 12 hourly daily on day- 2 to day-5-10.”

 

  • “Qatar Prospective RCT Of Therapy Eliminating Covid Transmission (Q-PROTECT).” Tim Richard Edmund Harris, principal investigator. Hamad Medical Corporation. NCT04349592.

From the Q-PROTECT Trial detailed description: “In this study we will randomise ambulatory patients with Covid 19 (confirmed by PCR in combination with clinical symptoms) to receive HC/AZ or HC/placebo or placebo for 7 days.”

Details: 456 participants, April-May 2020. Experimental: HC/AZ. Hydroxychloroquine 200 mg oral tablet three times daily for 7 days + Azithromycin 500 mg ( 2 caps) oral capsules on day one then 250 mg ( 1 cap) daily from day 2-5.

 

  • “Adjuvant Use of Ivermectin To Hydroxychloroquine in Patients With Covid19: A Novel Double Blind Placebo Controlled Pilot Study.” Faiq Gorial, principal investigator. University of Baghdad. NCT04343092.

From the detailed description: “Comparing the efficacy and safety of adjuvant use of Ivermectin in covid19 patients with pneumonia using Ivermectin 0.2mg/kg (12 mg adult dose ) single dose at once repeated after 1 week combined with hydroxychloroquine 400mg daily compared to HCQ 400 daily plus placebo single one dose repeated after 1 week.”

Details: 50 participants, April-August 2020. 

 

  • “Efficacy and Safety of Azithromycin Compared to the Base Therapeutic Regiment of Hydroxychloroquine in Moderate to Severe COVID-19: A Randomized, Controlled, Double-Blind, Clinical Trial.” Seyed Sina Naghibi Irvani, principal investigator. Shahid Beheshti University of Medical Sciences. NCT04359316.

From AIC Trial detailed description: “Chloroquine has been a broadly-utilized anti-malaria agent which back in 2006, had been proved to be a powerful wide-spectrum antiviral. Moreover, Chloroquine has the characteristics of anti-inflammatory and immune-modulatory by inhibiting the production of TNF-α along with IL-6. In the first half of February, a study illustrated puissant inhibition of SARS-CoV-2 by Chloroquine, when taking two 500-mg tablets of it by mouth per day; similar to some clinical studies in China through this outbreak.”

Details: 40 participants, April-May 2020. Drug: Hydroxychloroquine. This Drug will be used in all arms as mandated by our governmental guidelines. Drug: Azithromycin. This will be drug only used in the intervention arm of our study, designed mainly to assess the additional efficacy and safety of Azithromycin in COVID-19 patients.

 

  • “Efficacy and Safety of Favipiravir Compared to the Base Therapeutic Regiment in Moderate to Severe COVID-19: A Randomized, Controlled, Double-Blind, Clinical Trial.” Seyed Sina Naghibi Irvani, principal investigator. Shahid Beheshti University of Medical Sciences. NCT04359615.

From FIC Trial brief summary: “Favipiravir, previously known as T-705, is a prodrug of a purine nucleotide, favipiravir ribofuranosyl-5′-triphosphate. The active agent inhibits the RNA polymerase, halting viral replication. Most of favipiravir’s preclinical data are derived from its influenza and Ebola activity; however, the agent also demonstrated broad activity against other RNA viruses. In vitro, the 50% effective concentration (EC50) of favipiravir against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was 61.88 μM/L in Vero E6 cells.”

Details: 40 participants, April-May 2020. Drug: Favipiravir This will be drug only used in the intervention arm of our study, designed mainly to assess the additional efficacy and safety of Favipiravir in COVID-19 patients. Drug: Hydroxychloroquine. This Drug will be used in all arms as mandated by our governmental guidelines.

 

  • “An Investigation Into Beneficial Effects of Interferon Beta 1a, Compared to The Base Therapeutic Regiment in Moderate to Severe COVID-19: A Randomized, Double-Blind, Placebo-Controlled, Clinical Trial.” Seyed Sina Naghibi Irvani, principal investigator. Shahid Beheshti University of Medical Sciences. NCT04350671.

From the IB1aIC Trial arms and interventions: “Drug: Interferon Beta-1A. This will be drug only used in the intervention arm of our study, designed mainly to assess the additional efficacy and safety of Interferon-β 1a in COVID-19 patients.”

Details: 40 participants, April 2020. Drug: Lopinavir / Ritonavir. This Drug will be used in all arms as mandated by our governmental guidelines. Drug: Single Dose of Hydroxychloroquine. This Drug will be used in all arms as mandated by our governmental guidelines.

 

  • “Efficacy and Safety of Umifenovir as an Adjuvant Therapy Compared to the Control Therapeutic Regiment of Interferon Beta 1a, Lopinavir / Ritonavir and a Single Dose of Hydroxychloroquine in Moderate to Severe COVID-19: A Randomized, Double-Blind, Placebo-Controlled, Clinical Trial.” Seyed Sina Naghibi Irvani, principal investigator. Shahid Beheshti University of Medical Sciences, Teheran. NCT04350684.

From UAIIC Trial arms and interventions: “Drug: Umifenovir. This will be drug only used in the intervention arm of our study, designed mainly to assess the additional efficacy and safety of Umifenovir in COVID-19 patients.”

Details: 40 participants, April 2020. Hydroxychloroquine included in both experimental and comparator per government guidelines.

 

  • “An Investigation Into Beneficial Effects of Interferon Beta 1a, Compared to Interferon Beta 1b And The Base Therapeutic Regiment in Moderate to Severe COVID-19: A Randomized Clinical Trial (DIC).” Seyed Sina Naghibi Irvani, principal investigator. Shahid Beheshti University of Medical Sciences, Teheran. NCT04343768.

From detailed description: “In a 2003 study, SARS was treated with different human interferons and found that IFN-β was 5 to 10 times more effective than other types of interferons and the strongest antiviral drug possible against SARS-CoV.”

Details: 60 participants, April 2020. Drug: Hydroxychloroquine. This Drug will be used in all arms.

 

  • “An Open-Label Study to Compare the Efficacy, Safety, and Tolerability of Hydroxychloroquine Combined With Azithromycin Compared to Hydroxychloroquine Combined With Camostat Mesylate and to “no Treatment” in Hospitalized Patients Suffering From a Mild or Moderate SARS CoV 2 Virus.” Itsik Levy, principal investiagtor. Sheba Medical Center. NCT04355052.

From the COSTA Trial detailed description: “This prospective, open-label, placebo-controlled, randomized clinical trial will determine if hydroxychloroquine for 5 days plus camostat mesylate for 10 days, initiated in patients older than 60 years or younger but with risk factors for severe COVID 19 disease will reduce the risk of progression to severe COVID-19 disease compared to hydroxychloroquine plus azithromycin for 5 days or not treating with neither.”

Details: 250 participants, April-October 2020.  Active Comparator: A – HCQ + AZT. Hydroxychloroquine 400 mg BID on day 1 and than 200 mg BID on days 2-5 + Azithromycin 500 mg QD on day 1 and 250 mg QD on days 2-5. Hydroxychloroquine 400 mg BID on day 1 and than 200 mg BID on days 2-5 + Camostat mesylat 200 mg TID for 10 days.

 

  • “Chloroquine for Mild Symptomatic and Asymptomatic COVID-19 in A Two Staged, Multicenter, Open Label and Randomized Trial.”  Lee Goldstein, contact. HaEmek Medical Center, Israel. NCT04333628.

From brief summary: “In the treatment of malaria, the benefit of low dosage of the drug has been shown to be effective due to the fact that the intracellular concentration of the drug is probably higher, and therefore the logic to examine this issue in COVID-19 treatment. The purpose of this study is to test whether a low dose of Chloroquine will reduce the duration of the viral shedding and prevent the disease from worsening.”

Details: 210 participants. “This study will compare three groups of treatment, identical of their size (by randomization table) group 1- 125mgx1 / d low dose chloroquine group for 7 days (or until the condition worsens, whichever comes first) group 2- Regular dose chloroquine dose at 500mgx2 / d for 7 days (or until the condition worsens, whichever comes first) 3. Standard treatment group.” April 2020-April 2021.

 

  • “Hydroxychloroquine for the Treatment of Patients With Mild to Moderate COVID-19 to Prevent Progression to Severe Infection or Death.” Paul Rambam, principal investigator. Rambam Health Care Campus, Rabin Medical Center. NCT04323631.

From brief summary: “This is a multi-center, randomized controlled, superiority, open label trial. The objective of this trial is to evaluate the efficacy of HCQ in patients with newly diagnosed COVID-19 who have mild to moderate disease or at risk for complications. We aim to demonstrate decrease in progression to severe pneumonia and hospital related complications among patients who are treated with HCQ compared to patients who are not.”

Details: 1,116 participants, March-December 2020. 

 

  • “Proflaxis Using Hydroxychloroquine Plus Vitamins-Zinc During COVID-19 Pandemia.” Mahir M Ozmen, contact. Istinye University Medical University. NCT04326725.  

From brief summary: “Healthcare professionals mainly doctors, nurses and their first degree relatives (spouse, father, mother, sister, brother, child) who have been started hydroxychloroquine(plaquenil) 200mg single dose repeated every three weeks plus vitaminC including zinc once a day were included in the study. Study has conducted on 20th of march. Main purpose of the study was to cover participants those who are facing or treating COVID19 infected patients in Ankara.”

Details: 80 participants, March-July 2020. 

 

Asia

 

  • “Efficacy and Safety of Hydroxychloroquine for COVID-19 Post-Exposure Prophylaxis of Healthcare Workers in the Philippine General Hospital and UP Manila National Institutes of Health: A Randomized, Double-blind, Placebo-controlled Trial.” Belen L Dofitas, principal investigator. University of the Philippines. NCT04364815.

From detailed description: “To compare the efficacy and safety of hydroxychloroquine with an oral loading dose of 400 mg two times a day on D1 followed by 400mg/day from Day 2-10 plus standard preventive measures and standard preventive measures alone as post-exposure prophylaxis for healthcare workers in a Metro Manila COVID Referral Center.”

Details: 960 participants, April 2020-May 2021.

 

  • “The Randomized, Open, Phase 2 Study to Evaluate the Safety and Efficacy of Clevudine in Patients With Moderate COVID-19.” Bukwang Pharmaceutical, South Korea. NCT04347915.

From brief summary: “The purpose of this clinical trial is to assess the safety and efficacy of Clevudine 120 mg once a day for 14 days (maximum up to 21 days) and of Hydroxychloroquine 200mg twice a day for 14 days (maximum up to 21 days) of administration in patients with moderate COVID-19.”

Details: 60 participants, April-September 2020. Clevudine 120mg once a day for 14 days (up to 21 days). Hydroxychloroquine for 200 mg twice a day for 14 days (up to 21 days).

 

  • “Safety And Efficacy Of Hydroxychloroquine As COVID-19 Prophylaxis For At-Risk Population (SHARP): A Cluster Randomized Controlled Trial.” Rupesh Agrawal, principal investigator. Tan Tock Seng Hospital, National Center for Infectious Diseases, Singapore Clinical Research Institute, Singapore Eye Research Institute, Saw Swee Hock School of Public Health, Duke-NUS Graduate Medical School, Netherlands: Ministry of Health, Welfare and Sports. NCT04342156.

From the SHARP Trial brief summary: “This cluster randomized trial will evaluate the safety and efficacy of oral HCQ PEP, taken over for 5 days, in reducing the number of infected household contacts of confirmed COVID-19 patients under home quarantine.”

Details: 3,000 participants, April-October 2020. Experimental: Hydroxychloroquine post exposure prophylaxis Treatment arm will be given Hydroxychloroquine sulfate. Dose: 800 milligrams (mg) (4 pills of 200mg) as single dose on day 1 followed by 400mg (2 pills of 200mg) single dose on day 2, 3,4, 5.

 

  • “An Open-label Randomized Controlled Trial on Interferon β-1b and Hydroxychloroquine Combination Versus Hydroxychloroquine Alone, as Treatment for COVID-19 Infection.” Ivan FN Hung, principal investigator. The University of Hong Kong. NCT04350281.

From the detailed description: “This is a prospective open-label randomised controlled trial among adult patients hospitalised after April 2020 for virologically confirmed SARS-CoV-2 infection. Patients will be randomly assigned to either the treatment group: a 3-day course of 3 doses of subcutaneous injection of interferon β-1b 1mL (0.25mg; 8 million IU) consecutively on day 1 to day 3 and hydroxychloroquine 800mg on day 1, then 400mg daily for 2 days plus standard care, or the control group: a 3-day course of hydroxycholoroquine 800mg on day 1, then 400mg daily for 2 days plus standard care alone (1:1). For the control group, if the day 4 nasopharyngeal swab (NPS) viral load remains positive, then patients will receive another 3 days of subcutaneous injection of interferon β-1b 1mL (0.25mg; 8 million IU) and hydroxychloroquine 400mg daily.”

Details: 80 participants, April 2020-March 2022. Active Comparator: Treatment group. Subcutaneous injection of interferon β-1b 1mL (0.25mg; 8 million IU) consecutively on day 1 to day 3 and hydroxychloroquine 800mg on day 1, then 400mg daily for 2 days plus standard care. Active Comparator: Control group. Hydroxychloroquine 800mg on day 1, then 400mg daily for 2 days plus standard care alone.

 

  • “Efficacy and Safety of Hydroxychloroquine for Treatment of Pneumonia Caused by 2019-nCoV (HC-nCoV).” Hongzhou Lu, principal investigator. Shanghai Public Health Clinical Center. NCT04261517.

From the HC-nCoV Trial brief summary: “The study aims to evaluate the efficacy and safety of hydroxychloroquine in the treatment of pneumonia caused by the 2019 novel coronavirus.”

Details: 30 participants. After randomization, subjects take hydroxychloroquine 400mg per day for 5 days, also take conventional treatments. February 2020.

 

  • “A Study of Hydroxychloroquine as Post Exposure Prophylaxis for SARS-CoV-2(HOPE Trial).” Young Goo Soon, principal investigator. Gangnam Severance Hospital, Seoul, South Korea. NCT04330144.

From the HOPE Trial study description: “…we aim to evaluate the efficacy and safety of hydroxychloroquine as post exposure prophylaxis for SARS-CoV-2.”

Details: 2,486 estimated participants. “Drug: Hydroxychloroquine as post exposure prophylaxis. 1day: Hydroxychloroquine 800mg Qd po 2-5dy: Hydroxychloroquine 400mg Qd po.” April 2020-March 2021.

 

  • Various Combination of Protease Inhibitors, Oseltamivir, Favipiravir, and Hydroxychloroquine for Treatment of COVID19 : A Randomized Control Trial (THDMS-COVID19) .” Dr Subsai Kongsaengdao. Rajavithi Hospital, Thailand. NCT04303299.

From THDMS-COVID19 brief summary: A 6-Week Prospective, Open label, Randomized, in Multicenter Study of… [multiple drugs] in moderate to critically illness in COVID 19.”

Details: 80 participants. Overall Study Design and Plan Various Combination of Protease inhibitors, Oseltamivir, Favipiravir, and Chloroquin for treatment of COVID19. Non parametric and parametric statistical analysis will be analysed in the efficacy of treatment. March-October 2020.

 

  • “Efficacy and Safety of Hydroxychloroquine in Primary Prophylaxis of SARS-CoV-2 Infection in Healthcare Workers at Risk of Exposure: Randomised Control Trial.” Saira Burney, principal investigator. Services Institute of Medical Sciences, Pakistan. NCT04370015.

From detailed description: “An interventional randomised control trial that will include 374 participants who will be healthcare workers at variable risks of exposure to SARS-CoV-2 while managing patients both suspected and confirmed with COVID-19 infection.”

Details: 374 participants, April-October, 2020. Experimental: Treatment group. Health care workers at high risk of contracting SARS-CoV-2 randomized to this arm will be treated with oral hydroxychloroquine 400 mg twice a day (four 200 mg tablets) on day 1 followed by 400mg (two 200 mg tablets) once a week for 11 weeks.

 

  • “Comparative Efficacy of Various Doses of Hydroxychloroquine in Pre-Exposure Prophylaxis for COVID 19 in Healthcare Personnel.” Fibhaa Syed, principal investigator. Shaheed Zulfiqar Ali Bhutto Medical University. NCT04359537.

From CHEER Trial brief summary: “In this study we will be comparing three different doses of Hydroxychloroquine and additionally have a control group in order to determine the efficacy of hydroxychloroquine as pre- exposure prophylaxis in healthcare personnel in various doses.”

Details:  200 participants, April-August 2020. Experimental group 1: Hydroxychloroquine 400 mg twice a day 1,followed by 400 mg weekly for a total of 12 weeks Drug: Hydroxychloroquin HCQ 200 mg, oral. Experimental group 2:Hydroxychloroquine 400 mg on day 1 followed by 400mg once every 3 weeks for a total of 12 weeks Drug: Hydroxychloroquin HCQ 200 mg, oral. Experimental group 3:Hydroxychloroquine 200 mg on day 1 followed by 200 mg once every 3 weeks for a total of 12 weeks Drug: Hydroxychloroquin HCQ 200 mg, oral. Control Group : Placebo 200mg will be given on day 1 followed by Placebo 200mg every three weeks for a total of 12 weeks.

 

  • “Use and Dosage of Hydroxychloroquine and Chloroquine to Convert Symptomatic RT-PCR Positive Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Coronavirus Infectious Disease 2019 (COVID-19) Patients to RT- PCR-Negative as a Means to Reduce Hospitalization Rate.” Ammar Sarwar, responsible party. Government of Punjab, Specialized Healthcare and Medical Education Department. NCT04351191.

From PRECISE Trial brief summary: “To treat Pakistani patients with non-life threatening symptomatic SARS-CoV-2 infection with an intent to reduce burden on institutional healthcare services by determining efficacy of different chloroquine and hydroxychloroquine dosing regimens in controlling SARS-CoV-2 infection.”

Details: 400 participants, April-May 2020. Active Comparator: HCQ Regular dose. Hydroxychloroquine loading dose (400 mg BID for 2 days) followed by 200 mg BID for 4 days plus standard of care. Experimental: HCQ Loading dose, Hydroxychloroquine loading dose (400 mg BID) alone plus standard of care. Active Comparator: CQ regular dose Cholorquine 500 mg BID for 5 days plus standard of care.

 

  • “Use and Dosage of Hydroxychloroquine and Chloroquine to Convert Real Time Polymerase Chain Reaction (RT-PCR) Positive Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Coronavirus Infectious Disease 2019 (COVID-19) Patients to RT- PCR-Negative as a Means to Reduce Hospitalization Rate.” Ammar Sarwar, principal investigator. Government of Punjab, Specialized Healthcare and Medical Education Department. NCT04346667.

From the brief summary: “To create a protocol for treatment of Pakistani patients with SARS-CoV-2 infection with an intent to reduce burden on institutional healthcare services by determining efficacy of different quinone drug dosing regimens in controlling SARS-CoV-2 infection for asymptomatic patients.”

Details: 400 participants, April 2020-May 2021.

 

  • “Effectiveness of Hydroxychloroquine in Covid-19 Patients: A Single Centred Single-blind RCT Study.” Prof. Dr. Umar Farooq, principal investigator. Ayub Medical College, Abbottabad, Pakistan. NCT04328272.

From brief summary: “To find the effectiveness of hydroxychloroquine alone and adjuvant with azithromycin in mild to severe Covide-19 pneumonia patients admitted to Coronavirus cell/ward of Ayub Teaching hospital, Abbottabad Pakistan. A single centered, single-blind randomized control trial study.”

Details: 75 participants, March-June 2020. Experimental: Hydroxychloroquine. tablet hydroxychloroquine (HCQ). Day-1 (initial) 1st dose, 3 tablets (200 mg per tablet), 2nd dose after 6 hours, 3 tablets (200 mg per tablet) per oral. From day 2 to 7 (maintenance dose), 2 tablets twice a day. Active Comparator: Azithromycin Tablet azithromycin (AZC) 500 mg orally as a single dose on day 1, followed by 250 mg orally once a day on days 2 to 7. 

 

  • “Hydroxychloroquine, Oseltamivir and Azithromycin for the Treatment of COVID-19 Infection: An RCT (PROTECT).” Shehnoor Azhar, University of Health Sciences Lahore, Federal Task Force on Science & Technology. NCT04338698.

From the PROTECT Trial brief summary: “To evaluate the effectiveness of Hydroxychloroquine Phosphate/Sulfate (200 mg orally 8hr thrice a day for 5 days) vs oseltamivir (75 mg orally twice a day for 5 days) vs Azithromycin (500 mg orally daily on day 1, followed by 250 mg orally twice a day on days 2-5) alone and in combination (in all seven groups), in clearing the coronavirus nucleic acid from throat and nasal swab and in bringing about clinical improvement on day 7 of follow-up (primary outcomes).”

Details: April-September 2020, 500 participants. 

 

 

South America

  • “Effectiveness and Safety of Medical Treatment for SARS-CoV-2 (COVID-19) in Colombia: A Pragmatic Randomized Controlled Trial.” Hernando G Gaitán-Duarte, principal investigator. Universidad Nacional de Colombia. NCT04359095.
From brief summary: “The study will be carried out in two phases. The first phase will be conducted with 480 participants and aims to identify treatments with higher or minimum potential, discontinue treatments with higher toxicity and have opportunity of introducing new treatments with potential efficacy. The second phase will be conducted with 1,120 participants to evaluate the effectiveness of the selected treatments. Four interventions have been defined: I1 HCQ, I2 HCQ plus Lop/r, I3 HCQ plus Azithro and I4 standard treatment.”
Details: 1,600 participants, May-October 2020.
  • “Immune Monitoring of Prophylactic Effect of Hydroxychloroquine in Healthcare Providers Highly Exposed to SARS-Cov-2.” Carlos Alberto Parra Lopez, principal investigator. Universidad Nacional de Colombia. NCT04346329.
From detailed description: “This is a PILOT STUDY, a Phase III double-blind, randomized, placebo-controlled clinical study in which we assess the clinical effect of the prophylactic administration of hydroxychloroquine vs. placebo to healthcare workers working at our University Hospital (HUN). Participants in each arm (n = 43) will be administered with a unique loading dose of 800 mg of hydroxychloroquine the first day followed by 400 mg/week for 90 days.”
Details: 86 participants, April-October 2020.
  • “Convalescent Plasma for Patients With COVID-19: A Randomized, Open Label, Parallel, Controlled Clinical Study.” Juan Manuel Anaya Cabrera, study director. Universidad del Rosario, Fundación Universitaria de Ciencias de la Salud, CES University, Instituto Distrital de Ciencia Biotecnología e Innovacion en Salud. NCT04332835.

From the CP-COVID-19 Trial detailed description: “The process is based on obtaining plasma from patients recovered from COVID-19 in Colombia, and through a donation of plasma from the recovered, the subsequent transfusion of this to patients infected with coronavirus disease (COVID-19). Our group has reviewed the scientific evidence regarding the application of convalescent plasma for emergency viral outbreaks and has recommended the following protocol.”

Details: 80 participants, April-August 2020. Experimental Arm. Drug: Plasma Day 1: CP-COVID19, 250 milliliters. Day 2: CP-COVID19, 250 milliliters. Drug: Hydroxychloroquine 400 milligrams each 12 hours for 10 days.  Control group: Drug: Hydroxychloroquine 400 milligrams each 12 hours for 10 days. Drug: Azithromycin 500 milligrams daily for 10 days.

 

  • “Hydroxychloroquine or Hydroxychloroquine Associated With Azithromycin for Inpatients With Moderate or Severe Lung Disease Due to SARS-CoV-2 (COVID-19).” Eduardo Alexandrino Servolo de Medeiros, principal investigator. Apsen Farmaceutica S.A., Hospital São Paulo. NCT04361461.

From brief summary: “China recently approved the use of favipiravir, an antiviral used for influenza, as an experimental therapy for COVID-19. Hydroxychloroquine is a drug with great potential treatment, as it can inhibit the pH-dependent steps of replication of various viruses, with a potent effect on SARS-CoV infection and spread. In this way, the present study will evaluate the safety and efficacy of the hydroxychloroquine in patients with symptomatic SARS-Cov2.”

Details: May-November 2020, 500 participants. Experimental: Group 1 Drug: Hydroxychloroquine Sulfate 400 mg orally, every 12 hours x 2 doses (loading dose) and then 400 mg, once daily, orally, for 10 days. Other Name: Reuquinol®. Experimental: Group 2  Drug: Hydroxychloroquine Sulfate + Azythromycin 400 mg, orally, every 12 hours x 2 doses (loading dose) and then 400 mg, once a day, orally, for 10 days associated with azithromycin, intravenously or orally, 500 mg / day, for 1 day and then 250mg / day for another 4 days. Other Name: Reuquinol® + Azythromycin.

 

  • “Open Label, Multicentric, Non Randomized, Exploratory Clinical Trial to Assess the Efficacy and Safety of Hydroxychloroquine and Azithromycin for the Treatment of Mild Acute Respiratory Syndrome (COVID-19) Caused by SARS-CoV-2 Virus.” Rafael Souza, contact. Azidus Brasil. NCT04348474.

From detailed description: “This is an exploratory study to evaluate the efficacy of hydroxychloroquine (400 mg BID on D1 and 400 mg/day on D2 to D7) and azithromycin (500 mg/ 5 days) to treat mild ambulatory COVID-19 patients.”

Details: 200 participants, April-July 2021. Experimental: HCQ + AZT. All patients included in the study will receive hydroxychloroquine (HCQ) 400 mg (00 mg BID on D1 and 400 mg/day on D2 to D7) and azithromycin (AZT) (500 mg/ 5 days) on top of standard care.

 

  • “An Open-label, Randomized Controlled Trial of Hydroxychloroquine and Azytromicyn for COVID-19 Infection on Hospitalized, Noncritical Patients.” Fernando Zampieri, principal investigator. Hospital Israelita Albert Einstein. NCT04322123.

From the brief summary: “COALITION I study aims to compared standard of care, hydroxychloroquine plus azythromycin and hydroxychloroquine monotherapy for treatment of hospitalized patients with COVID-19. COALITION I will recruit 630 patients with infection by COVID-19 (210 per arm). Ordinal endpoint of status at 15 days will be the primary endpoint.”

Details: April-August 2020. Hydroxychloroquine after randomization, Hydroxychloroquine [400mg 2x/day, 12/12h] for 07 days. Hydroxychloroquine + azythromycin. After randomization, Hydroxychloroquine [400mg 2x/day, 12/12h] + azythromycin [500mg 1x/day]) for 07 days.

 

  • “Evaluation of the Safety and Clinical Efficacy of Hydroxychloroquine Associated With Azithromycin in Patients With Pneumonia Caused by Infection by the SARS-CoV2 Virus – Coalition COVID-19 Brasil II – Severely-ill Patients.” Fernando Zampieri, principal investigator. Hospital Israelita Albert Einstein.  NCT04321278.

From Coalition Covid-19 Brasil II detailed description: “… the present study will evaluate the effectiveness and safety of the use of hydroxychloroquine combined with azithromycin compared to hydroxychloroquine monotherapy in the clinical evolution by the ordinal scale of 7 points in adult patients hospitalized with pneumonia caused by infection by the SARS-CoV2 virus in Brazil.”

Details: 440 participants.  1. Intervention Group: Hydroxychloroquine + azithromycin. After randomization, Hydroxychloroquine [400mg 2x/day, 12/12h] + azithromycin [500mg 1x/day]) for 10 days. Standard treatment is according to the treatment protocol for 2019-nCoV infection.  2. Active Control Group: Hydroxychloroquine. After randomization, Hydroxychloroquine [400mg 2x/day, 12/12h] for 10 days. Standard treatment is according to the treatment protocol for 2019-nCoV infection. March-August 2020.

 


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