Endotoxins and Cytokines Removal During Continuous Hemofiltration With oXiris™ (ECRO)

December 4, 2023 updated by: Hospices Civils de Lyon

Sepsis is a major cause of death in Intensive Care Units and therefore finding new therapies to improve survival rates and limit morbidity is a major goal. Over the past decades, blood purification has been proposed as an adjuvant therapy for sepsis. The goal of blood purification is to restore the immune homeostasis and efficiency through the removal of bacterial products including endotoxins, broad-spectrum cytokines and other inflammatory mediators. Indeed, the large and overwhelmed release of these mediators in the early phase of sepsis may induce multiple organ failure syndrome. In 2017, different techniques are proposed for blood purification. Among them, the highly adsorptive membrane, oXiris™, seems promising. This membrane can be used in case of Acute Kidney Injury associated with sepsis and exhibits enhanced blood purification capacities. Previous studies on animals have already proven that this membrane can remove broad-spectrum cytokines but also endotoxins from the blood. This ability to remove endotoxins is particularly interesting since endotoxins are believed to be the trigger of the immune cascade at the initiation of sepsis.

The lack of clinical evidence is the main limit to a wider use of this membrane. Therefore, the aim of the present clinical trial is to characterize the blood purification properties of the membrane in a human clinical setting. The oXiris™ membrane is specifically designed to improve the adsorptive capacities of the polyacrylonitrile-based AN69 membrane. Its extremely rich coating of polyethyleneimine (PEI) gives the membrane the ability to bind and remove not only cytokines but also endotoxins due to the positive charges of PEI at the surface of the membrane. The tested hypothesis is that the oXiris™ filter allows for a greater endotoxin and cytokine removal compared to a standard polysulfone ("PrismafleX HF1400") filter in patients with septic shock.

Study Overview

Study Type

Interventional

Enrollment (Actual)

39

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

      • Clermont-Ferrand, France, 63003
        • Hopital Universitaire de Clermont Ferrand
      • Dijon, France, 21033
        • CHU Francois Mitterrand
      • Dijon, France, 21079
        • CHU Dijon - Bocage central
      • Gleizé, France, 69400
        • L'Hôpital Nord-Ouest - Villefranche sur Saone
      • Lyon, France, 69337
        • Clinique de la Sauvegarde
      • Lyon, France, 69003
        • Anesthesia and Critical Care Medicine Department - Edouard Herriot Hospital
      • Nice, France, 06000
        • Hôpital Pasteur 2 - Hôpital Universitaire de Nice
      • Pessac, France, 33600
        • Hopital Haut Lévèque - CHU Bordeaux

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Male or female aged ≥ 18 years old,
  • "Early" septic shock (in the first 12 hours after Intensive Care Unit (ICU) admission or readmission in the ICU after surgery), with lactatemia > 2 mmol/L and norepinephrine needs > 0.2 µg/kg/min 2 hours after the end of the initial surgery (to ensure that a potential anesthesia effect as disappeared),
  • Secondary to a community-acquired or a nosocomial peritonitis (secondary or tertiary but not primary peritonitis),
  • AKI KDIGO ≥ stage 2 or another indication for renal replacement therapy, according to the clinician in charge (if baseline creatinine is unknown, KDIGO ≥ stage 2 can be defined by a serum creatinine ≥ 2-fold the normal creatinine for age, gender, and ethnicity).

Exclusion Criteria:

  • Inability to obtain informed consent from the patient or next of kin,
  • Actual participation in another interventional study,
  • Contraindications to citrate,
  • Allergy to heparin,
  • Pregnant or breastfeeding woman,
  • Neutropenia < 0.5 G/L resulting from chemotherapy or other iatrogenic causes
  • Patient receiving immunosuppressive therapy, long-term corticosteroids, therapeutic antibodies, chemotherapy in the last 6 months (whatever the dose),
  • Patient with innate or acquired immune deficiency (for example severe combined immunodeficiency, HIV or AIDS)
  • Onco-hematological disease (lymphoma, leukemia, myeloma) treated within the last 5 years (but inclusion of a patient with solid cancer who did not receive chemotherapy during the past 6 months is possible),
  • Patient with expected ICU length of stay < 48 hours,
  • Patient for whom a limitation of active care was pronounced at the time of enrollment,
  • Patient with no social security insurance, with restricted liberty, or under legal protection.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: CVVH using oXiris™ filter

Patients included in this arm will have renal replacement therapy by performing Continuous Veno-Venous Hemofiltration (CVVH) using oXiris™ membrane.

They will also have arterial blood sampling and ultrafiltrate sampling during the CVVH.

All patients will have arterial blood sampling to assess pre-filter and post-filter plasma endotoxin mass and activity and plasma cytokine levels
All patients will have ultrafiltrate sampling to assess cytokine levels
Patients included in the experimental arm will have renal replacement therapy by performing CVVH using oXiris™ filter
Active Comparator: CVVH using PrismafleX HF1400 filter

Patients included in this arm will have renal replacement therapy by performing CVVH using a standard polysulfone filter (PrismafleX HF1400).

They will also have arterial blood sampling and ultrafiltrate sampling during the CVVH.

All patients will have arterial blood sampling to assess pre-filter and post-filter plasma endotoxin mass and activity and plasma cytokine levels
All patients will have ultrafiltrate sampling to assess cytokine levels
Patients included in the experimental arm will have renal replacement therapy by performing CVVH using PrismafleX HF1400 filter

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Interleukin 6 (IL-6) plasmatic concentration
Time Frame: 24 hours after the initiation of CVVH
24 hours after the initiation of CVVH
Endotoxin plasmatic mass concentration
Time Frame: 24 hours after the initiation of CVVH
24 hours after the initiation of CVVH

Secondary Outcome Measures

Outcome Measure
Time Frame
Pre-filter plasma endotoxin mass
Time Frame: At initiation of CCVH (H0) then 1, 4, 12 and 24 hours after the initiation of CVVH
At initiation of CCVH (H0) then 1, 4, 12 and 24 hours after the initiation of CVVH
Pre-filter plasma endotoxin activity
Time Frame: At initiation of CCVH (H0) then 1, 4, 12 and 24 hours after the initiation of CVVH
At initiation of CCVH (H0) then 1, 4, 12 and 24 hours after the initiation of CVVH
Post-filter plasma endotoxin mass
Time Frame: 1, 4, 12 and 24 hours after the initiation of CVVH
1, 4, 12 and 24 hours after the initiation of CVVH
Post-filter plasma endotoxin activity
Time Frame: 1, 4, 12 and 24 hours after the initiation of CVVH
1, 4, 12 and 24 hours after the initiation of CVVH
Pre-filter plasma cytokine level
Time Frame: At initiation of CCVH (H0) then 1, 4, 12 and 24 hours after the initiation of CVVH
At initiation of CCVH (H0) then 1, 4, 12 and 24 hours after the initiation of CVVH
Post-filter plasma cytokine level
Time Frame: 1, 4, 12 and 24 hours after the initiation of CVVH
1, 4, 12 and 24 hours after the initiation of CVVH
Ultrafiltrate cytokine level
Time Frame: 1, 4, 12 and 24 hours after the initiation of CVVH
1, 4, 12 and 24 hours after the initiation of CVVH
Pre-filter plasma lipids level
Time Frame: At initiation of CCVH (H0) then 1, 4, 12 and 24 hours after the initiation of CVVH
At initiation of CCVH (H0) then 1, 4, 12 and 24 hours after the initiation of CVVH
Post-filter plasma lipids level
Time Frame: 1, 4, 12 and 24 hours after the initiation of CVVH
1, 4, 12 and 24 hours after the initiation of CVVH
Pre-filter plasma Procalcitonin level
Time Frame: At initiation of CCVH (H0) then 1, 4, 12 and 24 hours after the initiation of CVVH
At initiation of CCVH (H0) then 1, 4, 12 and 24 hours after the initiation of CVVH
Post-filter plasma Procalcitonin level
Time Frame: 1, 4, 12 and 24 hours after the initiation of CVVH
1, 4, 12 and 24 hours after the initiation of CVVH
Pre-filter plasma Phospholipid Transfer Protein level
Time Frame: At initiation of CCVH (H0) then 1, 4, 12 and 24 hours after the initiation of CVVH
At initiation of CCVH (H0) then 1, 4, 12 and 24 hours after the initiation of CVVH
Post-filter plasma Phospholipid Transfer Protein level
Time Frame: 1, 4, 12 and 24 hours after the initiation of CVVH
1, 4, 12 and 24 hours after the initiation of CVVH
Pre-filter plasma Cholesteryl Ester Transfer Protein level
Time Frame: At initiation of CCVH (H0) then 1, 4, 12 and 24 hours after the initiation of CVVH
At initiation of CCVH (H0) then 1, 4, 12 and 24 hours after the initiation of CVVH
Post-filter plasma Cholesteryl Ester Transfer Protein level
Time Frame: 1, 4, 12 and 24 hours after the initiation of CVVH
1, 4, 12 and 24 hours after the initiation of CVVH
Pre-filter plasma lipopolysaccharide (LPS) Binding Protein level
Time Frame: At initiation of CCVH (H0) then 1, 4, 12 and 24 hours after the initiation of CVVH
At initiation of CCVH (H0) then 1, 4, 12 and 24 hours after the initiation of CVVH
Post-filter plasma LPS-Binding Protein level
Time Frame: 1, 4, 12 and 24 hours after the initiation of CVVH
1, 4, 12 and 24 hours after the initiation of CVVH
Norepinephrine requirements
Time Frame: 4, 12 and 24 hours after the initiation of CVVH
4, 12 and 24 hours after the initiation of CVVH
Fluids infused
Time Frame: 4, 12 and 24 hours after the initiation of CVVH
4, 12 and 24 hours after the initiation of CVVH
Patient survival
Time Frame: At day 7
At day 7
Patient survival
Time Frame: At day 30
At day 30
Patient survival
Time Frame: At day 90
At day 90
Comparison of the results obtained on the above-mentioned parameters, according to the type of bacteria identified from standard care microbiological exams.
Time Frame: At day 7
At day 7

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Thomas RIMMELE, MD, PhD, Hospices Civils de Lyon

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 21, 2018

Primary Completion (Actual)

June 3, 2022

Study Completion (Actual)

June 3, 2022

Study Registration Dates

First Submitted

February 2, 2018

First Submitted That Met QC Criteria

February 2, 2018

First Posted (Actual)

February 8, 2018

Study Record Updates

Last Update Posted (Estimated)

December 5, 2023

Last Update Submitted That Met QC Criteria

December 4, 2023

Last Verified

October 1, 2022

More Information

Terms related to this study

Other Study ID Numbers

  • 69HCL17_0014
  • 2017-A03366-47 (Other Identifier: ID-RCB)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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