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Clinical Trial
. 2021 Jul 1;131(13):e150646.
doi: 10.1172/JCI150646.

A randomized double-blind controlled trial of convalescent plasma in adults with severe COVID-19

Max R O'Donnell  1   2   3 , Beatriz Grinsztejn  4 , Matthew J Cummings  1   3 , Jessica E Justman  2   5   6 , Matthew R Lamb  2   5 , Christina M Eckhardt  1 , Neena M Philip  5 , Ying Kuen Cheung  7 , Vinay Gupta  8 , Esau João  9 , Jose Henrique Pilotto  10 , Maria Pia Diniz  4 , Sandra Wagner Cardoso  4 , Darryl Abrams  1 , Kartik N Rajagopalan  1 , Sarah E Borden  1 , Allison Wolf  1 , Leon Claude Sidi  9 , Alexandre Vizzoni  4 , Valdilea G Veloso  4 , Zachary C Bitan  11 , Dawn E Scotto  1 , Benjamin J Meyer  12 , Samuel D Jacobson  12 , Alex Kantor  1 , Nischay Mishra  3 , Lokendra V Chauhan  3 , Elizabeth F Stone  11 , Flavia Dei Zotti  11 , Francesca La Carpia  11 , Krystalyn E Hudson  11 , Stephen A Ferrara  11 , Joseph Schwartz  11 , Brie A Stotler  11 , Wen-Hsuan W Lin  11 , Sandeep N Wontakal  11 , Beth Shaz  13 , Thomas Briese  3 , Eldad A Hod  11 , Steven L Spitalnik  11 , Andrew Eisenberger  14 , Walter I Lipkin  2   3   11
Affiliations
Clinical Trial

A randomized double-blind controlled trial of convalescent plasma in adults with severe COVID-19

Max R O'Donnell et al. J Clin Invest. .

Abstract

BACKGROUNDAlthough convalescent plasma has been widely used to treat severe coronavirus disease 2019 (COVID-19), data from randomized controlled trials that support its efficacy are limited.METHODSWe conducted a randomized, double-blind, controlled trial among adults hospitalized with severe and critical COVID-19 at 5 sites in New York City (USA) and Rio de Janeiro (Brazil). Patients were randomized 2:1 to receive a single transfusion of either convalescent plasma or normal control plasma. The primary outcome was clinical status at 28 days following randomization, measured using an ordinal scale and analyzed using a proportional odds model in the intention-to-treat population.RESULTSOf 223 participants enrolled, 150 were randomized to receive convalescent plasma and 73 to receive normal control plasma. At 28 days, no significant improvement in the clinical scale was observed in participants randomized to convalescent plasma (OR 1.50, 95% confidence interval [CI] 0.83-2.68, P = 0.180). However, 28-day mortality was significantly lower in participants randomized to convalescent plasma versus control plasma (19/150 [12.6%] versus 18/73 [24.6%], OR 0.44, 95% CI 0.22-0.91, P = 0.034). The median titer of anti-SARS-CoV-2 neutralizing antibody in infused convalescent plasma units was 1:160 (IQR 1:80-1:320). In a subset of nasopharyngeal swab samples from Brazil that underwent genomic sequencing, no evidence of neutralization-escape mutants was detected.CONCLUSIONIn adults hospitalized with severe COVID-19, use of convalescent plasma was not associated with significant improvement in day 28 clinical status. However, convalescent plasma was associated with significantly improved survival. A possible explanation is that survivors remained hospitalized at their baseline clinical status.TRIAL REGISTRATIONClinicalTrials.gov, NCT04359810.FUNDINGAmazon Foundation, Skoll Foundation.

Keywords: COVID-19; Hypoxia.

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Conflict of interest statement

Conflict of interest: MRO and MJC participated as investigators for clinical trials evaluating the efficacy and safety of remdesivir in hospitalized patients with COVID-19, sponsored by Gilead Sciences. VG is employed by Amazon Care.

Figures

Figure 1
Figure 1. Trial flow diagram.
Figure 2
Figure 2. Kaplan-Meier estimates of mortality, stratified by treatment group.
Figure 3
Figure 3. Time-to-clinical improvement with death considered a competing risk, stratified by treatment group.
Figure 4
Figure 4. Subgroup analyses of primary outcome of clinical status at 28 days, adjusted for age and sex.
pOR, proportional odds ratio.
See this image and copyright information in PMC

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