Therapeutic Plasma Exchange to Alleviate Hyperinflammatory Condition During Severe Covid-19 Infections (CovidEP)

Civil Hospices of Lyon

Status: Completed

Conditions: Intensive Care Units; Covid19; ARDS, Human

Treatments: Other: Therapeutic plasma exchange : 3 sessions in 3 consecutive days (day 1 to day 3); Other: Usual treatments in intensive care unit according to the current state of knowledge

Study type: Interventional

Funder types: Other

Identifiers

NCT04751643

2020-A03039-30 (Other Identifier)

69HCL20_0518

Details and patient eligibility

About

Severe Covid-19 (Coronavirus Disease 2019) infections generate major but inappropriate production of cytokines and, in some cases, generate anti-IFN (Interferon) auto-antibodies, inducing acute respiratory distress syndrom (ARDS). Therapeutic plasma exchange (TPE) have been reported to be efficient for improving the hyperinflammatory condition state and the respiratory function, which has been described in case reports or small series.

The study aims to remove cytokines during cytokine storm and anti-IFN auto-antibodies (when present) to prevent developpement of an inappropriate immune response and to improve the clinical response to reanimation treatment, in particular the respiratory parameters leading to a rapid improvement of clinical status. To that aim, the study investigates to compare a treatment using TPE plus usual treatments in intensive care unit (experimental arm) versus usual treatments in intensive care unit (routine arm) in a randomised trial.

Enrollment: 21 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Age ≥ 18 years
• Hospitalized for COVID-19 confirmed by Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR) or scanner
• Patients with PaO2/FiO2 between 75 and 175 mmHg requiring non invasive ventilation or high flow oxygen
• peripheral venous state allowing PE to be performed, according to the investigator's judgement, or possibility of placing a Sheldon-type veinous central line
• At least two biological results suggesting a cytokine storm or hyperinflammatory condition state among : C-reactive protéine (CRP)>50mg/L, Procalcitonin (PCT)>1µg/L, Fibrinogen>5g/L, D-dimer >1000ng/mL, Ferritin > 800ng/mL during the last 72 hours.
• Treatment with corticosteroids (at least 2 intakes of dexamethasone 6 mg or equivalent with another form of corticosteroids)
• Patient affiliated to a social security or similar scheme
• Information and written consent from the patient or if not possible from a confident person

Exclusion criteria

• Ventilated intubated patients
• Patient with advanced cancer and without curative possibility
• Bacterial or viral (HIV) infection explaining the worsening (the main reason)
• Body Mass Index > 40
• Severe hemodynamic instability with mean arterial pressure < 65 mmHg (whatever the noradrenaline dosage used)
• Known Immunoglobulin A (IgA) deficiency with anti-IgA antibodies
• Inclusion in another study that could interact with the Covidep study (investigator's judgement)
• Patient under legal protection measure
• Pregnant or breastfeeding women
• In case of allergy to amotosalen (psoralens) or AI-FFP (Amotosalen Inactivated Fresh Frozen Plasma) , use Se-FFP (Secured Fresh Frozen Plasma)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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21 participants in 2 patient groups

TPE + usual treatments in intensive care unit according to the current state of knowledge.

Experimental group

Description:

TPE + usual treatments in intensive care unit according to the current state of knowledge : 3 TPE sessions i.e. one per day during 3 consecutive days on day 1-3 (day 0 = inclusion Visit date)) + usual treatments in intensive care unit. Usual treatments of patients in intensive care unit with hyperinflammatory condition due to Covid-19 infection consist in supporting respiratory function, oxygen supplementation, non invasive ventilation, invasive ventilation, antibiotic, vasopressive support and corticosteroids (in absence of bacterial secondary infection)

Treatment:

Other: Usual treatments in intensive care unit according to the current state of knowledge

Other: Therapeutic plasma exchange : 3 sessions in 3 consecutive days (day 1 to day 3)

Usual treatments in intensive care unit according to the current state of knowledge

Active Comparator group

Description:

Usual treatments of patients in intensive care unit with hyperinflammatory condition due to Covid-19 infection consist in supporting respiratory function, oxygen supplementation, non invasive ventilation, invasive ventilation, antibiotic, vasopressive support and corticosteroids (in absence of bacterial secondary infection)

Treatment:

Other: Usual treatments in intensive care unit according to the current state of knowledge