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

Phase 3

Terminated

• Conditions: COVID-19
• Interventions: Drug: Transfusion of SARS-CoV-2 Convalescent Plasma.; Drug: Transfusion of standard Plasma.

• Registration Number: NCT04372979
• Lead Sponsor: Direction Centrale du Service de Santé des Armées

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2020-04-24
• Study First Submitted QC: 2020-04-29
• Study First Posted: 2020-05-04
• Study Start: 2020-09-14
• Primary Completion: 2021-06-01
• Study Completion: 2021-06-01
• Status Verified: 2022-04
• Last Update Submitted: 2022-04-06
• Last Update Posted: 2022-04-14

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 18

Inclusion Criteria

1. Age 18-90 years ;

2. COVID-19 confirmed case ;

3. Cases showing respiratory symptoms, checking at least one of the following criteria:

   1. Cough, dyspnea, respiratory rate > 24 breaths/min
   2. Oxygen saturation < 95% at rest in ambient air
   3. PaO2 < 70mmHg
   4. Scanographic pulmonary compatible with COVID in the absence of any other etiology

4. Risk of deterioration, checking at least one of the following comorbidity criteria :

   1. Chronic respiratory pathology
   2. Diabetes
   3. Cancer pathology
   4. Cardiovascular disease
   5. Chronic kidney failure
   6. Congenital or acquired immunodeficiency
   7. Cirrhosis at stage B
   8. Major sickle cell syndrome
   9. BMI > 30 kg/m2

OR one of the biological criteria :

1. D-dimer 1 µg/mL,
2. Lymphocytes < 0.8 G/L,
3. Ferritin > 300 µg/L,
4. 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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
SARS-CoV-2 patients treated with convalescent plasma	Transfusion of SARS-CoV-2 Convalescent Plasma.	Subjects will receive an intravenous injection of SARS-CoV-2 Convalescent Plasma.
SARS-CoV-2 patients treated with standard plasma	Transfusion of standard Plasma.	Subjects will receive an intravenous injection of standard Plasma.

Primary Outcome Measures

Name	Time	Method
Survival time without needs of a ventilator.	Day 30	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.

Secondary Outcome Measures

Name	Time	Method
Length of stay	Day 30
Effect on viral blood specimen clearance	At inclusion and Day 7	Quantitative SARS-CoV2 PCR carried out on blood specimen.
Morbidity	Day 30	Difference of the SOFA (Sequential Organ Failure Assessment) mean score per patient between the two groups.
Decrease in the consumption of antibiotics	30 days
Mortality	Day 30
Transfusion endotheliopathy effect	At inclusion, Day 1, Day 7	Evolution of biological endotheliopathy parameters
Transfusion hemovigilance	30 days	Number of transfusion adverse events
Effect on viral pharyngeal specimen clearance	At inclusion and Day 7	Quantitative SARS-CoV2 PCR carried out on pharyngeal specimen.
Effect on hemostasis disorders	At inclusion, Day 1 and every 48 hours	Effects on biological hemostasis parameters disorders.
Kinetics of appearance of neutralizing antibodies	At inclusion, Day 7	Anti-SARS-Cov2 immunoglobulin G/A level and anti-SARS-Cov2 neutralizing antibody levels.
Transfusion biological Inflammation effect	At inclusion, Day 1, Day 7	Evaluation of biological dosages on inflammation effects

Trial Locations

Locations (4)

HIA Percy; 🇫🇷 Clamart, France

HIA Laveran; 🇫🇷 Marseille, France

HIA Bégin; 🇫🇷 Saint-Mandé, France

HIA Sainte Anne; 🇫🇷 Toulon, France