Lopinavir-ritonavir and hydroxychloroquine for critically ill patients with COVID-19: REMAP-CAP randomized controlled trial

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...

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Veröffentlicht in:Intensive care medicine 2021-08, Vol.47 (8), p.867-886
Hauptverfasser: Arabi, Yaseen M., Gordon, Anthony C., Derde, Lennie P. G., Nichol, Alistair D., Murthy, Srinivas, Beidh, Farah Al, Annane, Djillali, Swaidan, Lolowa Al, Beane, Abi, Beasley, Richard, Berry, Lindsay R., Bhimani, Zahra, Bonten, Marc J. M., Bradbury, Charlotte A., Brunkhorst, Frank M., Buxton, Meredith, Buzgau, Adrian, Cheng, Allen, De Jong, Menno, Detry, Michelle A., Duffy, Eamon J., Estcourt, Lise J., Fitzgerald, Mark, Fowler, Rob, Girard, Timothy D., Goligher, Ewan C., Goossens, Herman, Haniffa, Rashan, Higgins, Alisa M., Hills, Thomas E., Horvat, Christopher M., Huang, David T., King, Andrew J., Lamontagne, Francois, Lawler, Patrick R., Lewis, Roger, Linstrum, Kelsey, Litton, Edward, Lorenzi, Elizabeth, Malakouti, Salim, McAuley, Daniel F., McGlothlin, Anna, Mcguinness, Shay, McVerry, Bryan J., Montgomery, Stephanie K., Morpeth, Susan C., Mouncey, Paul R., Orr, Katrina, Parke, Rachael, Parker, Jane C., Patanwala, Asad E., Rowan, Kathryn M., Santos, Marlene S., Saunders, Christina T., Seymour, Christopher W., Shankar-Hari, Manu, Tong, Steven Y. C., Turgeon, Alexis F., Turner, Anne M., Van de Veerdonk, Frank Leo, Zarychanski, Ryan, Green, Cameron, Berry, Scott, Marshall, John C., McArthur, Colin, Angus, Derek C., Webb, Steven A.
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Zusammenfassung: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.
ISSN:0342-4642
1432-1238
DOI:10.1007/s00134-021-06448-5