Journal Article

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

Higgins, Alisa M., Beidh, Farah Al, Lewis, Roger, Berry, Scott, Morpeth, Susan C., Tong, Steven Y. C., Mouncey, Paul R., Santos, Marlene S., Berry, Lindsay R., Linstrum, Kelsey, Swaidan, Lolowa Al, Mcguinness, Shay, Buzgau, Adrian, Fitzgerald, Mark, McVerry, Bryan J., Seymour, Christopher W., Green, Cameron, Bhimani, Zahra, Lawler, Patrick R., Lorenzi, Elizabeth, Van de Veerdonk, Frank Leo, Bradbury, Charlotte A., Zarychanski, Ryan, Turgeon, Alexis F., Lamontagne, Francois, Derde, Lennie P. G., Bonten, Marc J. M., Goossens, Herman, Webb, Steven A., De Jong, Menno, Shankar-Hari, Manu, Haniffa, Rashan, Arabi, Yaseen M., Girard, Timothy D., McArthur, Colin, Angus, Derek C., Cheng, Allen, Parker, Jane C., Litton, Edward, Montgomery, Stephanie K., Annane, Djillali, Gordon, Anthony C., Nichol, Alistair D., Brunkhorst, Frank M., Parke, Rachael, Turner, Anne M., Beane, Abi, McGlothlin, Anna, Orr, Katrina, Buxton, Meredith, Detry, Michelle A., Goligher, Ewan C., Saunders, Christina T., Hills, Thomas E., McAuley, Daniel F., Estcourt, Lise J., King, Andrew J., Fowler, Rob, Malakouti, Salim, Patanwala, Asad E., Hor

2021

Overview

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.

• Publisher: Springer Berlin Heidelberg,Springer,Springer Nature B.V,Springer Verlag
• Subject: Adult / Analysis / Anesthesiology / Antiretroviral drugs / Antiviral agents / Antiviral Agents - therapeutic use / Antiviral drugs / Bayes Theorem / Bayesian analysis / Clinical outcomes / Clinical trials / Coronavirus / Coronaviruses / COVID-19 / COVID-19 Drug Treatment / Critical Care Medicine / Critical Illness / Drug Combinations / Drug therapy / Ecology, environment / Emergency Medicine / Health / Humans / Hydroxychloroquine / Hydroxychloroquine - therapeutic use / Immunomodulators / Intensive / Intensive care / Life Sciences / Lopinavir / Lopinavir - therapeutic use / Marshall, Jack (Canadian hockey player) / McArthur, Colin / Medicine / Medicine & Public Health / NCT / NCT02735707 / Original / Pain Medicine / Patients / Pediatrics / Pneumology/Respiratory System / Ritonavir / Ritonavir - therapeutic use / SARS-CoV-2 / Severe acute respiratory syndrome coronavirus 2 / Therapy / Viral diseases