TY - JOUR
T1 - Lopinavir-ritonavir and hydroxychloroquine for critically ill patients with COVID-19: REMAP-CAP randomized controlled trial: REMAP-CAP randomized controlled trial
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 - Hamilton, Olly
PY - 2021/8/1
Y1 - 2021/8/1
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 - Adaptive platform trial
KW - COVID-19
KW - Hydroxychloroquine
KW - Intensive care
KW - Lopinavir-ritonavir
KW - Pandemic
KW - Pneumonia
U2 - 10.1007/s00134-021-06448-5
DO - 10.1007/s00134-021-06448-5
M3 - Article
SN - 0342-4642
VL - 47
SP - 867
EP - 886
JO - Intensive Care Medicine
JF - Intensive Care Medicine
IS - 8
ER -