Comparing Cytokines, Toxins Adsorbing oXiris Filter to ST150 Filter During CRRT in Patients With Septic Shock (oXiris)

The Oxiris® filter is a registered product for CRRT already safely used in routine care.

In in vitro experiments, the Oxiris® filter has been demonstrated to adsorb endotoxin and cytokines. Compared to conventional filters this may be advantageous in patients with severe sepsis but neither decreased levels of endotoxin and cytokines nor an improved outcome has been demonstrated with clinical use.

But there are so far little clinical data on the oXiris® filter on humans. The oXiris® filter will be investigated in a double blind randomized crossover setting against a traditional filter (ST150). Either filter will be used for 24 hours after which it will be changed to the opposite filter for another 24 hours.

Arterial blood samples will be drawn at start and then 1, 3, 8, 16 and 24 hours after the start of each filter, and analyzed for endotoxin (EAA assay), TNF-α, IL-1β, IL-6 and IL-10 (ELISA) levels. Standard blood tests will be analyzed simultaneously. Data concerning mode and settings of CRRT, heart rate, blood pressure, medication, data concerning ventilatory support and pathogen will be registered.

Primary endpoint: Levels of endotoxin and cytokines will be compared using Student's paired t-test on AUC values for each 24-hour period.

Study Overview

• Status: Completed
• Conditions: Septic Shock; Acute Kidney Injury
• Intervention / Treatment: Device: oXiris

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Sweden
  • Skåne
    • Lund, Skåne, Sweden, 22241
      • Perioperative and Intensive Care (Adult), Skåne University Hospital, Lund

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients admitted to intensive care unit (ICU) of age >18 years with decision based on the clinical situation of the patient taken by the physician in charge that continuous renal replacement therapy will be started.
2. Vasoconstrictor and volume dependent septic shock with known Gram-negative infectious agent in blood culture.
3. Vasoconstrictor and volume dependent septic shock suspected to be caused by a Gram-negative agent and with positive plasma endotoxin test.

Exclusion Criteria:

1. Infected with Hepatitis B or C or HIV.
2. Dependence on dialysis treatment before the actual ICU episode.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: oXiris; Continuous renal replacement therapy with filter that adsorbs cytokines/toxins.	Device: oXiris; oXiris CRRT filter which adsorbs cytokines, toxins.
No Intervention: ST150; Continuous renal replacement therapy with filter that does not adsorb cytokines/toxins.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
endotoxin level in blood	Describes the load of toxins from the septic state. Higher load means increased impact from the infectious state mediated through the septic shock. Expected mean differences in endotoxin levels including standard deviation is based on data from a previous study on extracorporeal endotoxin removal in sepsis patients (reference 1).	change from baseline to 48 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
mean blood pressure	Additional parameter that describes the clinical impact from the septic state.	hourly up to 48 hours
TNF-α level in blood	Additional parameter that describes the load from the septic shock.	change from baseline to 48 hours
IL-1β level in blood	Additional parameter that describes the load from the septic shock.	change from baseline to 48 hours
IL-6 level in blood	Additional parameter that describes the load from the septic shock.	change from baseline to 48 hours
IL-10	Additional parameter that describes the load from the septic shock.	change from baseline to 48 hours

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
level of vasoconstrictive infusion	Need of vasoconstrictor because of shock, higher degree of shock means increased requirement of vasoconstrictor infusion.	hourly up to 48 hours

Collaborators and Investigators

• Sponsor: Skane University Hospital
• Investigators: Principal Investigator: Marcus Broman, Associate professor, Dep Perioperative and Intensive Care, Skåne University Hospital, Lund, Sweden

Publications and helpful links

General 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.
• Ala-Kokko TI, Laurila J, Koskenkari J. A new endotoxin adsorber in septic shock: observational case series. Blood Purif. 2011;32(4):303-9. doi: 10.1159/000330323. Epub 2011 Sep 2.

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2015
• Primary Completion (Actual): January 1, 2018
• Study Completion (Actual): January 1, 2018

Study Registration Dates

• First Submitted: October 30, 2015
• First Submitted That Met QC Criteria: November 6, 2015
• First Posted (Estimate): November 9, 2015

Study Record Updates

• Last Update Posted (Actual): July 26, 2019
• Last Update Submitted That Met QC Criteria: July 25, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Kidney Diseases; Urologic Diseases; Systemic Inflammatory Response Syndrome; Inflammation; Renal Insufficiency; Sepsis; Shock, Septic; Shock; Acute Kidney Injury
• Other Study ID Numbers: OXIRIS