Lopinavir-ritonavir and hydroxychloroquine for critically ill patients with COVID-19: REMAP-CAP randomized controlled trial.
Type
ArticleAuthor/s
Arabi, Yaseen MGordon, Anthony C
Derde, Lennie P G
Nichol, Alistair D
Murthy, Srinivas
Beidh, Farah Al
Annane, Djillali
Swaidan, Lolowa Al
Beane, Abi
Beasley, Richard
Berry, Lindsay R
Bhimani, Zahra|Bonten, Marc J M
Bradbury, Charlotte A
Brunkhorst, Frank M
Buxton, Meredith
Buzgau, Adrian
Cheng, Allen
De Jong, Menno
Detry, Michelle A
Duffy, Eamon J
Estcourt, Lise J
Fitzgerald, Mark
Fowler, Rob
Girard, Timothy D
Goligher, Ewan C
Goossens, Herman
Haniffa, Rashan
Higgins, Alisa M
Hills, Thomas E
Horvat, Christopher M
Huang, David T
King, Andrew J
Lamontagne, Francois
Lawler, Patrick R
Lewis, Roger
Linstrum, Kelsey
Litton, Edward
Lorenzi, Elizabeth
Malakouti, Salim
McAuley, Daniel F
McGlothlin, Anna
Mcguinness, Shay
McVerry, Bryan
Montgomery, Stephanie K
Morpeth, Susan C
Mouncey, Paul R
Orr, Katrina
Parke, Rachael
Parker, Jane C
Patanwala, Asad E
Rowan, Kathryn M
Santos, Marlene S
Saunders, Christina T
Seymour, Christopher W
Shankar-Hari, Manu
Tong, Steven Y C
Turgeon, Alexis F
Turner, Anne M
Van de Veerdonk, Frank Leo
Zarychanski, Ryan
Green, Cameron
Berry, Scott
Marshall, John C
McArthur, Colin
Angus, Derek C
Webb, Steven A
REMAP-CAP Investigators
Abstract
PURPOSE: To study the efficacy of lopinavir-ritonavir and hydroxychloroquine in critically ill patients with coronavirus disease 2019 (COVID-19). METHODS: Critically ill adults with COVID-19 were randomized to receive lopinavir-ritonavir, hydroxychloroquine, combination therapy ...
See morePURPOSE: To study the efficacy of lopinavir-ritonavir and hydroxychloroquine in critically ill patients with coronavirus disease 2019 (COVID-19). METHODS: Critically ill adults with COVID-19 were randomized to receive lopinavir-ritonavir, hydroxychloroquine, combination therapy of lopinavir-ritonavir and hydroxychloroquine or no antiviral therapy (control). The primary endpoint was an ordinal scale of organ support-free days. Analyses used a Bayesian cumulative logistic model and expressed treatment effects as an adjusted odds ratio (OR) where an OR > 1 is favorable. RESULTS: We randomized 694 patients to receive lopinavir-ritonavir (n = 255), hydroxychloroquine (n = 50), combination therapy (n = 27) or control (n = 362). The median organ support-free days among patients in lopinavir-ritonavir, hydroxychloroquine, and combination therapy groups was 4 (- 1 to 15), 0 (- 1 to 9) and-1 (- 1 to 7), respectively, compared to 6 (- 1 to 16) in the control group with in-hospital mortality of 88/249 (35%), 17/49 (35%), 13/26 (50%), respectively, compared to 106/353 (30%) in the control group. The three interventions decreased organ support-free days compared to control (OR [95% credible interval]: 0.73 [0.55, 0.99], 0.57 [0.35, 0.83] 0.41 [0.24, 0.72]), yielding posterior probabilities that reached the threshold futility (>= 99.0%), and high probabilities of harm (98.0%, 99.9% and > 99.9%, respectively). The three interventions reduced hospital survival compared with control (OR [95% CrI]: 0.65 [0.45, 0.95], 0.56 [0.30, 0.89], and 0.36 [0.17, 0.73]), yielding high probabilities of harm (98.5% and 99.4% and 99.8%, respectively). CONCLUSION: Among critically ill patients with COVID-19, lopinavir-ritonavir, hydroxychloroquine, or combination therapy worsened outcomes compared to no antiviral therapy.
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See morePURPOSE: To study the efficacy of lopinavir-ritonavir and hydroxychloroquine in critically ill patients with coronavirus disease 2019 (COVID-19). METHODS: Critically ill adults with COVID-19 were randomized to receive lopinavir-ritonavir, hydroxychloroquine, combination therapy of lopinavir-ritonavir and hydroxychloroquine or no antiviral therapy (control). The primary endpoint was an ordinal scale of organ support-free days. Analyses used a Bayesian cumulative logistic model and expressed treatment effects as an adjusted odds ratio (OR) where an OR > 1 is favorable. RESULTS: We randomized 694 patients to receive lopinavir-ritonavir (n = 255), hydroxychloroquine (n = 50), combination therapy (n = 27) or control (n = 362). The median organ support-free days among patients in lopinavir-ritonavir, hydroxychloroquine, and combination therapy groups was 4 (- 1 to 15), 0 (- 1 to 9) and-1 (- 1 to 7), respectively, compared to 6 (- 1 to 16) in the control group with in-hospital mortality of 88/249 (35%), 17/49 (35%), 13/26 (50%), respectively, compared to 106/353 (30%) in the control group. The three interventions decreased organ support-free days compared to control (OR [95% credible interval]: 0.73 [0.55, 0.99], 0.57 [0.35, 0.83] 0.41 [0.24, 0.72]), yielding posterior probabilities that reached the threshold futility (>= 99.0%), and high probabilities of harm (98.0%, 99.9% and > 99.9%, respectively). The three interventions reduced hospital survival compared with control (OR [95% CrI]: 0.65 [0.45, 0.95], 0.56 [0.30, 0.89], and 0.36 [0.17, 0.73]), yielding high probabilities of harm (98.5% and 99.4% and 99.8%, respectively). CONCLUSION: Among critically ill patients with COVID-19, lopinavir-ritonavir, hydroxychloroquine, or combination therapy worsened outcomes compared to no antiviral therapy.
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Date
2021Share