Convalescent Plasma Compared to the Best Available Therapy for the Treatment of SARS-CoV-2 Pneumonia

Study Overview
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Brief Summary
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In early December 2019, cases of pneumonia of unknown origin were identified in Wuhan, China. The causative virus was called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The World Health Organization (WHO) has recently declared coronavirus disease 2019 (COVID-19) a public health emergency of international concern. According to the World Health Organization (WHO), the management of COVID-19 has focused primarily on infection prevention, detection and patient monitoring. However, there is no vaccine or specific treatment for SARS-CoV-2 due to the lack of evidence. Treatment options currently include broad-spectrum antiviral drugs but the efficacy and safety of these drugs is still unknown. Convalescent plasma has previously been used to treat various outbreaks of other respiratory infections; however, it has not been shown to be effective in all the diseases studied. Therefore, clinical trials are required to demonstrate its safety and efficacy in patients with VIDOC-19. The present work seeks to determine the mortality from any cause up to 14 days after plasma randomization of patients cured of COVID-19 compared to the Best Available Therapy in subjects with SARS-CoV-2 pneumonia. This is a 2:1 randomized, double-blind, single-center, phase 2, controlled clinical trial (plasma: best available therapy) for the treatment of SARS-CoV-2 pneumonia.

Detailed Description
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Randomized clinical trial comparing convalescent plasma to best available therapy (BAT) for the treatment of severely ill and critically ill patient with COVID-19: Patients will be electronically randomized 2:1 (plasma vs BAT) in a double blind fashion. Patients with SARS-CoV-2 PCR confirmed infection with pulmonary infiltrates and hypoxemia will be screened and invited to participate. Primary outcomes will be early all-cause mortality, and secondary outcomes will include all cause in hospital mortality, length of mechanical ventilation and hospital stay, time to PAO2 >200, progression of pulmonary infiltrates, antibody titers and time to negative PCR detection

Official Title
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Phase II, Randomized, Double-blind, Controlled Clinical Trial Evaluating the Efficacy and Safety of Plasma From Patients Cured of COVID-19 Compared to the Best Available Therapy in Subjects With SARS-CoV-2 Pneumonia

Conditions
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Coronavirus Infection

Intervention / Treatment
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* Biological: Plasma
* Other: Best Available Therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men or women ≥18 years. If you are a woman of childbearing age, you must agree to practice abstinence or to use an effective method of contraception during the study period. Vascular access suitable for administration of hemocomponents. SARS-CoV-2 positive RT-PCR. Negative pregnancy test in case of a woman of reproductive age Signing of evidentiary document of informed consent. Hospital admission for SARS-CoV-2 pneumonia with supplemental oxygen requirements. Subjects who access the storage of biological samples for future examination. Exclusion Criteria: Respiratory rate >30 RPM, SO2 <93%, PaO2/FiO2 <200 despite intervention with oxygen therapy after 60 minutes of hospitalization. New alteration of the state of alert that does not revert after interventions 60 minutes after admission to hospital. PAM ≤ 65mmHg despite initial resuscitation on arrival at the centre. Pregnant or breastfeeding patients. Patients that the investigators consider inappropriate to participate in the clinical trial Contraindication to transfusion or history of previous severe reaction to blood products. Have received any blood products in the last 120 days.

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: RCT double blind comparative study
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Plasma<br>Convalescent plasma from cured COVID-19 patients y Supportive management depending on individual needs | Biological: Plasma<br>* The plasma unit will be fractionated in 200 mL aliquots for storage at -80°C until use. After thawing, it shall be administered in a single 200 mL dose to subjects who are randomized to that arm.<br>|
| Experimental: Best Available Therapy<br>Will receive supportive management depending on individual needs including. | Other: Best Available Therapy<br>* It shall include, but not be limited to, oxygen therapy by means of a nasal cannula; high-flow nasal cannula; invasive or non-invasive mechanical ventilation; intravenous hydration; antibiotic therapy; thrombus prophylaxis; pain and fever management.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Early all-cause mortality | any cause mortality during the first 14 days of treatment | 14 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time in days for SARS-CoV-2 RT-PCR negatives | (48-hour sampling interval from day 3 of hospitalization to two consecutive negatives). | 90 days | 
| The serum anti-SARS-CoV-2 antibody titres | In subjects of both arms at day 0, 3, 7, 14 and 90. | 90 days | 
| Detection of serum antibodies | Comparison of anti-SARS-CoV-2 antibody titers | days 0, 3, 7, 14 and 90. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COVID-19, Plasma from patients cured, SARS-CoV-2 pneumonia