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Hydroxychloroquine as pre-exposure prophylaxis for COVID-19 in healthcare workers: a randomized trial

2020; Cold Spring Harbor Laboratory; Linguagem: Inglês

10.1101/2020.09.18.20197327

Radha Rajasingham, Ananta Bangdiwala, Melanie R. Nicol, Caleb P Skipper, Katelyn A Pastick, Margaret L. Axelrod, Matthew F Pullen, Alanna A Nascene, Darlisha A Williams, Nicole Engen, Elizabeth C Okafor, Brian I. Rini, Ingrid A. Mayer, Emily G. McDonald, Todd C. Lee, Peter Li, Lauren MacKenzie, Justin M. Balko, Stephen J. Dunlop, Katherine Huppler Hullsiek, David R. Boulware, Sarah M Lofgren,

SARS-CoV-2 and COVID-19 Research

Abstract 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 Covid-19, 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 (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. Key Points In this randomized clinical trial of 1483 high-risk healthcare workers, there was no significant reduction in incidence of Covid-19 with once weekly or twice weekly hydroxychloroquine compared to placebo.