Results from the Pre-exposure Prophylaxis (PrEP) for SARS-Coronavirus-2: A Pragmatic Randomized Clinical Trial for COVID-19 in healthcare workers study was published this week as preprint.
Researchers from the University of Minnesota conducted this randomized, double-blind, placebo-controlled clinical trial with 1,483 healthcare workers from across the U.S. and in the Canadian province of Manitoba. Participants were randomized to either 400 mg of HCQ once or twice weekly or a placebo for 12 weeks. The primary endpoint was confirmed or probable COVID-19-compatible illness. The HERO Research leadership commends the Minnesota research team for making their results available.
It is important to note that this paper has not been reviewed by experts in this area and that results from this study should not guide clinical practice. But, the results do provide additional evidence that HCQ is safe and generally well tolerated in the prevention setting. The study researchers concluded pre-exposure prophylaxis with HCQ once or twice weekly did not significantly reduce laboratory-confirmed COVID-19 or COVID-19-compatible illness among healthcare workers.
The research team acknowledged several study limitations: (1) the study was originally powered to detect a 50% relative effect size with a goal of enrolling 1,050 participants per arm (3,150 total), but it was stopped early (~495 per arm) due to slow enrollment and (2) the doses of HCQ studied were low (400 mg weekly or twice weekly) and resulted in low systemic exposures to HCQ. With these limitations in mind, the study reported that the primary outcome event rate was the same for both HCQ arms (5.9%), which was numerically lower than the event rate in the placebo arm (7.9%). This difference between the HCQ and placebo arms suggests those participants receiving HCQ had a 28% (weekly dosing) and 26% (twice weekly dosing) lower risk of confirmed or probable COVID-19-compatible illness than those receiving placebo. This difference did not meet statistical significance. When the arms of HCQ were combined, there was a 27% lower risk of COVID-19-compatible illness with a confidence interval ranging from 52% lower risk to 9% higher risk.
What does this all mean? First, due to the early closure, this study is underpowered and thus cannot provide a definitive answer on the role of HCQ for prevention. The similar effect sizes in the HCQ arms and a trend towards significance when compared to placebo either alone or in combination underscores the need for a powered study to definitively answer this question.
Additional limitations of the study may be insufficient HCQ dosing. The dose in the Minnesota PrEP study at 400 mg weekly or twice weekly is lower than the dose in the HERO-HCQ study, which is 600 mg orally twice daily on day 1, followed by 400 mg daily for an additional 29 days.
HERO Research leadership are encouraged by the results from this study and are committed to finishing the HERO-HCQ study to return aggregate results to study participants, study sites, and the broader research community.
“Results from this study should not deter our efforts in HERO-HCQ but instead fuel our determination to complete enrollment and conduct a definitive study,” said Susanna Naggie, Vice Dean of Clinical Research at Duke University School of Medicine and Principal Investigator for the HERO-HCQ. “We are confident that the HERO-HCQ trial results will further contribute to the scientific community by definitively addressing the role of daily dosed HCQ for the prevention of clinical COVID-19 in people who work in health care.”
Learn more about this study and sign up to join the HERO Registry to be linked to opportunities to participate in HERO-HCQ and other clinical trials and study opportunities.