Passive Immunity Trial for Our Nation to Treat COVID-19 in Hospitalized Adults (PassItOn)

Passive Immunity Trial for Our Nation (PassItOn)

The purpose of this study is to test the safety and efficacy of convalescent donor plasma to treat COVID-19 in hospitalized adults in a randomized, placebo-controlled setting. The effect of convalescent plasma will be compared to placebo on clinical outcomes, measured using the COVID-19 7-point Ordinal Clinical Progression Outcomes Scale at Day 15, among adults with COVID-19 requiring hospitalization.

Study Overview

• Status: Completed
• Conditions: COVID-19; SARS-CoV-2; Coronavirus
• Intervention / Treatment: Biological: pathogen reduced SARS-CoV-2 convalescent plasma; Biological: Placebo

Detailed Description

After being informed about the study and potential risks, participants confirmed to meet all eligibility criteria who have provided informed consent will be randomized 1:1 to convalescent plasma versus placebo. Transfusion of convalescent plasma or placebo will be administered by clinical or research personnel while the patient is hospitalized on Study Day 1. On Study Days 1-7, participants will be monitored for adverse reactions to the transfusion. Research personnel will also assess patients at Day 14 and Day 28; these assessments will be completed by phone if the participant has been discharged from the hospital.

• Study Type: Interventional
• Enrollment (Actual): 974
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • University of Arkansas for Medical Sciences
  • California
    • La Jolla, California, United States, 92037
      • Scripps Health
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Denver
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • MedStar Health Research Institute/MedStar Washington Hospital Center
  • Florida
    • Weston, Florida, United States, 33331
      • Cleveland Clinic Florida
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago
    • Maywood, Illinois, United States, 60153
      • Loyola University Medical Center
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • The University of Kansas Medical Center
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70808
      • Our Lady of the Lake Regional Medical Center
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland, Baltimore (University of Maryland Medical Center)
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center
    • Newton, Massachusetts, United States, 012462
      • Newton-Wellelsey Hospital
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • University of Mississippi Medical Center
  • New Mexico
    • Albuquerque, New Mexico, United States, 87131
      • University of New Mexico Health Sciences Center
  • New York
    • Buffalo, New York, United States, 14203
      • University at Buffalo/Buffalo General Medical Center
    • Rochester, New York, United States, 14621
      • Rochester General Hospital
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Ohio
    • Columbus, Ohio, United States, 43210
      • The Ohio State University Wexner Medical Center and James Cancer Hospital
  • Tennessee
    • Nashville, Tennessee, United States, 37208
      • Meharry Medical College
    • Nashville, Tennessee, United States, 37203
      • Vanderbilt University Medical Center
  • Utah
    • Provo, Utah, United States, 84604
      • Utah Valley Hospital
    • Salt Lake City, Utah, United States, 84132
      • University of Utah Health
  • Virginia
    • Norfolk, Virginia, United States, 23507
      • Sentara Norfolk General Hospital
    • Richmond, Virginia, United States, 23298
      • Virginia Commonwealth University
  • Washington
    • Seattle, Washington, United States, 98104
      • University of Washington

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age greater than or equal to 18 years
2. Currently hospitalized or in an emergency department with anticipated hospitalization

3. Symptoms of acute respiratory infection, defined as one or more of the following:

   1. Cough
   2. Chills, or a fever (greater than 37.5° C or 99.5° F)
   3. Shortness of breath, operationalized as a patient having any of the following:

   i. Subjective shortness of breath reported by a patient or surrogate. ii. Tachypnea with respiratory rate of greater than 22 breaths per minute iii. Hypoxemia, defined as SpO2 less than 92% on room air, new receipt of supplemental oxygen to maintain SpO2 greater than or equal to 92%, or increased supplemental oxygen to maintain SpO2 greater than or equal to 92% for a patient on chronic oxygen therapy

4. Laboratory-confirmed SARS-CoV-2 infection within the past 14 days

Exclusion Criteria:

1. Prisoner
2. Unable to randomize within 14 days after onset of acute respiratory infection symptoms
3. Patient, legal representative, or physician not committed to full support (Exception: a patient who will receive all supportive care except for attempts at resuscitation from cardiac arrest will not be excluded.)
4. Inability to be contacted on Day 29-36 for clinical outcome assessment
5. Receipt of any SARS-CoV-2 passive immunity therapy, such as convalescent plasma, monoclonal antibodies, or pooled immunoglobulin, in the past 30 days
6. Contraindications to transfusion or history of prior reactions to transfused blood products
7. Plan for hospital discharge within 24 hours of enrollment
8. Previous enrollment in this trial
9. Previous laboratory-confirmed SARS-CoV-2 infection before the current illness
10. Enrollment in another clinical trial evaluating monoclonal antibodies, convalescent plasma, or another passive immunity therapy
11. Prior receipt of SARS-CoV-2 vaccine

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: pathogen reduced SARS-CoV-2 convalescent plasma; Transfusion of convalescent plasma will be administered by clinical or research personnel while the participant is hospitalized on Study Day 0. Plasma will be administered at a rate of 500 mL/hour and will be administered within 12 hours of randomization.	Biological: pathogen reduced SARS-CoV-2 convalescent plasma; Convalescent COVID-19 donor plasma is the liquid part of blood that is collected from patients who have recovered from COVID-19 infection. This plasma contains SARS-CoV-2 specific antibodies that may help fight the infection.
Placebo Comparator: Placebo; Participants randomized to the control group will receive 250mL of Lactate Ringers containing multivitamins intravenously on Day 1 as a placebo.	Biological: Placebo; Lactated Ringer's solution with multivitamins

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
COVID-19 7-point Ordinal Clinical Progression Outcomes Scale Score	Outcome measured clinical status of the participant defined by the Covid-19 7-point Ordinal Clinical Progression Outcomes Scale: This scale reflects a range from baseline to death as follows: Not hospitalized with resumption of normal activities.; Not hospitalized, but unable to resume normal activities.; Hospitalized, not on supplemental oxygen.; Hospitalized, on supplemental oxygen.; Hospitalized, on nasal high-flow oxygen therapy, noninvasive mechanical ventilation, or both; Hospitalized, on ECMO, invasive mechanical ventilation, or both.; Death	Study Day 15

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
All-location, All-cause 14-day Mortality	All-location, all-cause 14-day mortality; mortality was assessed via EHR review, phone call, social media review	Baseline to Study Day 14
All-location, All-cause 28-day Mortality	All-location, all-cause 28-day mortality	Baseline to Study Day 28
Survival Through 28 Days	Number of participants survived through Day 28	Baseline to Day 28 (assessed on Study Day 29)
COVID-19 7-point Ordinal Clinical Progression Outcomes Scale on Study Day 3	Outcome measured clinical status of the participant defined by the Covid-19 7-point Ordinal Clinical Progression Outcomes Scale: This scale reflects a range from baseline to death as follows: Not hospitalized with resumption of normal activities.; Not hospitalized, but unable to resume normal activities.; Hospitalized, not on supplemental oxygen.; Hospitalized, on supplemental oxygen.; Hospitalized, on nasal high-flow oxygen therapy, noninvasive mechanical ventilation, or both; Hospitalized, on ECMO, invasive mechanical ventilation, or both.; Death	Baseline to Study Day 3
COVID-19 7-point Ordinal Clinical Progression Outcomes Scale on Study Day 8	Outcome measured clinical status of the participant defined by the Covid-19 7-point Ordinal Clinical Progression Outcomes Scale: This scale reflects a range from baseline to death as follows: Not hospitalized with resumption of normal activities.; Not hospitalized, but unable to resume normal activities.; Hospitalized, not on supplemental oxygen.; Hospitalized, on supplemental oxygen.; Hospitalized, on nasal high-flow oxygen therapy, noninvasive mechanical ventilation, or both; Hospitalized, on ECMO, invasive mechanical ventilation, or both.; Death	Study Day 8
COVID-19 7-point Ordinal Clinical Progression Outcomes Scale on Study Day 29	Outcome measured clinical status of the participant defined by the Covid-19 7-point Ordinal Clinical Progression Outcomes Scale: This scale reflects a range from baseline to death as follows: Not hospitalized with resumption of normal activities.; Not hospitalized, but unable to resume normal activities.; Hospitalized, not on supplemental oxygen.; Hospitalized, on supplemental oxygen.; Hospitalized, on nasal high-flow oxygen therapy, noninvasive mechanical ventilation, or both; Hospitalized, on ECMO, invasive mechanical ventilation, or both.; Death	Study Day 29
Oxygen-free Days Through Day 28	Number of days without use of oxygen	Baseline to Day 28
Ventilator-free Days Through Day 28	Number of days without use of a ventilator	Baseline to Day 28
Vasopressor-free Days Through Day 28	Number of days without use of vasopressors	Baseline to Day 28
ICU-free Days Through Day 28	Number of days outside of ICU	Baseline to Day 28
Hospital-free Days Through Day 28	Number of days outside of the hospital	Baseline to Day 28

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Acute Kidney Injury	Number of participants with Acute kidney injury	Baseline to Day 28
Renal Replacement Therapy	Number of participants requiring renal replacement therapy	Baseline to Day 28
Documented Venous Thromboembolic Disease (DVT or PE)	Number of participants with documented venous thromboembolic disease (DVT or PE)	Baseline to Day 28
Documented Cardiovascular Event (Myocardial Infarction or Ischemic Stroke)	Number of Participants with myocardial infarction or ischemic stroke	Baseline to Day 28
Transfusion Reaction	Number of participants with transfusion reaction (fever/rash)	Baseline to Day 28
Transfusion Related Acute Lung Injury (TRALI)	Number of participants with transfusion related acute lung injury (TRALI)	Baseline to Day 28
Transfusion Associated Circulatory Overload (TACO)	Number of participants with transfusion associated circulatory overload (TACO)	Baseline to Day 28
Transfusion Related Infection	Number of participants with transfusion related infection	Baseline to Day 28

Collaborators and Investigators

• Sponsor: Vanderbilt University Medical Center
• Collaborators: National Center for Advancing Translational Sciences (NCATS); Dolly Parton

Publications and helpful links

General Publications

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• Self WH, Wheeler AP, Stewart TG, Schrager H, Mallada J, Thomas CB, Cataldo VD, O'Neal HR Jr, Shapiro NI, Higgins C, Ginde AA, Chauhan L, Johnson NJ, Henning DJ, Jaiswal SJ, Mammen MJ, Harris ES, Pannu SR, Laguio-Vila M, El Atrouni W, de Wit M, Hoda D, Cohn CS, McWilliams C, Shanholtz C, Jones AE, Raval JS, Mucha S, Ipe TS, Qiao X, Schrantz SJ, Shenoy A, Fremont RD, Brady EJ, Carnahan RH, Chappell JD, Crowe JE Jr, Denison MR, Gilchuk P, Stevens LJ, Sutton RE, Thomsen I, Yoder SM, Bistran-Hall AJ, Casey JD, Lindsell CJ, Wang L, Pulley JM, Rhoads JP, Bernard GR, Rice TW; Passive Immunity Trial for Our Nation (PassITON) Investigators. Neutralizing COVID-19 Convalescent Plasma in Adults Hospitalized With COVID-19: A Blinded, Randomized, Placebo-Controlled Trial. Chest. 2022 Nov;162(5):982-994. doi: 10.1016/j.chest.2022.06.029. Epub 2022 Jul 1.
• 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.
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Helpful Links

• Discovery of a novel coronavirus associated with the recent pneumonia outbreak in humans and its potential bat origin
• China puts 245 COVID-19 patients on convalescent plasma therapy - Xinhua
• Elevated Serum IgM Levels Indicate Poor Outcome in Patients with Coronavirus Disease 2019 Pneumonia: A Retrospective Case-Control Study. Rochester, NY: Social Science Research Network
• FDA Recommendations for Investigational COVID-19 Convalescent Plasma
• WHO | Coronavirus disease (COVID-2019) R&D

Study record dates

Study Major Dates

• Study Start (Actual): April 24, 2020
• Primary Completion (Actual): July 6, 2021
• Study Completion (Actual): August 6, 2021

Study Registration Dates

• First Submitted: April 21, 2020
• First Submitted That Met QC Criteria: April 23, 2020
• First Posted (Actual): April 24, 2020

Study Record Updates

• Last Update Posted (Actual): November 3, 2022
• Last Update Submitted That Met QC Criteria: October 6, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: COVID-19 drug treatment; convalescent plasma
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19
• Other Study ID Numbers: 200738; 3UL1TR002243-04S3 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No