Hydroxychloroquine as Pre-exposure Prophylaxis for Coronavirus Disease 2019 (COVID-19) in Healthcare Workers: A Randomized Trial

作者：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 J MacKenzie, Justin M. Balko, Stephen J. Dunlop, Katherine Huppler Hullsiek, David R. Boulware, Sarah M Lofgren, COVID PREP team, Mahsa Abassi, Andrew Balster, Lindsey Collins, Glen Drobot, Douglas Krakower, Sylvain Lother, Dylan MacKay, Cameron Meyer‐Mueller, Stephen Selinsky, Dayna Solvason, Ryan Zarychanski, Rebecca Zash · 发表于：Clinical Infectious Diseases · 年份：2020 · DOI：10.1093/cid/ciaa1571 · 被引用次数：128 · 研究领域：COVID-19 Clinical Research Studies、Long-Term Effects of COVID-19、SARS-CoV-2 and COVID-19 Research

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 wer...