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

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.

• Authors: 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 Zarychanski, Nick 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
• Journal: Trials (Trials) Vol. 22 Issue 1 Pg. 323 (May 04 2021) ISSN: 1745-6215 [Electronic] England
• PMID: 33947446 (Publication Type: Clinical Trial Protocol, Journal Article)

Chemical References

• Bisoprolol

Topics

• Adult
• Bisoprolol
• COVID-19 (therapy)
• Coronavirus Infections
• Humans
• Immunization, Passive
• Multicenter Studies as Topic
• Randomized Controlled Trials as Topic
• SARS-CoV-2
• Treatment Outcome
• COVID-19 Serotherapy