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Lopinavir-ritonavir and hydroxychloroquine for critically ill patients with COVID-19: REMAP-CAP randomized controlled trial.
Arabi, Yaseen M; Gordon, Anthony C; Derde, Lennie P G; Nichol, Alistair D; Murthy, Srinivas; Beidh, Farah Al; Annane, Djillali; Swaidan, Lolowa Al; Beane, Abi; Beasley, Richard; Berry, Lindsay R; Bhimani, Zahra; Bonten, Marc J M; Bradbury, Charlotte A; Brunkhorst, Frank M; Buxton, Meredith; Buzgau, Adrian; Cheng, Allen; De Jong, Menno; Detry, Michelle A; Duffy, Eamon J; Estcourt, Lise J; Fitzgerald, Mark; Fowler, Rob; Girard, Timothy D; Goligher, Ewan C; Goossens, Herman; Haniffa, Rashan; Higgins, Alisa M; Hills, Thomas E; Horvat, Christopher M; Huang, David T; King, Andrew J; Lamontagne, Francois; Lawler, Patrick R; Lewis, Roger; Linstrum, Kelsey; Litton, Edward; Lorenzi, Elizabeth; Malakouti, Salim; McAuley, Daniel F; McGlothlin, Anna; Mcguinness, Shay; McVerry, Bryan J; Montgomery, Stephanie K; Morpeth, Susan C; Mouncey, Paul R; Orr, Katrina; Parke, Rachael; Parker, Jane C.
  • Arabi YM; Intensive Care Department, Ministry of the National Guard-Health Affairs, ICU 1425, P.O. Box 22490, Riyadh, 11426, Kingdom of Saudi Arabia. arabi@ngha.med.sa.
  • Gordon AC; King Abdullah International Medical Research Center, Riyadh, Kingdom of Saudi Arabia. arabi@ngha.med.sa.
  • Derde LPG; King Saud Bin Abdulaziz University for Health Sciences, Riyadh, Kingdom of Saudi Arabia. arabi@ngha.med.sa.
  • Nichol AD; Division of Anaesthetics, Pain Medicine and Intensive Care, Imperial College London, London, UK.
  • Murthy S; Intensive Care Unit, Imperial College Healthcare NHS Trust, London, UK.
  • Beidh FA; Intensive Care Center, University Medical Center Utrecht, Utrecht, The Netherlands.
  • Annane D; Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands.
  • Swaidan LA; University College Dublin Clinical Research Centre At St Vincents University Hospital, Dublin, Ireland.
  • Beane A; The Australian and New Zealand Intensive Care Research Centre, Monash University, Melbourne, Australia.
  • Beasley R; The Alfred Hospital, Melbourne, Australia.
  • Berry LR; Department of Pediatrics, University of British Columbia, Vancouver, Canada.
  • Bhimani Z; Division of Anaesthetics, Pain Medicine and Intensive Care, Imperial College London, London, UK.
  • Bonten MJM; Department of Intensive Care, Hôpital Raymond Poincaré (APHP), 92380, Garches, France.
  • Bradbury CA; Laboratory of Infection and Inflammation, U1173, School of Medicine Simone Veil, University Versailles Saint Quentin and University Paris Saclay, INSERM, 78423, Montigny le Bretonneux, France.
  • Brunkhorst FM; FHU SEPSIS (Saclay and Paris Seine Nord Endeavour To PerSonalize Interventions for Sepsis) and RHU RECORDS (Rapid rEcognition of CORticosteroiD Resistant Or Sensitive Sepsis), ANR-18-RHUS60004, 92380, Garches, France.
  • Buxton M; King Abdullah International Medical Research Center, Riyadh, Kingdom of Saudi Arabia.
  • Buzgau A; King Saud Bin Abdulaziz University for Health Sciences, Riyadh, Kingdom of Saudi Arabia.
  • Cheng A; Pharmaceutical Care Services, Ministry of National Guard Health Affairs, Riyadh, Kingdom of Saudi Arabia.
  • De Jong M; Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK.
  • Detry MA; Medical Research Institute of New Zealand, Wellington, New Zealand.
  • Duffy EJ; Berry Consultants, Austin, TX, USA.
  • Estcourt LJ; St. Michael's Hospital Unity Health Toronto, Toronto, Canada.
  • Fitzgerald M; Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands.
  • Fowler R; Department of Medical Microbiology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
  • Girard TD; Faculty of Health Sciences, University of Bristol, Bristol, UK.
  • Goligher EC; Bristol Hematology and Oncology Centre, University Hospitals Bristol and Weston NHS Foundation Trust, Bristol, UK.
  • Goossens H; Anesthesiology and Intensive Care Medicine, Jena University Hospital, Jena, Germany.
  • Haniffa R; Global Coalition for Adaptive Research, San Francisco, CA, USA.
  • Higgins AM; Monash University, Melbourne, Australia.
  • Hills TE; Monash University, Melbourne, Australia.
  • Horvat CM; Department of Infectious Diseases, Alfred Health, Melbourne, Australia.
  • Huang DT; Department of Medical Microbiology and Infection Prevention, Amsterdam University Medical Centers, Amsterdam, The Netherlands.
  • King AJ; Berry Consultants, Austin, TX, USA.
  • Lamontagne F; Infectious Disease, Auckland City Hospital, Auckland, New Zealand.
  • Lawler PR; NHS Blood and Transplant, Oxford, UK.
  • Lewis R; Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
  • Linstrum K; Berry Consultants, Austin, TX, USA.
  • Litton E; University of Toronto, Toronto, ON, Canada.
  • Lorenzi E; Sunnybrook Health Sciences Centre, Toronto, Canada.
  • Malakouti S; Canadian Critical Care Trials Group, Toronto, Canada.
  • McAuley DF; UPMC Health System, Pittsburgh, PA, USA.
  • McGlothlin A; University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
  • Mcguinness S; Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, Canada.
  • McVerry BJ; University of Antwerp, Wilrijk, Belgium.
  • Montgomery SK; National Intensive Care Surveillance-Mahidol Oxford Research Unit, Colombo, Sri Lanka.
  • Morpeth SC; Centre for Tropical Medicine and Global Health, University of Oxford, Oxford, UK.
  • Mouncey PR; Critical Care Department, University College Hospital, London, UK.
  • Orr K; The Australian and New Zealand Intensive Care Research Centre, Monash University, Melbourne, Australia.
  • Parke R; Medical Research Institute of New Zealand, Wellington, New Zealand.
  • Parker JC; Auckland District Health Board, Auckland, New Zealand.
Intensive Care Med ; 47(8): 867-886, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-1305144
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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Ritonavir / COVID-19 Type of study: Controlled clinical trial / Observational study / Prognostic study / Randomized controlled trials Limits: Adult / Humans Language: English Journal: Intensive Care Med Year: 2021 Document Type: Article

Full text: Available Collection: International databases Database: MEDLINE Main subject: Ritonavir / COVID-19 Type of study: Controlled clinical trial / Observational study / Prognostic study / Randomized controlled trials Limits: Adult / Humans Language: English Journal: Intensive Care Med Year: 2021 Document Type: Article