High Cut-Off Continuous Veno-venous Hemodialysis (CVVHD) in Patients Treated for Acute Renal Failure After Systemic Inflammatory Response Syndrome (SIRS)/Septic Shock

Study Overview
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Brief Summary
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This study will assess the influence of the High Cut-Off (HCO) CVVHD treatment on the disease progression in septic patients. The primary aim of the study is to evaluate whether HCO CVVHD leads to a significant improvement of the hemodynamic status (mean arterial pressure, vasopressor requirements) in septic patients in comparison to CVVHD treatment with conventional high-flux filters. For the HCO-group the investigators expect a 50% lower dosage of vasopressors needed to maintain an adequate organ perfusion.

Detailed Description
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Severe sepsis is a devastating disorder that results from a complex host response to insult after infection. Despite advances in intensive care technologies sepsis remains an important and life-threatening problem. Sepsis is the most common cause of death in the intensive care unit. Local or systemic release of bacteria-derived compounds, leading to the production of proinflammatory cytokines, induce systemic inflammatory reactions in septic patients. Continuous renal replacement therapies (CRRT) such as hemodialysis (CVVHD), hemofiltration (CVVH) or hemodiafiltration (CVVHDF) with conventional high-flux membranes allow to control fluid and electrolyte balance, and to improve the hemodynamic status of the patients. However, conventional high flux membranes have a limited permeability for sepsis-associated mediators with molecular weights in the range of 15.000 to 60.000 Da. A promising approach to enhance the mediator removal is to use membranes having larger pores and permeability characteristics than those currently used in CRRT. For that purpose a High Cut-Off (HCO) membrane has been developed and is manufactured by Gambro Research.After demonstrating the safety as well as the cytokine removal effectiveness in a clinical pilot study this study will assess the influence of the HCO treatment on the disease progression in septic patients.

Official Title
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High Cut-off Continuous Venovenous Hemodialysis (CVVHD) to Improve Hemodynamic Stability and Organ Function Scores in Patients Treated for Acute Renal Failure After Systemic Inflammatory Response Syndrome (SIRS)/Septic Shock

Conditions
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Systemic Inflammatory Response Syndrome, Kidney Failure, Acute

Intervention / Treatment
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* Device: continuous venovenous hemodialysis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Fulfilling at least two of the SIRS criteria as defined by the American College of Chest Physicians (ACCP)/Society of Critical Care Medicine (SCCM) Consensus Conference Having signs of renal dysfunction Requirement for catecholamine administration (norepinephrine or others) Acute Physiology And Chronic Health Evaluation (APACHE II) score at enrolment greater than or equal to 19 and less than or equal to 30 Exclusion Criteria: Lack of written informed consent from patients or a legally authorized surrogate Duration of septic shock greater than 4 days Hypoproteinemia (characterized by serum albumin less than 18 g/l) End stage renal failure Known active malignancy Known human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV) infection Age younger than 18 years or older than 80 years Known pregnancy Immunosuppression after transplantation Participation in another clinical study Renal replacement therapy greater than 24 hours before randomization

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HCO<br>High cut-off filters HCO1100 | Device: continuous venovenous hemodialysis<br>* dialysate flow rate 35 ml/h/kg. Blood flow rate should be aimed at 200 ml/min, but not less than 150 ml/min. Bicarbonate- or lactate-buffered solutions will be used as dialysis fluids. Study dialyzers will be changed routinely every 24 h or earlier if the filter is obstructed by clotting.<br>|
| Active Comparator: control<br>conventional high-flux filters | Device: continuous venovenous hemodialysis<br>* dialysate flow rate 35 ml/h/kg. Blood flow rate should be aimed at 200 ml/min, but not less than 150 ml/min. Bicarbonate- or lactate-buffered solutions will be used as dialysis fluids. Study dialyzers will be changed routinely every 24 h or earlier if the filter is obstructed by clotting.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dosage of vasopressors |  | day 1 to day 5 | 
| Mean arterial pressure |  | day before inclusion and day 1 to day 5 | 
| Heart rate |  | day before inclusion and day 1 to day 5 | 
| Central venous pressure |  | day before inclusion and day 1 to day 5 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sequential organ failure assessment (SOFA) score |  | at ICU admission, at inclusion and day 1 to day 5 | 
| Survival |  | 28 days | 
| Length of need for catecholamine application |  | 28 days follow up | 
| Length of need for mechanical ventilation |  | 28 days | 
| Length of need for renal replacement therapy |  | 28 days | 
| Length of stay in intensive care unit (ICU) |  | 28 days |