COVID-19 Evidence Alerts
from McMaster PLUSTM

Current best evidence for clinical care (more info)

Primary Prevention Boulware DR, Pullen MF, Bangdiwala AS, et al. A Randomized Trial of Hydroxychloroquine as Postexposure Prophylaxis for Covid-19. N Engl J Med. 2020 Aug 6;383(6):517-525. doi: 10.1056/NEJMoa2016638. Epub 2020 Jun 3.

BACKGROUND: Coronavirus disease 2019 (Covid-19) occurs after exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). For persons who are exposed, the standard of care is observation and quarantine. Whether hydroxychloroquine can prevent symptomatic infection after SARS-CoV-2 exposure is unknown.

METHODS: We conducted a randomized, double-blind, placebo-controlled trial across the United States and parts of Canada testing hydroxychloroquine as postexposure prophylaxis. We enrolled adults who had household or occupational exposure to someone with confirmed Covid-19 at a 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). Within 4 days after exposure, we randomly assigned participants to receive either placebo or hydroxychloroquine (800 mg once, followed by 600 mg in 6 to 8 hours, then 600 mg daily for 4 additional days). The primary outcome was the incidence of either laboratory-confirmed Covid-19 or illness compatible with Covid-19 within 14 days.

RESULTS: We enrolled 821 asymptomatic participants. Overall, 87.6% of the participants (719 of 821) reported a high-risk exposure to a confirmed Covid-19 contact. The incidence of new illness compatible with Covid-19 did not differ significantly between participants receiving hydroxychloroquine (49 of 414 [11.8%]) and those receiving placebo (58 of 407 [14.3%]); the absolute 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.

CONCLUSIONS: After high-risk or moderate-risk exposure to Covid-19, hydroxychloroquine did not prevent illness compatible with Covid-19 or confirmed infection when used as postexposure prophylaxis within 4 days after exposure. (Funded by David Baszucki and Jan Ellison Baszucki and others; number, NCT04308668.).

Discipline / Specialty Area Score
Infectious Disease
Public Health
Emergency Medicine
Hospital Doctor/Hospitalists
Internal Medicine
General Internal Medicine-Primary Care(US)
Family Medicine (FM)/General Practice (GP)
Occupational and Environmental Health
Comments from MORE raters

Emergency Medicine rater

This double-blind RCT included adults with exposure to a person with confirmed COVID-19 at a distance < 6ft for more than 10 minutes. The primary outcome was symptomatic illness. Patients were randomized to receive HCQ 800 mg once, followed by 600 mg every 6-8 hours, and then 600 mg every day for 4 days. 545 patients were healthcare workers, out of the 821 asymptomatic patients included. There was a new diagnosis of COVID-19 in 13% of those included, with no difference between groups based on HCQ. There are some limitations, including recruitment through media, subjective exposure history, and most patients were unable to receive formal COVID testing. Patients were also younger and healthier than those at risk for severe COVID-19. While authors found no serious adverse events, the study was not powered for this and not all patients received ECG. This study provides important data that suggest HCQ does not prevent COVID-19 when used as postexposure prophylaxis within 4 days of exposure.

Emergency Medicine rater

Important and timely. Questions remaining include: (1) would subsets of post-exposure patients benefit (older, underlying lung disease)?; and (2) is 4 days post-exposure too late?

Emergency Medicine rater

Important manuscript for any front-line worker considering taking HCQ for prophylaxis. The results do not show a benefit, but some faults with the study include looking only at symptoms, so many asymptomatic patients could have been missed.

Family Medicine (FM)/General Practice (GP) rater

A highly effective treatment for COVID-19 that could be used early in the course of infection would provide enormous health as well as economic benefit. I hope the scientists are working hard to identify this treatment. This trial provides very strong evidence that hydroxychloroquine is not it.

Internal Medicine rater

Important and well done study confirming the lack of a role for HCQ, not just in treatment of COVID but also for prophylaxis.

Occupational and Environmental Health rater

Good information with a reasonable sample size; however, only one dosage schedule studied, so we don`t know whether it might work in another dose or duration. So, data suggest that hydroxychloroquine doesn`t prevent COVID-19 after recent exposure at the studied dose and duration.

Public Health rater

This is a first well controlled trial of hydroxychloroquine for prophylaxis of Covid-19. It appears to be well done, but the recruitment was via the internet and the followup was done in a distance manner. Most of the enrollees were health care workers, so the potential exposure was relatively large. There probably will be more studies, but this one doesn't much support for use of hydroxychloroquine in this setting.