Passive Immunity Trial for Our Nation (PassITON): study protocol for a randomized placebo-control clinical trial evaluating COVID-19 convalescent plasma in hospitalized adults

Abstract

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 United States 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. Date of trial registration: April 24, 2020, https://clinicaltrials.gov/ct2/show/NCT04362176

Convalescent plasma associates with reduced mortality and improved clinical trajectory in patients hospitalized with COVID-19

“…Although over 100,000 patients were infused under the EAP, the absence of a matched comparison cohort limits the use of this data to assess the effectiveness of CP (8,17). Furthermore, randomized control trials (RCTs) struggled with enrollment, design and cohort selection, nimbleness, and aligning site selection with local outbreaks, which resulted in underpowered and/or inconsistent conclusions on the efficacy of convalescent plasma (6,16,(18)(19)(20)(21)(22)(23)(24). Most matched studies and RCTs around the globe have shown a trend of CP providing survival benefit, but all had relatively small cohorts except the RECOVERY trial (N=11,558), which failed to show benefit with CP (20,25).…”

Understanding the challenges to COVID-19 vaccines and treatment options, herd immunity and probability of reinfection

“…Need for mechanical ventilation 4. SOFA scale ≥3 at 72 h after randomization or an increase in 2 points or more from the basal level 2.44%, 14 and 28 days Low titer: Vircell SL (Spain) test, correlates to ≥1:320 S-RBD IgG 309 , 312 NCT04362176 3 2021 USA Completed 1000 Inpatients with or without supplemental oxygen COVID-19 7-point Ordinal Clinical Progression Outcomes Scale (ranging from 1 (not hospitalized with resumption of normal activities) to 7 (death)) Not defined, 14 and 28 days 50% neutralization titer >1:50 (neutralizing antibodies) are selected for transfusion in the trial, Abbott™ ARCHITECT™ platform and the RBD Luminex assay 313 NCT04323800 2 2021 USA Completed 180 Outpatients 1. Efficacy of treatment at day 28 2.…”