TY - JOUR
T1 - Lopinavir-ritonavir and hydroxychloroquine for critically ill patients with COVID-19 : REMAP-CAP randomized controlled trial
AU - Arabi, Y. M.
AU - Gordon, A. C.
AU - Derde, L. P. G.
AU - Nichol, A.D.
AU - Murthy, S.
AU - Beidh, F. A.
AU - Annane, D.
AU - Swaidan, L. A.
AU - Beane, A.
AU - Beasley, R.
AU - Berry, L. R.
AU - Bhimani, Z.
AU - Bonten, M. J. M.
AU - Bradbury, C. A.
AU - Brunkhorst, F. M.
AU - Buxton, M.
AU - Buzgau, A.
AU - Cheng, A.
AU - De Jong, M.
AU - Detry, M. A.
AU - Duffy, E. J.
AU - Estcourt, L. J.
AU - Fitzgerald, M.
AU - Fowler, R.
AU - Girard, T. D.
AU - Goligher, E. C.
AU - Goossens, H.
AU - Haniffa, R.
AU - Higgins, A. M.
AU - Hills, T. E.
AU - Horvat, C. M.
AU - Huang, D. T.
AU - King, A. J.
AU - Lamontagne, F.
AU - Lawler, P. R.
AU - Lewis, R.
AU - Linstrum, K.
AU - Litton, E.
AU - Lorenzi, E.
AU - Malakouti, S.
AU - McAuley, D. F.
AU - McGlothlin, A.
AU - Mcguinness, S.
AU - McVerry, B. J.
AU - Montgomery, S. K.
AU - Morpeth, S. C.
AU - Mouncey, P. R.
AU - Orr, K.
AU - Parke, R.
AU - Gosbell, I.
AU - et al., null
PY - 2021
Y1 - 2021
N2 - 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 (–Â 1 to 15), 0 (–Â 1 to 9) and—1 (–Â 1 to 7), respectively, compared to 6 (–Â 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.
AB - 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 (–Â 1 to 15), 0 (–Â 1 to 9) and—1 (–Â 1 to 7), respectively, compared to 6 (–Â 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.
UR - http://hdl.handle.net/1959.7/uws:66964
U2 - 10.1007/s00134-021-06448-5
DO - 10.1007/s00134-021-06448-5
M3 - Article
SN - 0342-4642
VL - 47
SP - 867
EP - 886
JO - Intensive Care Medicine
JF - Intensive Care Medicine
IS - 8
ER -