Clinical trial NCT03426943: Endotoxins and Cytokines Removal During Continuous Hemofiltration With oXiris™
Official title: Endotoxins and Cytokines Removal During Continuous Hemofiltration With oXiris™
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Septic Shock
Peritonitis
Lead sponsor: Hospices Civils de Lyon
Sponsor class: OTHER
Collaborators: name: Baxter Healthcare Corporation
First posted: 2018-02-08
Enrollment: 39
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

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.


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.

Primary outcomes:
measure: Interleukin 6 (IL-6) plasmatic concentration
timeFrame: 24 hours after the initiation of CVVH
measure: Endotoxin plasmatic mass concentration
timeFrame: 24 hours after the initiation of CVVH
Secondary outcomes:
measure: Pre-filter plasma endotoxin mass
timeFrame: At initiation of CCVH (H0) then 1, 4, 12 and 24 hours after the initiation of CVVH
measure: Pre-filter plasma endotoxin activity
timeFrame: At initiation of CCVH (H0) then 1, 4, 12 and 24 hours after the initiation of CVVH
measure: Post-filter plasma endotoxin mass
timeFrame: 1, 4, 12 and 24 hours after the initiation of CVVH
measure: Post-filter plasma endotoxin activity
timeFrame: 1, 4, 12 and 24 hours after the initiation of CVVH
measure: Pre-filter plasma cytokine level
timeFrame: At initiation of CCVH (H0) then 1, 4, 12 and 24 hours after the initiation of CVVH
measure: Post-filter plasma cytokine level
timeFrame: 1, 4, 12 and 24 hours after the initiation of CVVH
measure: Ultrafiltrate cytokine level
timeFrame: 1, 4, 12 and 24 hours after the initiation of CVVH
measure: Pre-filter plasma lipids level
timeFrame: At initiation of CCVH (H0) then 1, 4, 12 and 24 hours after the initiation of CVVH
measure: Post-filter plasma lipids level
timeFrame: 1, 4, 12 and 24 hours after the initiation of CVVH
measure: Pre-filter plasma Procalcitonin level
timeFrame: At initiation of CCVH (H0) then 1, 4, 12 and 24 hours after the initiation of CVVH
measure: Post-filter plasma Procalcitonin level
timeFrame: 1, 4, 12 and 24 hours after the initiation of CVVH
measure: Pre-filter plasma Phospholipid Transfer Protein level
timeFrame: At initiation of CCVH (H0) then 1, 4, 12 and 24 hours after the initiation of CVVH
measure: Post-filter plasma Phospholipid Transfer Protein level
timeFrame: 1, 4, 12 and 24 hours after the initiation of CVVH
measure: Pre-filter plasma Cholesteryl Ester Transfer Protein level
timeFrame: At initiation of CCVH (H0) then 1, 4, 12 and 24 hours after the initiation of CVVH
measure: Post-filter plasma Cholesteryl Ester Transfer Protein level
timeFrame: 1, 4, 12 and 24 hours after the initiation of CVVH
measure: Pre-filter plasma lipopolysaccharide (LPS) Binding Protein level
timeFrame: At initiation of CCVH (H0) then 1, 4, 12 and 24 hours after the initiation of CVVH
measure: Post-filter plasma LPS-Binding Protein level
timeFrame: 1, 4, 12 and 24 hours after the initiation of CVVH
measure: Norepinephrine requirements
timeFrame: 4, 12 and 24 hours after the initiation of CVVH
measure: Fluids infused
timeFrame: 4, 12 and 24 hours after the initiation of CVVH
measure: Patient survival
timeFrame: At day 7
measure: Patient survival
timeFrame: At day 30
measure: Patient survival
timeFrame: At day 90
measure: Comparison of the results obtained on the above-mentioned parameters, according to the type of bacteria identified from standard care microbiological exams.
timeFrame: At day 7
Other outcomes:
Locations:
city: Clermont-Ferrand
country: France
facility: Hopital Universitaire de Clermont Ferrand
city: Dijon
country: France
facility: CHU Francois Mitterrand
city: Dijon
country: France
facility: CHU Dijon - Bocage central
city: Gleizé
country: France
facility: L'Hôpital Nord-Ouest - Villefranche sur Saone
city: Lyon
country: France
facility: Anesthesia and Critical Care Medicine Department - Edouard Herriot Hospital
city: Lyon
country: France
facility: Clinique de la Sauvegarde
city: Nice
country: France
facility: Hôpital Pasteur 2 - Hôpital Universitaire de Nice
city: Pessac
country: France
facility: Hopital Haut Lévèque - CHU Bordeaux
Study officials:
affiliation: Hospices Civils de Lyon
name: Thomas RIMMELE, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.