Table 2.
Characteristics of included studies
| Study first author | Design∗ | Population | Age (y) | Female sex (%) | Baseline comorbidities | Drugs studied | ECG monitoring | Follow-up |
|---|---|---|---|---|---|---|---|---|
| Non–COVID-19 participants | ||||||||
| Haeusler17 | SR of RCTs and cohort studies (n = 1207) | Malaria treatment, prophylaxis, or healthy volunteers | 20.8 | 36.3 | 65% of trials excluded patients with comorbidities | CQ | At least 2 ECGs in all studies | NR |
| Pfizer18 | RCT (n = 119) | Healthy volunteers | 35.5 | 16.4 | NA | CQ phosphate 1000 mg/d, CQ phosphate 1000 mg/d plus azithromycin 500 mg/d, or placebo for 3 days | Baseline and day 3 | Three patients not included in the analysis |
| WHO Evidence Review Group19 | SR of RCTs and cohort studies (n = 23,773) | Malaria treatment | NR | NR | NR | CQ | NR | At least 14 days of follow-up; exact loss to follow-up uncertain |
| COVID-19 participants | ||||||||
| Borba20 | RCT (n = 56) | Patients with ARDS and suspected COVID-19 | 51.1 | 24.7 | Any 67.5%, hypertension 46.3%, DM 25.9%, alcoholism 26%, heart disease 9.3%, asthma 6.2%, CKD 7.5%, liver disease 3.7%, HIV 1.9% | High-dose CQ (CQ diphosphate 1 g twice daily for 6 days) vs low-dose CQ (day 1: CQ diphosphate 750 mg twice daily; days 2–5: 750 mg daily); all patients on IV azithromycin | Baseline and at clinical discretion | No patients reported as lost to follow-up |
| Chen21 | RCT (n = 15) | Moderate COVID-19 patients | 48.6 | 30 | Hypertension 33.3%, DM 6.7% | HCQ sulfate 400 mg/d for 5 days (vs no treatment) | NR | No patients reported as lost to follow-up |
| Chen (unpublished preprint) | RCT (n = 31) | Mild COVID-19 patients | 44.7 | 53.2 | Relevant exclusion criteria: arrhythmias, severe liver disease, or eGFR ≤30 mL/min/1.73 m2 | HCQ sulfate 400 mg/d for 5 days (vs no treatment) | NR | No patients reported as lost to follow-up |
| Chorin22 | Cohort study (n = 84) | Hospitalized COVID-19 patients | 63 | 26 | CAD 11%, CKD 7%, DM 20%, COPD 8%, HF 2%, acute renal failure 6% | HCQ and azithromycin | Baseline and daily | All patients included |
| Gautret23 | Cohort study (n = 80) | Hospitalized COVID-19 patients | 52.5 | 46.2 | Cancer 6.3%, DM 11.2%, hypertension 16.3%, chronic respiratory disease 10.0%, obesity 5.0%, immunosuppression 5.0% | HCQ and azithromycin; other QT-prolonging drugs discontinued | Baseline and day 2 | All patients hospitalized and with 6 days of follow-up included |
| Huang24 | RCT (n = 10) | Moderate and severe COVID-19 patients | 41.5 | 30.0 | 10% hypertension, 10% DM; excluded history of chronic liver or kidney disease, arrhythmia, or other chronic heart disease | CQ phosphate 500 mg twice daily for 10 days | NR | All patients followed for 14 days |
| Mahévas25 | Retrospective cohort study (n = 84) | Hospitalized COVID-19 patients | 59 | 21.7 | Chronic respiratory disease 6%, chronic HF (NYHA III or IV) 1.2%, any cardiovascular condition 45.2%, IDDM 4.8%, CKD 5.0%, liver cirrhosis 1.2%, immunosuppression 9.5% | HCQ sulfate 600 mg/d; 20% also received azithromycin | Baseline, days 3–5 | Follow-up until death, discharge, or day 7 of hospitalization |
| Million (unpublished abstract) | Cohort study (n = 1061) | Hospitalized COVID-19 patients | 43.6 | 53.6 | NR | HCQ and azithromycin for at least 3 days | NR | NR |
| Molina26 | Case series (n = 11) | Hospitalized COVID-19 patients | 58.7 | 36.3 | Obesity 18%, solid cancer 27%, hematologic cancer 18%, HIV 9% | HCQ sulfate 600 mg/d for 10 days and azithromycin 500 mg day 1, then 250 mg/d for 4 days | NR | Follow-up of 10 days |
| Perinel27 | Prospective PK study (n = 13) | COVID-19 patients in critical care | 68 | 15 | 30.7% moderate or severe renal failure, 92% mechanically ventilated | HCQ 200 mg 3 times daily, with dose adjustment to reach trough 1–2 mg/L | NR | Follow-up of ≥5 days |
| Tang28 | Open-label RCT (n = 70) | Mild–moderate (99%) or severe (1%) COVID-19 patients | 48.0 | 44 | DM 16.0%, hypertension 8.0%; liver and renal impairment were exclusion criteria | HCQ sulfate 1200 mg/d for 3 days, then 800 mg/d thereafter (median duration 14 days) | NR | No patients reported as lost to follow-up (median duration 20 days) |
ARDS = acute respiratory distress syndrome; CAD = coronary artery disease; CKD = chronic kidney disease; COPD = chronic obstructive pulmonary disease; CQ = chloroquine; DM = diabetes mellitus; ECG = electrocardiogram; eGFR = estimated glomerular filtration rate; HCQ = hydroxychloroquine; HF = heart failure; HIV = human immunodeficiency virus; IDDM = insulin-dependent diabetes mellitus; IV = intravenous; NA = not applicable; NR = not reported; NYHA = New York Heart Association (functional class); PK = pharmacokinetic; RCT = randomized controlled trial; SR = systematic review; WHO = World Health Organization.
∗
Number of patients treated with chloroquine or hydroxychloroquine (not total number enrolled in the trial). In the Pfizer study, only total number of participants was provided, so this number is shown.