No statistically significant difference in the primary outcome of either laboratory-confirmed COVID-19 or illness compatible with COVID-19 within 14 days of exposure was found in a randomized, double-blind trial comparing hydroxychloroquine against placebo. The results were reported in the New England Journal of Medicine.

David R. Boulware, MD, MPH, et al., enrolled 821 asymptomatic participants from the U.S. and parts of Canada, of whom 87.6% reported a high-risk exposure to a confirmed COVID-19 contact. Study participants had household or occupational exposure to someone with confirmed COVID-19 at a distance of less than six feet for more than 10 minutes while not wearing a face mask or an eye shield (high-risk exposure) or while wearing a face mask but no eye shield (moderate-risk exposure). The median age of the participants was 40 years, 51.6% were women, and 27.4% reported chronic health conditions, mostly hypertension followed by asthma.

Health care workers comprised 66.4% of the study participants (of whom 62.8% were physicians or physician assistants and 23.5% were nurses or nursing assistants). Their exposure was mostly from patients or ill coworkers.

After exposure, within four days, participants were randomized to either hydroxychloroquine (800 mg once, followed by 600 mg in six to eight hours, then 600 mg daily for four additional days) or placebo.

Results showed no difference in the incidence of new illness compatible with COVID-19 between the two groups: 11.8% with hydroxychloroquine and 14.3% with placebo. The absolute between-group difference was –2.4 percentage points (95% confidence interval, –7.0 to 2.2; p= 0.35).

Side effects were more common with hydroxychloroquine than with placebo (40.1% vs. 16.8%), but no serious adverse reactions were reported.

Recruitment to the study was primarily through social media and traditional medial platforms and participants self-enrolled using a secure internet-based survey system, which the authors acknowledge as a study limitation. They also note the lack of available diagnostic testing for COVID-19 in the U.S.

In an accompanying editorial comment, Myron S. Cohen, MD, writes, "The results reported by Boulware et al., are more provocative than definitive, suggesting that the potential prevention benefits of hydroxychloroquine remain to be determined." Along with noting the delay between perceived exposure and starting hydroxychloroquine he writes the results suggest "that what was being assessed was prevention of symptoms or progression of COVID-19, rather than prevention of SARS-CoV-2 infection."

Clinical Topics: COVID-19 Hub, Novel Agents, Statins

Keywords: Coronavirus, Coronavirus Infections, severe acute respiratory syndrome coronavirus 2, COVID-19, Hydroxychloroquine

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