PT  - JOURNAL ARTICLE
AU  - Ali, Karim
AU  - Azher, Tanweer
AU  - Baqi, Mahin
AU  - Binnie, Alexandra
AU  - Borgia, Sergio
AU  - Carrier, François M.
AU  - Cavayas, Yiorgos Alexandroa
AU  - Chagnon, Nicolas
AU  - Cheng, Matthew P.
AU  - Conly, John
AU  - Costiniuk, Cecilia
AU  - Daley, Peter
AU  - Daneman, Nick
AU  - Douglas, Josh
AU  - Downey, Catarina
AU  - Duan, Erick
AU  - Duceppe, Emmanuelle
AU  - Durand, Madeleine
AU  - English, Shane
AU  - Farjou, George
AU  - Fera, Evradiki
AU  - Fontela, Patricia
AU  - Fowler, Rob
AU  - Fralick, Michael
AU  - Geagea, Anna
AU  - Grant, Jennifer
AU  - Harrison, Luke B.
AU  - Havey, Thomas
AU  - Hoang, Holly
AU  - Kelly, Lauren E.
AU  - Keynan, Yoav
AU  - Khwaja, Kosar
AU  - Klein, Gail
AU  - Klein, Marina
AU  - Kolan, Christophe
AU  - Kronfli, Nadine
AU  - Lamontagne, Francois
AU  - Lau, Rob
AU  - Fralick, Michael
AU  - Lee, Todd C.
AU  - Lee, Nelson
AU  - Lim, Rachel
AU  - Longo, Sarah
AU  - Lostun, Alexandra
AU  - MacIntyre, Erika
AU  - Malhamé, Isabelle
AU  - Mangof, Kathryn
AU  - McGuinty, Marlee
AU  - Mergler, Sonya
AU  - Munan, Matthew P.
AU  - Murthy, Srinivas
AU  - O’Neil, Conar
AU  - Ovakim, Daniel
AU  - Papenburg, Jesse
AU  - Parhar, Ken
AU  - Parvathy, Seema Nair
AU  - Patel, Chandni
AU  - Perez-Patrigeon, Santiago
AU  - Pinto, Ruxandra
AU  - Rajakumaran, Subitha
AU  - Rishu, Asgar
AU  - Roba-Oshin, Malaika
AU  - Rushton, Moira
AU  - Saleem, Mariam
AU  - Salvadori, Marina
AU  - Scherr, Kim
AU  - Schwartz, Kevin
AU  - Semret, Makeda
AU  - Silverman, Michael
AU  - Singh, Ameeta
AU  - Sligl, Wendy
AU  - Smith, Stephanie
AU  - Somayaji, Ranjani
AU  - Tan, Darrell H.S.
AU  - Tobin, Siobhan
AU  - Todd, Meaghan
AU  - Tran, Tuong-Vi
AU  - Tremblay, Alain
AU  - Tsang, Jennifer
AU  - Turgeon, Alexis
AU  - Vakil, Erik
AU  - Weatherald, Jason
AU  - Yansouni, Cedric
AU  - Zarychanski, Ryan
AU  - ,
AU  - ,
TI  - Remdesivir for the treatment of patients in hospital with COVID-19 in Canada: a randomized controlled trial
AID  - 10.1503/cmaj.211698
DP  - 2022 Jan 01
TA  - Canadian Medical Association Journal
PG  - cmaj.211698
4099  - http://www.cmaj.ca/content/early/2022/01/19/cmaj.211698.short
4100  - http://www.cmaj.ca/content/early/2022/01/19/cmaj.211698.full
AB  - Background: 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.Methods: 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.Results: Across 52 Canadian hospitals, we randomized 1282 patients between Aug. 14, 2020, and Apr. 1, 2021, to remdesivir (n = 634) or standard of care (n = 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 (p = 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.Interpretation: 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.Trial registration: ClinicalTrials.gov, no.NCT04330690.