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

• ClinicalTrials.gov Identifier: NCT04362176
• Recruitment Status: Completed
• First Posted: April 24, 2020
• Results First Posted: November 3, 2022
• Last Update Posted: November 3, 2022
• Sponsor: Vanderbilt University Medical Center
• Collaborators: Dolly Parton; National Center for Advancing Translational Sciences (NCATS)
• Information provided by (Responsible Party): Todd Rice, Vanderbilt University Medical Center

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
COVID-19; Coronavirus; SARS-CoV-2	Biological: pathogen reduced SARS-CoV-2 convalescent plasma; Biological: Placebo	Phase 3

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 974 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Eligible participants will be randomized 1:1 to convalescent plasma versus lactated Ringer's solution with multivitamins. Randomization will be completed in permuted blocks and stratified by site, gender, and age. Participants, treating clinicians and outcomes assessors will all be blinded to study group assignment. Study personnel will not be blinded to the study group assignment.
• Masking: Triple (Participant, Care Provider, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Passive Immunity Trial for Our Nation (PassItOn)
• Actual Study Start Date: April 24, 2020
• Actual Primary Completion Date: July 6, 2021
• Actual Study Completion Date: August 6, 2021

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. COVID-19 7-point Ordinal Clinical Progression Outcomes Scale Score [ Time Frame: Study Day 15 ]

   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:

   1. Not hospitalized with resumption of normal activities.
   2. Not hospitalized, but unable to resume normal activities.
   3. Hospitalized, not on supplemental oxygen.
   4. Hospitalized, on supplemental oxygen.
   5. Hospitalized, on nasal high-flow oxygen therapy, noninvasive mechanical ventilation, or both
   6. Hospitalized, on ECMO, invasive mechanical ventilation, or both.
   7. Death

Secondary Outcome Measures :

1. All-location, All-cause 14-day Mortality [ Time Frame: Baseline to Study Day 14 ]
   All-location, all-cause 14-day mortality; mortality was assessed via EHR review, phone call, social media review
2. All-location, All-cause 28-day Mortality [ Time Frame: Baseline to Study Day 28 ]
   All-location, all-cause 28-day mortality
3. Survival Through 28 Days [ Time Frame: Baseline to Day 28 (assessed on Study Day 29) ]
   Number of participants survived through Day 28
4. COVID-19 7-point Ordinal Clinical Progression Outcomes Scale on Study Day 3 [ Time Frame: Baseline to 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:

   1. Not hospitalized with resumption of normal activities.
   2. Not hospitalized, but unable to resume normal activities.
   3. Hospitalized, not on supplemental oxygen.
   4. Hospitalized, on supplemental oxygen.
   5. Hospitalized, on nasal high-flow oxygen therapy, noninvasive mechanical ventilation, or both
   6. Hospitalized, on ECMO, invasive mechanical ventilation, or both.
   7. Death
5. COVID-19 7-point Ordinal Clinical Progression Outcomes Scale on Study Day 8 [ Time Frame: 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:

   1. Not hospitalized with resumption of normal activities.
   2. Not hospitalized, but unable to resume normal activities.
   3. Hospitalized, not on supplemental oxygen.
   4. Hospitalized, on supplemental oxygen.
   5. Hospitalized, on nasal high-flow oxygen therapy, noninvasive mechanical ventilation, or both
   6. Hospitalized, on ECMO, invasive mechanical ventilation, or both.
   7. Death
6. COVID-19 7-point Ordinal Clinical Progression Outcomes Scale on Study Day 29 [ Time Frame: 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:

   1. Not hospitalized with resumption of normal activities.
   2. Not hospitalized, but unable to resume normal activities.
   3. Hospitalized, not on supplemental oxygen.
   4. Hospitalized, on supplemental oxygen.
   5. Hospitalized, on nasal high-flow oxygen therapy, noninvasive mechanical ventilation, or both
   6. Hospitalized, on ECMO, invasive mechanical ventilation, or both.
   7. Death
7. Oxygen-free Days Through Day 28 [ Time Frame: Baseline to Day 28 ]
   Number of days without use of oxygen
8. Ventilator-free Days Through Day 28 [ Time Frame: Baseline to Day 28 ]
   Number of days without use of a ventilator
9. Vasopressor-free Days Through Day 28 [ Time Frame: Baseline to Day 28 ]
   Number of days without use of vasopressors
10. ICU-free Days Through Day 28 [ Time Frame: Baseline to Day 28 ]
    Number of days outside of ICU
11. Hospital-free Days Through Day 28 [ Time Frame: Baseline to Day 28 ]
    Number of days outside of the hospital

Other Outcome Measures:

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

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

United States, Arkansas

University of Arkansas for Medical Sciences

Little Rock, Arkansas, United States, 72205

United States, California

Scripps Health

La Jolla, California, United States, 92037

United States, Colorado

University of Colorado Denver

Aurora, Colorado, United States, 80045

United States, District of Columbia

MedStar Health Research Institute/MedStar Washington Hospital Center

Washington, District of Columbia, United States, 20010

United States, Florida

Cleveland Clinic Florida

Weston, Florida, United States, 33331

United States, Illinois

University of Chicago

Chicago, Illinois, United States, 60637

Loyola University Medical Center

Maywood, Illinois, United States, 60153

United States, Kansas

The University of Kansas Medical Center

Kansas City, Kansas, United States, 66160

United States, Louisiana

Our Lady of the Lake Regional Medical Center

Baton Rouge, Louisiana, United States, 70808

United States, Maryland

University of Maryland, Baltimore (University of Maryland Medical Center)

Baltimore, Maryland, United States, 21201

United States, Massachusetts

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States, 02215

Newton-Wellelsey Hospital

Newton, Massachusetts, United States, 012462

United States, Minnesota

University of Minnesota

Minneapolis, Minnesota, United States, 55455

United States, Mississippi

University of Mississippi Medical Center

Jackson, Mississippi, United States, 39216

United States, New Mexico

University of New Mexico Health Sciences Center

Albuquerque, New Mexico, United States, 87131

United States, New York

University at Buffalo/Buffalo General Medical Center

Buffalo, New York, United States, 14203

Rochester General Hospital

Rochester, New York, United States, 14621

United States, Ohio

Cleveland Clinic Ohio

Cleveland, Ohio, United States, 44195

The Ohio State University Wexner Medical Center and James Cancer Hospital

Columbus, Ohio, United States, 43210

United States, Tennessee

Vanderbilt University Medical Center

Nashville, Tennessee, United States, 37203

Meharry Medical College

Nashville, Tennessee, United States, 37208

United States, Utah

Utah Valley Hospital

Provo, Utah, United States, 84604

University of Utah Health

Salt Lake City, Utah, United States, 84132

United States, Virginia

Sentara Norfolk General Hospital

Norfolk, Virginia, United States, 23507

Virginia Commonwealth University

Richmond, Virginia, United States, 23298

United States, Washington

University of Washington

Seattle, Washington, United States, 98104

Sponsors and Collaborators

Vanderbilt University Medical Center

Dolly Parton

National Center for Advancing Translational Sciences (NCATS)

Investigators

• Principal Investigator: Todd Rice, MD; Vanderbilt University Medical Center

  Study Documents (Full-Text)

Documents provided by Todd Rice, Vanderbilt University Medical Center:

Study Protocol  [PDF] January 28, 2021

Statistical Analysis Plan  [PDF] December 12, 2020

Informed Consent Form  [PDF] March 9, 2021

More Information

Additional Information:

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 

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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

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. Passive Immunity Trial for Our Nation (PassITON): study protocol for a randomized placebo-control clinical trial evaluating COVID-19 convalescent plasma in hospitalized adults. Res Sq. 2021 Mar 2:rs.3.rs-227796. doi: 10.21203/rs.3.rs-227796/v1. Preprint.

• Responsible Party: Todd Rice, Associate Professor of Medicine, Vanderbilt University Medical Center
• ClinicalTrials.gov Identifier: NCT04362176
• Other Study ID Numbers: 200738; 3UL1TR002243-04S3 ( U.S. NIH Grant/Contract )
• First Posted: April 24, 2020
• Results First Posted: November 3, 2022
• Last Update Posted: November 3, 2022
• Last Verified: October 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Todd Rice, Vanderbilt University Medical Center:

COVID-19 drug treatment; convalescent plasma

Additional relevant MeSH terms:

COVID-19; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases