Passive Immunity Trial for Our Nation (PassITON): Study Protocol for a Randomized Placebo-control Clinical Trial Evaluating COVID-19 Convalescent Plasma in Hospitalized Adults

Authors

Wesley H. Self, Vanderbilt Institute for Clinical and Translational Research (VICTR), Vanderbilt University Medical Center, 1313 21st Ave South, 312 Oxford House, Nashville, TN, 37232, USA; Department of Emergency Medicine, Vanderbilt University Medical Center, Nashville, USAFollow
Thomas G. Stewart, Department of Biostatistics, Vanderbilt University Medical Center, Nashville, USA
Allison P. Wheeler, Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, USA
Wissam El Atrouni, Division of Infectious Diseases, Department of Internal Medicine, The University of Kansas School of Medicine, Kasas, US
Amanda J. Bistran-Hall, Vanderbilt Institute for Clinical and Translational Research (VICTR), Vanderbilt University Medical Center, 1313 21st Ave South, 312 Oxford House, Nashville, TN, 37232, USA
Jonathan D. Casey, Department of Medicine, Division of Allergy, Pulmonary, and Critical Care Medicine, Vanderbilt University Medical Center, Nashville, USA
Vince D. Cataldo, Division of Hematology and Oncology, Louisiana State University Health-Sciences Center, New Orleans, USA
James D. Chappell, Division of Infectious Diseases, Department of Pediatrics, Vanderbilt University Medical Center, Nashville, USA
Claudia S. Cohn, Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, USA
Jessica B. Collins, Vanderbilt Institute for Clinical and Translational Research (VICTR), Vanderbilt University Medical Center, 1313 21st Ave South, 312 Oxford House, Nashville, TN, 37232, USA
Mark R. Denison, Division of Infectious Diseases, Department of Pediatrics, Vanderbilt University Medical Center, Nashville, USA
Marjolein de Wit, Division of Pulmonary Disease and Critical Care Medicine, Department of Internal Medicine, Virginia Commonwealth University, Richmond, USA
Sheri L. Dixon, Vanderbilt Institute for Clinical and Translational Research (VICTR), Vanderbilt University Medical Center, 1313 21st Ave South, 312 Oxford House, Nashville, TN, 37232, USA
Abhijit Duggal, Department of Critical Care, Respiratory Institute, Cleveland Clinical Healthcare System, Cleveland, USA
Terri L. Edwards, Vanderbilt Institute for Clinical and Translational Research (VICTR), Vanderbilt University Medical Center, 1313 21st Ave South, 312 Oxford House, Nashville, TN, 37232, USA
Magali J. Fontaine, Division of Transfusion Services, Department of Pathology, University of Maryland School of Medicine, Baltimore, USA
Adit A. Ginde, Department of Emergency Medicine, University of Colorado School of Medicine, Boulder, USA
Michelle S. Harkins, Department of Medicine, University of New Mexico School of Medicine, Albuquerque, USA
Thelma Harrington, Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Maryland School of Medicine, College Park, USA
Estelle S. Harris, Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Utah, Salt Lake City, USA
Daanish Hoda, Intermountain Healthcare, Salt Lake City, USA
Tina S. Ipe, Department of Pathology and Laboratory Medicine, University of Arkansas for Medical Sciences, Fayetteville, USA
Stuti J. Jaiswal, Division of Hospital Medicine, Scripps Clinic, Scripps Research Translational Institute, The Scripps Research Institute, San Diego, USA
Nicholas J. Johnson, Department of Emergency and Division of Pulmonary, Critical Care, and Sleep Medicine, University of Washington, Seattle, USA
Alan E. Jones, Department of Emergency Medicine, University of Mississippi Medical Center, Oxford, USA
Maryrose Laguio-Vila, Department of Internal Medicine, Division of Infectious Disease, Rochester General Hospital, Rochester, USA
Christopher J. Lindsell, Department of Biostatistics, Vanderbilt University Medical Center, Nashville, USA
Jason Mallada, Department of Pharmacy, Newton-Wellesley Hospital, Massachusetts College of Pharmacy and Health Sciences, Boston, USA
Manoj J. Mammen, Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, State University of New York at Buffalo, Buffalo, USA
Ryan A. Metcalf, Department of Pathology, University of Utah, Salt Lake City, USA
Elizabeth A. Middleton, Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Utah, Salt Lake City, USA
Simon Mucha, Department of Critical Care, Respiratory Institute, Cleveland Clinical Healthcare System, Cleveland, USA
Hollis R. O'Neal, Division of Pulmonary and Critical Care, Louisiana State University Health-Sciences Center, New Orleans, USA
Sonal R. Pannu, Division of Pulmonary, Critical Care, and Sleep Medicine, The Ohio State University, Columbus, USA
Jill M. Pulley, Vanderbilt Institute for Clinical and Translational Research (VICTR), Vanderbilt University Medical Center, 1313 21st Ave South, 312 Oxford House, Nashville, TN, 37232, USA
Xian Qiao, Sentara Pulmonary, Critical Care, and Sleep Specialists, Sentara Health, Eastern Virginia Medical School, Norfolk, USA
Jay S. Raval, Department of Pathology, University of New Mexico School of Medicine, Albuquerque, USA
Jillian P. Rhoads, Vanderbilt Institute for Clinical and Translational Research (VICTR), Vanderbilt University Medical Center, 1313 21st Ave South, 312 Oxford House, Nashville, TN, 37232, USA
Harry Schrager, Newton-Wellesley Hospital, Department of Medicine, Tufts School of Medicine, Boston, USA
Carl Shanholtz, Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Maryland School of Medicine, College Park, USA
Nathan I. Shapiro, Department of Emergency Medicine, Beth Israel Deaconess Medical Center, Boston, USA
Stephen J. Schrantz, Department of Medicine, University of Chicago, Chicago, USA
Isaac Thomsen, Division of Infectious Diseases, Department of Pediatrics, Vanderbilt University Medical Center, Nashville, USA
Krista K. Vermillion, Vanderbilt Institute for Clinical and Translational Research (VICTR), Vanderbilt University Medical Center, 1313 21st Ave South, 312 Oxford House, Nashville, TN, 37232, USA
Gordon R. Bernard, Vanderbilt Institute for Clinical and Translational Research (VICTR), Vanderbilt University Medical Center, 1313 21st Ave South, 312 Oxford House, Nashville, TN, 37232, USA; Department of Medicine, Division of Allergy, Pulmonary, and Critical Care Medicine, Vanderbilt University Medical Center, Nashville, USA
Todd W. Rice, Vanderbilt Institute for Clinical and Translational Research (VICTR), Vanderbilt University Medical Center, 1313 21st Ave South, 312 Oxford House, Nashville, TN, 37232, USA; Department of Medicine, Division of Allergy, Pulmonary, and Critical Care Medicine, Vanderbilt University Medical Center, Nashville, USA

Document Type

Article

Publication Date

3-20-2021

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.

Recommended Citation

Self WH, Stewart TG, Wheeler AP, El Atrouni W, Bistran-Hall AJ, Casey JD, Cataldo VD, Chappell JD, Cohn CS, Collins JB, Denison MR, de Wit M, Dixon SL, Duggal A, Edwards TL, Fontaine MJ, Ginde AA, Harkins MS, Harrington T, Harris ES, Hoda D, Ipe TS, Jaiswal SJ, Johnson NJ, Jones AE, Laguio-Vila M, Lindsell CJ, Mallada J, Mammen MJ, Metcalf RA, Middleton EA, Mucha S, O'Neal HR Jr, Pannu SR, Pulley JM, Qiao X, Raval JS, Rhoads JP, Schrager H, Shanholtz C, Shapiro NI, Schrantz SJ, Thomsen I, Vermillion KK, Bernard GR, Rice TW; Passive Immunity Trial for Our Nation (PassITON) Investigators. Passive Immunity Trial for Our Nation (PassITON): study protocol for a randomized placebo-control clinical trial evaluating COVID-19 convalescent plasma in hospitalized adults. Trials. 2021 Mar 20;22(1):221. doi: 10.1186/s13063-021-05171-2. PMID: 33743799; PMCID: PMC7980732.