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

The REMAP-CAP Investigators, Yaseen M. Arabi, Anthony C. Gordon, Lennie Derde, Alistair D. Nichol, Srinivas Murthy, Farah Al-Beidh, Djillali Annane, Lolowa Al Swaidan, Abi Beane, Richard Beasley, Lindsay R. Berry, Zahra Bhimani, Marc Bonten, Charlotte Bradbury, Frank Brunkhorst, Meredith Buxton, Adrian Buzgau, Allen Cheng, Menno de JongMichelle A. Detry, Eamon Duffy, Lise J. Estcourt, Mark Fitzgerald, Rob Fowler, Timothy Girard, Ewan Goligher, Herman Goossens, Rashan Haniffa, Alisa M. Higgins, Thomas E. Hills, Christopher Horvat, David Huang, Andrew King, Francois Lamontagne, Patrick Lawler, Roger Lewis, Kelsey Linstrum, Edward Litton, Elizabeth Lorenzi, Salim Malakouti, Daniel F. McAuley, Anna McGlothlin, Shay Mcguinness, Bryan McVerry, Stephanie Montgomery, Susan C. Morpeth, Paul Mouncey, Katrina Orr, Rachael Parke, Jane C. Parker, Asad Patanwala, Kathryn M. Rowan, Marlene Santos, Christina T. Saunders, Christopher Seymour, Manu Shankar-Hari, Steven Y.C. Tong, Alexis Turgeon, Anne M. Turner, Frank van de Veerdonk, Ryan Zarychanski, Cameron Green, Scott Berry, John Marshall, Colin McArthur, Derek Angus, Steven A. Webb, Farah Al-Beidh, Derek Angus, Wilma van Bentum-Puijk, Marc Bonten, Charlotte Bradbury, Frank Brunkhorst, Lennie Derde, Patrick Lawler, John Marshall, Bryan McVerry, Stephanie Montgomery, Paul Mouncey, Jane Parker, Kathryn Rowan, Marlene Santos, Christopher Seymour, Alexis Turgeon, Anne Turner, Frank van de Veerdonk, Lewis Campbell, Lennie Derde, Andrew Forbes, David Gattas, Stephane Heritier, Peter Kruger, Jane Parker, Sandra Peake, Jeffrey Presneill, Ian Seppelt, Tony Trapani, Anne Turner, Paul Young, Brian Cuthbertson, John Marshall, Venika Manoharan, Marlene Santos, Alexis Turgeon, Diptesh Aryal, Arjen M. Dondrop, Madiha Hashmi, Issrah Jawad, Deva Jayakumar, John Marshall, Timo Tolppa, Vanessa Singh, Farah Al-Beidh, Derek Angus, Wilma van Bentum-Puijk, Marc Bonten, Frank Brunkhorst, Maurizio Cecconi, Lennie Derde, Stephan Ehrmann, Paul Mouncey, Lorraine Parker, Mathias Pletz, Pedro Póvoa, Gernot Rohde, Kathryn Rowan, Brian Alexander, Derek Angus, Kim Basile, Timothy Girard, Christopher Horvat, David Huang, Florian Mayr, Bryan McVerry, Stephanie Montgomery, Christopher Seymour, Marc Bonten, Nick Daneman, Lennie Derde, David Gattas, Peter Kruger, Steve McGloughlin, Susan Morpeth, David Paterson, Gernot Rohde, Derek Angus, Wilma van Bentum-Puijk, Lennie Derde, Peter Kruger, John Marshall, Bala Venkatesh, Derek Angus, Marc Bonten, Lennie Derde, Menno de Jong, John Marshall, Tim Uyeki, Derek Angus, Kenneth Baillie, Marc Bonten, Menno de Jong, Lennie Derde, Eamon Duffy, Susan Morpeth, Jane Parker, Asad Patanwala, Kathryn Rowan, Tim Uyeki, Frank van de Veerdonk, Derek Angus, Kenneth Baillie, Marc Bonten, Frank Brunkhorst, Nichola Cooper, Olaf Cremer, Menno de Jong, Lennie Derde, Eamon Duffy, James Galea, Andrew King, Helen Leavis, John Marshall, Florian Mayr, Bryan McVerry, Susan Morpeth, Mihai Netea, Kayode Ogungbenro, Jane Parker, Asad Patawala, Ville Pettilä, Emma Rademaker, Kathryn Rowan, Manoj Saxena, Christopher Seymour, Wendy Sligl, Steven Tong, Tim Uyeki, Frank van de Veerdonk Steve Webb, Taryn Youngstein, Derek Angus, Lennie Derde, David Huang, Florian Mayr, Bryan McVerry, Stephanie Montgomery, Derek Angus, Diptesh Aryal, Shilesh Bihari, Charlotte Bradbury, Marc Carrier, Dean Fergusson, Ewan Goligher, Christopher Horvat, David Huang, Anand Kumar, Devachandran Jayakumar, Anand Kumar, Mike Laffan, Patrick Lawler, Sylvain Lother, Bryan McVerry, John Marshall, Saskia Middeldorp, Zoe McQuilten, Matthew Neal, Christopher Seymour, Roger Schutgens, Simon Stanworth, Alexis Turgeon, Neill Adhikari, Derek Angus, Matthew Anstey, Emily Brant, Angelique de Man, Lennie Derde, David Huang, John Marshall, Marie Helene Masse, Paul Mouncey, Tony Trapani, Andrew Udy, Derek Angus, Donald Arnold, Phillipe Begin, Richard Charlewood, Adrian Regli, Naomi Hammond, Bradley Wibrow, Ed Fysh, Adrian Regli, Bart De Keulenaer, Andrew Currie, Andrew Nicholson

Research output: Contribution to journalArticlepeer-review

64 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)867-886
Number of pages20
JournalIntensive Care Medicine
Volume47
Issue number8
DOIs
Publication statusPublished - 1 Aug 2021

Fingerprint

Dive into the research topics of 'Lopinavir-ritonavir and hydroxychloroquine for critically ill patients with COVID-19: REMAP-CAP randomized controlled trial'. Together they form a unique fingerprint.

Cite this