Remdesivir for the treatment of patients in hospital with COVID-19 in Canada: a randomized controlled trial

被引：116

作者：

Ali, Karim ^{[1
]}

Azher, Tanweer ^{[2
]}

Baqi, Mahin ^{[3
]}

Binnie, Alexandra ^{[3
]}

Borgia, Sergio ^{[3
]}

Carrier, Francois M. ^{[29
]}

Cavayas, Yiorgos Alexandros ^{[4
]}

Chagnon, Nicolas ^{[5
]}

Cheng, Matthew P. ^{[9
,11
]}

Conly, John ^{[15
]}

Costiniuk, Cecilia ^{[9
,10
]}

Daley, Peter ^{[20
]}

Daneman, Nick ^{[25
]}

Douglas, Josh ^{[21
]}

Downey, Catarina ^{[22
]}

Duan, Erick ^{[27
]}

Duceppe, Emmanuelle ^{[30
]}

Durand, Madeleine ^{[31
]}

English, Shane ^{[32
,34
]}

Farjou, George ^{[1
]}

Fera, Evradiki ^{[35
]}

Fontela, Patricia ^{[6
]}

Fowler, Rob ^{[23
,24
]}

Fralick, Michael ^{[36
]}

Geagea, Anna ^{[37
]}

Grant, Jennifer ^{[39
]}

Harrison, Luke B. ^{[9
]}

Havey, Thomas ^{[3
]}

Hoang, Holly ^{[41
]}

Kelly, Lauren E. ^{[42
]}

Keynan, Yoav ^{[43
]}

Khwaja, Kosar ^{[7
,8
]}

Klein, Gail ^{[22
]}

Klein, Marina ^{[9
,10
,13
]}

Kolan, Christophe ^{[30
]}

Kronfli, Nadine ^{[9
,13
]}

Lamontagne, Francois ^{[45
]}

Lau, Michael ^{[22
]}

Lee, Todd C. ^{[9
,12
,13
]}

Lee, Nelson ^{[56
]}

Lim, Rachel ^{[14
]}

Longo, Sarah ^{[22
]}

Lostun, Alexandra ^{[37
]}

MacIntyre, Erika ^{[46
]}

Malhame, Isabelle ^{[12
]}

Mangoff, Kathryn ^{[22
]}

McGuinty, Marlee ^{[33
]}

Mergler, Sonya ^{[22
]}

Munan, Matthew ^{[49
]}

Murthy, Srinivas ^{[38
]}

机构：

[1] Niagara Hlth, St Catharines, ON, Canada

[2] Mem Univ Newfoundland, Biomed Sci, St John, NL, Canada

[3] William Oster Hlth Syst, Brampton, ON, Canada

[4] Hop Sacre Coeur Montreal, Montreal, PQ, Canada

[5] Montfort Hosp, Emergency Dept, Ottawa, ON, Canada

[6] McGill Univ, Dept Pediat, Montreal, PQ, Canada

[7] McGill Univ, Dept Surg, Montreal, PQ, Canada

[8] McGill Univ, Dept Crit Care Med, Montreal, PQ, Canada

[9] McGill Univ Hlth Ctr, Div Infect Dis, Montreal, PQ, Canada

[10] McGill Univ Hlth Ctr, Div Chron Viral Illness Serv, Montreal, PQ, Canada

[11] McGill Univ Hlth Ctr, Div Med Microbiol, Montreal, PQ, Canada

[12] McGill Univ Hlth Ctr, Div Internal Med, Montreal, PQ, Canada

[13] McGill Univ Hlth Ctr, Infect Dis & Immun Global Hlth Program, Montreal, PQ, Canada

[14] Univ Calgary, Div Respirol, Calgary, AB, Canada

[15] Univ Calgary, Cumming Sch Med, Calgary, AB, Canada

[16] Univ Calgary, Dept Crit Care Med, Calgary, AB, Canada

[17] Univ Calgary, Dept Repiratory Med, Calgary, AB, Canada

[18] Univ Calgary, Dept Intervent Pulm Med, Calgary, AB, Canada

[19] Univ Calgary, Hlth Sci Ctr, Calgary, AB, Canada

[20] Mem Univ Newfoundland, Discipline Lab Med, St John, NL, Canada

[21] Lions Gate Hosp, Vancouver, BC, Canada

[22] Sunnybrook Res Inst, Ctr Clin Trial Support, CCTS, Toronto, ON, Canada

[23] Sunnybrook Med Ctr, Dept Med, Toronto, ON, Canada

[24] Sunnybrook Med Ctr, Dept Crit Care Med, Toronto, ON, Canada

[25] Sunnybrook Med Ctr, Div Infect Dis, Toronto, ON, Canada

[26] Sunnybrook Hlth Sci Ctr, Dept Crit Care Med, Toronto, ON, Canada

[27] McMaster Univ, Div Crit Care, Hamilton, ON, Canada

[28] McMaster Univ, Dept Med, Hamilton, ON, Canada

[29] Ctr Hosp Univ Montreal CHUM, Dept Anesthesiol, Montreal, PQ, Canada

[30] Ctr Hosp Univ Montreal CHUM, Dept Med, Montreal, PQ, Canada

[31] Ctr Hosp Univ Montreal CHUM, Dept Internal Med Serv, Montreal, PQ, Canada

[32] Ottawa Hosp, Dept Med, Ottawa, ON, Canada

[33] Ottawa Hosp, Dept Infect Dis, Ottawa, ON, Canada

[34] Ottawa Hosp Res Inst, Dept Med, Ottawa, ON, Canada

[35] Markham Stouffville Hosp, Markham, ON, Canada

[36] Sinai Hlth Syst, Dept Med, Div Gen Internal Med, Toronto, ON, Canada

[37] North York Gen Hosp, Dept Med & Crit Care Med, Toronto, ON, Canada

[38] Univ British Columbia, Dept Pediat, Fac Med, Vancouver, BC, Canada

[39] Univ British Columbia, Dept Pathol & Lab Med, Fac Med, Vancouver, BC, Canada

[40] Univ British Columbia, Isl Hlth Author, Vancouver, BC, Canada

[41] Grey Nuns Community Hosp, Dept Med, Div Infect Dis, Edmonton, AB, Canada

[42] Univ Manitoba, George & Fay Yee Ctr Healthcare Innovat, Dept Pharmacol & Therapeut, Winnipeg, MB, Canada

[43] Univ Manitoba, Dept Infect Dis & Med Microbiol, Winnipeg, MB, Canada

[44] Univ Manitoba, Dept Internal Med, Winnipeg, MB, Canada

[45] Ctr Hosp Univ Sherbrooke, Ctr Integre Univ Sante & Serv Sociaux Estrie, Sherbrooke, PQ, Canada

[46] Univ Alberta, Dept Crit Care, Edmonton, AB, Canada

[47] Univ Alberta, Dept Med, Edmonton, AB, Canada

[48] Univ Alberta, Div Infect Dis, Edmonton, AB, Canada

[49] Misericordia Community Hosp, Dept Crit Care Med, Edmonton, AB, Canada

[50] Misericordia Hosp Covenant Hlth, Edmonton, AB, Canada

来源：

CANADIAN MEDICAL ASSOCIATION JOURNAL | 2022年 / 194卷 / 07期

基金：

加拿大健康研究院;

关键词：

CRITICAL-CARE;

D O I：

10.1503/cmaj.211698

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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.

引用

页码：E242 / E251

页数：10

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