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.
Other: Therapeutic plasma exchange : 3 sessions in 3 consecutive days (day 1 to day 3)
Therapeutic plasma exchange (TPE) ; 3 sessions in 3 consecutive days (Day 1 to Day 3) in intensive care unit in addition to usual treatments.
Plasma removed is replaced by thawed fresh frozen plasma. Plasma blood volume exchanged : 1.2 Apheresis type: centrifugation
Other: Usual treatments in intensive care unit according to the current state of knowledge
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)
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 100 and 200 mmHg requiring non invasive ventilation or
high flow oxygen
- 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
- Impossibility to put a central venous catheter according to investigator's judgement
- Severe hemodynamic instability with mean arterial pressure < 65 mmHg (whatever the
noradrenaline dosage used)
- 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)
Centre Hospitalier William Morey
Chalon-sur-Saône, France
Hôpital Edouard Herriot
Lyon, France
Hôpital Edouard Herriot
Lyon, France
Hôpital Croix Rousse
Lyon, France
Clinique de la Sauvegarde
Lyon, France
Groupement Hospitalier Porte de Valence - Montélimar
Montelimar, France
Hôpital Pitié Salpétrière - Assistante Publique des Hôpitaux de Paris
Paris, France
Centre Hospitalier Lyon Sud
Pierre-Bénite, France
Medipole Villeurbanne
Villeurbanne, France
Olivier HEQUET, MD, PhD
06 31 91 88 87 - +33
olivier.hequet@efs.sante.fr
Fabrice COGNASSE, PhD
06 83 97 58 83 - +33
fabrice.cognasse@efs.sante.fr
Olivier HEQUET, MD, PhD, Principal Investigator
Hospices Civils de Lyon - Etablissement Français du Sang