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

Philippe Bégin, Jeannie Callum, Nancy M. Heddle, Richard Cook, Michelle P. Zeller, Alan Tinmouth, Dean A. Fergusson, Melissa M. Cushing, Marshall J. Glesby, Michaël Chassé, Dana V. Devine, Nancy Robitalle, Renée Bazin, Nadine Shehata, Andrés Finzi, Allison McGeer, Damon C. Scales, Lisa Schwartz, Alexis F. Turgeon, Ryan ZarychanskiNick Daneman, Richard Carl, Luiz Amorim, Caroline Gabe, Martin Ellis, Bruce S. Sachais, Kent Cadogan Loftsgard, Erin Jamula, Julie Carruthers, Joanne Duncan, Kayla Lucier, Na Li, Yang Liu, Chantal Armali, Amie Kron, Dimpy Modi, Marie Christine Auclair, Sabrina Cerro, Meda Avram, Donald M. Arnold

Research output: Contribution to journalArticlepeer-review

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.govNCT04348656. Registered on 16 April 2020.

Original languageEnglish
Article number323
JournalTrials
Volume22
Issue number1
DOIs
StatePublished - Dec 2021

Keywords

  • Convalescent plasma
  • Coronavirus
  • COVID-19
  • Randomized controlled trial
  • SARS-CoV-2

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