Endotoxins and Cytokines Removal During Continuous Hemofiltration With oXiris™

NCT ID: NCT03426943

Last Updated: 2023-12-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 39 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-12-21
• Study Completion Date: 2022-06-03

Brief Summary

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.

Conditions

Septic Shock; Peritonitis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Arterial blood sampling

Intervention Type: BIOLOGICAL

All patients will have arterial blood sampling to assess pre-filter and post-filter plasma endotoxin mass and activity and plasma cytokine levels

Ultrafiltrate sampling

Intervention Type: BIOLOGICAL

All patients will have ultrafiltrate sampling to assess cytokine levels

CVVH using oXiris™ filter

Intervention Type: DEVICE

Patients included in the experimental arm will have renal replacement therapy by performing CVVH using oXiris™ filter

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.

Group Type: ACTIVE_COMPARATOR

Arterial blood sampling

Intervention Type: BIOLOGICAL

All patients will have arterial blood sampling to assess pre-filter and post-filter plasma endotoxin mass and activity and plasma cytokine levels

Ultrafiltrate sampling

Intervention Type: BIOLOGICAL

All patients will have ultrafiltrate sampling to assess cytokine levels

CVVH using PrismafleX HF1400 filter

Intervention Type: DEVICE

Patients included in the experimental arm will have renal replacement therapy by performing CVVH using PrismafleX HF1400 filter

Interventions

Arterial blood sampling

All patients will have arterial blood sampling to assess pre-filter and post-filter plasma endotoxin mass and activity and plasma cytokine levels

Intervention Type: BIOLOGICAL

Ultrafiltrate sampling

All patients will have ultrafiltrate sampling to assess cytokine levels

Intervention Type: BIOLOGICAL

CVVH using oXiris™ filter

Patients included in the experimental arm will have renal replacement therapy by performing CVVH using oXiris™ filter

Intervention Type: DEVICE

CVVH using PrismafleX HF1400 filter

Patients included in the experimental arm will have renal replacement therapy by performing CVVH using PrismafleX HF1400 filter

Intervention Type: DEVICE

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Baxter Healthcare Corporation

INDUSTRY

Sponsor Role: collaborator

Hospices Civils de Lyon

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Thomas RIMMELE, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Hospices Civils de Lyon

Locations

Hopital Universitaire de Clermont Ferrand

Clermont-Ferrand, , France

CHU Francois Mitterrand

Dijon, , France

CHU Dijon - Bocage central

Dijon, , France

L'Hôpital Nord-Ouest - Villefranche sur Saone

Gleizé, , France

Anesthesia and Critical Care Medicine Department - Edouard Herriot Hospital

Lyon, , France

Clinique de la Sauvegarde

Lyon, , France

Hôpital Pasteur 2 - Hôpital Universitaire de Nice

Nice, , France

Hopital Haut Lévèque - CHU Bordeaux

Pessac, , France

Countries

France

References

Tsujimoto Y, Miki S, Shimada H, Tsujimoto H, Yasuda H, Kataoka Y, Fujii T. Non-pharmacological interventions for preventing clotting of extracorporeal circuits during continuous renal replacement therapy. Cochrane Database Syst Rev. 2021 Sep 14;9(9):CD013330. doi: 10.1002/14651858.CD013330.pub2.

Reference Type: DERIVED

PMID: 34519356 (View on PubMed)

Other Identifiers

2017-A03366-47

Identifier Type: OTHER

Identifier Source: secondary_id

69HCL17_0014

Identifier Type: -

Identifier Source: org_study_id