Effects of COVID-19 Convalescent Plasma (CCP) on Coronavirus-associated Complications in Hospitalized Patients

Study Overview
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Brief Summary
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The purpose of this study assess the efficacy and safety of anti-SARS-CoV-2 convalescent plasma in hospitalized patients with acute respiratory symptoms up to 14 days after the onset of initial symptoms.

Detailed Description
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A total of 50 eligible subjects will be randomized in a 1:1 ratio to receive either convalescent fresh frozen plasma (frozen within 8 hours of collection) of PF24 (frozen within 24 hours) from blood donors who have recovered from COVID-19 containing antibodies to SARS-CoV-2 or control (standard fresh frozen plasma collected prior to 12/1/2019 or with documented negative SARS-CoV-2 antibody). Should additional anti-COVID agents (anti-viral and/or anti-inflammatory) become available for use as standard of care during implementation, the sample size will be recalculated and increased to account for the estimated impact that these agents may have on the reducing the progression to the primary endpoint of severe hypoxemia.

Official Title
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A Randomized Controlled Adaptive Study Comparing COVID-19 Convalescent Plasma (CCP) to Non-immune Plasma to Limit Coronavirus-associated Complications in Hospitalized Patients

Conditions
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COVID-19, Sars-CoV2

Intervention / Treatment
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* Biological: COVID-19 Convalescent Plasma (CCP)
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria for Enrollment: Patients ≥18 years of age Hospitalized with COVID-19 Enrolled within 72 hours of hospitalization OR within day 14 from first signs of illness Pulmonary infiltrates on chest imaging Oxygenation of <95% on room air Laboratory confirmed COVID-19 Exclusion Criteria Contraindication to transfusion due to inability to tolerate additional fluid, such as due to decompensated congestive heart failure Baseline requirement for oxygen supplementation prior to COVID-19 infection or use of positive pressure therapy for sleep disordered breathing Currently experiencing severe hypoxemic failure, as defined in study endpoints Prior receipt of plasma products, IVIG, or hyperimmune globulin within past 3 months Not currently enrolled another interventional clinical trial of COVID-19 treatment. Note: If taking medications with potential anti-COVID activity for the purpose of COVID-19 treatment that do not yet have data to support efficacy, such as IL-6 antagonists, these medications must be stopped prior to enrollment. Receipt of current standard of care COVID-19 treatment, including remdesivir and dexamethasone is permitted and should be recorded as a concomitant medication. Note: Pregnancy is not exclusionary but will merit additional discussion of risks & benefits in the context of ongoing pregnancy

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: Subjects enrolled in the study will be randomized using a web based randomization procedure to receive convalescent plasma versus non-immune plasma at a 1:1 ratio.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: COVID-19 Convalescent Plasma<br>Subjects in the COVID-19 convalescent plasma group will receive a single infusion of 250 ml anti-SARS-CoV-2 convalescent fresh frozen plasma, ABO compatible with the patient, within 24 hours of randomization. | Biological: COVID-19 Convalescent Plasma (CCP)<br>* COVID-19 Convalescent Plasma (CCP) is a form of passive antibody therapy that involves the administration of anti-SARS-CoV-2 antibodies to a susceptible individual for the purpose of preventing or treating the infectious disease it causes. Convalescent plasma for this trial will be obtained from Vitalant (or American Red Cross if necessary). Patients identified as having recovered from COVID-19 will serve as potential donors. Potential donors will be screened using an anti-SARS-CoV-2 serologic assay and antibody levels will be determined.<br>|
| Placebo Comparator: Placebo<br>Subjects in the placebo group will receive a single infusion of 250 ml of standard fresh frozen plasma, ABO compatible with the patient, within 24 hours of randomization. | Biological: Placebo<br>* Standard plasma will be obtained from Vitalant (or American Red Cross if necessary) and will be either collected prior to 12/1/2019 or tested and confirmed to be negative for anti-SARS-CoV-2.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mechanical Ventilation or Death Endpoint | Number of participants that progressed to mechanical ventilation or death within the first 14 days of enrollment. | Day 14 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mechanical Ventilation or Death Endpoint | Progression to mechanical ventilation or death within the first 28 days of enrollment. | Day 28 | 
| 8-Point Ordinal Scale Endpoint | Clinical efficacy of CCP relative to the control arm in adults hospitalized with COVID-19 according to clinical status as assessed by 8-point ordinal scale. 8 Point WHO Ordinal Scale of Clinical Status: Uninfected (No clinical or virological evidence of infection) - 0 Ambulatory (No limitation of activities) - 1 Ambulatory (Limitation of Activities) - 2 Hospitalized Mild Disease (Hospitalized, no oxygen therapy) - 3 Hospitalized Mild Disease (Oxygen by mask or nasal prongs) - 4 Hospitalized Severe Disease (Non-invasive ventilation or high flow oxygen) - 5 Hospitalized Severe Disease (Intubation and mechanical ventilation) - 6 Hospitalized Severe Disease (Ventilation + Additional organ support (pressors, RRT, ECMO)) - 7 Dead (Death) - 8 | Day 29 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COVID-19, Sars-CoV2, Convalescent plasma