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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
21
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
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)
Centre Hospitalier William Morey
Chalon-sur-Saône, France
Hôpital Edouard Herriot
Lyon, France
Hôpital Croix Rousse
Lyon, France
Clinique de la Sauvegarde
Lyon, France
Groupement Hospitalier Porte de Valence - Montélimar
Montélimar, France
Hôpital Pitié Salpétrière - Assistante Publique des Hôpitaux de Paris
Paris, France
Centre Hospitalier Lyon Sud
Pierre-Bénite, France
Medipole Villeurbanne
Villeurbanne, France
Use of intubation and invasive ventilation (IV) between Day 0 (Inclusion Visit) and Day 10
Proportion of patients requiring intubation between Day 0 and Day 10. Intubation use will be measured in both arms at Day 10.
Time frame: At day 10
Assess the adverse events according to CTCAE v5.0
Adverse events according to CTCAE v5.0 measured throughout the study, in both groups, including tolerance to TPEs in the experimental group over the course of the study sessions.
Time frame: Throughout the study : Day 1 to Day 10 and to the end of the study (Day 60 +/- 2 days)
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)
PaO2/FIO2 (mmHg) at day 4 after inclusion. This parameter will be compared between day 4 and day 0.The change corresponds to an increase of PaO2/FIO2 ratio equal or superior than 20%. The proportion of patients with a PaO2/FiO2 change at Day 4 will be compared between both arms.
Time frame: At Day 4
Percentage of patients weaned from non invasive ventilation
Percentage of patients weaned from high flow oxygen. This parameter is compared between both arms (experimental and control arms).
Time frame: At day 10
O2 weaning capacity and duration of O2 dependence
This parameter is compared between both arms (experimental and control arms).
Time frame: At day 60
Survival at day 10
Percentage of patients alive at day 10 after inclusion. This parameter is compared between both arms.
Time frame: At day 10
Survival at 2 months
Percentage of patients alive at 2 months after inclusion. This parameter is compared between both arms.
Time frame: At day 60 (+/- 2 days)
Percentage of patients without any increase in inflammatory parameters (analysis of C-reactive protein, Fibrinogen,D-Dimers, procalcitonin, Ferritin)
Percentage of patients without any increase in inflammatory parameters (analysis of C-reactive protein, Fibrinogen,D-Dimers, procalcitonin, Ferritin ) at day 4 compared to values at day 0. This parameter is compared between both arms.
Time frame: At day 4
Variation in cytokine and chemokine levels in the cytokine storm
Percentage of patients without any increase in cytokine or chemokine levels. Leucocyte and platelet cytokine or chemokine levels in ng/ml are assessed in both arms. Analysis of the entire panel of cytokines or chemokines defines an improvement or not. Comparison between both arms.
Time frame: At day 4
Percentage of patients with improved phenotype (decreased phenotype of exhausted cells) and improved function (improved proliferation)
Lymphocyte and NK (Natural Killer) labeling and analysis by flow cytometry at day 0 and day 7. Analysis of lymphocyte proliferation (after stimulation) at day 0 and day 7. Analysis of percentage of patients with improved phenotype (decreased phenotype of exhausted cells) and improved function (improved proliferation) ; this parameter is compared between both arms.
Time frame: At day 7
Percentage of patients with decreased platelet activation
Phenotype of platelets and flow cytometry analysis performed before and after TPE or usual treatment. Percentage of patients with decreased platelet activation at day 4 ; this parameter is compared between both arms.
Time frame: At Day 4
Percentage of patients with decreased platelet activation
Phenotype of platelets and flow cytometry analysis performed before and after TPE or usual treatment. Percentage of patients with decreased platelet activation at day 7 ; this parameter is compared between both arms.
Time frame: At Day 7
Change in anti-IFN auto-antibodies type I (α and ω) level
Change in anti-IFN auto-antibodies type I (α and ω) level at day 0 and day 4.
Time frame: Day 0 and Day 4
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