Chloroquine or hydroxychloroquine for prevention and treatment of COVID-19.
Level 1 - systematic review of randomized trials
Systematic review and meta-analysis of randomized controlled trials
PubMed 33624299 · doi:10.1002/14651858.CD013587.pub2
What was done
This Cochrane systematic review searched CENTRAL, MEDLINE, Embase, clinical trial registries, and COVID-19 databases up to September 15, 2020. It included randomized controlled trials assessing chloroquine (CQ) or hydroxychloroquine (HCQ) for COVID-19 treatment, pre-exposure prophylaxis, and post-exposure prophylaxis. Primary outcomes included all-cause mortality, viral clearance, progression to mechanical ventilation, and adverse events. Effect sizes were pooled using random-effects meta-analyses, and evidence certainty was graded using the GRADE approach.
What was found
For COVID-19 treatment (12 trials, 8,569 participants): - All-cause mortality: HCQ showed little to no difference compared to standard care or placebo (RR 1.09, 95% CI 0.99 to 1.19; 8,208 participants, 9 trials; high-certainty evidence). - Mechanical ventilation: HCQ probably results in little to no difference in progression to mechanical ventilation (RR 1.11, 95% CI 0.91 to 1.37; 4,521 participants, 3 trials; moderate-certainty evidence). - Viral clearance: HCQ may make little or no difference to negative PCR status at day 14 (RR 1.00, 95% CI 0.91 to 1.10; 213 participants, 3 trials; low-certainty evidence). - Adverse events: HCQ probably increased the risk of any adverse event nearly three-fold (RR 2.90, 95% CI 1.49 to 5.64; 1,394 participants, 6 trials; moderate-certainty evidence), with no clear difference in serious adverse events (RR 0.82, 95% CI 0.37 to 1.79; 1,004 participants, 6 trials; low-certainty evidence). For prevention: - Pre-exposure: No completed trials were available. - Post-exposure: In one RCT (n=821), certainty was very low for confirmed COVID-19 (20/821) and hospitalization (2/821), while HCQ probably increased adverse events (RR 2.39, 95% CI 1.83 to 3.11). A cluster-RCT (n=2,525) found no difference in symptomatic COVID-19 or antibody development.
Why it matters
High-certainty evidence demonstrates that hydroxychloroquine does not decrease mortality or prevent mechanical ventilation in COVID-19 treatment, while substantially increasing adverse events.
Limits
The review search ended in September 2020. Included treatment trials had substantial variation in disease severity, dosing schedules, comorbidities, and co-interventions, with potential risks of bias across multiple domains. Pre-exposure prophylaxis data were completely lacking, and post-exposure prophylaxis trials were limited by low event rates and very low-to-moderate certainty.
Cited by
- contradicts A small study of 20 patients found that combining hydroxychloroquine with azithromycin was dramatically effective in clearing SARS-CoV-2.