Endotoxins and Cytokines Removal During Continuous Hemofiltration With oXiris™

Septic Shock Clinical Trial

— ECRO  

Official title:

Endotoxins and Cytokines Removal During Continuous Hemofiltration With oXiris™

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03426943
• Other study ID #: 69HCL17_0014
• Secondary ID: 2017-A03366-47
• Status: Completed
• Phase: N/A
• Start date: December 21, 2018
• Est. completion date: June 3, 2022

Study information

• Verified date: October 2022
• Source: Hospices Civils de Lyon
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 39
• Est. completion date: June 3, 2022
• Est. primary completion date: June 3, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Peritonitis
• Septic Shock

Intervention

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

Locations

Country	Name	City	State
France	Hopital Universitaire de Clermont Ferrand	Clermont-Ferrand
France	CHU Dijon - Bocage central	Dijon
France	CHU Francois Mitterrand	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

Sponsors (2)

Lead Sponsor	Collaborator
Hospices Civils de Lyon	Baxter Healthcare Corporation

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Interleukin 6 (IL-6) plasmatic concentration		24 hours after the initiation of CVVH
Primary	Endotoxin plasmatic mass concentration		24 hours after the initiation of CVVH
Secondary	Pre-filter plasma endotoxin mass		At initiation of CCVH (H0) then 1, 4, 12 and 24 hours after the initiation of CVVH
Secondary	Pre-filter plasma endotoxin activity		At initiation of CCVH (H0) then 1, 4, 12 and 24 hours after the initiation of CVVH
Secondary	Post-filter plasma endotoxin mass		1, 4, 12 and 24 hours after the initiation of CVVH
Secondary	Post-filter plasma endotoxin activity		1, 4, 12 and 24 hours after the initiation of CVVH
Secondary	Pre-filter plasma cytokine level		At initiation of CCVH (H0) then 1, 4, 12 and 24 hours after the initiation of CVVH
Secondary	Post-filter plasma cytokine level		1, 4, 12 and 24 hours after the initiation of CVVH
Secondary	Ultrafiltrate cytokine level		1, 4, 12 and 24 hours after the initiation of CVVH
Secondary	Pre-filter plasma lipids level		At initiation of CCVH (H0) then 1, 4, 12 and 24 hours after the initiation of CVVH
Secondary	Post-filter plasma lipids level		1, 4, 12 and 24 hours after the initiation of CVVH
Secondary	Pre-filter plasma Procalcitonin level		At initiation of CCVH (H0) then 1, 4, 12 and 24 hours after the initiation of CVVH
Secondary	Post-filter plasma Procalcitonin level		1, 4, 12 and 24 hours after the initiation of CVVH
Secondary	Pre-filter plasma Phospholipid Transfer Protein level		At initiation of CCVH (H0) then 1, 4, 12 and 24 hours after the initiation of CVVH
Secondary	Post-filter plasma Phospholipid Transfer Protein level		1, 4, 12 and 24 hours after the initiation of CVVH
Secondary	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
Secondary	Post-filter plasma Cholesteryl Ester Transfer Protein level		1, 4, 12 and 24 hours after the initiation of CVVH
Secondary	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
Secondary	Post-filter plasma LPS-Binding Protein level		1, 4, 12 and 24 hours after the initiation of CVVH
Secondary	Norepinephrine requirements		4, 12 and 24 hours after the initiation of CVVH
Secondary	Fluids infused		4, 12 and 24 hours after the initiation of CVVH
Secondary	Patient survival		At day 7
Secondary	Patient survival		At day 30
Secondary	Patient survival		At day 90
Secondary	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