NCT04751643

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
21

participants targeted

Target at below P25 for not_applicable

Timeline
Completed

Started Apr 2021

Geographic Reach
1 country

8 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

February 5, 2021

Completed
7 days until next milestone

First Posted

Study publicly available on registry

February 12, 2021

Completed
2 months until next milestone

Study Start

First participant enrolled

April 19, 2021

Completed
1.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 19, 2022

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 19, 2022

Completed
Last Updated

September 3, 2025

Status Verified

September 1, 2025

Enrollment Period

1.7 years

First QC Date

February 5, 2021

Last Update Submit

September 2, 2025

Conditions

Intensive Care UnitsARDS, HumanCovid19

Keywords

Covid19Therapeutic plasma exchangeCytokine stormHyperinflammatory conditionAnti-IFN antibodies

Outcome Measures

Primary Outcomes (1)

  • 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.

    At day 10

Secondary Outcomes (12)

  • Assess the adverse events according to CTCAE v5.0

    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)

    At Day 4

  • Percentage of patients weaned from non invasive ventilation

    At day 10

  • O2 weaning capacity and duration of O2 dependence

    At day 60

  • Survival at day 10

    At day 10

  • +7 more secondary outcomes

Study Arms (2)

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

EXPERIMENTAL

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)

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

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

ACTIVE COMPARATOR

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)

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

Interventions

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

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

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

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)

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

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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
  • 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)

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (8)

Centre Hospitalier William Morey

Chalon-sur-Saône, 71100, France

Location

Hôpital Edouard Herriot

Lyon, 69003, France

Location

Hôpital Croix Rousse

Lyon, 69004, France

Location

Clinique de la Sauvegarde

Lyon, 69337, France

Location

Groupement Hospitalier Porte de Valence - Montélimar

Montélimar, 26216, France

Location

Hôpital Pitié Salpétrière - Assistante Publique des Hôpitaux de Paris

Paris, 75013, France

Location

Centre Hospitalier Lyon Sud

Pierre-Bénite, 69310, France

Location

Medipole Villeurbanne

Villeurbanne, 69100, France

Location

Related Publications (1)

  • Guironnet-Paquet A, Hamzeh-Cognasse H, Berard F, Cognasse F, Richard JC, Yonis H, Mezidi M, Desebbe O, Delannoy B, Demeret S, Marois C, Saheb S, Le QV, Schoeffler M, Pugliesi PS, Debord S, Bastard P, Cobat A, Casanova JL, Pescarmona R, Viel S, Nicolas JF, Nosbaum A, Vocanson M, Hequet O. Therapeutic plasma exchange accelerates immune cell recovery in severe COVID-19. Front Immunol. 2025 Jan 17;15:1492672. doi: 10.3389/fimmu.2024.1492672. eCollection 2024.

    PMID: 39896810BACKGROUND

MeSH Terms

Conditions

Respiratory Distress SyndromeCOVID-19Cytokine Release Syndrome

Condition Hierarchy (Ancestors)

Lung DiseasesRespiratory Tract DiseasesRespiration DisordersPneumonia, ViralPneumoniaRespiratory Tract InfectionsInfectionsVirus DiseasesCoronavirus InfectionsCoronaviridae InfectionsNidovirales InfectionsRNA Virus InfectionsSystemic Inflammatory Response SyndromeInflammationPathologic ProcessesPathological Conditions, Signs and SymptomsShock

Study Officials

  • Olivier HEQUET, MD, PhD

    Hospices Civils de Lyon - Etablissement Français du Sang

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

February 5, 2021

First Posted

February 12, 2021

Study Start

April 19, 2021

Primary Completion

December 19, 2022

Study Completion

December 19, 2022

Last Updated

September 3, 2025

Record last verified: 2025-09

Data Sharing

IPD Sharing
Will not share

Locations

FR(8)