Restoration of Endothelial Integrity in Patients With COVID-19 (RELIC)

Study Overview
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Brief Summary
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This is a pilot study designed to demonstrate the feasibility of conducting a larger study of standard plasma therapy in COVID-19 patients.

Detailed Description
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This is a randomized trial in hospitalized COVID-19-positive patients. This trial compares standard care to standard care plus an infusion of non-convalescent thawed plasma. Blood will be collected from all participants at eight timepoints, and clinical data will be collected for 30 days or until discharge/death.

Official Title
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Restoration of Endothelial Integrity in Patients With COVID-19 (RELIC)

Conditions
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COVID-19

Intervention / Treatment
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* Biological: Thawed plasma


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 years of age or older COVID-19 positive by PCR or assay within 72 hours or less Oxygen saturation of ≤94% on room air or requiring supplemental oxygen at screening Exclusion Criteria: mechanically ventilated pregnant prisoners receiving resuscitation with blood products for hemorrhagic shock receiving an investigational therapy for COVID-19 diagnosed with severe comorbidities not expected to survive more than 24 hours

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: Group 1: Standard care for COVID-19 Group 2: Standard care plus non-convalescent plasma infusion
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Standard Arm<br>Participants randomized to standard care will not receive an intervention but will participate in other study procedures, which are blood collection and data collection. | |
| Experimental: Intervention Arm<br>Participants randomized to the intervention arm will receive standard care plus an infusion of thawed plasma, starting rate 30 ml/hour for 24 hours, increased to 50 ml/hour if deemed to be hypovolemic (low fluid volume). Only non-convalescent (COVID-antibody-free) plasma will be used. | Biological: Thawed plasma<br>* Plasma not labeled convalescent plasma is presumed to be free of COVID antibodies, but is not tested for antibodies. To ensure that we are using antibody-free plasma, we will test each unit of plasma with a quick COVID test before it is utilized in this study.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants completing plasma infusion for COVID-19 | Identification of patient population who are COVID-19-positive and transfused with plasma | Track patient progress for 30 days post transfusion. | 
| Number of participants intubated | Participants who are intubated during hospital stay | Track patient progress for 30 days post transfusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sequential Organ Failure Assessment (SOFA) score change | SOFA is used as a clinical indicator of morbidity severity. The scale is 0-24, with 0 being normal. | Track patient progress for 30 days post transfusion | 
| National Early Warning Score change | This score is used as a clinical indicator of patient deterioration. The total possible score ranges from 0 to 20. The higher the score the greater the clinical risk. | Track patient progress for 30 days post transfusion | 
| Ventilator-free Days | Number of in-hospital days that patient is not ventilated | Track patient progress for 30 days post transfusion | 
| Intensive care unit-free Days | Number of days patient is hospitalized and not in ICU | Track patient progress for 30 days post transfusion | 
| In hospital mortality | Number of patients who receive transfusion but do not survive for 30 days | Track patient progress for 30 days post transfusion | 
| Angiopoietin 1&2 blood test | Angiopoietin, a protein, that plays a role in blood vessel formation | 0, 12, 24, 48, 72 hours. Day 7, 14 and 30. | 
| Soluble Tie2 blood test | Soluble Tie2 is a protein that mediates the function of angiopoietin | 0, 12, 24, 48, 72 hours. Day 7, 14 and 30. | 
| Soluble Thrombomodulin blood test | This test indicates blood vessel injury | 0, 12, 24, 48, 72 hours. Day 7, 14 and 30. | 
| Syndecan-1 blood test | This test indicates blood vessel injury | 0, 12, 24, 48, 72 hours. Day 7, 14 and 30. | 
| Prothrombin time blood test | This test measures blood coagulation | 0, 12, 24, 48, 72 hours. Day 7, 14 and 30. | 
| Partial thromboplastin time blood test | This test measures blood coagulation | 0, 12, 24, 48, 72 hours. Day 7, 14 and 30. | 
| D-dimer blood test | This test measures for D-dimer concentration, indicating that the blood has been breaking down blood clots | 0, 12, 24, 48, 72 hours. Day 7, 14 and 30. | 
| Fibrinogen blood test | Tests for a protein important to clotting | 0, 12, 24, 48, 72 hours. Day 7, 14 and 30. | 
| Thromboelastography blood test | Measures blood coagulation | 0, 12, 24, 48, 72 hours. Day 7, 14 and 30. | 
| Von Willebrand Factor Antigen blood test | This test measures a blood clotting protein | 0, 12, 24, 48, 72 hours. Day 7, 14 and 30. | 
| Factor VIII blood test | This test measures a blood clotting protein | 0, 12, 24, 48, 72 hours. Day 7, 14 and 30. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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plasma