Endotoxins and Cytokines Removal During Continuous Hemofiltration With oXiris™

Not Applicable

Completed

• Conditions: Peritonitis; Septic Shock
• Interventions: Biological: Arterial blood sampling; Biological: Ultrafiltrate sampling; Device: CVVH using oXiris™ filter; Device: CVVH using PrismafleX HF1400 filter

• Registration Number: NCT03426943
• Lead Sponsor: Hospices Civils de Lyon

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2018-02-02
• Study First Submitted QC: 2018-02-02
• Study First Posted: 2018-02-08
• Study Start: 2018-12-21
• Primary Completion: 2022-06-03
• Study Completion: 2022-06-03
• Status Verified: 2022-10
• Last Update Submitted: 2023-12-04
• Last Update Posted: 2023-12-05

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 39

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).

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
CVVH using oXiris™ filter	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.
CVVH using PrismafleX HF1400 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.
CVVH using oXiris™ filter	Arterial blood sampling	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.
CVVH using oXiris™ filter	Ultrafiltrate sampling	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.
CVVH using PrismafleX HF1400 filter	Arterial blood sampling	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.
CVVH using PrismafleX HF1400 filter	Ultrafiltrate sampling	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.

Primary Outcome Measures

Name	Time	Method
Endotoxin plasmatic mass concentration	24 hours after the initiation of CVVH
Interleukin 6 (IL-6) plasmatic concentration	24 hours after the initiation of CVVH

Secondary Outcome Measures

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

Trial Locations

Locations (8)

Hopital Universitaire de Clermont Ferrand; 🇫🇷 Clermont-Ferrand, France

CHU Francois Mitterrand; 🇫🇷 Dijon, France

Anesthesia and Critical Care Medicine Department - Edouard Herriot Hospital; 🇫🇷 Lyon, France

Clinique de la Sauvegarde; 🇫🇷 Lyon, France

CHU Dijon - Bocage central; 🇫🇷 Dijon, France

Hôpital Pasteur 2 - Hôpital Universitaire de Nice; 🇫🇷 Nice, France

L'Hôpital Nord-Ouest - Villefranche sur Saone; 🇫🇷 Gleizé, France

Hopital Haut Lévèque - CHU Bordeaux; 🇫🇷 Pessac, France