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Convalescent plasma for adults with acute COVID-19 respiratory illness (CONCOR-1): study protocol for an international, multicentre, randomized, open-label trial Bégin, Philippe; Callum, Jeannie; Heddle, Nancy M; Cook, Richard; Zeller, Michelle P; Tinmouth, Alan; Fergusson, Dean A; Cushing, Melissa M; Glesby, Marshall J; Chassé, Michaël; Devine, Dana V; Robitalle, Nancy; Bazin, Renée; Shehata, Nadine; Finzi, Andrés; McGeer, Allison; Scales, Damon C; Schwartz, Lisa; Turgeon, Alexis F; Zarychanski, Ryan; Daneman, Nick; Carl, Richard; Amorim, Luiz; Gabe, Caroline; Ellis, Martin; Sachais, Bruce S; Loftsgard, Kent C; Jamula, Erin; Carruthers, Julie; Duncan, Joanne; Lucier, Kayla; Li, Na; Liu, Yang; Armali, Chantal; Kron, Amie; Modi, Dimpy; Auclair, Marie-Christine; Cerro, Sabrina; Avram, Meda; Arnold, Donald M

Abstract

Background: Convalescent 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. Methods: CONCOR-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). Discussion: This 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 registration Clinicaltrials.gov NCT04348656 . Registered on 16 April 2020.

Item Metadata

Title
Convalescent plasma for adults with acute COVID-19 respiratory illness (CONCOR-1): study protocol for an international, multicentre, randomized, open-label trial
Creator
Bégin, Philippe; Callum, Jeannie; Heddle, Nancy M; Cook, Richard; Zeller, Michelle P; Tinmouth, Alan; Fergusson, Dean A; Cushing, Melissa M; Glesby, Marshall J; Chassé, Michaël; Devine, Dana V; Robitalle, Nancy; Bazin, Renée; Shehata, Nadine; Finzi, Andrés; McGeer, Allison; Scales, Damon C; Schwartz, Lisa; Turgeon, Alexis F; Zarychanski, Ryan; Daneman, Nick; Carl, Richard; Amorim, Luiz; Gabe, Caroline; Ellis, Martin; Sachais, Bruce S; Loftsgard, Kent C; Jamula, Erin; Carruthers, Julie; Duncan, Joanne; Lucier, Kayla; Li, Na; Liu, Yang; Armali, Chantal; Kron, Amie; Modi, Dimpy; Auclair, Marie-Christine; Cerro, Sabrina; Avram, Meda; Arnold, Donald M
Publisher
BioMed Central
Date Issued
2021-05-04
Description
Background: Convalescent 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. Methods: CONCOR-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). Discussion: This 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 registration Clinicaltrials.gov NCT04348656 . Registered on 16 April 2020.
Subject
Convalescent plasma; SARS-CoV-2; Coronavirus; COVID-19; Randomized controlled trial
Genre
Article
Type
Text
Language
eng
Date Available
2021-05-05
Provider
Vancouver : University of British Columbia Library
Rights
Attribution 4.0 International (CC BY 4.0)
DOI
10.14288/1.0397254
URI
http://hdl.handle.net/2429/78109
Affiliation
Medicine, Faculty of; Non UBC; Pathology and Laboratory Medicine, Department of
Citation
Trials. 2021 May 04;22(1):323
Publisher DOI
10.1186/s13063-021-05235-3
Peer Review Status
Reviewed
Scholarly Level
Faculty
Copyright Holder
The Author(s)
Rights URI
http://creativecommons.org/licenses/by/4.0/
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Attribution 4.0 International (CC BY 4.0)