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Randomized Controlled Trial
. 2021 Mar;174(3):344-352.
doi: 10.7326/M20-6519. Epub 2020 Dec 8.

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 ; Hydroxychloroquine COVID-19 PEP Study Team
Collaborators, Affiliations
Randomized Controlled Trial

Hydroxychloroquine as Postexposure Prophylaxis to Prevent Severe Acute Respiratory Syndrome Coronavirus 2 Infection : A Randomized Trial

Ruanne V Barnabas et al. Ann Intern Med. 2021 Mar.

Erratum in

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.

PubMed Disclaimer

Conflict of interest statement

Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M20-6519.

Figures

Visual Abstract.
Visual Abstract.. Postexposure Hydroxychloroquine Prophylaxis to Prevent SARS-CoV-2 Infection
Clinical trials have ruled out a role of hydroxychloroquine in the treatment of COVID-19, but it has been hypothesized that hydroxychloroquine's activity against SARS-CoV-2 in the laboratory suggests a role in prevention. This randomized controlled trial tests hydroxychloroquine as postexposure prophylaxis for SARS-CoV-2 infection.
Figure 1.
Figure 1.. Study flow diagram.
HCQ = hydroxychloroquine; SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2.
Figure 2.
Figure 2.. Cumulative incidence of SARS-CoV-2.
HCQ = hydroxychloroquine; SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2.
See this image and copyright information in PMC

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