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

Study Overview
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Brief Summary
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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.

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

Conditions
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Septic Shock, Acute Kidney Injury

Intervention / Treatment
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* Device: oXiris


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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. Vasoconstrictor and volume dependent septic shock with known Gram-negative infectious agent in blood culture. Vasoconstrictor and volume dependent septic shock suspected to be caused by a Gram-negative agent and with positive plasma endotoxin test. Exclusion Criteria: Infected with Hepatitis B or C or HIV. Dependence on dialysis treatment before the actual ICU episode.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

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

What is the study measuring?
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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 |