Early treatment trial of hydroxychloroquine shows no symptomatic benefit for COVID-19 patients

Outpatient adults with mild symptoms of COVID-19 don’t benefit from taking hydroxychloroquine, shows a new study. The results from the second arm of a randomized clinical trial conducted at the Research Institute of the McGill University Health Centre (RI-MUHC) and coordinated with a study led by the University of Minnesota are published today in Annals of Internal Medicine.

The team of researchers assessed whether the administration of HCQ to self-isolating adults with early, mild COVID-19, within the first few days of symptoms, could reduce symptom severity, symptom duration and prevent hospitalizations.

Dr. Emily G. McDonald
Dr. Emily G. McDonald
“Our conclusion is that HCQ was not better than a placebo at helping people feel better,” says Dr. Emily McDonald, investigator at the RI-MUHC, director of the MUHC Clinical Practice Assessment Unit and co-author of the study.

In this study, symptomatic, non-hospitalized adults with lab-confirmed or probable COVID-19 were randomly assigned either oral hydroxychloroquine 800 mg once, followed by 600 mg in 6-8 hours, then 600mg daily for four more days, or a masked placebo. Of 423 patients with available endpoint data, 82 percent had lab-confirmed infection, and 56 percent were enrolled within one day of symptoms starting. Change in symptom severity over 14 days did not differ between hydroxychloroquine and placebo groups. At 14 days, 24 percent receiving hydroxychloroquine had ongoing symptoms compared with 30 percent receiving placebo. Side effects were mild, but more common with hydroxychloroquine than with placebo. The researchers note that the study was limited by shortages in U.S. testing capacity and challenges in enrollment in hydroxychloroquine trials. Only 58 percent of participants received SARS-COV-2 testing.

“These findings may not inform whether an effect would be observed in populations at higher risk for severe COVID-19, and the study was not large enough to discount a difference in hospitalization rate,” says Dr. Matthew Cheng, co-author and assistant professor of Medicine, division of Infectious Diseases at McGill University.

Dr. Todd C. Lee
Dr. Todd C. Lee

“We are continuing to enroll in a sister trial which looks at the efficiency of early administration of HCQ for COVID-19 aimed at preventing hospitalization, because we believe it remains an important outcome and because early data suggested it might still be beneficial,” says Dr. Todd Lee, Canadian lead investigator and scientist at the RI-MUHC and associate professor of Medicine, division of Infectious Diseases at McGill University. “However, due to a relatively low enrollment of participants since June, we are part of a group which is considering merging major HCQ trials worldwide to pool data to arrive at the answer for hospitalization.”


About the study

Hydroxychloroquine in non-hospitalized adults with early COVID-19: a randomized trial was conducted in the United States by the University of Minnesota and in Canada by the Research Institute of the McGill University Health Centre, the University of Manitoba, and the University of Alberta. The study was authored by Caleb P. Skipper, Katelyn A. Pastick, Nicole W Engen, Ananta S. Bangdiwala, Mahsa Abassi, Sarah M. Lofgren, Darlisha A Williams, Elizabeth C. Okafor, Matthew F. Pullen, Melanie R. Nicol, Alanna A. Nascene, Kathy H. Hullsiek, Matthew P. Cheng, Darlette Luke, Sylvain A. Lother, Lauren J. MacKenzie, Glen Drobot, Lauren E. Kelly, Ilan S. Schwartz, Ryan Zarychanski, Emily G. McDonald, Todd C. Lee, Radha Rajasingham, and David R. Boulware.

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. The hydroxychloroquine used was donated by Apotex Incorporated. The investigators wish to acknowledge all volunteers who participated in this study.