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A Randomized Trial of Hydroxychloroquine as Postexposure Prophylaxis for COVID-19

Our take —

In this randomized, placebo-controlled trial, the use of hydroxychloroquine within 4 days of COVID-19 exposure did not reduce incidence of illness consistent with COVID-19 or confirmed COVID-19 infection.

Study design

Randomized Controlled Trial

Study population and setting

821 persons with household or occupational exposure to someone with confirmed SARS-CoV-2 infection in the United States and Canada (“exposure” = contact with distance of less than 6 ft for more than 10 minutes while wearing neither a face mask nor an eye shield [high-risk exposure] or while wearing a face mask but no eye shield [moderate-risk exposure]). Participants were recruited through social media and traditional media platforms. Study participants were randomized to either hydroxychloroquine or placebo in a 1:1 ratio within 4 days of exposure.

Summary of Main Findings

87.6% of the participants (719 of 821) reported a high-risk exposure to a confirmed COVID-19 contact. The population was generally healthy and not at increased risk for severe COVID-19. The incidence of new illness compatible with COVID-19 did not differ between those receiving hydroxychloroquine (49 of 414 [11.8%]) and those receiving placebo (58 of 407 [14.3%]); absolute difference −2.4 percentage points (95% confidence interval, −7.0 to 2.2; P=0.35). Side effects were more common among participants receiving hydroxychloroquine compared to placebo (40.1% vs. 16.8%); no serious adverse reactions were reported in either group. Of note, approximately 60% of patients received the drug (hydroxychloroquine or placebo) on days 3 or 4.

Study Strengths

Well conducted randomized controlled trial with a geographically diverse population.


Given the median incubation time for SARS-CoV-2 is approximately 5 days, the optimal timing of prophylaxis administration is unknown. The study relied upon participant self-report of symptoms rather than laboratory-confirmed detection of SARS-CoV-2. Authors were also unable to capture asymptomatic infections. The study population was younger and healthier than populations at higher risk for severe COVID-19.

Value added

This is the first randomized controlled trial to evaluate the efficacy of hydroxychloroquine as a post-exposure prophylactic agent for COVID-19.

This review was posted on: 12 June 2020