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 The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.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Yale School of Public Health, New Haven, CT; harvey.risch@yale.edu NOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice.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 The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.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 The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.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. 2 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..