Hydroxychloroquine as Postexposure Prophylaxis to Prevent Severe Acute Respiratory Syndrome Coronavirus 2 Infection
Ruanne V. Barnabas, Elizabeth R. Brown, Anna Bershteyn, Helen C. Stankiewicz Karita, Christine Johnston, Lorna E. Thorpe, Angelica C Kottkamp, Kathleen M. Neuzil, Miriam K. Laufer, Meagan E. Deming, Michael K. Paasche‐Orlow, Patricia Kissinger, Alfred Luk, Kristopher Paolino, Raphael J. Landovitz, Risa M. Hoffman, Torin Schaafsma, Meighan Krows, Katherine K. Thomas, Susan Morrison, Harald S. Haugen, Lara Kidoguchi, Mark H. Wener, Alexander L. Greninger, Meei‐Li Huang, Keith R. Jerome, Anna Wald, Connie Celum, Helen Y. Chu, Jared M. Baeten, Hydroxychloroquine COVID-19 PEP Study Team*
Abstract
BACKGROUND: Effective prevention against coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is currently limited to nonpharmaceutical strategies. Laboratory and observational data suggested that hydroxychloroquine had biological activity against SARS-CoV-2, potentially permitting its use for prevention. OBJECTIVE: To test hydroxychloroquine as postexposure prophylaxis for SARS-CoV-2 infection. DESIGN: Household-randomized, double-blind, controlled trial of hydroxychloroquine postexposure prophylaxis. (ClinicalTrials.gov: NCT04328961). SETTING: National U.S. multicenter study. PARTICIPANTS: Close contacts recently exposed (<96 hours) to persons with diagnosed SARS-CoV-2 infection. INTERVENTION: Hydroxychloroquine (400 mg/d for 3 days followed by 200 mg/d for 11 days) or ascorbic acid (500 mg/d followed by 250 mg/d) as a placebo-equivalent control. MEASUREMENTS: Participants self-collected mid-turbinate swabs daily (days 1 to 14) for SARS-CoV-2 polymerase chain reaction (PCR) testing. The primary outcome was PCR-confirmed incident SARS-CoV-2 infection among persons who were SARS-CoV-2 negative at enrollment. RESULTS: = 0.026). LIMITATION: The delay between exposure, and then baseline testing and the first dose of hydroxychloroquine or ascorbic acid, was a median of 2 days. CONCLUSION: This rigorous randomized controlled trial among persons with recent exposure excluded a clinically meaningful effect of hydroxychloroquine as postexposure prophylaxis to prevent SARS-CoV-2 infection. PRIMARY FUNDING SOURCE: Bill & Melinda Gates Foundation.