Randomized Controlled Trials of Early Ambulatory Hydroxychloroquine in the Prevention of COVID-19 Infection, Hospitalization, and Death: Meta-Analysis
Ladapo et al.,
Randomized Controlled Trials of Early Ambulatory Hydroxychloroquine in the Prevention of COVID-19 Infection,..,
medRxiv, doi:10.1101/2020.09.30.20204693 (Preprint) (meta analysis)
Meta analysis of prophylactic and early treatment RCTs, 24% reduction in cases, hospitalization or death with HCQ, RR 0.76,
p=0.025. No serious adverse cardiac events were reported. 5,577 patients.
The Boulware study provides a breakdown for treatment delay. For the case of < ~4 days (2 days enrollment, ~46 hours shipping), the result of the meta analysis becomes RR 0.68,
p=0.0097.
The actual effect may be larger due to treatment delays, followup loss, protocol deviation, active placebos, no severity analysis for cases, and suboptimal regimens.
For the individual studies see
[Boulware, Mitjà, Mitjà (B), Rajasingham, Skipper].
Currently there are
36 HCQ early treatment studies and meta analysis shows:
risk of death/hospitalization/cases, 24.0% lower, RR 0.76, p = 0.03.
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Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
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Ladapo et al., 30 Sep 2020, preprint, 4 authors.
Abstract: medRxiv preprint doi: https://doi.org/10.1101/2020.09.30.20204693; this version posted September 30, 2020. The copyright holder for this
preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
It is made available under a CC-BY-ND 4.0 International license .
1
Randomized Controlled Trials of Early Ambulatory
Hydroxychloroquine in the Prevention of COVID-19 Infection,
Hospitalization, and Death: Meta-Analysis
1
2
3
Joseph A. Ladapo, MD, PhD ; John E. McKinnon, MD, MSc ; Peter A. McCullough, MD, MPH ;
4
Harvey A. Risch, MD, PhD
1
Division of General Internal Medicine and Health Services Research, David Geffen School of
Medicine at University of California, Los Angeles, CA; JLadapo@mednet.ucla.edu
2
Division of Infectious Diseases, Henry Ford Hospital, Detroit, MI; JMCKINN3@hfhs.org
3
Department of Internal Medicine, Baylor University Medical Center, Baylor Heart and Vascular
Institute, Baylor Jack and Jane Hamilton Heart and Vascular Hospital, Dallas, TX;
peteramccullough@gmail.com
4
Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, CT;
harvey.risch@yale.edu
NOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice.
medRxiv preprint doi: https://doi.org/10.1101/2020.09.30.20204693; this version posted September 30, 2020. The copyright holder for this
preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
It is made available under a CC-BY-ND 4.0 International license .
2
Address for Correspondence
Harvey A. Risch, MD, PhD
Yale School of Public Health
60 College St, PO Box 208034
New Haven, CT 06520-8034
Phone: 203-785-2848
E-mail: harvey.risch@yale.edu
medRxiv preprint doi: https://doi.org/10.1101/2020.09.30.20204693; this version posted September 30, 2020. The copyright holder for this
preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
It is made available under a CC-BY-ND 4.0 International license .
3
Abstract
Objective—To determine if hydroxychloroquine (HCQ) reduces the incidence of new illness,
hospitalization or death among outpatients at risk for or infected with SARS-CoV-2 (COVID-19).
Design—Systematic review and meta-analysis of randomized clinical trials.
Data sources—Search of MEDLINE, EMBASE, PubMed, medRxiv, PROSPERO, and the Cochrane
Central Register of Controlled Trials. Also review of reference lists from recent meta-analyses.
Study selection—Randomized clinical trials in which participants were treated with HCQ or
placebo/standard-of-care for pre-exposure prophylaxis, post-exposure prophylaxis, or
outpatient therapy for COVID-19.
Methods—Two investigators independently extracted data on trial design and outcomes.
Medication side effects and adverse reactions were also assessed. The primary outcome was
COVID-19 hospitalization or death. When unavailable, new COVID-19 infection was used. We
calculated random effects meta-analysis according to the method of DerSimonian and Laird.
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Heterogeneity between the studies was evaluated by calculation of Cochran Q and I
parameters. An Egger funnel plot was drawn to investigate publication bias. We also calculated
the fixed effects meta-analysis summary of the..
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