Hydroxychloroquine for pre-exposure prophylaxis of COVID-19 in health care workers: a randomized, multicenter, placebo-controlled trial Healthcare Worker Exposure Response and Outcomes of Hydroxychloroquine (HERO-HCQ)
MD, MHS Susanna Naggie, MD, MHS b Aaron Milstone, MD, MPH c , Mario Castro, MD Sean P Collins, MD e , Deverick Seetha Lakshmi, Deverick J Anderson, MD g , Lizbeth Cahuayme-Zuniga, BS Kisha Batey Turner, MA Lauren W Cohen, MD h , Judith Currier, RN, BSN a , Elizabeth Fraulo, MD Anne Friedland, MS a , Jyotsna Garg, RTT, MPA i Anoop George, PhD Hillary Mulder, RN, MS, MBA a , Rachel E Olson, PhD Emily C O'brien, MD, MPP d Russell L Rothman, PhD Elizabeth Shenkman, MBA a , Jack Shostak, MD a , Christopher W Woods, PhD Kevin J Anstrom, MD, MHS a , Adrian F Hernandez
International Journal of Infectious Diseases, doi:10.1016/j.ijid.2023.01.019
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DISCUSSION
Statement of Principal Findings The study was not powered to detect a small beneficial effect and the test of the primary endpoint does not provide evidence of a benefit for HCQ for PrEP in a high-risk HCW population.
Strengths and Weaknesses in Context The original study design was powered to show a 20% relative treatment effect assuming a 5% event rate in the placebo arm. However, due to slowed enrollment early in the study, the study was amended to decrease the sample size and hence the power, increasing the detectable relative treatment effect to 50%. Thus, the study was not powered to detect a small treatment effect. This outcome was not unique to this randomized trial; a 2021 analysis concluded that among the early COVID-19 studies, only 5% were both randomized and adequately powered [24] . While the partially remote nature of the trial was novel and improved feasibility during a pandemic, it also resulted in the limitation that we did not have laboratory confirmation for COVID-19-like illness. Early in the pandemic, in some regions, testing was not performed per local policies in HCW with suspected infection and mild or moderate symptoms. Per the study protocol, these events were defined as suspected cases and were combined with the confirmed cases in the primary composite outcome. This resulted in few confirmed COVID-19 infections; thus, our primary outcome was primarily comprised of suspected COVID-19 clinical infections. While the study did not have..
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