Remdesivir for the treatment of patients in hospital with COVID-19 in Canada: a randomized controlled trial
Karim Ali, Tanweer Azher, Mahin Baqi, Alexandra Binnie, Sergio Borgia, François M. Carrier, Yiorgos Alexandroa Cavayas, Nicolas Chagnon, Matthew P. Cheng, John Conly, Cecilia Costiniuk, Peter Daley, Nick Daneman, Josh Douglas, Catarina Downey, Erick Duan, Emmanuelle Duceppe, Madeleine Durand, Shane English, George Farjou, Evradiki Fera, Patricia Fontela, Rob Fowler, Michael Fralick, Anna Geagea, Jennifer Grant, Luke B. Harrison, Thomas Havey, Holly Hoang, Lauren E. Kelly, Yoav Keynan, Kosar Khwaja, Gail Klein, Marina Klein, Christophe Kolan, Nadine Kronfli, Francois Lamontagne, Rob Lau, Michael Fralick, Todd C. Lee, Nelson Lee, Rachel Lim, Sarah Longo, Alexandra Lostun, Erika MacIntyre, Isabelle Malhamé, Kathryn Mangof, Marlee McGuinty, Sonya Mergler, Matthew P. Munan, Srinivas Murthy, Conar O’Neil, Daniel Ovakim, Jesse Papenburg, Ken Parhar, Seema Nair Parvathy, Chandni Patel, Santiago Perez-Patrigeon, Ruxandra Pinto, Subitha Rajakumaran, Asgar Rishu, Malaika Roba-Oshin, Moira Rushton, Mariam Saleem, Marina Salvadori, Kim Scherr, Kevin Schwartz, Makeda Semret, Michael Silverman, Ameeta Singh, Wendy Sligl, Stephanie Smith, Ranjani Somayaji, Darrell H.S. Tan, Siobhan Tobin, Meaghan Todd, Tuong-Vi Tran, Alain Tremblay, Jennifer Tsang, Alexis Turgeon, Erik Vakil, Jason Weatherald, Cedric Yansouni, Ryan Zarychanski, Canadian Treatments for COVID-19 (CATCO)
Abstract
<h3>Background:</h3> The role of remdesivir in the treatment of patients in hospital with COVID-19 remains ill defined in a global context. The World Health Organization Solidarity randomized controlled trial (RCT) evaluated remdesivir in patients across many countries, with Canada enrolling patients using an expanded data collection format in the Canadian Treatments for COVID-19 (CATCO) trial. We report on the Canadian findings, with additional demographics, characteristics and clinical outcomes, to explore the potential for differential effects across different health care systems. <h3>Methods:</h3> We performed an open-label, pragmatic RCT in Canadian hospitals, in conjunction with the Solidarity trial. We randomized patients to 10 days of remdesivir (200 mg intravenously [IV] on day 0, followed by 100 mg IV daily), plus standard care, or standard care alone. The primary outcome was in-hospital mortality. Secondary outcomes included changes in clinical severity, oxygen- and ventilator-free days (at 28 d), incidence of new oxygen or mechanical ventilation use, duration of hospital stay, and adverse event rates. We performed a priori subgroup analyses according to duration of symptoms before enrolment, age, sex and severity of symptoms on presentation. <h3>Results:</h3> Across 52 Canadian hospitals, we randomized 1282 patients between Aug. 14, 2020, and Apr. 1, 2021, to remdesivir (<i>n</i> = 634) or standard of care (<i>n</i> = 648). Of these, 15 withdrew consent or were still in hospital, for a total sample of 1267 patients. Among patients assigned to receive remdesivir, in-hospital mortality was 18.7%, compared with 22.6% in the standard-of-care arm (relative risk [RR] 0.83 (95% confidence interval [CI] 0.67 to 1.03), and 60-day mortality was 24.8% and 28.2%, respectively (95% CI 0.72 to 1.07). For patients not mechanically ventilated at baseline, the need for mechanical ventilation was 8.0% in those assigned remdesivir, and 15.0% in those receiving standard of care (RR 0.53, 95% CI 0.38 to 0.75). Mean oxygen-free and ventilator-free days at day 28 were 15.9 (± standard deviation [SD] 10.5) and 21.4 (± SD 11.3) in those receiving remdesivir and 14.2 (± SD 11) and 19.5 (± SD 12.3) in those receiving standard of care (<i>p</i> = 0.006 and 0.007, respectively). There was no difference in safety events of new dialysis, change in creatinine, or new hepatic dysfunction between the 2 groups. <h3>Interpretation:</h3> Remdesivir, when compared with standard of care, has a modest but significant effect on outcomes important to patients and health systems, such as the need for mechanical ventilation. <b>Trial registration</b>: ClinicalTrials.gov, no. NCT04330690.