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June 3, 2020
Montreal, — A new study suggests that hydroxychloroquine is not effective in preventing the development of COVID-19 in individuals exposed to SARS-CoV-2, the virus responsible for the disease. This is the main conclusion of the first double-blind, randomized, placebo- controlled trial of hydroxychloroquine for disease prevention to be completed. Coordinated with a large study led by Dr. David Boulware at the University of Minnesota, this clinical trial was led in Canada by Drs. Todd C. Lee and Emily G. McDonald at the Research Institute of the McGill University Health Centre (RI-MUHC), in collaboration with partners at the Universities of Manitoba and Alberta. The results are published today in the New England Journal of Medicine.
“While we had hope this drug would work in this context, our study demonstrates that hydroxychloroquine is no better than placebo when used as post-exposure prophylaxis within 4 days of exposure to someone infected with the new coronavirus,” says Dr. Lee, Scientist at the RI-MUHC and Associate Professor of Medicine, Division of Infectious Diseases at McGill University and one of the lead authors of the study.
This trial included 821 asymptomatic adults with household or healthcare exposure to someone with confirmed COVID-19, who were enrolled nationwide in the United States and in the Canadian provinces of Quebec, Manitoba, and Alberta. Among them, 719 participants reported a high-risk exposure, of less than six feet (2 metres) for more than 10 minutes without one of the components of personal protective equipment (e.g. mask or face shield), to a confirmed COVID-19contact. For the most part, they were healthy younger community dwelling adults (average age 40 years).
Within four days of exposure, the participants received either placebo or hydroxychloroquine by commercial courier which were to be taken over five days, starting with a stronger dose on day 1. Investigators and participants were blinded to the treatment assignments, and an independent data and safety monitoring board (DSMB) externally reviewed the data.
“This is the gold standard method for this type of intervention,” says Dr. McDonald, Investigator at the RI-MUHC, Director of the MUHC Clinical Practice Assessment Unit and co-author of the study. “It is incredibly important that we complete randomized controlled trials so that we have the best available evidence for how to prevent the spread of COVID-19.”
Overall, 107 of 821 of participants developed COVID-19 (either confirmed with a test or symptomatically compatible disease) over the 14 days of follow-up. Both confirmed cases and probable cases were included, due to some lack of availability of diagnostic testing in the United States. Amongst those who received hydroxychloroquine, 49 developed the disease (or compatible symptoms such as fever or cough), vs 58 in the group that received the placebo. Two patients were hospitalized, one in each group. No deaths occurred.
Medication side effects like nausea and abdominal discomfort were more common for patients taking hydroxychloroquine compared to placebo (40% vs. 17%), but no serious treatment-related adverse reactions were reported, including any heart arrhythmia.
‘’Our study’s results set politics aside and provide unbiased evidence to guide practice in the prevention of COVID-19 and reinforce the importance of randomized clinical trials as we work together nationally and internationally to combat the novel coronavirus,’’ said Dr. Ryan Zarychanski, Manitoba lead and Associate Professor of Internal medicine, Max Rady College of Medicine, University of Manitoba and Senior scientist, Research Institute in Oncology and Hematology.
Canadian co-investigators include Matthew Cheng, Ilan Schwartz, Lauren MacKenzie, Glen Drobot, Nicole Marten, Lauren Kelly and Sylvain Lother.
Ongoing hydroxychloroquine clinical trials
More research is needed to determine whether hydroxychloroquine can be effective for the early treatment of COVID-19, and whether pre-exposure prophylaxis could be effective in high-risk populations. Various trials are ongoing worldwide, including in Canada (covid- 19research.ca). At the MUHC, a trial looking at early treatment in the community is underway.
About the study
The study A Randomized Trial of Hydroxychloroquine as Postexposure Prophylaxis for Covid-19 was conducted by David R. Boulware MD MPH, Matthew F Pullen MD, Ananta S Bangdiwala MS, Katelyn A Pastick BSc, Sarah M Lofgren MD, Elizabeth C Okafor BSc, Caleb P Skipper MD, Alanna A Nascene BA, Melanie R Nicol PharmD PhD, Mahsa Abassi DO MPH, Nicole W Engen MS, Matthew P Cheng MD, Derek LaBar PharmD, Sylvain A Lother MD, Lauren J MacKenzie MD, MPH, Glen Drobot MD, Nicole Marten RN, Ryan Zarychanski MD MSc, Lauren E Kelly PhD, Ilan S Schwartz MD PhD, Emily G McDonald MD MSc, Radha Rajasingham MD, Todd C Lee MD MPH, Kathy H Hullsiek PhD
This work was made possible through funding from the MUHC Clinical Practice Assessment Unit (CPAU) and is one of the critical research programs being supported by the McGill Interdisciplinary Initiative in Infection and Immunity (MI4) with seed funding from the MUHC Foundation.
PMID: 32492293; DOI: 10.1056/NEJMoa2016638
About the RI-MUHC
The Research Institute of the McGill University Health Centre (RI-MUHC) is a world-renowned biomedical and healthcare research centre. The Institute, which is affiliated with the Faculty of Medicine of McGill University, is the research arm of the McGill University Health Centre (MUHC) – an academic health centre located in Montreal, Canada, that has a mandate to focus on complex care within its community. The RI- MUHC supports over 420 researchers and close to 1,200 research trainees devoted to a broad spectrum of fundamental, clinical and health outcomes research at the Glen and the Montreal General Hospital sites of the MUHC. Its research facilities offer a dynamic multidisciplinary environment that fosters collaboration and leverages discovery aimed at improving the health of individual patients across their lifespan. The RI-MUHC is supported in part by the Fonds de recherche du Québec – Santé (FRQS). www.rimuhc.ca
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