Application of Convalescent Plasma in the Treatment of SARS CoV-2 Disease (COVID-19) With Evaluation of Therapy Effectiveness

Study Overview
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Brief Summary
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A Multi-centre, 18-months, Single-group Study of Application of Convalescent Plasma in the Treatment of SARS CoV-2 Disease (COVID-19) With Metabolomic and Laboratory Evaluation of Plasma Therapy Effectiveness.

Detailed Description
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The trial is designed as multi-centre, non-randomized, single-group with a primary endpoint of death of convalescent plasma recipient in twenty eight days. We are planning to recruit 300 donor patients who recovered from COVID-19 and who offer to take part in an experiment based on the informed consent form. The recovery criteria involve body temperature normalization for more than 3 days, resolution of respiratory tract symptoms, and two consecutively negative results of SARS-CoV-2 RT-PCR assay test. The donor's blood will be collected after four weeks post-onset of illness. 600 ml ABO-compatible plasma sample will be harvested during apheresis from each donor and each sample will be divided and stored as 200 mL aliquots. The plasma recipients are adult patients diagnosed with COVID-19 according to the WHO Interim Guidance with confirmation by real-time RT-PCR assay The inclusion criteria to receive plasma assume to meet at least one of following : respiratory distress with tachypnoe ≥30 breaths per minute, oxygen level less than 94% in resting-state, partial pressure of oxygen (PO2) ≤ 80 mmHg. Patients who meet the criteria receive one dose (200 mL) of ABO compatible inactivated convalescent plasma with a confirmed neutralization activity. The recipient are going to undergo detailed clinical evaluation along with the assessment of biochemical parameters, complete blood count and inflammation indicators. The study involves a comprehensive assessment of the serological response of patients with different course of SARS-Cov-2 infection, as well as an analysis of the impact of the level of antibodies in the donor's plasma on the clinical response in patients with COVID-19. In addition, a comprehensive metabolomic analysis of donor and recipient blood was planned to identify prognostic and predictive factors. The endpoints include the safety of convalescents plasma transfusion, as well as the improvement of clinical symptoms and laboratory parameters.

Official Title
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A Multi-centre, 18-months, Single-group Study of Application of Convalescent Plasma in the Treatment of SARS CoV-2 Disease (COVID-19) With Metabolomic and Laboratory Evaluation of Plasma Therapy Effectiveness

Conditions
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COVID-19 Convalescent Plasma Treatment

Intervention / Treatment
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* Biological: COVID-19 convalescent plasma treatment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Donors: Age >18 and <65 years Confirmed previous SARS CoV-2 infection Signed informed consent to participate in this clinical trial, to donate plasma and to store the specimen for future testing. At least 28 days from the end of isolation or resolution of symptoms of infection Male donors, or female donors who have not been pregnant, or female donors who have been pregnant tested negative for HLA antibodies Individuals who meet all regular voluntary donor eligibility requirements Recipiants: Signed informed consent to participate in this clinical trial. Confirmed previous SARS CoV-2 infection Respiratory distress with tachypnoe ≥30 breaths per minute, Oxygen level less than 94% in resting-state, Partial pressure of oxygen (PO2) ≤ 80 mmHg Exclusion Criteria: Donors: Age : <18 or >65 years Female subjects who are pregnant HIV1,2 hepatitis B,C or syphilis infection Donors ineligible for regular voluntary blood donation Recipiants: No informed consent to participate in the study Patients with a history of plasma hypersensitivity, including anaphylactic shock in previous transfusions, allergic reactions to citrate or primary IgA deficiency Patients with symptoms of severe multi-organ failure Patients with known allergic reactions to chemical compounds used or generated in the procedure of inactivation of pathogens Patients with active thrombosis

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
Interventional Model Description: The study is going to recruit 300 convalescent plasma donors and 200 recipients
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Hospitalized patients with SARS CoV-2 infection<br>Hospitalized patients with SARS CoV-2 infection will receive an anti SARS-CoV-2 convalescent plasma | Biological: COVID-19 convalescent plasma treatment<br>* The donor's blood will be collected after four weeks post-onset of illness. 600 ml ABO-compatible plasma sample will be harvested during apheresis from each donor and each sample will be divided and stored as 200 mL aliquots. Patients who meet the criteria receive one dose (200 mL) of ABO compatible inactivated convalescent plasma with a confirmed neutralization activity.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Death, for any reason | Death, for any reason | 28 days after transfusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| For patients with respiratory support, the time to take one's own breath (extubation) | For patients with respiratory support, the time to take one's own breath (extubation) | 28 days after transfusion | 
| Stay in the intensive care unit (ICU) | Stay in the intensive care unit (ICU) | 28 days after transfusion | 
| Time to disconnect CPAP respiratory support | Time to disconnect CPAP respiratory support | 28 days after transfusion | 
| Time to elimination of SARS-Cov-2 (RT-PCR) | Time to elimination of SARS-Cov-2 (RT-PCR) | 28 days after transfusion | 
| Time to serological response (anti-SARS-COv-2 antibodies) | Time to serological response (anti-SARS-COv-2 antibodies) | 3, 7, 28 days after transfusion |