Convalescent plasma for adults with acute COVID-19 respiratory illness (CONCOR-1): study protocol for an international, multicentre, randomized, open-label trial

Trials

Dana V. Devine¹  Dean A. Fergusson²  Marie-Christine Auclair³  Meda Avram³  Sabrina Cerro³  Alexis F. Turgeon⁴  Damon C. Scales⁵  Lisa Schwartz⁶  Ryan Zarychanski⁷  Chantal Armali⁸  Dimpy Modi⁸  Amie Kron⁸  Jeannie Callum⁹  Michaël Chassé^1,10  Nick Daneman^1,11  Richard Carl^1,12  Donald M. Arnold^1,12  Nancy M. Heddle^1,12  Michelle P. Zeller^1,13  Alan Tinmouth^1,14  Allison McGeer^1,15  Bruce S. Sachais^1,16  Richard Cook^1,17  Nadine Shehata^1,18  Marshall J. Glesby^1,19  Andrés Finzi^2,20  Martin Ellis^2,21  Luiz Amorim^2,22  Nancy Robitalle^2,23  Joanne Duncan^2,24  Yang Liu^2,24  Caroline Gabe^2,24  Julie Carruthers^2,24  Kayla Lucier^2,24  Kent Cadogan Loftsgard^2,24  Erin Jamula^2,24  Na Li^2,25  Renée Bazin^2,26  Philippe Bégin^2,27  Melissa M. Cushing^2,28 

[1] Canadian Blood Services, Ottawa, Ontario, Canada;Department of Pathology and Laboratory Medicine, University of British Columbia, Ottawa, Ontario, Canada;Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada;Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada;Adjunct Scientist, Canadian Blood Services, Ottawa, Ontario, Canada;Clinical Research Department, Centre de recherche du CHU Sainte-Justine, Centre Hospitalier Universitaire Sainte-Justine Centre, Montreal, Canada;Department of Anesthesiology and Critical Care Medicine, Division of Critical Care Medicine, Faculty of Medicine, Université Laval, Quebec, Quebec, Canada;CHU de Québec – Université Laval Research Centre, Population Health and Optimal Health Practices Research Unit, Trauma - Emergency - Critical Care Medicine, Université Laval, Quebec, Quebec, Canada;Department of Critical Care Medicine, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada;Department of Medicine, Interdepartmental Division of Critical Care, University of Toronto, Toronto, Ontario, Canada;Department of Health Research Methods, Evidence & Impact, Faculty of Health Sciences, McMaster University, Hamilton, Ontario, Canada;Department of Internal Medicine, Sections of Hematology/Medical Oncology and Critical Care, University of Manitoba, Winnipeg, Manitoba, Canada;Department of Laboratory Medicine and Molecular Diagnostics, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada;Department of Laboratory Medicine and Molecular Diagnostics, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada;Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada;Department of Medicine (Critical Care), University of Montreal Health Centre (CHUM), Montreal, Quebec, Canada;Department of Medicine, University of Montreal, Montreal, Quebec, Canada;Department of Medicine, Division of Infectious Diseases, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada;Department of Medicine, McMaster University, Hamilton, Ontario, Canada;McMaster Centre for Transfusion Research, McMaster University, Hamilton, Ontario, Canada;Department of Medicine, McMaster University, Hamilton, Ontario, Canada;McMaster Centre for Transfusion Research, McMaster University, Hamilton, Ontario, Canada;Canadian Blood Services, Ottawa, Ontario, Canada;Department of Medicine, Ottawa Hospital, University of Ottawa, Ottawa, Ontario, Canada;Ottawa Hospital Centre for Transfusion Research, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada;Canadian Blood Services, Ottawa, Ontario, Canada;Department of Microbiology, Sinai Health System, Toronto, Ontario, Canada;Department of Laboratory Medicine and Pathobiology and Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada;Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA;New York Blood Center Enterprises, New York, NY, USA;Department of Statistics and Actuarial Science, University of Waterloo, Waterloo, Ontario, Canada;Departments of Medicine, Laboratory Medicine and Pathobiology, Institute of Health Policy Management and Evaluation, University of Toronto, Toronto, Ontario, Canada;Division of Hematology, Mount Sinai Hospital, Toronto, Ontario, Canada;Canadian Blood Services, Toronto, Ontario, Canada;Division of Infectious Diseases, Weill Cornell Medical College, Weill Cornell Medicine, New York, NY, USA;Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montreal, Quebec, Canada;CHUM Research Center, Montreal, Quebec, Canada;Hematology Institute and Blood Bank, Meir Medical Center, Tel Aviv, Israël;Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israël;Hemorio, Rio de Janeiro, Brazil;Héma-Québec, Saint-Laurent, Montreal, Canada;Division of Hematology and Oncology, Department of Pediatrics, CHU Sainte-Justine, Université de Montréal, Ottawa, Ontario, Canada;McMaster Centre for Transfusion Research, McMaster University, Hamilton, Ontario, Canada;McMaster Centre for Transfusion Research, McMaster University, Hamilton, Ontario, Canada;Department of Computing and Software, McMaster University, Hamilton, Ontario, Canada;Department of Community Health Sciences, University of Calgary, Hamilton, Ontario, Canada;Medical Affairs and Innovation, Héma-Québec, Saint-Laurent, Montreal, Canada;Section of Allergy, Immunology and Rheumatology, Department of Pediatrics, CHU Sainte-Justine, Montreal, Quebec, Canada;Department of Medicine, CHUM, Université de Montréal, Montreal, Quebec, Canada;Transfusion Medicine and Cellular Therapy, NewYork-Presbyterian, New York, NY, USA;Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA;

关键词: Convalescent plasma;    SARS-CoV-2;    Coronavirus;    COVID-19;    Randomized controlled trial;   

DOI  :  10.1186/s13063-021-05235-3

来源: Springer

【 摘 要 】

BackgroundConvalescent plasma has been used for numerous viral diseases including influenza, severe acute respiratory syndrome, Middle East respiratory syndrome and Ebola virus; however, evidence to support its use is weak. SARS-CoV-2 is a novel coronavirus responsible for the 2019 global pandemic of COVID-19 community acquired pneumonia. We have undertaken a randomized controlled trial to assess the efficacy and safety of COVID-19 convalescent plasma (CCP) in patients with SARS-CoV-2 infection.MethodsCONCOR-1 is an open-label, multicentre, randomized trial. Inclusion criteria include the following: patients > 16 years, admitted to hospital with COVID-19 infection, receiving supplemental oxygen for respiratory complications of COVID-19, and availability of blood group compatible CCP. Exclusion criteria are : onset of respiratory symptoms more than 12 days prior to randomization, intubated or imminent plan for intubation, and previous severe reactions to plasma. Consenting patients are randomized 2:1 to receive either approximately 500 mL of CCP or standard of care. CCP is collected from donors who have recovered from COVID-19 and who have detectable anti-SARS-CoV-2 antibodies quantified serologically. The primary outcome is intubation or death at day 30. Secondary outcomes include ventilator-free days, length of stay in intensive care or hospital, transfusion reactions, serious adverse events, and reduction in SARS-CoV-2 viral load. Exploratory analyses include patients who received CCP containing high titre antibodies. A sample size of 1200 patients gives 80% power to detect a 25% relative risk reduction assuming a 30% baseline risk of intubation or death at 30 days (two-sided test; α = 0.05). An interim analysis and sample size re-estimation will be done by an unblinded independent biostatistician after primary outcome data are available for 50% of the target recruitment (n = 600).DiscussionThis trial will determine whether CCP will reduce intubation or death non-intubated adults with COVID-19. The trial will also provide information on the role of and thresholds for SARS-CoV-2 antibody titres and neutralization assays for donor qualification.Trial registrationClinicaltrials.govNCT04348656. Registered on 16 April 2020.

【 授权许可】

CC BY