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Therapeutic Plasma Exchange to Alleviate Hyperinflammatory Condition During Severe Covid-19 Infections (CovidEP)

Primary Purpose

Intensive Care Units, ARDS, Human, Covid19

Status

Unknown status

Phase

Not Applicable

Locations

France

Study Type

Interventional

Intervention

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

About this trial

This is an interventional treatment trial for Intensive Care Units focused on measuring Covid19, Therapeutic plasma exchange, Cytokine storm, Hyperinflammatory condition, Anti-IFN antibodies

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

Centre Hospitalier William Morey
Hôpital Edouard Herriot
Hôpital Edouard Herriot
Hôpital Croix RousseRecruiting
Clinique de la Sauvegarde
Groupement Hospitalier Porte de Valence - Montélimar
Hôpital Pitié Salpétrière - Assistante Publique des Hôpitaux de Paris
Centre Hospitalier Lyon Sud
Medipole Villeurbanne

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

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

Arm Description

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)

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)

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

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.

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).

Survival at day 10

Percentage of patients alive at day 10 after inclusion. This parameter is compared between both arms.

Survival at 2 months

Percentage of patients alive at 2 months after inclusion. This parameter is compared between both arms.

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.

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.

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.

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.

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.

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.

Full Information

NCT ID

NCT04751643

First Posted

February 5, 2021

Last Updated

April 20, 2021

Sponsor

Hospices Civils de Lyon

1. Study Identification

Unique Protocol Identification Number

NCT04751643

Brief Title

Therapeutic Plasma Exchange to Alleviate Hyperinflammatory Condition During Severe Covid-19 Infections

Acronym

CovidEP

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

2. Study Status

Record Verification Date

April 2021

Overall Recruitment Status

Unknown status

Study Start Date

April 19, 2021 (Actual)

Primary Completion Date

December 2022 (Anticipated)

Study Completion Date

December 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Hospices Civils de Lyon

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Intensive Care Units, ARDS, Human, Covid19

Keywords

Covid19, Therapeutic plasma exchange, Cytokine storm, Hyperinflammatory condition, Anti-IFN antibodies

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

132 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

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

Arm Type

Experimental

Arm Description

Arm Title

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

Arm Type

Active Comparator

Arm Description

Intervention Type

Other

Intervention Name(s)

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

Intervention Description

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

Intervention Type

Other

Intervention Name(s)

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

Intervention Description

Primary Outcome Measure Information:

Title

Use of intubation and invasive ventilation (IV) between Day 0 (Inclusion Visit) and Day 10

Description

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

Secondary Outcome Measure Information:

Title

Assess the adverse events according to CTCAE v5.0

Description

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)

Title

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)

Description

Time Frame

At Day 4

Title

Percentage of patients weaned from non invasive ventilation

Description

Percentage of patients weaned from high flow oxygen. This parameter is compared between both arms (experimental and control arms).

Time Frame

At day 10

Title

Survival at day 10

Description

Percentage of patients alive at day 10 after inclusion. This parameter is compared between both arms.

Time Frame

At day 10

Title

Survival at 2 months

Description

Percentage of patients alive at 2 months after inclusion. This parameter is compared between both arms.

Time Frame

At day 60 (+/- 2 days)

Title

Percentage of patients without any increase in inflammatory parameters (analysis of C-reactive protein, Fibrinogen,D-Dimers, procalcitonin, Ferritin)

Description

Time Frame

At day 4

Title

Variation in cytokine and chemokine levels in the cytokine storm

Description

Time Frame

At day 4

Title

Percentage of patients with improved phenotype (decreased phenotype of exhausted cells) and improved function (improved proliferation)

Description

Time Frame

At day 7

Title

Percentage of patients with decreased platelet activation

Description

Time Frame

At Day 4

Title

Percentage of patients with decreased platelet activation

Description

Time Frame

At Day 7

Title

Change in anti-IFN auto-antibodies type I (α and ω) level

Description

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

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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)

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Olivier HEQUET, MD, PhD

Phone

06 31 91 88 87

Ext

+33

olivier.hequet@efs.sante.fr

First Name & Middle Initial & Last Name or Official Title & Degree

Fabrice COGNASSE, PhD

Phone

06 83 97 58 83

Ext

+33

fabrice.cognasse@efs.sante.fr

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Olivier HEQUET, MD, PhD

Organizational Affiliation

Hospices Civils de Lyon - Etablissement Français du Sang

Official's Role

Principal Investigator

Facility Information:

Facility Name

Centre Hospitalier William Morey

City

Chalon-sur-Saône

ZIP/Postal Code

71100

Country

France

Individual Site Status

Not yet recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Mael HAMET, MD

Phone

03 85 91 01 11

Ext

+33

Mael.Hamet@ch-chalon71.fr

First Name & Middle Initial & Last Name & Degree

Mael HAMET, MD

First Name & Middle Initial & Last Name & Degree

Paul-Simon PUGLIESI, MD

Facility Name

Hôpital Edouard Herriot

City

Lyon

ZIP/Postal Code

69003

Country

France

Individual Site Status

Not yet recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Thomas RIMMELE, MD, PhD

Phone

04.72.11.02.81

Ext

+33

thomas.rimmele@chu-lyon.fr

First Name & Middle Initial & Last Name & Degree

Thomas RIMMELE, MD, PhD

Facility Name

Hôpital Edouard Herriot

City

Lyon

ZIP/Postal Code

69003

Country

France

Individual Site Status

Not yet recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Laurent ARGAUD, MD, PhD

Phone

04.72.11.28.51

Ext

+33

laurent.argaud@chu-lyon.fr

First Name & Middle Initial & Last Name & Degree

MD, PhD

First Name & Middle Initial & Last Name & Degree

Laurent ARGAUD, MD, PhD

Facility Name

Hôpital Croix Rousse

City

Lyon

ZIP/Postal Code

69004

Country

France

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Jean Christophe RICHARD, MD, PhD

Phone

04.26.10.92.72

Ext

+33

j-christophe.richard@chu-lyon.fr

First Name & Middle Initial & Last Name & Degree

Jean Christophe RICHARD, MD, PhD

Facility Name

Clinique de la Sauvegarde

City

Lyon

ZIP/Postal Code

69337

Country

France

Individual Site Status

Not yet recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Olivier DESEBBE, MD

Phone

06.51.05.80.65

Ext

+33

oldesebbe@yahoo.com

First Name & Middle Initial & Last Name & Degree

Olivier DESEBBE, MD

First Name & Middle Initial & Last Name & Degree

Bertrand DELANNOY, MD

Facility Name

Groupement Hospitalier Porte de Valence - Montélimar

City

Montelimar

ZIP/Postal Code

26216

Country

France

Individual Site Status

Not yet recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Mathieu Schoeffler, MD

Phone

04 75 53 47 68

Ext

+33

Mathieu.SCHOEFFLER@gh-portesdeprovence.fr

First Name & Middle Initial & Last Name & Degree

Mathieu Schoeffler, MD

Facility Name

Hôpital Pitié Salpétrière - Assistante Publique des Hôpitaux de Paris

City

Paris

ZIP/Postal Code

75013

Country

France

Individual Site Status

Not yet recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Benjamin Rohaut, MD

benjamin.rohaut@aphp.fr

First Name & Middle Initial & Last Name & Degree

Benjamin Rohaut, MD

First Name & Middle Initial & Last Name & Degree

Nicolas Weiss, MD

First Name & Middle Initial & Last Name & Degree

Sophie Demeret, MD

First Name & Middle Initial & Last Name & Degree

Samir Saheb, MD

Facility Name

Centre Hospitalier Lyon Sud

City

Pierre-Bénite

ZIP/Postal Code

69310

Country

France

Individual Site Status

Not yet recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Vincent PIRIOU, MD, PhD

Phone

04.78.86.20.70

Ext

+33

vincent.piriou@chu-lyon.fr

First Name & Middle Initial & Last Name & Degree

Vincent PIRIOU, MD, PhD

Facility Name

Medipole Villeurbanne

City

Villeurbanne

ZIP/Postal Code

69100

Country

France

Individual Site Status

Not yet recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Quoc-Viet LE, MD

Phone

04 87 65 00 00

Ext

+33

qvle@scprea.fr

First Name & Middle Initial & Last Name & Degree

Quoc-Viet LE, MD

12. IPD Sharing Statement

Learn more about this trial

Therapeutic Plasma Exchange to Alleviate Hyperinflammatory Condition During Severe Covid-19 Infections

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