Hydroxychloroquine as Pre-exposure Prophylaxis for Coronavirus Disease 2019 (COVID-19) in Healthcare Workers: A Randomized Trial
Radha Rajasingham, Ananta S Bangdiwala, Melanie R Nicol, Caleb P Skipper, Katelyn A Pastick, Margaret L Axelrod, Matthew F Pullen, Alanna A Nascene, Darlisha A Williams, Nicole W Engen, Elizabeth C Okafor, Brian I Rini, Ingrid A Mayer, Emily G Mcdonald, Todd C Lee, Peter Li, Lauren J Mackenzie, Justin M Balko, Stephen J Dunlop, Katherine H Hullsiek, David R Boulware, Sarah M Lofgren, Mahsa Abassi, Andrew Balster, Lindsey B Collins, Glen Drobot, Douglas S Krakower, Sylvain A Lother, Dylan S Mackay, Cameron Meyer-Mueller, Stephen Selinsky, Dayna Solvason, Ryan Zarychanski, Rebecca Zash
Clinical Infectious Diseases, doi:10.1093/cid/ciaa1571
Background. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a rapidly emerging virus causing the ongoing coronavirus disease 2019 (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 loading dose then 400 mg once 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 whom 79% reported performing aerosol-generating procedures. The incidence of COVID-19 (laboratory-confirmed or symptomatic compatible illness) was 0.27 events/person-year with once-weekly and 0.28 events/person-year with twice-weekly hydroxychloroquine compared with 0.38 events/person-year with placebo. For once-weekly hydroxychloroquine prophylaxis, the hazard ratio was .72 (95% CI, .44-1.16; P = .18) and for twice-weekly was .74 (95% CI, .46-1.19; P = .22) compared with placebo. Median hydroxychloroquine concentrations in whole blood were 98 ng/mL (IQR, 82-120) with onceweekly 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 = .08). Conclusions. Pre-exposure prophylaxis with hydroxychloroquine once or twice weekly did not significantly reduce laboratoryconfirmed COVID-19 or COVID-19-compatible illness among healthcare workers. clinical Trials Registration. NCT04328467.
Supplementary Data Supplementary materials are available at Clinical Infectious Diseases online. Consisting of data provided by the authors to benefit the reader, the posted materials are not copyedited and are the sole responsibility of the authors, so questions or comments should be addressed to the corresponding author.
Notes
References
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' <jats:title>Methods</jats:title>\n'
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' <jats:title>Results</jats:title>\n'
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'CI, .44–1.16; P = .18) and for twice-weekly was .74 (95% CI, .46–1.19; P = .22) compared with '
'placebo. Median hydroxychloroquine concentrations in whole blood were 98 ng/mL (IQR, 82–120) '
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' <jats:p>Pre-exposure prophylaxis with hydroxychloroquine once or twice '
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'illness among healthcare workers.</jats:p>\n'
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' <jats:title>Clinical Trials Registration</jats:title>\n'
' <jats:p>Clinicaltrials.gov NCT04328467.</jats:p>\n'
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