Convalescent plasma for adults with acute COVID-19 respiratory illness (CONCOR-1): study protocol for an international, multicentre, randomized, open-label trial
Creators: name: Bégin, Philippe
name: Callum, Jeannie
name: Heddle, Nancy M.
name: Cook, Richard
name: Zeller, Michelle P.
name: Tinmouth, Alan
name: Fergusson, Dean A.
name: Cushing, Melissa M.
name: Glesby, Marshall J.
name: Chassé, Michaël
name: Devine, Dana V.
name: Robitalle, Nancy
name: Bazin, Renée
name: Shehata, Nadine
name: Finzi, Andrés
name: McGeer, Allison
name: Scales, Damon C.
name: Schwartz, Lisa
name: Turgeon, Alexis F.
name: Zarychanski, Ryan
name: Daneman, Nick
name: Carl, Richard
name: Amorim, Luiz
name: Gabe, Caroline
name: Ellis, Martin
name: Sachais, Bruce S.
name: Loftsgard, Kent C.
name: Jamula, Erin
name: Carruthers, Julie
name: Duncan, Joanne
name: Lucier, Kayla
name: Li, Na
name: Liu, Yang
name: Armali, Chantal
name: Kron, Amie
name: Modi, Dimpy
name: Auclair, Marie-Christine
name: Cerro, Sabrina
name: Avram, Meda
name: Arnold, Donald M.
Publisher: name: BioMed Central
Year: 2021

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 &gt; 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.