TY - JOUR
T1 - Lopinavir-ritonavir and hydroxychloroquine for critically ill patients with COVID-19
T2 - REMAP-CAP randomized controlled trial
AU - REMAP-CAP Investigators
AU - Arabi, Yaseen M
AU - Gordon, Anthony C
AU - Derde, Lennie P G
AU - Nichol, Alistair D
AU - Murthy, Srinivas
AU - Beidh, Farah Al
AU - Annane, Djillali
AU - Swaidan, Lolowa Al
AU - Beane, Abi
AU - Beasley, Richard
AU - Berry, Lindsay R
AU - Bhimani, Zahra
AU - Bonten, Marc J M
AU - Bradbury, Charlotte A
AU - Brunkhorst, Frank M
AU - Buxton, Meredith
AU - Buzgau, Adrian
AU - Cheng, Allen
AU - De Jong, Menno
AU - Detry, Michelle A
AU - Duffy, Eamon J
AU - Estcourt, Lise J
AU - Fitzgerald, Mark
AU - Fowler, Rob
AU - Girard, Timothy D
AU - Goligher, Ewan C
AU - Goossens, Herman
AU - Haniffa, Rashan
AU - Higgins, Alisa M
AU - Hills, Thomas E
AU - Horvat, Christopher M
AU - Huang, David T
AU - King, Andrew J
AU - Lamontagne, Francois
AU - Lawler, Patrick R
AU - Lewis, Roger
AU - Linstrum, Kelsey
AU - Litton, Edward
AU - Lorenzi, Elizabeth
AU - Malakouti, Salim
AU - McAuley, Daniel F
AU - McGlothlin, Anna
AU - Mcguinness, Shay
AU - McVerry, Bryan J
AU - Montgomery, Stephanie K
AU - Morpeth, Susan C
AU - Mouncey, Paul R
AU - Orr, Katrina
AU - Parke, Rachael
AU - Parker, Jane C
AU - Patanwala, Asad E
AU - Rowan, Kathryn M
AU - Santos, Marlene S
AU - Saunders, Christina T
AU - Seymour, Christopher W
AU - Shankar-Hari, Manu
AU - Tong, Steven Y C
AU - Turgeon, Alexis F
AU - Turner, Anne M
AU - Van de Veerdonk, Frank Leo
AU - Zarychanski, Ryan
AU - Green, Cameron
AU - Berry, Scott
AU - Marshall, John C
AU - McArthur, Colin
AU - Angus, Derek C
AU - Webb, Steven A
N1 - © 2021. Springer-Verlag GmbH Germany, part of Springer Nature.
PY - 2021/7/12
Y1 - 2021/7/12
N2 - 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 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.
AB - 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 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.
KW - Adult
KW - Antiviral Agents/therapeutic use
KW - Bayes Theorem
KW - COVID-19/drug therapy
KW - Critical Illness
KW - Drug Combinations
KW - Humans
KW - Hydroxychloroquine/therapeutic use
KW - Lopinavir/therapeutic use
KW - Ritonavir/therapeutic use
KW - SARS-CoV-2
U2 - 10.1007/s00134-021-06448-5
DO - 10.1007/s00134-021-06448-5
M3 - Article
C2 - 34251506
SN - 0342-4642
VL - 47
SP - 867
EP - 886
JO - Intensive Care Medicine
JF - Intensive Care Medicine
IS - 8
ER -