Hyperimmune Convalescent Plasma in Moderate and Severe COVID-19 Disease

Study Overview
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Brief Summary
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The clinical trial aims to study the safety and efficacy of transfusion of COVID-19 convalescent hyperimmune plasma for the treatment of moderate and severe forms of COVID-19 disease in comparison with non-convalescent fresh frozen plasma (standard plasma).

Detailed Description
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This is a study of the safety and efficacy of the use of COVID-19 convalescent plasma (from subjects who have recovered from SARS-CoV-2) in the treatment of moderate and severe forms of the SARS-CoV-2 infection. Currently, there are no registered drugs for the treatment of the SARS-CoV-2 infection in the world. The use of hyperimmune plasma is a well-known method used for many decades to treat many dangerous infections. The effectiveness of such a therapy for COVID-19 patients has recently been demonstrated in a number of clinical studies in China. Therefore, we plan to study the feasibility of administering multiple doses of COVID-19 convalescent plasma in comparison with standard plasma to moderate and severe patients with COVID-19.

Official Title
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Randomized, Open Label, Prospective Study of the Safety and Efficacy of Hyperimmune Convalescent Plasma in Moderate and Severe COVID-19 Disease

Conditions
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COVID-19

Intervention / Treatment
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* Biological: COVID-19 convalescent hyperimmune plasma
* Biological: Non-convalescent fresh frozen plasma (Standard plasma)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men or women aged 18-75 years. The presence of COVID-19 infection, confirmed by PCR testing The presence of the COVID-19 pneumonia pattern on the chest HRCT with a damage to more than 25% of the lung parenchyma Morning fever ≥ 38.0 °C over the last three days CRP blood level ≥ 50 mg / ml or ferritin blood level ≥ 600 μg / ml A signed informed consent Exclusion Criteria: Respiratory index ≤200 Contraindications for the transfusion of donor immune plasma or history of prior reactions to blood transfusions Mechanical ventilation The presence of chronic lung diseases with chronic respiratory failure. The need for home continuous oxygen therapy before the onset of current disease. Serum creatinine level higher than 150 μmol / l Pregnancy or breastfeeding

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: COVID-19 convalescent hyperimmune plasma<br>Moderately and severely ill COVID-19 patients treated with convalescent hyperimmune plasma. Patients will be infused with two units of 300 ml | Biological: COVID-19 convalescent hyperimmune plasma<br>* Subjects to receive double convalescent hyperimmune plasma units of 300 ml each, with the 2nd unit administered no later than 24 hrs after the first one<br>|
| Placebo Comparator: Non-convalescent fresh frozen plasma (Standard plasma)<br>Moderately and severely ill COVID-19 patients treated with non-convalescent fresh frozen plasma (standard plasma). Patients will be infused with two units of 300 ml | Biological: Non-convalescent fresh frozen plasma (Standard plasma)<br>* Subjects to receive double standard plasma units of 300 ml each, with the 2nd unit administered no later than 24 hrs after the first one<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The number and proportion of patients with the normal body temperature (≤37.2 C) at the day 1, 2, 3, 4, 5, 6, 7 after the start of therapy | The number and proportion of patients with the normal body temperature (≤37.2 C) at the days 1, 2, 3, 4, 5, 6, 7 after the start of therapy, for the statistical data comparison between the two arms. | Days 1, 2, 3, 4, 5, 6, 7 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Days before mechanical ventilation | For each patient, the number of days passed from the plasma administration to placing on mechanical ventilation will be noted, for the statistical data comparison between the two arms. | 30 days | 
| Days of need for oxygen therapy | For each patient, the number of days he or she spent on the oxygen support after the plasma administration will be noted, for the statistical data comparison between the two arms. | 30 days | 
| Days of stay in the ICU | For each patient, the entire duration of ICU stay after the plasma administration will be noted, for the statistical data comparison between the two arms. | 30 days | 
| Days of hospitalization | For each patient, the entire duration of hospital stay after the plasma administration will be noted, for the statistical data comparison between the two arms. | 30 days | 
| Changes of the titer of the SARS-CoV-2 antibodies in the blood plasma of patients | Changes of the plasma levels of the SARS-CoV-2 antibodies, days 14 and 30 after the treatment start vs those levels before the treatment start (day 0) for the same patients. | Days 0, 14, 30 | 
| Dynamics of the cytokine profile | Changes of the plasma levels of IL2, IL6, IL10, TNFalpha and INFgamma, days 3 and 7 after the treatment start vs those levels before the treatment start (day 0) for the same patients. | Days 0, 3, 7 | 
| Incidence of the cytokine storm development and the need of administering cytokine storm inhibitors | Incidence of administering IL6 receptor blockers (tocilizumab, sarilumab) | Days 3, 7 | 
| Dynamics of the level of C-reactive protein | Changes of the plasma levels of C-reactive protein, days 1, 2, 3, 4, 5, 6, 7 after the treatment start vs those levels before the treatment start (Day 0) for the same patients. | Days 0, 1, 2, 3, 4, 5, 6, 7 | 
| 30-day mortality rate | 30-day mortality rate, for the statistical data comparison between the two arms. | 30 days |