• Yaseen M Arabi, Anthony C Gordon, DerdeLennie P GLPGIntensive Care Center, University Medical Center Utrecht, Utrecht, The Netherlands.Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands., Alistair D Nichol, Srinivas Murthy, Farah Al Beidh, Djillali Annane, SwaidanLolowa AlLAKing Abdullah International Medical Research Center, Riyadh, Kingdom of Saudi Arabia.King Saud Bin Abdulaziz University for Health Sciences, Riyadh, Kingdom of Saudi Arabia.Pharmaceutical Care Services, Ministry of National Guard Health , Abi Beane, Richard Beasley, Lindsay R Berry, Zahra Bhimani, BontenMarc J MMJMJulius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands.Department of Medical Microbiology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands., Charlotte A Bradbury, Frank M Brunkhorst, Meredith Buxton, Adrian Buzgau, Allen Cheng, Menno De Jong, Michelle A Detry, Eamon J Duffy, Lise J Estcourt, Mark Fitzgerald, Rob Fowler, Timothy D Girard, Ewan C Goligher, Herman Goossens, Rashan Haniffa, Alisa M Higgins, Thomas E Hills, Christopher M Horvat, David T Huang, Andrew J King, Francois Lamontagne, Patrick R Lawler, Roger Lewis, Kelsey Linstrum, Edward Litton, Elizabeth Lorenzi, Salim Malakouti, Daniel F McAuley, Anna McGlothlin, Shay Mcguinness, Bryan J McVerry, Stephanie K Montgomery, Susan C Morpeth, Paul R Mouncey, Katrina Orr, Rachael Parke, Jane C Parker, Asad E Patanwala, Kathryn M Rowan, Marlene S Santos, Christina T Saunders, Christopher W Seymour, Manu Shankar-Hari, TongSteven Y CSYCVictorian Infectious Diseases Service, The Royal Melbourne Hospital, Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.Department of Infectious Diseases, The University of Melbourne at the Peter Doherty Institute fo, Alexis F Turgeon, Anne M Turner, Frank Leo Van de Veerdonk, Ryan Zarychanski, Cameron Green, Scott Berry, John C Marshall, Colin McArthur, Derek C Angus, Steven A Webb, and REMAP-CAP Investigators.
• Intensive Care Department, Ministry of the National Guard-Health Affairs, ICU 1425, P.O. Box 22490, Riyadh, 11426, Kingdom of Saudi Arabia. arabi@ngha.med.sa.
• Intensive Care Med. 2021 Aug 1; 47 (8): 867886867-886.

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.© 2021. Springer-Verlag GmbH Germany, part of Springer Nature.

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