Convalescent Plasma for the Treatment of Patients With Severe COVID-19 Infection

Study Overview
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Brief Summary
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This is a multicenter, Phase 2 study, to assess the efficacy of the treatment with convalescent plasma in patients with severe COVID-19 infection.

Detailed Description
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Convalescent plasma will be collected by plasmapheresis from patients fully recovered from COVID-19 infection and will be administered in patients with severe COVID-19 infection. The results will be compared with an historical matched control.

Official Title
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Convalescent Plasma for the Treatment of Patients With Severe COVID-19 Infection - A Multicenter Phase II Trial

Conditions
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COVID-19 Infection

Intervention / Treatment
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* Procedure: Convalescent Plasma


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age >18 years Confirmed SARS-CoV2 infection by PCR of the nasal/pharyngeal swab, sputum, BAL Onset of the disease symptoms no more than 12 days before the inclusion of the patients in the trial Severe COVID-19 infection as determined with one of the following: Respiratory rate 30/min Oxygen Hemoglobin Saturation SAT 93 CRP >1.5 (upper normal limit <0.5) Ferritin value >100 Ratio of PaO2:FiO2 <300mmHg Pulmonary infiltrates in Chest X-Ray or Chest CT scan >50% during 24-48 hours Life threatening infection as determined by one of the following: Respiratory failure Septic Shock Multiple organ failure Signature of informed consent by the patient or legal representative Patients fulfilling criteria 1, 2, 3, 6 and one of criteria 4 or 5 will be eligible for the study. Exclusion Criteria: Critical illness due to progressive COVID-19 with expected survival time <48 hours Intubated patients >72 hours Chronic Heart failure NYHA 3 and/or preexisting left ventricular ejection fraction 30% Cardiovascular failure requiring 0.5μg/Kg/min nor-adrenaline or equivalent or more than 2 types of vasopressor medication Liver Cirrhosis Child C Liver failure with bilirubin >5X ULN and increase of ALT/AST (at least one >10X ULN) Previous history of allergic reaction to blood or blood products transfusion Known IgA deficiency Pregnancy Breast feeding women Pulmonary edema

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: Single arm
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Convalescent Plasma<br>Convalescent Plasma - early treatment of patients with severe COVID-19 | Procedure: Convalescent Plasma<br>* Convalescent Plasma - early treatment of patients with severe COVID-19. Clinical and laboratory data of patients will be collected before initiation of the procedure, 30 minutes after the first dose, 30 minutes after the second dose and 30 minutes after the third plasma dose and then on days 1-7, 14, 21, 28, 35 from the start of treatment. In case of adverse reactions during transfusion such as acute shortness of breath, haemodynamic instability or high pre-existing and non-disease-related fever, the transfusion will be interrupted and detailed recording of the event as well as updating the Adverse Events Management Committee will be performed. In addition to the standard assessments, the titer of neutralizing anti-SARS-CoV-2 antibodies will be measured in a sample drawn prior to plasmapheresis. All donors will be tested for: the titer of IgG anti-SARS-CoV-2 antibodies (Pasteur Institute) the titer of neutralizing anti-SARS-CoV-2 antibodies (Pasteur Institute)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Survival | The primary endpoint of this trial is the survival on day 21. The primary endpoint, as a dichotomous composite of survival (yes/no) and no longer fulfilling criteria of severe COVID-19, will be analyzed according their classification. Specifically, categorical variables will be analyzed by means of absolute and relative frequencies, and all continuous variables will be described using arithmetic mean, standard deviation, median, quartiles. Also, geometric means, variance and 95% confidence intervals (CI), will be calculated for all pharmacokinetics parameters. | Day 21 | 
| Survival | The primary endpoint of this trial is the survival on day 35. | Day 35 | 
| Survival | The primary endpoint of this trial is the survival on day 60. | Day 60 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical improvement ie percentage of patients not fulfilling the criteria for severe disease | The secondary endpoint of this trial is that no longer fulfilling criteria of severe COVID-19 within 21 days after inclusion. This will be assessed on the basis of respiratory rate and ventilation support. | Day 21 |