학술논문
Lopinavir-ritonavir and hydroxychloroquine for critically ill patients with COVID-19: REMAP-CAP randomized controlled trial
Document Type
article
Author
Arabi, Yaseen M; Gordon, Anthony C; Derde, Lennie PG; Nichol, Alistair D; Murthy, Srinivas; Beidh, Farah Al; Annane, Djillali; Swaidan, Lolowa Al; Beane, Abi; Beasley, Richard; Berry, Lindsay R; Bhimani, Zahra; Bonten, Marc JM; 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 J; 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 YC; 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
Source
Intensive Care Medicine. 47(8)
Subject
Language
Abstract
PurposeTo study the efficacy of lopinavir-ritonavir and hydroxychloroquine in critically ill patients with coronavirus disease 2019 (COVID-19).MethodsCritically 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.ResultsWe 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).ConclusionAmong critically ill patients with COVID-19, lopinavir-ritonavir, hydroxychloroquine, or combination therapy worsened outcomes compared to no antiviral therapy.