Table 1: Clinical studies on the use of hydroxychloroquine or chloroquine in COVID-19 disease or COVID-19 prophylaxis organized by study design and date of publication. Table 1: Clinical studies on the use of hydroxychloroquine or chloroquine in COVID-19 disease or COVID-19 prophylaxis organized by study design and date of publication. Table 1: Clinical studies on the use of hydroxychloroquine or chloroquine in COVID-19 disease or COVID-19 prophylaxis organized by study design and date of publication. Table 1: Clinical studies on the use of hydroxychloroquine or chloroquine in COVID-19 disease or COVID-19 prophylaxis organized by study design and date of publication. Table 1: Clinical studies on the use of hydroxychloroquine or chloroquine in COVID-19 disease or COVID-19 prophylaxis organized by study design and date of publication. Table 1: Clinical studies on the use of hydroxychloroquine or chloroquine in COVID-19 disease or COVID-19 prophylaxis organized by study design and date of publication.
Article Population of interest Intervention Outcomes of interest Results Observations
Single-arm interventional studies
J. M. Molina et al. (France, March 30th, 2020) Confirmed hospitalized COVID-19 consecutive cases (n=11) HCQ 200 mg Q8h D1-D10) + AZI (500 mg D1 and 250 mg D2-D5). Viral negative conversion and clinical outcomes Nasopharyngeal PCR was positive in 8/10 (80%) patients at D6. 1/11 (0.9%) patient died, 2/11 (18.2%) patients were transferred to the ICU. 1/11 (0.9%) had prolongation of QTc 10/11 (91%) of patients required supplemental oxygen at the time of treatment initiation. The time between onset of symptoms and treatment initiation was not specified.
P. Gautret et al. (France, April 11th, 2020) Confirmed hospitalized COVID-19 cases with mild COVID-19 to severe COVID-19 pneumonia (n=80) HCQ (200 mg Q8h D1-D10) + AZI (500 mg D1 and 250 mg D2-D5). ICU transfer and oxygen requirement after D3, length of hospitalization, virus contagiousness (PCR cycle threshold value, and viral culture) 3/80 (0.4%) patients required supplemental oxygen, 12/80 (15%) patients required ICU transfer, 1/80 (1.3%) patient died upon publication date. Mean length of hospitalization in the ward was 4.6 days. No patient was presumably contagious by D12. 69/75 (92%) patients had low NEWS at baseline.
Retrospective studies
J. Magagnoli et al. (US, April 21st 2020) Confirmed hospitalized cases (n=368) HCQ (n= 97), HCQ + azithromycin (n=113), SOC (n=158) In-hospital mortality and need for mechanical ventilation HCQ was associated with greater in-hospital mortality compared to SOC. Risk of mechanical ventilation was similar between groups. Patient in the treatment arms had more severe disease at baseline. The study included only men, most were African-Americans (64%), and older (median age 65)
M. Million et al. (France, May 5th 2020) Confirmed cases with asymptomatic infection to severe COVID-19 pneumonia (n=1062) HCQ (200 mg Q8h D1-D10) + AZI (500 mg/d D1, 250 mg D2-D5) In-hospital mortality, need for ICU, length of hospitalization > 10 days, viral shedding > 10 days 46/1061 (4.3%) patients had a poor outcome (need for mechanical ventilation and/or death), 8/1061 (0.8%) patients died of respiratory failure. 91.7% patients had viral negative conversion at D10. 95% os patients had relatively mild disease (low NEWS)
M. R. Mehra et al. (Multinational, May 6th 2020) Confirmed hospitalized cases (n=96031) CQ vs CQ + macrolide vs HCQ vs HCQ + macrolide vs none In-hospital mortality and occurrence of de-novo ventricular arrhythmias All treatment groups were associated with increased in-hospital mortality and de-novo ventricular arrhythmias. Study was retracted. Data and statistical analysis were not shared with an independent group of researchers for evaluation.
E. S. Rosenberg et al. (US, May 11th 2020) Confirmed hospitalized cases (n=1438) HCQ (n=271) vs AZI (n=211) vs HCQ + AZI (n=735) vs SOC (n=221) In-hospital mortality In-hospital mortality was similar between groups. Treatment arms were associated with increased risk of cardiac arrest compared to SOC. Patients receiving HCQ with or without AZI were more likely to be male, have pre-existing conditions, and more severe disease at presentation. Readmissions were not captured.
B. Yu et al. (China, May 15th 2020) Confirmed cases with severe COVID-19 pneumonia requiring mechanical ventilation (n=550) HCQ (n=48, 200 mg Q12h D1-D7 or D10) vs SOC (n=512) In-hospital mortality, inflammatory cytokine levels HCQ was associated with decreased mortality and mortality was lower among patients who were started on HCQ within 5 days of admission compared to the ones who were started later. HCQ was associated with decrease in IL-6 levels It was not specified how the HCQ group was selected
M. Mahévas et al. (France, May 24th 2020) Confirmed hospitalized cases of COVID-19 pneumonia requiring supplemental oxygen, but not mechanical ventilation (n=181) HCQ (n=84, 600 mg/d) vs SOC (n=89) Survival without transfer to the ICU at D21, overall survival, survival without ARDS, weaning of supplemental oxygen, hospital discharge to home or rehabilitation at D21 HCQ was not associated with differences in survival, ICU transfer, weaning of supplemental oxygen. 8/92 (8.7%) patients in the HCQ group experienced EKG changes that required HCQ discontinuation. The decision on whether or not to use HCQ were based on centre’s protocols and not on individual’s clinical presentation
J. Geleris et al. (US, June 18th 2020) Confirmed hospitalized consecutive cases (n=1376) HCQ (n=811, 600 mg Q12h D1, 400 mg/d for a median of 5 days) with or without AZI vs SOC In-hospital mortality and need for mechanical ventilation HCQ was not associated with use of mechanical ventilation or death Patients in the HCQ group were more severely ill at baseline
S. Arshad et al. (US, July 2nd 2020) Confirmed hospitalized cases (n=2541) HCQ (n=1202, 400 mg Q12h D1, 200 mg Q12h D2-D5), AZI (n=147, 500 mg D1, 250 mg D2-D5), HCQ+ AZI (n=783) vs SOC (n=409) In-hospital mortality HCQ alone and HCQ+ AZI were associated with decreased hazard of in-hospital death Patients on HCQ and AZI were more likely to have received corticosteroids or tocilizumab.
Prospective, interventional and controlled studies:
P. Gautret et al. (France, March 20th, 2020) Confirmed cases with asymptomatic infection to severe COVID-19 pneumonia (n=36) HCQ (n=20, 200 mg Q8h D1-D10) vs SOC (n=16) Viral negative conversion at D6, virologic clearance at D14, symptoms, length of hospitalization, and mortality. Nasopharyngeal PCR was more likely to be negative in the HCQ group at D6. 6/26 (23.1%) patients in the HCQ group were not counted in the analysis due to loss of follow up or early cessation of therapy. 3/6 (50%) of these patients were transferred to the ICU.
Z. Chen et al. (China, April 1st, 2020) Confirmed hospitalized cases with mild COVID-19 pneumonia (n=62) HCQ (n=31, 400 mg/d D1-D5) vs SOC (n=31) Clinical recovery in 5 days; chest radiographic follow up in 5 days. Time to defervescence and cough was shorter in the HCQ group. Pneumonia radiographic improvement was more common in the HCQ group. Young patients (mean 44.7), mostly women (53.2%). Fever and cough was more prevalent in the HCQ arm at baseline.
M. G. Silva Borba et al. (Brazil, April 24th 2020) Suspected hospitalized cases with severe COVID-19 pneumonia (n=81) CQ (n=41, 600 mg Q12h D1-D10) vs CQ (n=40, 450 mg Q12h D1, 450 mg/day D2-D5) In-hospital mortality, adverse events, clinical status, viral negative conversion on D4 Mortality was higher in the high-dose CQ group at D13. QTc prolongation was more common in the high-dose CQ group. Patients in the high-dose CQ group were older and had more heart disease. All patients received AZI and most have received oseltamivir. 14/51 (27.5%) patients had alcohol use disorder.
W. Tang et al. (China, May 4th , 2020) Confirmed hospitalized cases with mild to moderate COVID-19 (n=150) HCQ (n=75, 1200 mg/d D1-D3, then HCQ 800 mg/d until D14 or D21) vs SOC (n=75) Viral negative conversion at D28, clinical and radiographic improvement Probability of viral negative conversion and alleviation of symptoms was similar between HCQ and SOC at D28. 30/70 (43%) patients reported adverse events, 2/70 (2.9%) patients reported severe adverse events due to disease progression and upper respiratory tract infection. Results on clinical, laboratory, and radiographic improvement were not reported due to under-powered sample size. Median of 16 days between symptoms onset and HCQ initiation.
D. R. Boulware et al. (US and Canada, June 3rd 2020) Asymptomatic participants who had moderate or high risk exposure to confirmed cases of COVID-19 (n=821) HCQ (n=414, 800 mg once, then 600 mg in 6-8h, then 600 mg D2-D5) vs placebo (n=407) Incidence of either laboratory confirmed or illness compatible with COVID-19 HCQ and placebo groups had similar incidence of laboratory confirmed or clinically suspected cases of COVID-19 Participants were overall young (median age 40), women (51.6%), healthy (75% did not have pre-existing hypertension, asthma, diabetes)
P. W. Horby et al. (UK, June 4th 2020) Suspected or confirmed hospitalized cases (n=4761) HCQ (n=1561, 800 mg once then in 6h, 400 mg at 12h, then 400 mg Q12h D2-D10) vs SOC (n=3155) Mortality in D28, length of hospitalization, need for mechanical ventilation, need for hemodialysis, incidence of major cardiac arrhythmia Patients in the HCQ arm were less likely to be discharged alive from the hospital and were more likely to reach a composite score of mechanical ventilation and death. There was one case of torsades de pointes in the HCQ arm. Preliminary results did not include case-specific mortality or other clinical and laboratory data.
A. B Cavalcanti et al. (Brazil, July 23rd 2020) Suspected or confirmed cases with mild-to-moderate COVID-19 requiring no oxygen or maximum of 4L O2 supplementation (n=665) HCQ (n=221, 400 mg Q12 D1-D7) vs HCQ + AZI (n=217, HCQ 400 mg Q12h D1-D7 and AZI 500 mg/d for D1-D5) vs SOC (n=227) Clinical outcomes assessed by a 7-levels ordinal scale and adverse events HCQ or HCQ+ AZI were not associated with a difference in the 7-points ordinal scale, need of mechanical ventilation, deaths, and thromboembolic complications compared to usual of care group. QTc prolongation and elevation of liver enzymes were more common in the treatment arms. Median time from symptom onset to randomization was 7 days
HCQ: hydroxychloroquine, CQ: chloroquine, AZI: azithromycin, SOC: standard of care, D (1-28): Day (1-28), Q8h/Q12h: every 8h/ every 12h, ICU: intensive care unit HCQ: hydroxychloroquine, CQ: chloroquine, AZI: azithromycin, SOC: standard of care, D (1-28): Day (1-28), Q8h/Q12h: every 8h/ every 12h, ICU: intensive care unit HCQ: hydroxychloroquine, CQ: chloroquine, AZI: azithromycin, SOC: standard of care, D (1-28): Day (1-28), Q8h/Q12h: every 8h/ every 12h, ICU: intensive care unit HCQ: hydroxychloroquine, CQ: chloroquine, AZI: azithromycin, SOC: standard of care, D (1-28): Day (1-28), Q8h/Q12h: every 8h/ every 12h, ICU: intensive care unit HCQ: hydroxychloroquine, CQ: chloroquine, AZI: azithromycin, SOC: standard of care, D (1-28): Day (1-28), Q8h/Q12h: every 8h/ every 12h, ICU: intensive care unit HCQ: hydroxychloroquine, CQ: chloroquine, AZI: azithromycin, SOC: standard of care, D (1-28): Day (1-28), Q8h/Q12h: every 8h/ every 12h, ICU: intensive care unit
Confirmed cases: confirmed by SARS-CoV-2 RNA by PCR from nasopharyngeal sample or other confirmatory laboratory assay specific for the virus. Confirmed cases: confirmed by SARS-CoV-2 RNA by PCR from nasopharyngeal sample or other confirmatory laboratory assay specific for the virus. Confirmed cases: confirmed by SARS-CoV-2 RNA by PCR from nasopharyngeal sample or other confirmatory laboratory assay specific for the virus. Confirmed cases: confirmed by SARS-CoV-2 RNA by PCR from nasopharyngeal sample or other confirmatory laboratory assay specific for the virus. Confirmed cases: confirmed by SARS-CoV-2 RNA by PCR from nasopharyngeal sample or other confirmatory laboratory assay specific for the virus. Confirmed cases: confirmed by SARS-CoV-2 RNA by PCR from nasopharyngeal sample or other confirmatory laboratory assay specific for the virus.
NEWS (National Early Warning Score): scoring system designed to be applied to hospitalized patients to allow for early detection of clinical deterioration. NEWS 1-4 (low score), NEWS 5-6 (medium score), NEWS >=7 (high score) NEWS (National Early Warning Score): scoring system designed to be applied to hospitalized patients to allow for early detection of clinical deterioration. NEWS 1-4 (low score), NEWS 5-6 (medium score), NEWS >=7 (high score) NEWS (National Early Warning Score): scoring system designed to be applied to hospitalized patients to allow for early detection of clinical deterioration. NEWS 1-4 (low score), NEWS 5-6 (medium score), NEWS >=7 (high score) NEWS (National Early Warning Score): scoring system designed to be applied to hospitalized patients to allow for early detection of clinical deterioration. NEWS 1-4 (low score), NEWS 5-6 (medium score), NEWS >=7 (high score) NEWS (National Early Warning Score): scoring system designed to be applied to hospitalized patients to allow for early detection of clinical deterioration. NEWS 1-4 (low score), NEWS 5-6 (medium score), NEWS >=7 (high score) NEWS (National Early Warning Score): scoring system designed to be applied to hospitalized patients to allow for early detection of clinical deterioration. NEWS 1-4 (low score), NEWS 5-6 (medium score), NEWS >=7 (high score)