Clinical trial NCT04751643: Therapeutic Plasma Exchange to Alleviate Hyperinflammatory Condition During Severe Covid-19 Infections
Official title: Assessment of Therapeutic Plasma Exchange to Improve Respiratory Function by Alleviating Cytokine Storm During Severe Covid-19 Infections Randomised Open-label Controlled Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Intensive Care Units
ARDS, Human
Covid19
Keywords: Covid19
Therapeutic plasma exchange
Cytokine storm
Hyperinflammatory condition
Anti-IFN antibodies
Lead sponsor: Hospices Civils de Lyon
Sponsor class: OTHER
First posted: 2021-02-12
Enrollment: 132
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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)

Primary outcomes:
measure: Use of intubation and invasive ventilation (IV) between Day 0 (Inclusion Visit) and Day 10
timeFrame: At day 10
Secondary outcomes:
measure: Assess the adverse events according to CTCAE v5.0
timeFrame: Throughout the study : Day 1 to Day 10 and to the end of the study (Day 60 +/- 2 days)
measure: PaO2/FIO2 (Partial Pressure of Oxygen/Fraction of Inspired Oxygen) (mmHg) at day 4 after inclusion (PaO2/FiO2 is a usual parameter for assessing evolution of ARDS)
timeFrame: At Day 4
measure: Percentage of patients weaned from non invasive ventilation
timeFrame: At day 10
measure: Survival at day 10
timeFrame: At day 10
measure: Survival at 2 months
timeFrame: At day 60 (+/- 2 days)
measure: Percentage of patients without any increase in inflammatory parameters (analysis of C-reactive protein, Fibrinogen,D-Dimers, procalcitonin, Ferritin)
timeFrame: At day 4
measure: Variation in cytokine and chemokine levels in the cytokine storm
timeFrame: At day 4
measure: Percentage of patients with improved phenotype (decreased phenotype of exhausted cells) and improved function (improved proliferation)
timeFrame: At day 7
measure: Percentage of patients with decreased platelet activation
timeFrame: At Day 4
measure: Percentage of patients with decreased platelet activation
timeFrame: At Day 7
measure: Change in anti-IFN auto-antibodies type I (α and ω) level
timeFrame: Day 0 and Day 4
Other outcomes:
Locations:
city: Chalon-sur-Saône
country: France
facility: Centre Hospitalier William Morey
city: Lyon
country: France
facility: Hôpital Edouard Herriot
city: Lyon
country: France
facility: Hôpital Edouard Herriot
city: Lyon
country: France
facility: Hôpital Croix Rousse
city: Lyon
country: France
facility: Clinique de la Sauvegarde
city: Montelimar
country: France
facility: Groupement Hospitalier Porte de Valence - Montélimar
city: Paris
country: France
facility: Hôpital Pitié Salpétrière - Assistante Publique des Hôpitaux de Paris
city: Pierre-Bénite
country: France
facility: Centre Hospitalier Lyon Sud
city: Villeurbanne
country: France
facility: Medipole Villeurbanne
Study officials:
affiliation: Hospices Civils de Lyon - Etablissement Français du Sang
name: Olivier HEQUET, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: