Transfusion of Convalescent Plasma for the Early Treatment of Patients With COVID-19

Study Overview
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Brief Summary
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No specific therapeutic agents or vaccines for COVID-19 are available. Several therapies, are under investigation, but the antiviral efficacy of these drugs is not yet known. The use of convalescent plasma was recommended as an empirical treatment during outbreaks of Ebola virus in 2014, and a protocol for treatment of Middle East respiratory syndrome coronavirus with convalescent plasma was established in 2015. Accordingly, we hypothesized that use of convalescent plasma transfusion could be beneficial in patients infected with SARS-CoV-2. This is a multicenter prospective randomized clinical trial to evaluate safety and efficacy of early use of convalescent plasma in patients with SARS-CoV2 pneumonia. Primary endpoint will be the efficacy, evaluated as the need of invasive mechanical ventilation defined by PaO2/FiO2 ratio <150. Secondary endpoints will be: mortality rates, time to invasive mechanical ventilation, time to virological cure, length of hospital stay, toxicity. Patients with SARS-CoV2 pneumonia not requiring mechanical ventilation (both non invasive and invasive) will be randomized 1:1 to receive or not convalescent plasma. Patients in the plasma group will receive 200 ml of convalescent plasma, continuing already administered standard therapy, while patients in the control group will continue to receive the standard therapy. A rescue therapy will be allowed in case of clinical worsening. Patients will be followed-up until 30 days from randomization.

Detailed Description
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This is a multicenter prospective randomized open-label clinical trials. Patients with pneumonia due to SARS-CoV-2 will be included and randomized to receive or not convalescent plasma. Convalescent plasma will be collected by cured patients with previous diagnosis of COVID-19. More specifically, inclusion and exclusion criteria for donors will be the following. Inclusion criteria for donors: age > 18 and <60 years confirmed diagnosis of COVID-19: PCR on nasopharynx swab or positive IgG presence of 2 negative nasopharynx swabs for patients with previous positive swab and presence of 1 negative nasopharynx swab for patients with positive IgG Exclusion criteria for donors: age < 18 ys or >60 ys other conditions that controindicate blood donation Collected plasma will undergo all procedures for blood preparation. Plasma will be tested with enzyme-linked immunosorbent assay (ELISA) and neutralizing antibody titers. Patients eligible for the study will be selected among hospitalized patients with SARS-CoV2 pneumonia. More specifically, the following criteria will used for inclusion in the study. Inclusion criteria for recipients: age >18 ys confirmed diagnosis of SARS-CoV2 pneumonia PaO2/FiO2 200-350 Exclusion criteria for recipients: PaO2/FiO2 <200 need of non invasive or invasive mechanical ventilation Patients will be randomized 1:1 to receive or not convalescent plasma. All patients will be followed-up for 30 days after randomization. Primary endpoint will be the need of mechanical ventilation, defined as PaO2/FiO2 <150.

Official Title
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Transfusion of Convalescent Plasma for the Early Treatment of pneumonIa Due to SARSCoV2: a Multicenter Open Label Randomized Control Trial

Conditions
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COVID, SARS-CoV 2

Intervention / Treatment
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* Biological: CONVALESCENT PLASMA


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Any gender Age > 18 years on day of signing informed consent Informed written consent for participation in the study Virological diagnosis of SARS-CoV-2 infection (real-time PCR) Hospitalized due to clinical instrumental diagnosis of pneumonia PaO2/FiO2 ratio 200-350 Exclusion Criteria: mechanical ventilation (both invasive and non-invasive) PaO2/FiO2<200 known hypersensitivity to immunoglobulin or blood components

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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention<br>Patients in the intervention group will receive 200 cc of convalescent plasma | Biological: CONVALESCENT PLASMA<br>* Convalescent plasma will be collected by healthy donors, cured by COVID-19 and, after standard preparation and dosage of neutralizing antibodies, will be administered to patients with SARS-CoV2 pneumonia<br>|
| No Intervention: Control<br>Patients will continue to receive standard therapy | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Need of invasive mechanical ventilation | Need of invasive mechanical ventilation defined as PaO2/FiO2 <150 | 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mortality rates | Thirty-day mortality rates | 30 days | 
| Time to invasive mechanical ventilation | Days from randomization to invasive mechanical ventilation | 30 days | 
| Time to virologic cure | Days from randomization to virologic cure defined as 2 consecutive negative nasopharynx swabs | 30 days | 
| Length of hospital stay | Days from randomization to discharge or death | 30 days | 
| Adverse events | Occurrence of adverse events | 30 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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covid-19, SARS-CoV2, pneumonia, convalescent plasma