Treatment of Patients With COVID-19 With Convalescent Plasma

Study Overview
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Brief Summary
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The COVID-19 pandemic has been spreading continuously, and in Brazil, until May 31, 2020, there have been more than 450.000 cases with more than 28.000 deaths, with daily increases. The present study proposes to evaluate the efficacy and safety of convalescent plasma in treatment of severe cases of COVID-19 in a multicenter, randomized, open-label and controlled study

Detailed Description
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Eligible patients will be randomized 1:1:1 into 3 treatment groups: A- standard (control); B- standard and convalescent plasma in a volume of 200ml (150-300ml); C- standard and convalescent plasma in a volume of 400ml (300-600ml). The Bayesian multi-arm and multi-stage model will be used, which will allow an interim analysis after the inclusion of 30 patients, with repeated interim analyses for every 30 additional patients. With this, we expect to define not only the efficacy of convalescent plasma, but also the volume of plasma needed if efficacy is proven. The study will be interrupted if the efficacy of the convalescent plasma group is proven, so that all severely ill patients as defined in the study can receive the convalescent plasma treatment. The same will occur if there is no difference in primary outcome with the use of convalescent plasma or serious adverse effects.

Official Title
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Treatment of Patients With COVID-19 With Convalescent Plasma Transfusion: a Multicenter, Open-labeled, Randomized and Controlled Study

Conditions
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COVID-19

Intervention / Treatment
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* Biological: convalescent plasma


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age = or > than 18 years; . Laboratory-proven COVID-19 infection by RT-PCR in any clinical sample . Time since symptom onset less than 10 days at the time of screening; - . Presence of COVID-19 pneumonia, with a typical, indeterminate or atypical compatible image in a chest tomography exam (see definition below) - Presence of one of the following criteria: Need for> 3L of O2 in the catheter / mask or> 25% in the Venturi mask to maintain O2 saturation> 92% B presence of respiratory distress syndrome with PaO2 / FiO2 <300mmHg If intubated, within 48 hours of orotracheal intubation Absence of a history of serious adverse reactions to transfusion, for example, anaphylaxis; - .Participation approval by the research clinician Exclusion Criteria: Already enrolled in another clinical trial evaluating antiviral or immunobiological therapy for the treatment of COVID-19. IgA deficiency Presence of a clinical condition that does not allow infusion of 400 ml of volume at clinical discretion Pregnancy or breastfeeding Receipt of immunoglobulin in the last 30 days Presence of significant risk of death within the next 48 hours at clinical discretion.

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: 1:1:1 into 3 treatment groups: A- standard (control); B- standard and convalescent plasma in a volume of 200ml (150-300ml); C- standard and convalescent plasma in a volume of 400ml (300-600ml)
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Sham Comparator: Group A<br>Participants will receive the standard of care treatment | Biological: convalescent plasma<br>* The study will be interrupted if the efficacy of the convalescent plasma group is proven, so that all severely ill patients as defined in the study can receive the convalescent plasma treatment. The same will occur if there is no difference in primary outcome with the use of convalescent plasma or serious adverse effects.<br>|
| Active Comparator: Group B<br>Participants will receive the standard treatment and convalescent plasma in a volume of 200ml (150-300ml) | Biological: convalescent plasma<br>* The study will be interrupted if the efficacy of the convalescent plasma group is proven, so that all severely ill patients as defined in the study can receive the convalescent plasma treatment. The same will occur if there is no difference in primary outcome with the use of convalescent plasma or serious adverse effects.<br>|
| Active Comparator: Group C<br>Participants will receive the standard treatment and convalescent plasma in a volume of 400ml (300-600ml) | Biological: convalescent plasma<br>* The study will be interrupted if the efficacy of the convalescent plasma group is proven, so that all severely ill patients as defined in the study can receive the convalescent plasma treatment. The same will occur if there is no difference in primary outcome with the use of convalescent plasma or serious adverse effects.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time elapsed until clinical improvement or hospital discharge | clinical improvement is defined as the time from the randomization date until the decline of 2 categories on the ordinal scale of 10 categories or hospital discharge (whichever comes first) | Follow up until 28 days after transfusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| acute adverse events | incidence of acute adverse events possibly or definitively realted to convalescent plasma transfusion | Up to 12 hours after transfusion | 
| Clinical Status | Evaluation according to an ordinal scale of 10 categories | Day 7, Day 14 and Day 28 | 
| Duration of clinical events | Duration of mechanical ventilation, length of hospital stay in survivors up to 28 days and time from the beginning of treatment to death | Up to 28 days | 
| SARS-CoV-2 in nasopharyngeal swab | Detection of SARS-CoV-2 in nasopharyngeal swab | Days 0, 1, 3, 7, 14 and 28 after transfusion and control groups | 
| IgG, IgM and IgA titers for SARS-CoV-2 | Specific IgG, IgM and IgA titers for SARS-CoV-2 | Days 0, 1, 3, 5, 7, 14 and 28 after transfusion and control groups | 
| Neutralizing antibodies | Titers of neutralizing antibodies | 0,1,7 14 and 28 days after transfusion and control groups | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COVID-19, convalescent plasma, efficacy, safety