Lopinavir-ritonavir and hydroxychloroquine for critically ill patients with COVID-19: REMAP-CAP randomized controlled trial
Yaseen M Arabi, Anthony C Gordon, Lennie P G Derde, Alistair D Nichol, Srinivas Murthy, Farah Al Beidh, Djillali Annane, Lolowa Al Swaidan, Abi Beane, Richard Beasley, Lindsay R Berry, Zahra Bhimani, Marc J M Bonten, 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, Steven Y C Tong, 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, Farah Al-Beidh, Derek C Angus, Djillali Annane, Yaseen M Arabi, Abi Beane, Wilma Van Bentum-Puijk, Scott Berry, Zahra Bhimani, Marc J M Bonten, Charlotte A Bradbury, Frank M Brunkhorst, Meredith Buxton, Allen Cheng, Lennie P G Derde, Lise J Estcourt, Herman Goossens, Anthony C Gordon, Cameron Green, Rashan Haniffa, Francois Lamontagne, Patrick R Lawler, Edward Litton, John C Marshall, Colin Mcarthur, Daniel F Mcauley, Shay Mcguinness, Bryan J Mcverry, Stephanie K Montgomery, Paul R Mouncey, Srinivas Murthy, Alistair D Nichol, Rachael Parke, Jane C Parker, Kathryn M Rowan, Marlene S Santos, Christopher W Seymour, Alexis F Turgeon, Anne M Turner, Frank Leo Van De Veerdonk, Steve Webb, Ryan Zarychanski, Yaseen M Arabi, Lewis Campbell, Allen Cheng, Lennie P G Derde, Andrew Forbes, David Gattas, Cameron Green, Stephane Heritier, Peter Kruger, Edward Litton, Colin Mcarthur, Shay Mcguinness, Alistair D Nichol, Rachael Parke, Jane C Parker, Sandra Peake, Jeffrey Presneill, Ian Seppelt, Tony Trapani, Anne M Turner, Steve Webb, Paul Young, Zahra Bhimani, Brian Cuthbertson, Rob Fowler, Francois Lamontagne, John C Marshall, Venika Manoharan, Srinivas Murthy, Marlene S Santos, Alexis F Turgeon, Ryan Zarychanski, Diptesh Aryal, Abi Beane, Arjen M Dondrop, Cameron Green, Rashan Haniffa, Madiha Hashmi, Issrah Jawad, Deva Jayakumar, John C Marshall, Colin Mcarthur, Srinivas Murthy, Timo Tolppa, Vanessa Singh, Steve Webb, Farah Al-Beidh, Derek C Angus, Djillali Annane, Wilma Van Bentum-Puijk, Scott Berry, Marc J M Bonten, Frank M Brunkhorst, Maurizio Cecconi, Lennie P G Derde, Stephan Ehrmann, Herman Goossens, Anthony C Gordon, Colin Mcarthur, Paul R Mouncey, Alistair D Nichol, Lorraine Parker, Mathias Pletz, Pedro Póvoa, Gernot Rohde, Kathryn M Rowan, Steve Webb, Brian Alexander, Derek C Angus, Kim Basile, Meredith Buxton, Timothy D Girard, Christopher M Horvat, David T Huang, Kelsey Linstrum, Florian Mayr, Bryan J Mcverry, Stephanie K Montgomery, Christopher W Seymour, Richard Beasley, Marc J M Bonten, Allen Cheng, Nick Daneman, Lennie P G Derde, Robert Fowler, David Gattas, Anthony C Gordon, Cameron Green, Peter Kruger, Colin Mcarthur, Steve Mcgloughlin, Susan C Morpeth, Srinivas Murthy, Alistair D Nichol, Mathias Pletz, David Paterson, Gernot Rohde, Steve Webb, Derek C Angus, Wilma Van Bentum-Puijk, Lennie P G Derde, Anthony C Gordon, Peter Kruger, Edward Litton, John C Marshall, Colin Mcarthur, Srinivas Murthy, Alistair D Nichol, Bala Venkatesh, Steve Webb, Derek C Angus, Scott Berry, Marc J M Bonten, Allen Cheng, Lennie P G Derde, Herman Goossens, Menno De Jong, John C Marshall, Colin Mcarthur, Srinivas Murthy, Tim Uyeki, Steve Webb, Derek C Angus, Yaseen M Arabi, Kenneth Baillie, Richard Beasley, Scott Berry, Marc J M Bonten, Allen Cheng, Menno De Jong, Lennie P G Derde, Eamon J Duffy, Rob Fowler, Herman Goossens, Anthony C Gordon, Cameron Green, Thomas E Hills, Colin Mcarthur, Susan C Morpeth, Srinivas Murthy, Alistair D Nichol, Katrina Orr
Intensive Care Medicine, doi:10.1007/s00134-021-06448-5
Purpose: To study the efficacy of lopinavir-ritonavir and hydroxychloroquine in critically ill patients with coronavirus disease 2019 . 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,
Supplementary Information The online version contains supplementary material available at https:// doi. org/ 10. 1007/ s00134-021-06448-5.
Author contributions For conceptualization: YMA, ACG, LPGD, ADN, SM, FAB, DA, LAS, AB, RB, ZB, MJMB, CAB, FMB, MB, AC, ADJ, EJD, LJE, RF, TDG, HG, RH, TEH, CMH, DTH, AJK, FL, PRL, KL, E Litton, DFM, AM, SMC, BJM, SKM, SCM, PRM, KO, RP, JCP, AEP, KMR, MSS, SWS, MSH, SYCT, AFT, AMT, FVV, RZ, CG, SB, JCM, CM, DA, SAW. Data curation: AB, AMH, CMH, KL, SSM, PRM, JCP, AMT, CG, CM. Formal analysis: LRB, MAD, MF, RJL, E Lorenzi, AM, CTS, SB, DA, SAW. Funding acquisition: ACG, LPGD, ADN, SM, MJMB, MB, KMR, JCM, CM, DA, SAW.
Ethics approval The trial was approved by the relevant ethics committees in all regions.
Consent to participate Written or verbal informed consent, in accordance with regional legislation, was obtained from all patients or from their surrogates.
Consent for publication All authors approved the manuscript for submission.
Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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