CompletedNCT03426943ECROUpdated Dec 5, 2023

Endotoxins and Cytokines Removal During Continuous Hemofiltration With oXiris™

An interventional study of Arterial blood sampling and Ultrafiltrate sampling in Septic Shock and Peritonitis, sponsored by Hospices Civils de Lyon. Completed at 8 sites in France. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2023-12-05.

Sponsored by Hospices Civils de Lyon · Not applicable, Interventional, and Other

Phase: Not applicable
Study type: Interventional
Enrollment: 39
Allocation: Randomized
Ages: 18 Years and older
Sex: All

Study 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 studied

Septic Shock
Peritonitis

Browse trials for

Peritonitis 185

Who can participate

Ages eligible: 18 Years and older
Sexes eligible: All
Accepts healthy volunteers: No

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

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 design

Phase: Not applicable
Primary purpose: Other
Allocation: Randomized
Intervention model: Parallel assignment
Masking: None (open label)
Enrollment: 39 participants (actual)

Study arms

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.
Biological: Arterial blood sampling · Biological: Ultrafiltrate sampling · Device: 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.
Biological: Arterial blood sampling · Biological: Ultrafiltrate sampling · Device: CVVH using PrismafleX HF1400 filter

Interventions

BiologicalArterial 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
BiologicalUltrafiltrate sampling
All patients will have ultrafiltrate sampling to assess cytokine levels
DeviceCVVH using oXiris™ filter
Patients included in the experimental arm will have renal replacement therapy by performing CVVH using oXiris™ filter
DeviceCVVH using PrismafleX HF1400 filter
Patients included in the experimental arm will have renal replacement therapy by performing CVVH using PrismafleX HF1400 filter

What researchers measure

Primary outcomes

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

Secondary outcomes

Pre-filter plasma endotoxin mass
Time frame: 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
Post-filter plasma endotoxin mass
Time frame: 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
Pre-filter plasma cytokine level
Time frame: 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
Ultrafiltrate cytokine level
Time frame: 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
Post-filter plasma lipids level
Time frame: 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
Post-filter plasma Procalcitonin level
Time frame: 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
Post-filter plasma Phospholipid Transfer Protein level
Time frame: 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
Post-filter plasma Cholesteryl Ester Transfer Protein level
Time frame: 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
Post-filter plasma LPS-Binding Protein level
Time frame: 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
Fluids infused
Time frame: 4, 12 and 24 hours after the initiation of CVVH
Patient survival
Time frame: At day 7
Patient survival
Time frame: At day 30
Patient survival
Time frame: 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

Study locations

8 sites

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

References and documents

Publications

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. PubMed 34519356 ↗

Registry details

Key details

Study ID: NCT03426943
Lead sponsor: Hospices Civils de Lyon
Collaborators: Baxter Healthcare Corporation
Responsible party: Sponsor
First posted: Feb 8, 2018
Start date: Dec 21, 2018
Primary completion: Jun 3, 2022
Completion: Jun 3, 2022
Last update: Dec 5, 2023

Study contacts

Thomas RIMMELE, MD, PhD

principal investigator · Hospices Civils de Lyon

Oversight

Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No

View the source record on ClinicalTrials.gov ↗

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