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

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dc.contributor.authorArabi, Y.M.
dc.contributor.authorGordon, A.C.
dc.contributor.authorDerde, L.P.G.
dc.contributor.authorNichol, A.D.
dc.contributor.authorMurthy, S.
dc.contributor.authorBeidh, F.A.
dc.contributor.authorAnnane, D.
dc.contributor.authorSwaidan, L.A.
dc.contributor.authorBeane, A.
dc.contributor.authorBeasley, R.
dc.contributor.authorBerry, L.R.
dc.contributor.authorBhimani, Z.
dc.contributor.authorBonten, M.J.M.
dc.contributor.authorBradbury, C.A.
dc.contributor.authorBrunkhorst, F.M.
dc.contributor.authorBuxton, M.
dc.contributor.authorBuzgau, A.
dc.contributor.authorCheng, A.
dc.contributor.authorDe Jong, M.
dc.contributor.authorDetry, M.A.
dc.contributor.authoret al.
dc.date.issued2021
dc.description.abstractPurpose: 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 supportfree 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.
dc.description.statementofresponsibilityYaseen M. Arabi ... et al. on behalf of the REMAP-CAP Investigators: Farah Al-Beidh ... Vishwanath Biradar ... Sandra Peake ... Patricia Williams ... Samuel Gluck ... Stephanie O’Connor ... Marianne Chapman ... et al.
dc.identifier.citationIntensive Care Medicine, 2021; 47(8):867-886
dc.identifier.doi10.1007/s00134-021-06448-5
dc.identifier.issn0342-4642
dc.identifier.issn1432-1238
dc.identifier.orcidPeake, S. [0000-0001-6682-7973]
dc.identifier.urihttps://hdl.handle.net/2440/135310
dc.language.isoen
dc.publisherSpringer-Verlag
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1101719
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1116530
dc.rights© 2021 Springer-Verlag GmbH Germany, part of Springer Nature
dc.source.urihttps://doi.org/10.1007/s00134-021-06448-5
dc.subjectAdaptive platform trial; Intensive care; Pneumonia; Pandemic; COVID-19; Lopinavir-ritonavir; Hydroxychloroquine
dc.subject.meshHumans
dc.subject.meshCritical Illness
dc.subject.meshRitonavir
dc.subject.meshHydroxychloroquine
dc.subject.meshDrug Combinations
dc.subject.meshAntiviral Agents
dc.subject.meshBayes Theorem
dc.subject.meshAdult
dc.subject.meshLopinavir
dc.subject.meshCOVID-19
dc.subject.meshSARS-CoV-2
dc.titleLopinavir-ritonavir and hydroxychloroquine for critically ill patients with COVID-19: REMAP-CAP randomized controlled trial
dc.typeJournal article
pubs.publication-statusPublished

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