Endotoxins and Cytokines Removal During Continuous Hemofiltration With oXiris™

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

Interventions

BIOLOGICAL

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

BIOLOGICAL

Ultrafiltrate sampling

All patients will have ultrafiltrate sampling to assess cytokine levels

DEVICE

CVVH using oXiris™ filter

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

DEVICE

CVVH using PrismafleX HF1400 filter

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

Sponsors & Collaborators

• Baxter Healthcare Corporation

  collaborator INDUSTRY

• Hospices Civils de Lyon

  lead OTHER

Principal Investigators

• Thomas RIMMELE, MD, PhD · Hospices Civils de Lyon

Study Design

Allocation

RANDOMIZED

Purpose

OTHER

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2018-12-21

Primary Completion

2022-06-03

Completion

2022-06-03

Countries

• France

Study Locations