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Effect of Convalescent Plasma on Organ Support-Free Days in Critically Ill Patients With COVID-19: A Randomized Clinical Trial.
Estcourt, Lise J; Turgeon, Alexis F; McQuilten, Zoe K; McVerry, Bryan J; Al-Beidh, Farah; Annane, Djillali; Arabi, Yaseen M; Arnold, Donald M; Beane, Abigail; Bégin, Philippe; van Bentum-Puijk, Wilma; Berry, Lindsay R; Bhimani, Zahra; Birchall, Janet E; Bonten, Marc J M; Bradbury, Charlotte A; Brunkhorst, Frank M; Buxton, Meredith; Callum, Jeannie L; Chassé, Michaël; Cheng, Allen C; Cove, Matthew E; Daly, James; Derde, Lennie; Detry, Michelle A; De Jong, Menno; Evans, Amy; Fergusson, Dean A; Fish, Matthew; Fitzgerald, Mark; Foley, Claire; Goossens, Herman; Gordon, Anthony C; Gosbell, Iain B; Green, Cameron; Haniffa, Rashan; Harvala, Heli; Higgins, Alisa M; Hills, Thomas E; Hoad, Veronica C; Horvat, Christopher; Huang, David T; Hudson, Cara L; Ichihara, Nao; Laing, Emma; Lamikanra, Abigail A; Lamontagne, François; Lawler, Patrick R; Linstrum, Kelsey; Litton, Edward.
  • Estcourt LJ; NHS Blood and Transplant, Oxford, England.
  • Turgeon AF; Radcliffe Department of Medicine and BRC Hematology Theme, University of Oxford, Oxford, England.
  • McQuilten ZK; Division of Critical Care Medicine, Department of Anesthesiology and Critical Care Medicine, Université Laval, Quebec City, Quebec, Canada.
  • McVerry BJ; CHU de Québec-Université Laval Research Center, Population Health and Optimal Health Practices Unit, Trauma-Emergency-Critical Care Medicine, CHU de Québec-Université Laval, Quebec City, Quebec, Canada.
  • Al-Beidh F; Transfusion Research Unit, School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia.
  • Annane D; Department of Clinical Hematology, Monash Health, Melbourne, Australia.
  • Arabi YM; Department of Medicine, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania.
  • Arnold DM; Division of Anesthetics, Pain Medicine, and Intensive Care Medicine, Department of Surgery and Cancer, Imperial College London and Imperial College Healthcare NHS Trust, London, England.
  • Beane A; Intensive Care Unit, Raymond Poincaré Hospital, Paris, France.
  • Bégin P; Simone Veil School of Medicine, University of Versailles, Versailles, France.
  • van Bentum-Puijk W; University Paris Saclay, Garches, France.
  • Berry LR; Intensive Care Department, College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research Center, Ministry of National Guard Health Affairs, Riyadh, Saudi Arabia.
  • Bhimani Z; McMaster University, Hamilton, Ontario, Canada.
  • Birchall JE; Nuffield Department of Clinical Medicine, University of Oxford, Oxford, England.
  • Bonten MJM; Université de Montréal, Montreal, Quebec, Canada.
  • Bradbury CA; Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.
  • Brunkhorst FM; Berry Consultants LLC, Austin, Texas.
  • Buxton M; Li Ka Shing Knowledge Institute, Unity Health Toronto, St Michael's Hospital, Toronto, Ontario, Canada.
  • Callum JL; Welsh Blood Service, Cardiff, Wales.
  • Chassé M; Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.
  • Cheng AC; Department of Medical Microbiology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.
  • Cove ME; University Hospitals Bristol and Weston NHS Foundation Trust, Bristol, England.
  • Daly J; Faculty of Health Sciences, University of Bristol, Bristol, England.
  • Derde L; Center for Clinical Studies and Center for Sepsis Control and Care, Department of Anesthesiology and Intensive Care Medicine, Jena University Hospital, Jena, Germany.
  • Detry MA; Global Coalition for Adaptive Research, San Francisco, California.
  • De Jong M; Canadian Blood Services, Ottawa, Ontario, Canada.
  • Evans A; Department of Pathology and Molecular Medicine, Kingston Health Sciences Centre and Queens University, Kingston, Ontario, Canada.
  • Fergusson DA; Department of Laboratory Medicine and Molecular Diagnostics, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada.
  • Fish M; Université de Montréal, Montreal, Quebec, Canada.
  • Fitzgerald M; Infection Prevention and Healthcare Epidemiology Unit, Alfred Health, Melbourne, Australia.
  • Foley C; Australian and New Zealand Intensive Care Research Centre, School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia.
  • Goossens H; Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
  • Gordon AC; Australian Red Cross Lifeblood, Sydney and Perth, Australia.
  • Gosbell IB; Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.
  • Green C; Intensive Care Center, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.
  • Haniffa R; Berry Consultants LLC, Austin, Texas.
  • Harvala H; Department of Medical Microbiology, University of Amsterdam Medical Center, University of Amsterdam, the Netherlands.
  • Higgins AM; NHSBT Clinical Trials Unit, NHS Blood and Transplant, Cambridge, England.
  • Hills TE; Ottawa Hospital Research Institute, Clinical Epidemiology Unit, Ottawa, Ontario, Canada.
  • Hoad VC; School of Immunology and Microbial Sciences, Kings College London, London, England.
  • Horvat C; Berry Consultants LLC, Austin, Texas.
  • Huang DT; NHSBT Clinical Trials Unit, NHS Blood and Transplant, Cambridge, England.
  • Hudson CL; Department of Microbiology, Antwerp University Hospital, Antwerp, Belgium.
  • Ichihara N; Division of Anesthetics, Pain Medicine, and Intensive Care Medicine, Department of Surgery and Cancer, Imperial College London and Imperial College Healthcare NHS Trust, London, England.
  • Laing E; Australian Red Cross Lifeblood, Sydney and Perth, Australia.
  • Lamikanra AA; Western Sydney University, Sydney, Australia.
  • Lamontagne F; Australian and New Zealand Intensive Care Research Centre, School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia.
  • Lawler PR; Network for Improving Critical Care Systems and Training, Colombo, Sri Lanka.
  • Linstrum K; Mahidol Oxford Tropical Medicine Research Unit, Bangkok, Thailand.
  • Litton E; NHS Blood and Transplant, London, England.
JAMA ; 326(17): 1690-1702, 2021 Nov 02.
Article in English | MEDLINE | ID: covidwho-1525402
ABSTRACT
IMPORTANCE The evidence for benefit of convalescent plasma for critically ill patients with COVID-19 is inconclusive.

OBJECTIVE:

To determine whether convalescent plasma would improve outcomes for critically ill adults with COVID-19. DESIGN, SETTING, AND

PARTICIPANTS:

The ongoing Randomized, Embedded, Multifactorial, Adaptive Platform Trial for Community-Acquired Pneumonia (REMAP-CAP) enrolled and randomized 4763 adults with suspected or confirmed COVID-19 between March 9, 2020, and January 18, 2021, within at least 1 domain; 2011 critically ill adults were randomized to open-label interventions in the immunoglobulin domain at 129 sites in 4 countries. Follow-up ended on April 19, 2021.

INTERVENTIONS:

The immunoglobulin domain randomized participants to receive 2 units of high-titer, ABO-compatible convalescent plasma (total volume of 550 mL ± 150 mL) within 48 hours of randomization (n = 1084) or no convalescent plasma (n = 916). MAIN OUTCOMES AND

MEASURES:

The primary ordinal end point was organ support-free days (days alive and free of intensive care unit-based organ support) up to day 21 (range, -1 to 21 days; patients who died were assigned -1 day). The primary analysis was an adjusted bayesian cumulative logistic model. Superiority was defined as the posterior probability of an odds ratio (OR) greater than 1 (threshold for trial conclusion of superiority >99%). Futility was defined as the posterior probability of an OR less than 1.2 (threshold for trial conclusion of futility >95%). An OR greater than 1 represented improved survival, more organ support-free days, or both. The prespecified secondary outcomes included in-hospital survival; 28-day survival; 90-day survival; respiratory support-free days; cardiovascular support-free days; progression to invasive mechanical ventilation, extracorporeal mechanical oxygenation, or death; intensive care unit length of stay; hospital length of stay; World Health Organization ordinal scale score at day 14; venous thromboembolic events at 90 days; and serious adverse events.

RESULTS:

Among the 2011 participants who were randomized (median age, 61 [IQR, 52 to 70] years and 645/1998 [32.3%] women), 1990 (99%) completed the trial. The convalescent plasma intervention was stopped after the prespecified criterion for futility was met. The median number of organ support-free days was 0 (IQR, -1 to 16) in the convalescent plasma group and 3 (IQR, -1 to 16) in the no convalescent plasma group. The in-hospital mortality rate was 37.3% (401/1075) for the convalescent plasma group and 38.4% (347/904) for the no convalescent plasma group and the median number of days alive and free of organ support was 14 (IQR, 3 to 18) and 14 (IQR, 7 to 18), respectively. The median-adjusted OR was 0.97 (95% credible interval, 0.83 to 1.15) and the posterior probability of futility (OR <1.2) was 99.4% for the convalescent plasma group compared with the no convalescent plasma group. The treatment effects were consistent across the primary outcome and the 11 secondary outcomes. Serious adverse events were reported in 3.0% (32/1075) of participants in the convalescent plasma group and in 1.3% (12/905) of participants in the no convalescent plasma group. CONCLUSIONS AND RELEVANCE Among critically ill adults with confirmed COVID-19, treatment with 2 units of high-titer, ABO-compatible convalescent plasma had a low likelihood of providing improvement in the number of organ support-free days. TRIAL REGISTRATION ClinicalTrials.gov Identifier NCT02735707.
Subject(s)

Full text: Available Collection: International databases Database: MEDLINE Main subject: COVID-19 Type of study: Controlled clinical trial / Prognostic study / Randomized controlled trials / Risk factors Limits: Adult / Aged / Female / Humans / Male / Middle aged Language: English Journal: JAMA Year: 2021 Document Type: Article Affiliation country: Jama.2021.18178

Full text: Available Collection: International databases Database: MEDLINE Main subject: COVID-19 Type of study: Controlled clinical trial / Prognostic study / Randomized controlled trials / Risk factors Limits: Adult / Aged / Female / Humans / Male / Middle aged Language: English Journal: JAMA Year: 2021 Document Type: Article Affiliation country: Jama.2021.18178