Treatment of severe COVID-19 patients with either low- or high-volume of convalescent plasma versus standard of care: A multicenter Bayesian randomized open-label clinical trial (COOP-COVID-19-MCTI)

Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil. Fundação Pro Sangue Hemocentro de São Paulo, São Paulo, Brazil. Hospital das Clínicas, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brazil. Centro de Hematologia e Hemoterapia, Universidade Estadual de Campinas, Campinas, Brazil. Hospital Nossa Senhora da Conceição, Grupo Hospitalar Conceição, Porto Alegre, Brazil. Hospital Ernesto Dornelles, Porto Alegre, Brazil. Hospital Sírio-Libanês, São Paulo, Brazil. Hospital Israelita Albert Einstein, São Paulo, Brazil. Departamento de Microbiologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, Brazil. Biostatistical Department, Hôpital Saint-Louis, Paris University, Assistance Publique Hôpitaux de Paris, Paris, France.

Lancet Regional Health. Americas. 2022;10:100216
Abstract
BACKGROUND Administration of convalescent plasma may serve as an adjunct to supportive treatment to prevent COVID-19 progression and death. We aimed to evaluate the efficacy and safety of 2 volumes of intravenous convalescent plasma (CP) with high antibody titers for the treatment of severe cases of COVID-19. METHODS We conducted a Bayesian, randomized, open-label, multicenter, controlled clinical trial in 7 Brazilian hospitals. Adults admitted to hospital with positive RT-PCR for SARS-CoV2, within 10 days of the symptom onset, were eligible. Patients were randomly assigned (1:1:1) to receive standard of care (SoC) alone, or in combination with 200 mL (150-300 mL) of CP (Low-volume), or 400 mL (300-600 mL) of CP (High-volume); infusion had to be performed within 24 h of randomization. Randomization was centralized, stratified by center. The primary outcome was the time until clinical improvement up to day 28, measured by the WHO ten-point scale, assessed in the intention-to-treat population. Interim and terminal analyses were performed in a Bayesian framework. Trial registered at ClinicalTrials.gov: NCT04415086. FINDINGS Between June 2, 2020, and November 18, 2020, 129 patients were enrolled and randomly assigned to SoC (n = 42), Low-volume (n = 43) or High-volume (n = 44) CP. Donors presented a median titer of neutralizing antibodies of 1:320 (interquartile range, 1:160 to 1:1088). No evidence of any benefit of convalescent plasma was observed, with Bayesian estimate of 28-day clinical improvement of 72.7% (95%CI, 58.8 to 84.7) in the SoC versus 64.1% (95%ci, 53.8 to 73.7) in the pooled experimental groups (mean difference of -8.7%, 95%CI, -24.6 to 8.2). There was one case of cutaneous mild allergic reaction related to plasma transfusion and one case of suspected transfusion-related acute lung injury but deemed not to be related to convalescent plasma infusion. INTERPRETATION In this prospective, randomized trial of adult hospitalized patients with severe COVID-19, convalescent plasma was not associated with clinical benefits. FUNDING Brazilian Ministry of Science, Technology and Innovation, Fundação de Amparo à Pesquisa do Estado de São Paulo.
Study details
Language : eng
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