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Title: Lopinavir-ritonavir and hydroxychloroquine for critically ill patients with COVID-19: REMAP-CAP randomized controlled trial.
Author: Arabi, Y.
Gordon, A.
Derde, L.
Nichol, A.
Murthy, S.
Beidh, F.
Annane, D.
Swaidan, L.
Beane, A.
Beasley, R.
Berry, L.
Bhimani, Z.
Bonten, M.
Bradbury, C.
Brunkhorst, F.
Buxton, M.
Buzgau, A.
Cheng, A.
De Jong, M.
Detry, M.
Duffy, E.
Estcourt, L.
Fitzgerald, M.
Fowler, R.
Girard, T.
Goligher, E.
Goossens, H.
Haniffa, R.
Higgins, A.
Hills, T.
Horvat, C.
Huang, D.
King, A.
Lamontagne, F.
Lawler, P.
Lewis, R.
Linstrum, K.
Litton, E.
Lorenzi, E.
Malakouti, S.
McAuley, D.
McGlothlin, A.
Mcguinness, S.
McVerry, B.
Montgomery, S.
Morpeth, S.
Mouncy, P.
Orr, K.
Parke, R.
Parker, J.
Patanwala, A.
Rowan, K.
Santos, M.
Saunders, C.
Seymour, C.
Shankar-Hari, M.
Tong, S.
Turgeon, A.
Turner, A.
Van de Veerdonk, F.
Zarychanski, R.
Green, C.
Berry, S.
Marshall, J.
McArthur, C.
Angus, D.
Webb, S.
Institutional Author: REMAP-CAP Investigators
Issue Date: 2021
Publication Title: Intensive Care Medicine
Volume: 47
Issue: 8
Start Page: 867
End Page: 886
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 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.
Description: Includes data from BHS
DOI: https://doi: 10.1007/s00134-021-06448-5
Internal ID Number: 01775
Type: Journal Article
Appears in Collections:Research Output

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