. 2021 Mar 20;22(1):221.

doi: 10.1186/s13063-021-05171-2.

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

Wesley H Self^{1

2}, Thomas G Stewart³, Allison P Wheeler⁴, Wissam El Atrouni⁵, Amanda J Bistran-Hall⁶, Jonathan D Casey⁷, Vince D Cataldo⁸, James D Chappell⁹, Claudia S Cohn¹⁰, Jessica B Collins⁶, Mark R Denison⁹, Marjolein de Wit¹¹, Sheri L Dixon⁶, Abhijit Duggal¹², Terri L Edwards⁶, Magali J Fontaine¹³, Adit A Ginde¹⁴, Michelle S Harkins¹⁵, Thelma Harrington¹⁶, Estelle S Harris¹⁷, Daanish Hoda¹⁸, Tina S Ipe¹⁹, Stuti J Jaiswal²⁰, Nicholas J Johnson²¹, Alan E Jones²², Maryrose Laguio-Vila²³, Christopher J Lindsell³, Jason Mallada²⁴, Manoj J Mammen²⁵, Ryan A Metcalf²⁶, Elizabeth A Middleton¹⁷, Simon Mucha¹², Hollis R O'Neal Jr²⁷, Sonal R Pannu²⁸, Jill M Pulley⁶, Xian Qiao²⁹, Jay S Raval³⁰, Jillian P Rhoads⁶, Harry Schrager³¹, Carl Shanholtz¹⁶, Nathan I Shapiro³², Stephen J Schrantz³³, Isaac Thomsen⁹, Krista K Vermillion⁶, Gordon R Bernard^{6

7}, Todd W Rice^{6

7}; Passive Immunity Trial for Our Nation (PassITON) Investigators

Affiliations

¹ Vanderbilt Institute for Clinical and Translational Research (VICTR), Vanderbilt University Medical Center, 1313 21st Ave South, 312 Oxford House, Nashville, TN, 37232, USA. wesley.self@vumc.org.
² Department of Emergency Medicine, Vanderbilt University Medical Center, Nashville, USA. wesley.self@vumc.org.
³ Department of Biostatistics, Vanderbilt University Medical Center, Nashville, USA.
⁴ Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, USA.
⁵ Division of Infectious Diseases, Department of Internal Medicine, The University of Kansas School of Medicine, Kasas, USA.
⁶ Vanderbilt Institute for Clinical and Translational Research (VICTR), Vanderbilt University Medical Center, 1313 21st Ave South, 312 Oxford House, Nashville, TN, 37232, USA.
⁷ Department of Medicine, Division of Allergy, Pulmonary, and Critical Care Medicine, Vanderbilt University Medical Center, Nashville, USA.
⁸ Division of Hematology and Oncology, Louisiana State University Health-Sciences Center, New Orleans, USA.
⁹ Division of Infectious Diseases, Department of Pediatrics, Vanderbilt University Medical Center, Nashville, USA.
¹⁰ Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, USA.
¹¹ Division of Pulmonary Disease and Critical Care Medicine, Department of Internal Medicine, Virginia Commonwealth University, Richmond, USA.
¹² Department of Critical Care, Respiratory Institute, Cleveland Clinical Healthcare System, Cleveland, USA.
¹³ Division of Transfusion Services, Department of Pathology, University of Maryland School of Medicine, Baltimore, USA.
¹⁴ Department of Emergency Medicine, University of Colorado School of Medicine, Boulder, USA.
¹⁵ Department of Medicine, University of New Mexico School of Medicine, Albuquerque, USA.
¹⁶ Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Maryland School of Medicine, College Park, USA.
¹⁷ Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Utah, Salt Lake City, USA.
¹⁸ Intermountain Healthcare, Salt Lake City, USA.
¹⁹ Department of Pathology and Laboratory Medicine, University of Arkansas for Medical Sciences, Fayetteville, USA.
²⁰ Division of Hospital Medicine, Scripps Clinic, Scripps Research Translational Institute, The Scripps Research Institute, San Diego, USA.
²¹ Department of Emergency and Division of Pulmonary, Critical Care, and Sleep Medicine, University of Washington, Seattle, USA.
²² Department of Emergency Medicine, University of Mississippi Medical Center, Oxford, USA.
²³ Department of Internal Medicine, Division of Infectious Disease, Rochester General Hospital, Rochester, USA.
²⁴ Department of Pharmacy, Newton-Wellesley Hospital, Massachusetts College of Pharmacy and Health Sciences, Boston, USA.
²⁵ Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, State University of New York at Buffalo, Buffalo, USA.
²⁶ Department of Pathology, University of Utah, Salt Lake City, USA.
²⁷ Division of Pulmonary and Critical Care, Louisiana State University Health-Sciences Center, New Orleans, USA.
²⁸ Division of Pulmonary, Critical Care, and Sleep Medicine, The Ohio State University, Columbus, USA.
²⁹ Sentara Pulmonary, Critical Care, and Sleep Specialists, Sentara Health, Eastern Virginia Medical School, Norfolk, USA.
³⁰ Department of Pathology, University of New Mexico School of Medicine, Albuquerque, USA.
³¹ Newton-Wellesley Hospital, Department of Medicine, Tufts School of Medicine, Boston, USA.
³² Department of Emergency Medicine, Beth Israel Deaconess Medical Center, Boston, USA.
³³ Department of Medicine, University of Chicago, Chicago, USA.

PMID: 33743799
PMCID: PMC7980732
DOI: 10.1186/s13063-021-05171-2

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

Wesley H Self et al. Trials. 2021.

. 2021 Mar 20;22(1):221.

doi: 10.1186/s13063-021-05171-2.

Authors

Affiliations

¹ Vanderbilt Institute for Clinical and Translational Research (VICTR), Vanderbilt University Medical Center, 1313 21st Ave South, 312 Oxford House, Nashville, TN, 37232, USA. wesley.self@vumc.org.
² Department of Emergency Medicine, Vanderbilt University Medical Center, Nashville, USA. wesley.self@vumc.org.
³ Department of Biostatistics, Vanderbilt University Medical Center, Nashville, USA.
⁴ Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, USA.
⁵ Division of Infectious Diseases, Department of Internal Medicine, The University of Kansas School of Medicine, Kasas, USA.
⁶ Vanderbilt Institute for Clinical and Translational Research (VICTR), Vanderbilt University Medical Center, 1313 21st Ave South, 312 Oxford House, Nashville, TN, 37232, USA.
⁷ Department of Medicine, Division of Allergy, Pulmonary, and Critical Care Medicine, Vanderbilt University Medical Center, Nashville, USA.
⁸ Division of Hematology and Oncology, Louisiana State University Health-Sciences Center, New Orleans, USA.
⁹ Division of Infectious Diseases, Department of Pediatrics, Vanderbilt University Medical Center, Nashville, USA.
¹⁰ Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, USA.
¹¹ Division of Pulmonary Disease and Critical Care Medicine, Department of Internal Medicine, Virginia Commonwealth University, Richmond, USA.
¹² Department of Critical Care, Respiratory Institute, Cleveland Clinical Healthcare System, Cleveland, USA.
¹³ Division of Transfusion Services, Department of Pathology, University of Maryland School of Medicine, Baltimore, USA.
¹⁴ Department of Emergency Medicine, University of Colorado School of Medicine, Boulder, USA.
¹⁵ Department of Medicine, University of New Mexico School of Medicine, Albuquerque, USA.
¹⁶ Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Maryland School of Medicine, College Park, USA.
¹⁷ Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Utah, Salt Lake City, USA.
¹⁸ Intermountain Healthcare, Salt Lake City, USA.
¹⁹ Department of Pathology and Laboratory Medicine, University of Arkansas for Medical Sciences, Fayetteville, USA.
²⁰ Division of Hospital Medicine, Scripps Clinic, Scripps Research Translational Institute, The Scripps Research Institute, San Diego, USA.
²¹ Department of Emergency and Division of Pulmonary, Critical Care, and Sleep Medicine, University of Washington, Seattle, USA.
²² Department of Emergency Medicine, University of Mississippi Medical Center, Oxford, USA.
²³ Department of Internal Medicine, Division of Infectious Disease, Rochester General Hospital, Rochester, USA.
²⁴ Department of Pharmacy, Newton-Wellesley Hospital, Massachusetts College of Pharmacy and Health Sciences, Boston, USA.
²⁵ Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, State University of New York at Buffalo, Buffalo, USA.
²⁶ Department of Pathology, University of Utah, Salt Lake City, USA.
²⁷ Division of Pulmonary and Critical Care, Louisiana State University Health-Sciences Center, New Orleans, USA.
²⁸ Division of Pulmonary, Critical Care, and Sleep Medicine, The Ohio State University, Columbus, USA.
²⁹ Sentara Pulmonary, Critical Care, and Sleep Specialists, Sentara Health, Eastern Virginia Medical School, Norfolk, USA.
³⁰ Department of Pathology, University of New Mexico School of Medicine, Albuquerque, USA.
³¹ Newton-Wellesley Hospital, Department of Medicine, Tufts School of Medicine, Boston, USA.
³² Department of Emergency Medicine, Beth Israel Deaconess Medical Center, Boston, USA.
³³ Department of Medicine, University of Chicago, Chicago, USA.

PMID: 33743799
PMCID: PMC7980732
DOI: 10.1186/s13063-021-05171-2

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.

Keywords: COVID-19; Clinical trials; Neutralizing antibodies; Passive immunity; Randomized controlled trial; SARS-CoV-2: convalescent plasma.

PubMed Disclaimer

Conflict of interest statement

All authors submitted a competing interest form at the time of manuscript submission. The authors declare that they have no competing interests.

Figures

**Fig. 1**
Donor selection pipeline for obtaining COVID-19 convalescent plasma for PassITON. Images obtained from flaticon.com

**Fig. 2**
COVID-19 convalescent plasma selection for PassITON. Each convalescent plasma unit used in the trial is selected based on quantitative anti-SARS-CoV-2 antibody levels and neutralization

**Fig. 3**
Power of the trial to detect different effect sizes (treatment effect odds ratios) in the primary outcome with enrollment of 1000 participants. The primary outcome is the COVID-19 7-point Ordinal Clinical Progression Scale, analyzed with a cumulative probability model. An odds ratio < 1.0 indicates more favorable clinical outcomes on the scale in the convalescent plasma group than the placebo group. With enrollment of 1000 participants, the trial has power to detect on odds ratio ≤ 0.73

See this image and copyright information in PMC

Update of

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 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, 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. Self WH, et al. Res Sq [Preprint]. 2021 Mar 2:rs.3.rs-227796. doi: 10.21203/rs.3.rs-227796/v1. Res Sq. 2021. Update in: Trials. 2021 Mar 20;22(1):221. doi: 10.1186/s13063-021-05171-2. PMID: 33688640 Free PMC article. Updated. Preprint.

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

Affiliations

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

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