(84) Hydroxychloroquine for Pre-Exposure Prophylaxis of COVID-19 in Health Care Workers: A Randomized, Multicenter, Placebo-Controlled Trial (HERO-HCQ)

Publication Number: 758

Background: In March 2020, COVID-19 was declared a pandemic. Without vaccines and as health systems struggled to provide protective equipment to at-risk healthcare workers (HCWs), the scientific community considered repurposed drugs as possible treatment and prevention options. In vitro laboratory data suggested potential utility of hydroxychloroquine (HCQ).

Objectives: To evaluate the efficacy of HCQ in preventing clinical infection in HCW, and secondarily to assess its efficacy in preventing asymptomatic viral shedding and to assess safety and tolerability.

Methods: HERO-HCQ was a multicenter, double-blind, randomized, parallel-group study to evaluate the superiority of HCQ vs placebo for COVID-19 pre-exposure prophylaxis in HCWs. Eligible participants provided consent, were 18 or older, and worked in a healthcare setting. There were two on-site visits – one at baseline and another at 30 days – all other data were participant-reported through an online portal supplemented by call center back-up. In-person assessments included a nasopharyngeal swab for SARS-CoV-2 and a blood sample to assess SARS-CoV-2 nucleocapsid IgG antibody status.

Each participant was randomized in a 1:1 fashion to receive a loading dose of HCQ 600 mg twice on Day 1 followed by 400 mg daily for 29 days or matching placebo taken orally.

The primary outcome measure 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: At 34 US sites, 1360 HCW were enrolled between April and November 2020. Enrollment closed before full accrual due to recruitment challenges. 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 with 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.

Conclusions: Oral HCQ taken appeared to be safe in this group of HCW. No significant clinical benefits were observed. The study was underpowered to rule out a small reduction in COVID-19 infection.