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Ann Intern Med
. 2020 Dec 8.
doi: 10.7326/M20-6519. Online ahead of print.
Hydroxychloroquine as Postexposure Prophylaxis to Prevent Severe Acute Respiratory Syndrome Coronavirus 2 Infection : A Randomized Trial
Ruanne V Barnabas 1 , Elizabeth R Brown 1 , Anna Bershteyn 2 , Helen C Stankiewicz Karita 3 , Christine Johnston 1 , Lorna E Thorpe 2 , Angelica Kottkamp 2 , Kathleen M Neuzil 4 , Miriam K Laufer 4 , Meagan Deming 4 , Michael K Paasche-Orlow 5 , Patricia J Kissinger 6 , Alfred Luk 7 , Kristopher Paolino 8 , Raphael J Landovitz 9 , Risa Hoffman 9 , Torin T Schaafsma 3 , Meighan L Krows 3 , Katherine K Thomas 3 , Susan Morrison 3 , Harald S Haugen 3 , Lara Kidoguchi 3 , Mark Wener 3 , Alexander L Greninger 1 , Meei-Li Huang 10 , Keith R Jerome 1 , Anna Wald 1 , Connie Celum 3 , Helen Y Chu 3 , Jared M Baeten 3
Affiliations
- PMID: 33284679
- DOI: 10.7326/M20-6519
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: Between March and August 2020, 671 households were randomly assigned: 337 (407 participants) to the hydroxychloroquine group and 334 (422 participants) to the control group. Retention at day 14 was 91%, and 10 724 of 11 606 (92%) expected swabs were tested. Among the 689 (89%) participants who were SARS-CoV-2 negative at baseline, there was no difference between the hydroxychloroquine and control groups in SARS-CoV-2 acquisition by day 14 (53 versus 45 events; adjusted hazard ratio, 1.10 [95% CI, 0.73 to 1.66]; P > 0.20). The frequency of participants experiencing adverse events was higher in the hydroxychloroquine group than the control group (66 [16.2%] versus 46 [10.9%], respectively; P = 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.