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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Passive Immunity Trial for Our Nation (PassItOn)

Conditions
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COVID-19, Coronavirus, SARS-CoV-2

Intervention / Treatment
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* Biological: pathogen reduced SARS-CoV-2 convalescent plasma
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age greater than or equal to 18 years Currently hospitalized or in an emergency department with anticipated hospitalization Symptoms of acute respiratory infection, defined as one or more of the following: Cough Chills, or a fever (greater than 37.5° C or 99.5° F) 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 Laboratory-confirmed SARS-CoV-2 infection within the past 14 days Exclusion Criteria: Prisoner Unable to randomize within 14 days after onset of acute respiratory infection symptoms 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.) Inability to be contacted on Day 29-36 for clinical outcome assessment Receipt of any SARS-CoV-2 passive immunity therapy, such as convalescent plasma, monoclonal antibodies, or pooled immunoglobulin, in the past 30 days Contraindications to transfusion or history of prior reactions to transfused blood products Plan for hospital discharge within 24 hours of enrollment Previous enrollment in this trial Previous laboratory-confirmed SARS-CoV-2 infection before the current illness Enrollment in another clinical trial evaluating monoclonal antibodies, convalescent plasma, or another passive immunity therapy Prior receipt of SARS-CoV-2 vaccine

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional 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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: pathogen reduced SARS-CoV-2 convalescent plasma<br>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<br>* 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.<br>|
| Placebo Comparator: Placebo<br>Participants randomized to the control group will receive 250mL of Lactate Ringers containing multivitamins intravenously on Day 1 as a placebo. | Biological: Placebo<br>* Lactated Ringer's solution with multivitamins<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COVID-19 drug treatment, convalescent plasma