Intensive Care UnitsCovidEPNCT04751643
Therapeutic Plasma Exchange to Alleviate Hyperinflammatory Condition During Severe Covid-19 Infections
A study testing Therapeutic plasma exchange : 3 sessions in 3 consecutive days (day 1 to day 3) and Usual treatments in intensive care unit according to the current state of knowledge in people with Intensive Care Units and ARDS, Human, run by Hospices Civils de Lyon at 8 sites in France.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Intensive Care Units, ARDS, Human, Covid19
- What is being tested?
- Therapeutic plasma exchange : 3 sessions in 3 consecutive days (day 1 to day 3) and Usual treatments in intensive care unit according to the current state of knowledge
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 21 participants
- Where
- 8 sitesFrance
- Study dates
- 19 Apr 2021to 19 Dec 2022
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
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- 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 locations and contacts
8 sites in 1 country.
8 sites in 1 country
France8 sites
Centre Hospitalier William Morey
Chalon-sur-Saône, 71100
Hôpital Edouard Herriot
Lyon, 69003
Hôpital Croix Rousse
Lyon, 69004
Clinique de la Sauvegarde
Lyon, 69337
Groupement Hospitalier Porte de Valence - Montélimar
Montélimar, 26216
Hôpital Pitié Salpétrière - Assistante Publique des Hôpitaux de Paris
Paris, 75013
Centre Hospitalier Lyon Sud
Pierre-Bénite, 69310
Medipole Villeurbanne
Villeurbanne, 69100
About this study
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
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.
- Conditions
- Intensive Care Units, ARDS, Human, Covid19
- Being tested
- 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
- Keywords
- Covid19, Therapeutic plasma exchange, Cytokine storm, Hyperinflammatory condition, Anti-IFN antibodies
- Medical subject headings
- Respiratory Distress Syndrome, COVID-19, Cytokine Release Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
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
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)
| Study group | Role | What they receive |
|---|---|---|
| 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) Receives: 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) Receives: Other: Usual treatments in intensive care unit according to the current state of knowledge |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: At day 10
Secondary outcomes (12)
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.
Measured: 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.
Measured: 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).
Measured: At day 10
O2 weaning capacity and duration of O2 dependence
This parameter is compared between both arms (experimental and control arms).
Measured: At day 60
Survival at day 10
Percentage of patients alive at day 10 after inclusion. This parameter is compared between both arms.
Measured: At day 10
Survival at 2 months
Percentage of patients alive at 2 months after inclusion. This parameter is compared between both arms.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Day 0 and Day 4
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Feb 2021
- Study start19 Apr 2021
- Primary completion19 Dec 2022
- Study completion19 Dec 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Intensive Care UnitsStudies of the same condition, open and under way.
- More trials run by Hospices Civils de LyonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 21 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hospices Civils de Lyon
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Olivier HEQUET, MD, PhD, Principal investigator, Hospices Civils de Lyon - Etablissement Français du Sang
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04751643
- Sponsor's protocol ID
- 69HCL20_0518
- Other IDs
- 2020-A03039-30
- Acronym
- CovidEP
- Status last verified
- Sep 2025
- First submitted
- 5 Feb 2021
- Last updated
- 3 Sep 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 39896810
Study at a glance
From the registry record, last updated by the sponsor on 3 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04751643
- Acronym / sponsor ID
- CovidEP / 69HCL20_0518
- Conditions
- Intensive Care Units, ARDS, Human, Covid19
- Keywords
- Covid19, Therapeutic plasma exchange, Cytokine storm, Hyperinflammatory condition, Anti-IFN antibodies
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 21 participants (actual)
- Lead sponsor
- Hospices Civils de LyonUniversity, hospital or other
- Study start
- 19 Apr 2021 (actual)
- Primary completion
- 19 Dec 2022 (actual)
- Study completion
- 19 Dec 2022 (actual)
- First posted
- 12 Feb 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| TPE + usual treatments in intensive care unit according to the current state of knowledge. | Experimental | 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 knowledgeTPE + 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) |
| Usual treatments in intensive care unit according to the current state of knowledge | Active comparator | Other: Usual treatments in intensive care unit according to the current state of knowledgeUsual 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) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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.
Key exclusion criteria (10 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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 | 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 knowledgeUsual 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 | 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 |
Primary outcome
Use of intubation and invasive ventilation (IV) between Day 0 (Inclusion Visit) and Day 10
Time frame: At day 10
Proportion of patients requiring intubation between Day 0 and Day 10. Intubation use will be measured in both arms at Day 10.
12 secondary outcomes
Assess the adverse events according to CTCAE v5.0
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)
Time frame: At Day 4
Percentage of patients weaned from non invasive ventilation
Time frame: At day 10
O2 weaning capacity and duration of O2 dependence
Time frame: At day 60
Survival at day 10
Time frame: At day 10
Survival at 2 months
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)
Time frame: At day 4
Variation in cytokine and chemokine levels in the cytokine storm
Time frame: At day 4
Percentage of patients with improved phenotype (decreased phenotype of exhausted cells) and improved function (improved proliferation)
Time frame: At day 7
Percentage of patients with decreased platelet activation
Time frame: At Day 4
Percentage of patients with decreased platelet activation
Time frame: At Day 7
Change in anti-IFN auto-antibodies type I (α and ω) level
Time frame: Day 0 and Day 4
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Sep 2025.
- Results publication: PubMed 39896810Guironnet-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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Olivier HEQUET, MD, PhD principal investigator
Hospices Civils de Lyon - Etablissement Français du Sang
8 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Therapeutic plasma exchange : 3 sessions in 3 consecutive days (day 1 to day 3) and Usual treatments in intensive care unit according to the current state of knowledge in people with Intensive Care Units and ARDS, Human, run by Hospices Civils de Lyon at 8 sites in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Use of intubation and invasive ventilation (IV) between Day 0 (Inclusion Visit) and Day 10 (time frame: At day 10). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04751643, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Sep 2025; AzTrials last refreshed its copy on 6 Nov 2026.