• Neutralizing COVID-19 Convalescent Plasma in Adults Hospitalized with COVID-19: A Blinded Randomized Placebo-Controlled Trial.

      Self, Wesley H; Wheeler, Allison P; Stewart, Thomas G; Schrager, Harry; Mallada, Jason; Thomas, Christopher B; Cataldo, Vince D; O'Neal, Hollis R; Shapiro, Nathan I; Higgins, Conor; et al. (Elsevier, 2022-06-30)
      Background Convalescent plasma has been one of the most common treatments for COVID-19, but most clinical trial data to date have not supported its efficacy. Research Question Is rigorously selected COVID-19 convalescent plasma with neutralizing anti-SARS-CoV-2 antibodies an efficacious treatment for adults hospitalized with COVID-19? Study Design and Methods This was a multicenter, blinded, placebo-controlled randomized clinical trial among adults hospitalized with SARS-CoV-2 infection and acute respiratory symptoms for <14 days. Enrolled patients were randomly assigned to receive one unit of COVID-19 convalescent plasma (n=487) or placebo (n=473). The primary outcome was clinical status (illness severity) 14 days after study infusion measured with a seven-category ordinal scale ranging from discharged from the hospital with resumption of normal activities (lowest score) to death (highest score). The primary outcome was analyzed with a multivariable ordinal regression model, with an adjusted odds ratio (aOR) <1.0 indicating more favorable outcomes with convalescent plasma than placebo. In secondary analyses, trial participants were stratified by the presence of endogenous anti-SARS-CoV-2 antibodies (“serostatus”) at randomization. The trial included 13 secondary efficacy outcomes, including 28-day mortality. Results Among 974 randomized patients, 960 were included in the primary analysis. Clinical status on the ordinal outcome scale at 14 days did not differ between the convalescent plasma and placebo groups in the overall population (aOR: 1.04; 1/7 support interval (SI): 0.82-1.33), in patients without endogenous antibodies (aOR: 1.15; 1/7 SI: 0.74-1.80), or in patients with endogenous antibodies (aOR: 0.96; 1/7 SI: 0.72-1.30). None of the 13 secondary efficacy outcomes were different between groups. At 28 days, 89/482 (18.5%) patients in the convalescent plasma group and 80/465 (17.2%) patients in the placebo group had died (aOR: 1.04, 1/7 SI: 0.69-1.58). Interpretation Among adults hospitalized with COVID-19, including those seronegative for anti-SARS-CoV-2 antibodies, treatment with convalescent plasma did not improve clinical outcomes.
    • Passive Immunity Trial for Our Nation (PassITON): study protocol for a randomized placebo-control clinical trial evaluating COVID-19 convalescent plasma in hospitalized adults

      Self, Wesley H; Stewart, Thomas G; Wheeler, Allison P; El Atrouni, Wissam; Bistran-Hall, Amanda J; Casey, Jonathan D; Cataldo, Vince D; Chappell, James D; Cohn, Claudia S; Collins, Jessica B; et al. (Springer Nature, 2021-03-20)
      Background: Convalescent plasma is being used widely as a treatment for coronavirus disease 2019 (COVID-19). However, the clinical efficacy of COVID-19 convalescent plasma is unclear. Methods: The Passive Immunity Trial for Our Nation (PassITON) is a multicenter, placebo-controlled, blinded, randomized clinical trial being conducted in the USA to provide high-quality evidence on the efficacy of COVID-19 convalescent plasma as a treatment for adults hospitalized with symptomatic disease. Adults hospitalized with COVID-19 with respiratory symptoms for less than 14 days are eligible. Enrolled patients are randomized in a 1:1 ratio to 1 unit (200–399 mL) of COVID-19 convalescent plasma that has demonstrated neutralizing function using a SARS-CoV-2 chimeric virus neutralization assay. Study treatments are administered in a blinded fashion and patients are followed for 28 days. The primary outcome is clinical status 14 days after study treatment as measured on a 7-category ordinal scale assessing mortality, respiratory support, and return to normal activities of daily living. Key secondary outcomes include mortality and oxygen-free days. The trial is projected to enroll 1000 patients and is designed to detect an odds ratio ≤ 0.73 for the primary outcome. Discussion: This trial will provide the most robust data available to date on the efficacy of COVID-19 convalescent plasma for the treatment of adults hospitalized with acute moderate to severe COVID-19. These data will be useful to guide the treatment of COVID-19 patients in the current pandemic and for informing decisions about whether developing a standardized infrastructure for collecting and disseminating convalescent plasma to prepare for future viral pandemics is indicated. Trial registration: ClinicalTrials.gov NCT04362176. Registered on 24 April 2020. © 2021, The Author(s).