University of Minnesota Medical School physician researchers studied hydroxychloroquine as a treatment to prevent COVID-19 for those with high-risk for exposure to the virus – health care workers. The pre-exposure prophylaxis trial results determined that taking 400mg of hydroxychloroquine once or twice weekly did not prevent the development of COVID-19 in health care workers better than the placebo.
"This randomised placebo-controlled trial launched on April 6, with the objective of evaluating whether or not hydroxychloroquine taken once or twice weekly in health care workers at high risk for COVID-19 exposure could prevent COVID-19 infection," said principal investigator Dr Radha Rajasingham, an infectious diseases physician and researcher at the U of M Medical School.
The double-blind trial enrolled 1,483 health care workers and first responders from across the US and Canada. Participants were randomly assigned to receive once-weekly hydroxychloroquine, twice-weekly hydroxychloroquine or placebo. Participants were followed for a minimum of four weeks and up to twelve weeks to evaluate who developed COVID-19.
Overall, 7.9% assigned the placebo developed COVID-19, while 5.9% assigned hydroxychloroquine developed COVID-19. Those results were not statistically significant, meaning there was not a meaningful difference between hydroxychloroquine and the placebo. Side effects were reported in 21% of participants assigned the placebo; 31% in the once-weekly hydroxychloroquine group and 36% in the twice-weekly hydroxychloroquine group. The most common side effects were nausea, upset stomach and diarrhoea. There was no increased risk of serious side effects or cardiac complications from taking hydroxychloroquine compared to the placebo.
The study was in collaboration with colleagues at Vanderbilt University and Oregon Health & Science University.
Abstract
Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a rapidly emerging virus causing the ongoing Covid-19 pandemic with no known effective prophylaxis. We investigated whether hydroxychloroquine could prevent SARS-CoV-2 in healthcare workers at high risk of exposure.
Methods: We conducted a randomized, double-blind, placebo-controlled clinical trial of healthcare workers with ongoing exposure to persons with SARS-CoV-2, including those working in emergency departments, intensive care units, Covid-19 hospital wards, and first responders. Participants across the United States and in the Canadian province of Manitoba were randomized to hydroxychloroquine 400mg once weekly or twice weekly for 12 weeks. The primary endpoint was confirmed or probable Covid-19-compatible illness. We measured hydroxychloroquine whole blood concentrations.
Results: We enrolled 1483 healthcare workers, of which 79% reported performing aerosol-generating procedures. The incidence of Covid-19 (laboratory-confirmed or symptomatic compatible illness) was 0.27 events per person-year with once-weekly and 0.28 events per person-year with twice-weekly hydroxychloroquine compared with 0.38 events per person-year with placebo. For once weekly hydroxychloroquine prophylaxis, the hazard ratio was 0.72 (95%CI 0.44 to 1.16; P=0.18), and for twice-weekly was 0.74 (95%CI 0.46 to 1.19; P=0.22) as compared with placebo. Median hydroxychloroquine concentrations in whole blood were 98 ng/mL (IQR, 82-120) with once-weekly and 200 ng/mL (IQR, 159-258) with twice-weekly dosing. Hydroxychloroquine concentrations did not differ between participants who developed Covid-19-compatible illness (154 ng/mL) versus participants without Covid-19 (133 ng/mL; P=0.08).
Conclusions: Pre-exposure prophylaxis with hydroxychloroquine once or twice weekly did not significantly reduce laboratory-confirmed Covid-19 or Covid-19-compatible illness among healthcare workers.
Authors
Radha Rajasingham, Ananta S Bangdiwala, Melanie R Nicol, Caleb P Skipper, Katelyn A Pastick, Margaret L Axelrod, Matthew F Pullen, Alanna A Nascene, Darlisha A Williams, Nicole W Engen, Elizabeth C Okafor, Brian I Rini, Ingrid A Mayer, Emily G McDonald, Todd C Lee, Peter Li, Lauren J MacKenzie, Justin M Balko, Stephen J Dunlop, Katherine H Hullsiek, David R Boulware, Sarah M Lofgren
[link url="https://www.sciencedaily.com/releases/2020/10/201021163929.htm"]University of Minnesota material[/link]
[link url="https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciaa1571/5929230"]Clinical Infectious Disease abstract[/link]