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Primary Prevention Barnabas RV, Brown ER, Bershteyn A, et al. Hydroxychloroquine as Postexposure Prophylaxis to Prevent Severe Acute Respiratory Syndrome Coronavirus 2 Infection : A Randomized Trial. Ann Intern Med. 2021 Mar;174(3):344-352. doi: 10.7326/M20-6519. Epub 2020 Dec 8.
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.

Ratings
Discipline / Specialty Area Score
Family Medicine (FM)/General Practice (GP)
General Internal Medicine-Primary Care(US)
Infectious Disease
Emergency Medicine
Comments from MORE raters

Emergency Medicine rater

The article brings a Randomized Trial evaluating the efficacy and safety of Hydroxycloroquine for Postexposure Prophylaxis of Covid-19 infection. The study was overall well designed and concluded that there is no statistical difference between the control and intervention groups. The authors omitted to mention some limitations such as: the expected sample size was not reached, so the conclusions should not be generalized; the self collected swabs by participants could have influenced the results, even with remote training. Despite the limitations, the study raises the importance of deepening the investigations regarding Hydroxychloroquine on the prevention of SARS-COV-2 acquisition.