Arabi, Y.M.Gordon, A.C.Derde, L.P.G.Nichol, A.D.Murthy, S.Beidh, F.A.Annane, D.Swaidan, L.A.Beane, A.Beasley, R.Berry, L.R.Bhimani, Z.Bonten, M.J.M.Bradbury, C.A.Brunkhorst, F.M.Buxton, M.Buzgau, A.Cheng, A.De Jong, M.Detry, M.A.et al.2022-06-012022-06-012021Intensive Care Medicine, 2021; 47(8):867-8860342-46421432-1238https://hdl.handle.net/2440/135310Purpose: 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 supportfree 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.en© 2021 Springer-Verlag GmbH Germany, part of Springer NatureAdaptive platform trial; Intensive care; Pneumonia; Pandemic; COVID-19; Lopinavir-ritonavir; HydroxychloroquineHumansCritical IllnessRitonavirHydroxychloroquineDrug CombinationsAntiviral AgentsBayes TheoremAdultLopinavirCOVID-19SARS-CoV-2Journal article10.1007/s00134-021-06448-52022-06-01585498Peake, S. [0000-0001-6682-7973]