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 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.

Standardized two-step testing of antibody activity in COVID-19 convalescent plasma

“…This would precede the availability of validated recombinant antigens or chimeric viruses. To increase the efficiency of convalescent plasma screening further, we also developed a sequential RBD binding + neutralization-testing two-step workflow, which has been implemented to select transfusion units in the PassITON convalescent plasma trial (Self et al, 2021).…”

“…Samples with an antibody binding level above 8,000 EU/mL in the RBD-binding fluorescent assay and halfmaximal neutralization titer R50 were selected for transfusion in the PassITON trial (Self et al, 2021). The sensitivity and specificity to detect neutralizing activity above pre-specified binding threshold was 64% and 93%, respectively, as detailed in the STAR Methods.…”

“…This study describes a systematic evaluation of antibody reactivity and neutralization in a large set of human convalescent plasma units designated for transfusion in the Passive Immunity Trial for Our Nation (PassITON) (Self et al, 2021) using currently available clinical-use and newly developed laboratory methodologies. To harmonize the results from different studies and calibrate neutralizing activity in convalescent plasma, we propose a GMP-grade immunoglobulin standard composed of two recombinant human mAbs that broadly neutralize SARS-CoV-2 strains, including variants of concern.…”

Forty‐fifth ASPEN Presidential Address: Research in a pandemic—Why, what, how?

“…This was a randomized trial, convalescent plasma vs a placebo, which turned out to be a lactated ringer's solution with multivitamin in it to make it the same color as plasma. The objective was to truly understand whether convalescent plasma was beneficial to hospitalized patients with COVID‐19 20 . Using some of Dolly's donation, we got this study up and running in May 2020.…”

“…The objective was to truly understand whether convalescent plasma was beneficial to hospitalized patients with COVID‐19. 20 Using some of Dolly's donation, we got this study up and running in May 2020. We actually got it enrolling, and as you can see, we were enrolling slowly in May, June, and July 2020, only enrolling hospitalized patients with COVID‐19 at Vanderbilt as a single‐center study (Figure 2 ).…”