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

Naggie, S.; Milstone, A.; Castro, M.; Collins, S. P.; Seetha, L.; Anderson, D. J.; Cahuayme-Zuniga, L.; Batey-Turner, K.; Cohen, L. W.; Fraulo, E.; Friedland, A.; Garg, J.; George, A.; Mulder, H.; Olson, R. E.; O'Brien, E. C.; Rothman, R. L.; Shenkman, E.; Shostak, J.; Woods, C. W.; Anstrom, K. J.; Hernandez, A. F.; Program, HERO Research

Objective: To determine whether hydroxychloroquine (HCQ) is safe and effective at preventing COVID-19 infections among health care workers (HCW). Design: Multicenter, 1:1 randomized, placebo-controlled, double-blind, parallel-group, superiority trial. Setting: 34 clinical centers in the United States. Participants: 1360 HCW at risk for COVID-19 infection enrolled between April and November 2020. Interventions: A loading dose of HCQ 600 mg twice on Day 1 followed by 400 mg daily for 29 days or matching placebo taken orally. Main Outcome Measure: 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: Enrollment for the study was closed before full accrual due to difficulties recruiting additional participants. The primary composite endpoint occurred in 41 (6.0%) participants receiving HCQ and 53 (7.8%) participants receiving placebo. No statistically significant 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). We identified no significant safety issues. Conclusion: Oral HCQ taken as prescribed appeared to be safe in a group of HCW. No significant clinical benefits were observed. The study was underpowered to rule out a small but potentially important reduction in COVID-19 infections.