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

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abstract

  • 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.

authors

  • Bégin, Philippe
  • Callum, Jeannie
  • Heddle, Nancy
  • Cook, Richard
  • Zeller, Michelle
  • 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 Cadogan
  • 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

publication date

  • December 2021