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)

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.

Keywords: COVID-19; Convalescent plasma; SARS-CoV-2.

Conflict of interest statement

Authors declare no competing interests.

© 2022 The Author(s).

Figures

Figure 1

Flow chart of the study.

Figure 2

Estimated 28-day clinical improvement across randomized groups. (A) Overall cumulative incidence according to the randomization group, (B) Bayesian posterior density in each randomized group, (C) Bayesian posterior density of the difference in outcome probability in the experimental versus the control group.

Figure 3

Multistate model representation of the mean times in the different WHO scale states in each randomized group. MV: mechanical ventilation.

Figure 4

Cumulative incidence of hospital discharge (A) and overall survival (B) after randomization according to the randomization group.

Figure 5

Search for treatment by subset interaction on the main outcome according to days since symptom onset, recipients’ neutralizing antibody titers, age, and BMI.