Efficacy of Convalescent Plasma Therapy in the Early Care of COVID-19 Patients.

Study Overview
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Brief Summary
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COVID-19 (Corona Virus Disease 2019) hospitalized patients evolution is marked by the risk of worsening of the respiratory system during the second week of the disease. To date, treatments are currently being evaluated and none of them have shown to be effective in the care of these patients. The use of convalescent plasma is a passive immunotherapy. It has often been used in respiratory virus epidemic situations (during the 1918 or 2009 influenza pandemic, or during SARS-CoV-1 or MERS-CoV pandemic). Effects reported in literature are in favour of a beneficial impact of transfusion of these plasma without serious adverse effects reported. PlasCoSSA is a randomized, controlled, triple-blinded, parallel clinical trial. This study tests the efficacy of convalescent plasma transfusion therapy in the early care of COVID-19 hospitalized patients outside intensive care units.

Detailed Description
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During SARS-CoV-2 infection, two clinical-biological phases can be observed: an initial viral phase followed by an immunological phase whose onset has been associated with more severe prognosis. Hospitalized patients with comorbidities or clinical risk factors have a higher risk of respiratory functions deterioration and significant risk to need intensive care. Early transfusion of convalescent plasma (2 units of 200-230 mL of apheresis plasma inactivated by amotosalen) would prevent this secondary worsening and reduce the risk to be transferred to intensive care, length of stay and mortality. Considering clinical and biological manifestations of the disease, including coagulation disorders, endothelial alterations, immunological disorders, it seems interesting to compare this convalescent plasma with a SARS-CoV-2 lacking antibodies plasma.

Official Title
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Evaluation Of Efficacy Of COVID-19 Convalescent Plasma Versus Standard Plasma In The Early Care Of COVID-19 Patients Hospitalized Outside Intensive Care Units.

Conditions
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COVID-19

Intervention / Treatment
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* Drug: Transfusion of SARS-CoV-2 Convalescent Plasma.
* Drug: Transfusion of standard Plasma.


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-90 years ; COVID-19 confirmed case ; Cases showing respiratory symptoms, checking at least one of the following criteria: Cough, dyspnea, respiratory rate > 24 breaths/min Oxygen saturation < 95% at rest in ambient air PaO2 < 70mmHg Scanographic pulmonary compatible with COVID in the absence of any other etiology Risk of deterioration, checking at least one of the following comorbidity criteria : Chronic respiratory pathology Diabetes Cancer pathology Cardiovascular disease Chronic kidney failure Congenital or acquired immunodeficiency Cirrhosis at stage B Major sickle cell syndrome BMI > 30 kg/m2 OR one of the biological criteria : D-dimer 1 µg/mL, Lymphocytes < 0.8 G/L, Ferritin > 300 µg/L, Troponin I > 11 pg/mL or Troponin T > 24.8 pg/mL Exclusion Criteria: Patients admitted in intensive care within the first 6 hours of hospital care, Patients after 10 days from the start of symptoms Age < 18 years and > 90 years Long-term oxygen-dependent patients (at home), Decompensated chronic cardiac, respiratory, urological pathology Patient refusing administration of blood products, Allergic reaction to plasma products, IgA deficiency, Contraindication to transfusion Ig transfusion within 30 days, Patient currently participating to another clinical trial, Pregnant women, No affiliated to the social security, Person deprived of liberty by a legal or administrative decision, person under guardianship

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SARS-CoV-2 patients treated with convalescent plasma<br>Subjects will receive an intravenous injection of SARS-CoV-2 Convalescent Plasma. | Drug: Transfusion of SARS-CoV-2 Convalescent Plasma.<br>* 2 Convalescent Plasma units of 200-230mL each, inactivated by amotosalen.<br>|
| Active Comparator: SARS-CoV-2 patients treated with standard plasma<br>Subjects will receive an intravenous injection of standard Plasma. | Drug: Transfusion of standard Plasma.<br>* 2 Standard Plasma units of 200-230mL each, inactivated by amotosalen.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Survival time without needs of a ventilator. | Survival time without needs of ventilator, i.e. the time until oxygen supply (patient previously in ambient air), or an increase by more than 6L/min of O2 for more than 24 hours, or the use of non-invasive ventilation, or intubation, or death. | Day 30 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Morbidity | The percentage of patients i) not hospitalized, without limitation of activities, ii) Not hospitalized, with activity limitation, iii) Hospitalized without oxygen therapy, iv) Hospitalized with oxygen therapy, v) Hospitalized with intensive oxygen therapy or non- invasive ventilation (NIV), vi) Hospitalized and intubated or on extracorporeal membrane oxygenation (ECMO), vii) Dead. | Day 15 | 
| Morbidity | Difference of the SOFA (Sequential Organ Failure Assessment) mean score per patient between the two groups. | Day 30 | 
| Mortality |  | Day 30 | 
| Length of stay |  | Day 30 | 
| Effect on viral pharyngeal specimen clearance | Quantitative SARS-CoV2 PCR carried out on pharyngeal specimen. | At inclusion and Day 7 | 
| Effect on viral blood specimen clearance | Quantitative SARS-CoV2 PCR carried out on blood specimen. | At inclusion and Day 7 | 
| Effect on hemostasis disorders | Effects on biological hemostasis parameters disorders. | At inclusion, Day 1 and every 48 hours | 
| Kinetics of appearance of neutralizing antibodies | Anti-SARS-Cov2 immunoglobulin G/A level and anti-SARS-Cov2 neutralizing antibody levels. | At inclusion, Day 7 | 
| Transfusion endotheliopathy effect | Evolution of biological endotheliopathy parameters | At inclusion, Day 1, Day 7 | 
| Transfusion biological Inflammation effect | Evaluation of biological dosages on inflammation effects | At inclusion, Day 1, Day 7 | 
| Transfusion hemovigilance | Number of transfusion adverse events | 30 days | 
| Decrease in the consumption of antibiotics |  | 30 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SARS-CoV-2, COVID 19, Convalescent plasma