COVID-19
Conditions
Keywords
SARS-CoV-2, COVID 19, Convalescent plasma
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.
Interventions
DRUGTransfusion of SARS-CoV-2 Convalescent Plasma.
2 Convalescent Plasma units of 200-230mL each, inactivated by amotosalen.
DRUGTransfusion of standard Plasma.
2 Standard Plasma units of 200-230mL each, inactivated by amotosalen.
Sponsors
University Hospital, Grenoble
Direction Centrale du Service de Santé des Armées
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 90 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Mortality | Day 30 | — |
| Length of stay | Day 30 | — |
| Effect on viral pharyngeal specimen clearance | At inclusion and Day 7 | Quantitative SARS-CoV2 PCR carried out on pharyngeal specimen. |
| Effect on viral blood specimen clearance | At inclusion and Day 7 | Quantitative SARS-CoV2 PCR carried out on blood specimen. |
| Effect on hemostasis disorders | At inclusion, Day 1 and every 48 hours | Effects on biological hemostasis parameters disorders. |
| Morbidity | Day 15 | 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. |
| Transfusion endotheliopathy effect | At inclusion, Day 1, Day 7 | Evolution of biological endotheliopathy parameters |
| Transfusion biological Inflammation effect | At inclusion, Day 1, Day 7 | Evaluation of biological dosages on inflammation effects |
| Transfusion hemovigilance | 30 days | Number of transfusion adverse events |
| Decrease in the consumption of antibiotics | 30 days | — |
| Kinetics of appearance of neutralizing antibodies | At inclusion, Day 7 | Anti-SARS-Cov2 immunoglobulin G/A level and anti-SARS-Cov2 neutralizing antibody levels. |
Countries
France
Outcome results
None listed