Convalescent Plasma Therapy for Hospitalized Patients With COVID-19

Study Overview
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Brief Summary
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Plasma from donors who have recovered from coronavirus disease 2019 (COVID-19) contain antibodies to SARS-CoV-2 and may be a potential therapy for hospitalized patients with COVID-19. The efficacy of high-titer convalescent plasma for COVID-19, however, still unclear. The present study aims to evaluate the efficacy and safety of using convalescent plasma for treating hospitalized patients with COVID-19.

Detailed Description
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This is an open-label, randomized controlled trial aimed to evaluate the efficacy and safety of using convalescent plasma for treating hospitalized patients with COVID-19. Participants must be adult hospitalized patients with a confirmed diagnosis of COVID-19 and time Between symptom onset and inclusion ≤ 7 days. Two hundred participants will be randomized in a 1:1 ratio to receive either 200-400 mL of high-titer COVID-19 convalescent plasma or standard care. The primary endpoint is the proportion of patients with clinical improvement at day 14 following randomization, defined by an increase of two points in the 7-point ordinal scale based on that recommended by the World Health Organization. Safety will be daily assessed by monitoring the occurrence of adverse effects and reactions to convalescent plasma transfusion. Study visits will occur on Day 1, Day 3, Day 7, and Day 14 or until hospital discharge, whichever comes first.

Official Title
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Validation Protocol for The Clinical Use of Convalescent Plasma for Hospitalized Patients With COVID-19. A Prospective Study at a Hospital in Southern Brazil.

Conditions
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COVID-19, Convalescent Plasma, SARS-CoV-2, Pneumonia, Coronavirus Infections, Respiratory Tract Diseases

Intervention / Treatment
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* Biological: Convalescent plasma
* Drug: Standard of care


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Hospitalized patients aged ≥18 years. Confirmed diagnosis of COVID-19 by RT-PCR or antigen test in respiratory samples. Time between symptom onset and inclusion ≤ 7 days. Enrolled within 5 days of hospitalization. Sign the consent form. Exclusion Criteria: Contraindication to transfusion due to inability to tolerate additional fluid, such as due to decompensated congestive heart failure. History of previous severe allergic reactions to transfused blood products. Limiting comorbidity for administering the therapies provided for in this protocol in the opinion of the investigator. Not currently enrolled another interventional clinical trial of COVID-19 treatment. Critically ill patient with COVID-19 being treated in intensive care.

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: This is an open-label, randomized study design (1: 1), controlled trial, in hospitalized patients with COVID-19.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Convalescent Plasma<br>The investigational product is anti-SARS-CoV-2 convalescent plasma obtained from former patients identified as having recovered from COVID-19 and obtained by Centro de Hematologia e Hemoterapia do Paraná - Hemepar following national blood donation guidelines and Brazilian Health Regulatory Agency (ANVISA) criteria. Potential donors will be screened using an anti-SARS-CoV-2 serologic assay and antibody levels will be determined. Participants will receive the standard of care treatment and a single unit of convalescent plasma (volume=200 mL or 400 mL). | Biological: Convalescent plasma<br>* The intervention group will receive 200 or 400 mL of high-titer COVID-19 convalescent plasma, ABO compatible with the patient, within 24 hours of randomization.<br>|
| Active Comparator: Standard of care<br>Standard of care treatment according to the institutional protocol. | Drug: Standard of care<br>* The active comparator group will receive oxygen supplementation, corticoids, antiretrovirals, and/or monoclonal antibodies according to the institutional protocol.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical status on a 7-point ordinal scale | Patients' clinical status over time assessed by a 7-point ordinal scale from World Health Organization (WHO). Lower scores are seen with better clinical outcomes. The scale categories are as follows: (1), not hospitalized with resumption of normal activities; (2), not hospitalized, but unable to resume normal activities; (3), hospitalized, not requiring supplemental oxygen; (4), hospitalized, requiring supplemental oxygen; (5), hospitalized, requiring high-flow oxygen therapy or noninvasive mechanical ventilation; (6), hospitalized, requiring ECMO (extracorporeal membrane oxygenation), IMV (intermittent mandatory ventilation), or both; (7), death. Proportion of patients with clinical improvement, defined by an increase of two points in the ordinal scale of seven WHO categories. | From randomization to end of study at Day 14 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of participants at each clinical status on a 7-point ordinal scale | Measure of patients' clinical status using an ordinal scale for clinical improvement created by World Health Organization (WHO) and based on 7-point scale categories. Lower scores in this scale are seen with better clinical outcomes. The scale categories are as follows: (1), not hospitalized with resumption of normal activities; (2), not hospitalized, but unable to resume normal activities; (3), hospitalized, not requiring supplemental oxygen; (4), hospitalized, requiring supplemental oxygen; (5), hospitalized, requiring high-flow oxygen therapy or noninvasive mechanical ventilation; (6), hospitalized, requiring ECMO, IMV, or both; (7), death. | Day 1, Day 3, Day 7, and Day 14 after randomization | 
| Oxygen saturation |  | Day 1, Day 3, Day 7, and Day 14 after randomization | 
| Prevalence of oxygen-intake methods | Percentage of participants using oxygen by mask or nasal prongs, oxygen by non-invasive ventilation or high flow, intubation & mechanical ventilation and ECMO. | Day 1, Day 3, Day 7, and Day 14 after randomization | 
| Respiratory rate |  | Day 1, Day 3, Day 7, and Day 14 after randomization | 
| The PaO2 / FiO2 ratio (for patients on mechanical mechanisms) |  | Day 1, Day 3, Day 7, and Day 14 after randomization | 
| Number and /or extension of affected lung areas on chest computed tomography |  | Day 1, Day 3, Day 7, and Day 14 after randomization | 
| Length of hospital stay |  | Day 1, Day 3, Day 7, and Day 14 after randomization | 
| Length of stay in intensive care |  | Day 1, Day 3, Day 7, and Day 14 after randomization | 
| Time until independence from oxygen therapy in days |  | Day 1, Day 3, Day 7, and Day 14 after randomization | 
| Ventilator free days |  | Day 1, Day 3, Day 7, and Day 14 after randomization | 
| In patients who needed mechanical ventilation, time to initiate mechanical ventilation (calculated in days, from entry into the protocol until orotracheal intubation) |  | Day 1, Day 3, Day 7, and Day 14 after randomization | 
| Rate of transfusion reactions to convalescent plasma infusion |  | Daily, until Day 14 after randomization | 
| Percentage of participants who develop serious adverse events and adverse events considered as definitely or probably associated with plasma transfusion | Adverse events (worsening anemia, urticaria, skin rash, transfusion-associated circulatory overload, and others) assessed during hospitalization. | Daily, until Day 14 after randomization |