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

Jun 04, 2020
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Author/Summarized by Author:
Anthony A. Bavry, MD, MPH, FACC
Summary Reviewer:
Deepak L. Bhatt, MD, MPH, MBA, FACC
Trial Sponsor:
David Baszucki and Jan Ellison Baszucki and others.
Date Published:
06/03/2020
Date Updated:
06/04/2020
Original Posted Date:
06/04/2020
References

Contribution To Literature:

This trial failed to show that hydroxychloroquine was superior to placebo at preventing symptomatic infection.

Description:

The goal of the trial was to evaluate if hydroxychloroquine compared with placebo can prevent symptomatic infection among subjects exposed to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus (coronavirus disease 2019 [COVID-19]). In vitro studies have supported that hydroxychloroquine may be active against COVID-19. This activity is thought to be due to prevention of glycosylation of angiotensin-converting-enzyme 2, which is responsible for binding of the virus to the envelope spike glycoprotein.

Study Design

  • Randomized
  • Parallel
  • Placebo
  • Double-blind

Participants exposed to COVID-19 within the last 4 days were randomized to hydroxychloroquine (n = 414) versus placebo (n = 407). Participants randomized to hydroxychloroquine received 800 mg once, followed by 600 mg in 6-8 hours, then 600 mg daily for 4 additional days.

  • Total number of enrollees: 821
  • Duration of follow-up: 14 days
  • Mean patient age: 40 years
  • Percentage female: 52%
  • Percentage with diabetes: 3%

Inclusion criteria:

  • Participants ≥18 years of age who were exposed to someone with confirmed COVID-19 at a distance of <6 feet for >10 minutes
  • High-risk exposure, not wearing face mask or eye shield
  • Low-risk exposure, wearing face mask but no eye shield

Principal Findings:

Overall, symptomatic COVID-19 infection occurred in 19% of participants.

The primary outcome, incidence of laboratory-confirmed COVID-19 or illness compatible with COVID-19 within 14 days, occurred in 11.8% of the hydroxychloroquine group compared with 14.3% of the placebo group (p = 0.35).

Secondary outcomes:

  • Any side effect: 40.1% of the hydroxychloroquine group compared with 16.8% of the placebo group (p < 0.001)
  • Serious adverse events: 0 compared with 0
  • Deaths: 0 compared with 0

Interpretation:

Among participants exposed to COVID-19 within the last 4 days, hydroxychloroquine failed to prevent symptomatic infection. Hydroxychloroquine was associated with more side effects compared with placebo; however, no serious adverse events were reported. This trial was powered for 750 participants in each group to detect a 50% relative reduction in new infections. Accordingly, with only 821 enrolled participants, the negative trial result may have been due to lack of power. However, if an absolute reduction of approximately 2% was realized, it is doubtful this would be clinically meaningful.

References:

Boulware DR, Pullen MF, Bangdiwala AS, et al. A Randomized Trial of Hydroxychloroquine as Postexposure Prophylaxis for Covid-19. N Engl J Med 2020;Jun 3:[Epub ahead of print].

Editorial: Cohen MS. Hydroxychloroquine for the Prevention of Covid-19 — Searching for Evidence. N Engl J Med 2020;Jun 3:[Epub ahead of print].

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

Keywords: Coronavirus, COVID-19, Drug-Related Side Effects and Adverse Reactions, Glycoproteins, Glycosylation, Hydroxychloroquine, Masks, Post-Exposure Prophylaxis, Primary Prevention, SARS Virus, severe acute respiratory syndrome coronavirus 2


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