Hydroxychloroquine for pre-exposure prophylaxis of COVID-19 in health care workers: A randomized, multicenter, placebo-controlled trial (HERO-HCQ).

OBJECTIVE: To determine whether hydroxychloroquine (HCQ) is safe and effective at preventing COVID-19 infections among health care workers (HCW).

METHODS: IN A 1: :1 randomized, placebo-controlled, double-blind, parallel-group, superiority trial at 34 US clinical centers, 1360 HCW at risk for COVID-19 infection were enrolled between April and November 2020. Participants were randomized to HCQ or matched placebo for. The HCQ dosing included a loading dose of HCQ 600mg twice on Day 1 followed by 400mg daily for 29 days. The primary outcome was a composite of confirmed or suspected COVID-19 clinical infection by Day 30, defined as new onset fever, cough, or dyspnea and either a positive SARS-CoV-2 PCR test (confirmed) or a lack of confirmatory testing due to local restrictions (suspected).

RESULTS: Study enrollment closed before full accrual due to recruitment challenges. The primary endpoint occurred in 41 (6.0%) participants receiving HCQ and 53 (7.8%) participants receiving placebo. No difference in the proportion of participants experiencing clinical infection (estimated difference of -1.8%, 95% confidence interval -4.6% to 0.9%, p=0.20) was identified, nor any significant safety issues.

CONCLUSION: Oral HCQ taken as prescribed appeared safe in the HCW. No significant clinical benefits were observed. The study was not powered to detect a small but potentially important reduction in infection.

TRIAL REGISTRATION: NCT04334148.