COVID-19 Convalescent Plasma (CCP) Transfusion

Study Overview
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Brief Summary
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This research study evaluates the safety and effectiveness for the use of convalescent plasma transfusion as a treatment option for novel coronavirus SARS-CoV-2 infection (COVID-19). Donors who have recovered from COVID-19 with high antibody levels to the CoV-2 virus will donate plasma at a Mississippi Blood Services facility. Recipients with COIVD-19 who have severe or life threatening conditions will receive plasma from those persons who have recovered from COVID-19.

Detailed Description
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The research purpose is to evaluate the safety and clinical effectiveness of transfusing one unit of banked plasma obtained from patients who have recovered from the novel coronavirus SARS-C0V-2 infection with high titers of IgG antibody to this virus transfused into patients with severe or at high risk of progressing to severe coronavirus-induced disease (COVID-19). The research hypothesis is that COVID-19 convalescent plasma (CCP) transfusion improves outcomes in patients with COVID-19. The use of CCP to treat serious and life threatening COVID-19 has a sound biological as well as clinical rationale to provide virus-specific immune protection in patients unable to produce and/or maintain antiviral antibodies. This treatment protocol is designed primarily to offer a rescue therapy in patients with severe and life threatening disease and explore use in patients for whom a progression to serious disease is likely. Examining the specific antibody responses to the virus in transfused patients if/when they show signs of recovery and comparing these values with those obtained before the transfusion may provide information to design more extensive trials aimed at identifying the best patient population for future use of CCP.

Official Title
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An Open Label Trial of Transfusion of COVID-19 Convalescent Plasma (CCP) to Patients With Moderate to Severe COVID-19

Conditions
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COVID-19

Intervention / Treatment
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* Biological: COVID Convalescent Plasma


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 Clinician judged serious or life threatening COVID-19 (or at significant risk to develop serious COVID) manifested by at least one of the following: Laboratory confirmed diagnosis of SARS-CoV-2 infection Hypoxia (PaO2/FiO2 <300, Pulse oximetry <93% at rest Evidence of pulmonary infiltration Respiratory failure Sepsis Multiple organ dysfunction or failure (assessed by SOFA score) Informed consent provided by the patient or legally authorized representative (LAR) Exclusion Criteria: Greater than 21 days from confirmed COVID-19 diagnosis Receipt of pooled immunoglobulin transfusion in previous 28 days History of prior reaction to transfused blood products Currently enrolled in other drug trials that preclude investigational treatment with CoV-2 convalescent plasma transfusion

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Recipient of COVID-19 Convalescent Plasma (CCP) Transfusion<br>Transfusion of COVID-19 convalescent plasma to participants with serious or life threatening complications from COVID-19 or are at high risk to develop serious complications. | Biological: COVID Convalescent Plasma<br>* One unit of COVID Convalescent Plasma transfused on Day 0<br>* Other names: CCP, COVID-19 Convalescent Plasma;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in PaO2/FiO2 after CCP transfusion. | Change in pre-transfusion respiratory status compared to Day 3 respiratory status measured by PaO2/FiO2. | 3 Days | 
| Change in pulse oximetry status after CCP transfusion. | Change in pre-transfusion respiratory status compared to Day 3 respiratory status measured by pulse oximetry. | 3 Days | 
| Change in aO2 after CCP transfusion. | Change in pre-transfusion respiratory status compared to Day 3 respiratory status measured by aO2. | 3 Days | 
| Change in respiratory rate after CCP transfusion. | Change in pre-transfusion respiratory status compared to Day 3 respiratory status measured by respiratory rate. | 3 Days | 
| Change in intubation status after CCP transfusion. | Change in pre-transfusion respiratory status compared to Day 3 respiratory status measured by intubation status. | 3 Days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Sequential Organ Failure Assessment (SOFA). | Change in SOFA score pre-transfusion to Days 1, 3, 7, and 28 post-transfusion. | Days 1, 3, 7, and 28 | 
| Change in 8-point ordinal clinical deterioration scale. | Change in 8-point ordinal clinical deterioration scale pre-transfusion to Days 1, 3, 7, and 28 post-transfusion. The 8-point ordinal scale measured by: 8-death, 7-ventilation in addition to ECMO, CRRT and/or vasopressor; 6-intubation and mechanical ventilation; 5-non-invasive mechanical ventilation or high flow oxygen 4- supplemental oxygen by mask or nasal cannula; 3- hospitalization without supplemental oxygen; 2- limitation of activities and 1- no limitation of activities, discharge from hospital. | Days 1, 3, 7, and 28 | 
| Length of ICU/hospital stay. | Total length of stay in ICU/hospital. | Days 1, 3, 7, and 28 | 
| Development of plasma transfusion reactions. | Presence of any signs or symptoms of plasma transfusion reactions at Days 1, 3, 7, and 28 post-transfusion. | Days 1, 3, 7, and 28 | 
| Development of immune complex disorders. | Presence of any signs or symptoms of immune complex disorders (fever spike, urticarial lesion, arthralgias, myalgias, hematuria, non IgE-mediated anaphylaxis) at Days 1, 3, 7, and 28 post-transfusion. | Days 1, 3, 7, and 28 | 
| Change in anti CoV-2 IgM and IgG levels. | Change in anti CoV-2 IgM and IgG levels pre-transfusion compared to levels on Days 1, 3, 7, and 28 post-transfusion. | Days 1, 3, 7, and 28 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COVID-19 Convalescent Plasma, Coronavirus, SARS-CoV-2