COVID-19 Evidence Alerts
from McMaster PLUSTM

Current best evidence for clinical care (more info)

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Primary Prevention Rajasingham R, Bangdiwala AS, Nicol MR, et al. Hydroxychloroquine as pre-exposure prophylaxis for COVID-19 in healthcare workers: a randomized trial. Clin Infect Dis. 2020 Oct 17. pii: 5929230. doi: 10.1093/cid/ciaa1571.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a rapidly emerging virus causing the ongoing Covid-19 pandemic with no known effective prophylaxis. We investigated whether hydroxychloroquine could prevent SARS-CoV-2 in healthcare workers at high risk of exposure.

METHODS: We conducted a randomized, double-blind, placebo-controlled clinical trial of healthcare workers with ongoing exposure to persons with SARS-CoV-2, including those working in emergency departments, intensive care units, Covid-19 hospital wards, and first responders. Participants across the United States and in the Canadian province of Manitoba were randomized to hydroxychloroquine 400mg once weekly or twice weekly for 12 weeks. The primary endpoint was confirmed or probable Covid-19-compatible illness. We measured hydroxychloroquine whole blood concentrations.

RESULTS: We enrolled 1483 healthcare workers, of which 79% reported performing aerosol-generating procedures. The incidence of Covid-19 (laboratory-confirmed or symptomatic compatible illness) was 0.27 events per person-year with once-weekly and 0.28 events per person-year with twice-weekly hydroxychloroquine compared with 0.38 events per person-year with placebo. For once weekly hydroxychloroquine prophylaxis, the hazard ratio was 0.72 (95%CI 0.44 to 1.16; P=0.18), and for twice-weekly was 0.74 (95%CI 0.46 to 1.19; P=0.22) as compared with placebo. Median hydroxychloroquine concentrations in whole blood were 98 ng/mL (IQR, 82-120) with once-weekly and 200 ng/mL (IQR, 159-258) with twice-weekly dosing. Hydroxychloroquine concentrations did not differ between participants who developed Covid-19-compatible illness (154 ng/mL) versus participants without Covid-19 (133 ng/mL; P=0.08).

CONCLUSIONS: Pre-exposure prophylaxis with hydroxychloroquine once or twice weekly did not significantly reduce laboratory-confirmed Covid-19 or Covid-19-compatible illness among healthcare workers.

Discipline / Specialty Area Score
Emergency Medicine
Hospital Doctor/Hospitalists
Internal Medicine
Infectious Disease
Intensivist/Critical Care
Comments from MORE raters

Emergency Medicine rater

This study furthers our knowledge on hydroxychloroquine. It's good to know; yet, it's another nail in the coffin.

Infectious Disease rater

There are few randomized trials assessing the prevention of COVID-19. Hydroxychloroquine showed in vitro to decrease the endocytic pathway of SARS-CoV-2 and therefore could prevent the cytokine storm. Therefore, hydroxychloroquine could be a good candidate drug to prevent infection or severe infection caused by SARS-CoV-2. This trial showed a lack of efficacy of hydroxychloroquine a as preventive drug.