High Cut Off Dialysis in Systemic Inflammatory Response Syndrome Patients After Cardiac Surgery

Study Overview
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Brief Summary
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A high cut off dialyzer (septeX) is tested in patients after cardio-thoracic surgery with incidence of systemic inflammatory response syndrome (SIRS) and associated increased risk for acute kidney injury (AKI). Hypothesis: The high cut off dialyzer (septeX) can increase the postoperative IL-6/Il-10 ratio.

Detailed Description
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Cardiac surgery associated systemic inflammatory response syndrome (SIRS) plays an important pathophysiological role in the development of AKI in patients after cardiothoracic surgery. Previous studies have shown that the elimination of inflammatory mediators can be either achieved by Continuous Venous Venous Hemodialysis(CVVHD) or Continuous Venous Venous Hemofiltration (CVVH) by using a high-cutoff (HCO) membrane with a cut-off 45kD. Data from patients treated with HCO-CVVHD during septic shock show a reduction in systemic cytokines and improved hemodynamics. No data about the effects of early HCO-CVVH in cardiac surgery patients with a high risk of Cardiac Surgery associated AKI and consequently a high rate of postoperative renal replacement therapy (RRT) are available. It is of note that patients with Euroscore > 6 are on high risk to develop SIRS associated AKI. No pharmacological anti-inflammatory approach has convincingly shown to prevent renal dysfunction in these patients.

Official Title
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The Effects of High-cutoff (HCO) Hemofiltration in the Immediate Postoperative Period on Systemic Inflammatory Response Syndrome (SIRS) and Renal Recovery in Cardiac Surgery Patients With a High Risk for Renal Failure. (HICOSIRS)

Conditions
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Systemic Inflammatory Response Syndrome, Acute Kidney Injury

Intervention / Treatment
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* Device: septeX
* Other: standard therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years Scheduled for complex / prolonged cardiac surgery (i.e.combined CABG+ valve surgery, Redo surgery) with an anticipated CPB time > 120 min CKD with an e GFR < 50ml/min/m2 Euroscore > 6 Exclusion Criteria: End stage CKD (dialysis dependent) renal failure before surgery Radiocontrast exposure within 24 hours before surgery Active endocarditic with antibiotic treatment pulmonary disease with chronic hypoxia Clinically significant liver dysfunction (bilirubin > 1.8mg/dl (30µmol/L)) Known HIV, HCV infection Alcoholism Active uncontrolled infection Pregnancy or lactation Inability to give informed consent to participate in the study

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: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: septeX<br>septeX CVVH for 12h after cardiac surgery | Device: septeX<br>* 12 h septeX CVVH treatment after cardiac surgery<br>* Other names: high cut off;|
| Other: standard therapy<br>standard therapy according to local practice | Other: standard therapy<br>* standard therapy either pharmacological and /or continuous renal replacement therapy (CRRT)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| IL6/IL10 ratio | To test, if immediate postoperative HCO-CVVH reduces systemic inflammation (determined as the ratio between Il-6 / Il-10) in patients with a high risk for CSA-AKI in comparison with a treatment without early RRT. To calibrate for differences in baseline cytokine levels and with respect to the high variability of cytokines in the postoperative period the area-under-the-curve (AUC) of the postoperative increase in the IL-6/Il-10 ratio until 48h will be used. | Change from Baseline in IL6/IL10 ratio at 48h post cardiac surgery and last day at hospital (expected average of 2 weeks after cardiac surgery) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| determination of immediate postoperative HCO-CVVH improvement | Short- and medium term recovery of renal function time to extubation cardiac function need for vasoactive and inotropic drugs duration of treatment in a high-dependency unit | 6 month post cardiac surgery | 
| Laboratory assessments | GDF-15 urinary fatty acid binding protein (U-FABP) association of Human placental growth factor (PIGF) and Soluble fms-like tyrosine kinase (S-flt-1) | 48h after cardiac surgery and last day at hospital (expected average 2 weeks) | 
| adverse effects | To determine, if HCO - CVVH has adverse effects in comparison with no immediate RRT. | 48h after cardiac surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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septeX, high cut-off, Thoracic Surgery, Renal Replacement Therapy