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

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 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.

Effective post-exposure prophylaxis of Covid-19 is associated with use of hydroxychloroquine: Prospective re-analysis of a public dataset incorporating novel data

“…The early use of HCQ is supported by estimates for the incubation period of 3-8 days 22 We found an age-dependent, statistically significant reduction of Covid-19 associated with drug given Early. This finding is consistent with a 45% reduction of Covid-19 associated with HCQ pre-exposure prophylaxis (PrEP) 23 in younger patients (HR 0.55, CI 0.32-0.96, p=0.038, combined treatment groups) in a companion study and an observational study involving mainly younger HCW. 24 Apparent age-dependent and time stratified effects associated with HCQ may be confounded by increases in incubation period with age.…”

The efficacy and safety of hydroxychloroquine for COVID-19 prophylaxis: A systematic review and meta-analysis of randomized trials

“…Only one trial enrolled HCW at high risk for COVID-19 exposure, but did not mandate confirmed COVID-19 contact (i.e. pre-exposure prophylaxis) [ 17 ]. The remaining three trials required contact with a COVID-19 patient (i.e.…”

“…Only two trials (n = 2176 participants) reported on the risk of developing visual changes [ 15 , 17 ]. The pooled estimate showed uncertain effect of hydroxychloroquine on visual changes compared to placebo (RR 2.27, 95% CI 0.70 to 7.29; I 2 = 0%, P = 0.41; low certainty) ( S4 Fig ).…”

Prophylaxis for COVID-19: a systematic review

“…Amongst the five studies reporting on the results of completed RCTs, all focused on HCQ [ [27] , [28] , [29] , [30] , 32 ]. Two studies focused on PrEP [ 30 , 33 ] and three on PEP [ 28 , 29 , 32 ]. None of the studies established a prophylactic effect of HCQ against COVID-19 ( Table 3 ).…”