Display options
Cite
, Estcourt LJ, Turgeon AF, et al. Effect of Convalescent Plasma on Organ Support-Free Days in Critically Ill Patients With COVID-19: A Randomized Clinical Trial. JAMA. 2021;326(17):1690-1702doi: 10.1001/jama.2021.18178.
, Estcourt, L. J., Turgeon, A. F., McQuilten, Z. K., McVerry, B. J., Al-Beidh, F., Annane, D., Arabi, Y. M., Arnold, D. M., Beane, A., Bégin, P., van Bentum-Puijk, W., Berry, L. R., Bhimani, Z., Birchall, J. E., Bonten, M. J. M., Bradbury, C. A., Brunkhorst, F. M., Buxton, M., Callum, J. L., Chassé, M., Cheng, A. C., Cove, M. E., Daly, J., Derde, L., Detry, M. A., De Jong, M., Evans, A., Fergusson, D. A., Fish, M., Fitzgerald, M., Foley, C., Goossens, H., Gordon, A. C., Gosbell, I. B., Green, C., Haniffa, R., Harvala, H., Higgins, A. M., Hills, T. E., Hoad, V. C., Horvat, C., Huang, D. T., Hudson, C. L., Ichihara, N., Laing, E., Lamikanra, A. A., Lamontagne, F., Lawler, P. R., Linstrum, K., Litton, E., Lorenzi, E., MacLennan, S., Marshall, J., McAuley, D. F., McDyer, J. F., McGlothlin, A., McGuinness, S., Miflin, G., Montgomery, S., Mouncey, P. R., Murthy, S., Nichol, A., Parke, R., Parker, J. C., Priddee, N., Purcell, D. F. J., Reyes, L. F., Richardson, P., Robitaille, N., Rowan, K. M., Rynne, J., Saito, H., Santos, M., Saunders, C. T., Serpa Neto, A., Seymour, C. W., Silversides, J. A., Tinmouth, A. A., Triulzi, D. J., Turner, A. M., van de Veerdonk, F., Walsh, T. S., Wood, E. M., Berry, S., Lewis, R. J., Menon, D. K., McArthur, C., Zarychanski, R., Angus, D. C., Webb, S. A., Roberts, D. J., & Shankar-Hari, M. (2021). Effect of Convalescent Plasma on Organ Support-Free Days in Critically Ill Patients With COVID-19: A Randomized Clinical Trial. JAMA, 326(17), 1690-1702. https://doi.org/10.1001/jama.2021.18178
, et al. "Effect of Convalescent Plasma on Organ Support-Free Days in Critically Ill Patients With COVID-19: A Randomized Clinical Trial." JAMA vol. 326,17 (2021): 1690-1702. doi: https://doi.org/10.1001/jama.2021.18178
, Estcourt LJ, Turgeon AF, McQuilten ZK, McVerry BJ, Al-Beidh F, Annane D, Arabi YM, Arnold DM, Beane A, Bégin P, van Bentum-Puijk W, Berry LR, Bhimani Z, Birchall JE, Bonten MJM, Bradbury CA, Brunkhorst FM, Buxton M, Callum JL, Chassé M, Cheng AC, Cove ME, Daly J, Derde L, Detry MA, De Jong M, Evans A, Fergusson DA, Fish M, Fitzgerald M, Foley C, Goossens H, Gordon AC, Gosbell IB, Green C, Haniffa R, Harvala H, Higgins AM, Hills TE, Hoad VC, Horvat C, Huang DT, Hudson CL, Ichihara N, Laing E, Lamikanra AA, Lamontagne F, Lawler PR, Linstrum K, Litton E, Lorenzi E, MacLennan S, Marshall J, McAuley DF, McDyer JF, McGlothlin A, McGuinness S, Miflin G, Montgomery S, Mouncey PR, Murthy S, Nichol A, Parke R, Parker JC, Priddee N, Purcell DFJ, Reyes LF, Richardson P, Robitaille N, Rowan KM, Rynne J, Saito H, Santos M, Saunders CT, Serpa Neto A, Seymour CW, Silversides JA, Tinmouth AA, Triulzi DJ, Turner AM, van de Veerdonk F, Walsh TS, Wood EM, Berry S, Lewis RJ, Menon DK, McArthur C, Zarychanski R, Angus DC, Webb SA, Roberts DJ, Shankar-Hari M. Effect of Convalescent Plasma on Organ Support-Free Days in Critically Ill Patients With COVID-19: A Randomized Clinical Trial. JAMA. 2021 Nov 02;326(17):1690-1702. doi: 10.1001/jama.2021.18178. PMID: 34606578; PMCID: PMC8491132.
Copy Download .nbib Format: NLM
Share it on

JAMA. 2021 Nov 02;326(17):1690-1702. doi: 10.1001/jama.2021.18178.

Effect of Convalescent Plasma on Organ Support-Free Days in Critically Ill Patients With COVID-19: A Randomized Clinical Trial.

JAMA

Lise J Estcourt, Alexis F Turgeon, Zoe K McQuilten, Bryan J McVerry, Farah Al-Beidh, Djillali Annane, Yaseen M Arabi, Donald M Arnold, Abigail Beane, Philippe Bégin, Wilma van Bentum-Puijk, Lindsay R Berry, Zahra Bhimani, Janet E Birchall, Marc J M Bonten, Charlotte A Bradbury, Frank M Brunkhorst, Meredith Buxton, Jeannie L Callum, Michaël Chassé, Allen C Cheng, Matthew E Cove, James Daly, Lennie Derde, Michelle A Detry, Menno De Jong, Amy Evans, Dean A Fergusson, Matthew Fish, Mark Fitzgerald, Claire Foley, Herman Goossens, Anthony C Gordon, Iain B Gosbell, Cameron Green, Rashan Haniffa, Heli Harvala, Alisa M Higgins, Thomas E Hills, Veronica C Hoad, Christopher Horvat, David T Huang, Cara L Hudson, Nao Ichihara, Emma Laing, Abigail A Lamikanra, François Lamontagne, Patrick R Lawler, Kelsey Linstrum, Edward Litton, Elizabeth Lorenzi, Sheila MacLennan, John Marshall, Daniel F McAuley, John F McDyer, Anna McGlothlin, Shay McGuinness, Gail Miflin, Stephanie Montgomery, Paul R Mouncey, Srinivas Murthy, Alistair Nichol, Rachael Parke, Jane C Parker, Nicole Priddee, Damian F J Purcell, Luis F Reyes, Peter Richardson, Nancy Robitaille, Kathryn M Rowan, Jennifer Rynne, Hiroki Saito, Marlene Santos, Christina T Saunders, Ary Serpa Neto, Christopher W Seymour, Jon A Silversides, Alan A Tinmouth, Darrell J Triulzi, Anne M Turner, Frank van de Veerdonk, Timothy S Walsh, Erica M Wood, Scott Berry, Roger J Lewis, David K Menon, Colin McArthur, Ryan Zarychanski, Derek C Angus, Steve A Webb, David J Roberts, Manu Shankar-Hari

Affiliations

  1. NHS Blood and Transplant, Oxford, England.
  2. Radcliffe Department of Medicine and BRC Hematology Theme, University of Oxford, Oxford, England.
  3. Division of Critical Care Medicine, Department of Anesthesiology and Critical Care Medicine, Université Laval, Quebec City, Quebec, Canada.
  4. 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.
  5. Transfusion Research Unit, School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia.
  6. Department of Clinical Hematology, Monash Health, Melbourne, Australia.
  7. Department of Medicine, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania.
  8. 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.
  9. Intensive Care Unit, Raymond Poincaré Hospital, Paris, France.
  10. Simone Veil School of Medicine, University of Versailles, Versailles, France.
  11. University Paris Saclay, Garches, France.
  12. 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.
  13. McMaster University, Hamilton, Ontario, Canada.
  14. Nuffield Department of Clinical Medicine, University of Oxford, Oxford, England.
  15. Université de Montréal, Montreal, Quebec, Canada.
  16. Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.
  17. Berry Consultants LLC, Austin, Texas.
  18. Li Ka Shing Knowledge Institute, Unity Health Toronto, St Michael's Hospital, Toronto, Ontario, Canada.
  19. Welsh Blood Service, Cardiff, Wales.
  20. Department of Medical Microbiology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.
  21. University Hospitals Bristol and Weston NHS Foundation Trust, Bristol, England.
  22. Faculty of Health Sciences, University of Bristol, Bristol, England.
  23. Center for Clinical Studies and Center for Sepsis Control and Care, Department of Anesthesiology and Intensive Care Medicine, Jena University Hospital, Jena, Germany.
  24. Global Coalition for Adaptive Research, San Francisco, California.
  25. Canadian Blood Services, Ottawa, Ontario, Canada.
  26. Department of Pathology and Molecular Medicine, Kingston Health Sciences Centre and Queens University, Kingston, Ontario, Canada.
  27. Department of Laboratory Medicine and Molecular Diagnostics, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada.
  28. Infection Prevention and Healthcare Epidemiology Unit, Alfred Health, Melbourne, Australia.
  29. Australian and New Zealand Intensive Care Research Centre, School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia.
  30. Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
  31. Australian Red Cross Lifeblood, Sydney and Perth, Australia.
  32. Intensive Care Center, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.
  33. Department of Medical Microbiology, University of Amsterdam Medical Center, University of Amsterdam, the Netherlands.
  34. NHSBT Clinical Trials Unit, NHS Blood and Transplant, Cambridge, England.
  35. Ottawa Hospital Research Institute, Clinical Epidemiology Unit, Ottawa, Ontario, Canada.
  36. School of Immunology and Microbial Sciences, Kings College London, London, England.
  37. Department of Microbiology, Antwerp University Hospital, Antwerp, Belgium.
  38. Western Sydney University, Sydney, Australia.
  39. Network for Improving Critical Care Systems and Training, Colombo, Sri Lanka.
  40. Mahidol Oxford Tropical Medicine Research Unit, Bangkok, Thailand.
  41. NHS Blood and Transplant, London, England.
  42. Medical Research Institute of New Zealand, Wellington.
  43. UPMC Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania.
  44. Department of Critical Care Medicine, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania.
  45. NHSBT Clinical Trials Unit, Bristol, England.
  46. Department of Healthcare Quality Assessment, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
  47. Université de Sherbrooke, Sherbrooke, Quebec, Canada.
  48. Cardiac Intensive Care Unit, Peter Munk Cardiac Centre, University Health Network, Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, Ontario, Canada.
  49. Clinical Research Investigation and Systems Modeling of Acute Illness Center, Department of Critical Care Medicine, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania.
  50. School of Medicine and Pharmacology, University of Western Australia, Crawley.
  51. NHS Blood and Transplant, Barnsley, England.
  52. Interdepartmental Division of Critical Care, University of Toronto, Toronto, Ontario, Canada.
  53. Centre for Experimental Medicine, School of Medicine, Dentistry, and Biomedical Sciences, Queen's University Belfast, Belfast, Ireland.
  54. Cardiothoracic and Vascular Intensive Care Unit, Auckland City Hospital, Auckland, New Zealand.
  55. NHS Blood and Transplant, Bristol, England.
  56. UPMC Health System Office of Healthcare Innovation, Pittsburgh, Pennsylvania.
  57. Clinical Trials Unit, Intensive Care National Audit and Research Centre, London, England.
  58. School of Medicine, University of British Columbia, Vancouver, Canada.
  59. Department of Anesthesia and Intensive Care, St Vincent's University Hospital, Dublin, Ireland.
  60. School of Medicine and Medical Sciences, University College Dublin, Dublin, Ireland.
  61. Department of Intensive Care, Alfred Health, Melbourne, Australia.
  62. School of Nursing, University of Auckland, Auckland, New Zealand.
  63. Scottish National Blood Transfusion Service, Edinburgh, Scotland.
  64. Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Australia.
  65. Universidad de La Sabana, Chia, Colombia.
  66. Clinica Universidad de La Sabana, Chia, Colombia.
  67. Héma-Québec, Montreal, Quebec, Canada.
  68. Division of Hematology and Oncology, Department of Pediatrics, CHU Sainte-Justine, Montreal, Quebec, Canada.
  69. Department of Pediatrics, Université de Montréal, Montreal, Quebec, Canada.
  70. Department of Emergency and Critical Care Medicine, St Marianna University School of Medicine, Yokohama City Seibu Hospital, Yokohama, Japan.
  71. Department of Critical Care Medicine, Hospital Israelita Albert Einstein, São Paulo, Brazil.
  72. Department of Pathology, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania.
  73. Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands.
  74. University of Edinburgh, Edinburgh, Scotland.
  75. Department of Emergency Medicine, Harbor-UCLA Medical Center, Torrance, California.
  76. Department of Emergency Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California.
  77. University Division of Anesthesia, Addenbrooke's Hospital Cambridge, Cambridge, England.
  78. Department of Critical Care Medicine, Auckland City Hospital, Auckland, New Zealand.
  79. Department of Medicine, Critical Care and Hematology/Medical Oncology, University of Manitoba, Winnipeg, Canada.
  80. St John of God Hospital, Subiaco, Australia.
  81. Guy's and St Thomas' NHS Foundation Trust, ICU Support Offices, St Thomas' Hospital, London, England.

PMID: 34606578 PMCID: PMC8491132 DOI: 10.1001/jama.2021.18178

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.

Substances

MeSH terms

Publication Types

Grant support