Removal of Cytokines in Patients Undergoing Cardiac Surgery With CPB

Study Overview
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Brief Summary
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In a lot of cases during cardiac surgery cardiopulmonary bypass initiates SIRS due to release of cytokines during immunological response. They are induced by different types of inductors ( intrinsic and extrinsic). High levels of inflammation markers like TNF-a, IL 6 and IL 10 as well as TGF-ß are detectable after 2 hours of surgery. Beside the inflammation acute phase parameters like fibrinogen, ferritin are increased. These changes lead to rheology impairments. These strong reactions lead to dysfunction of different organs possibly culminating in a multi organ failure. There is a correlation between amounts of cytokines and mortality. Often AKI occurs after CPB with a rate of about 30%. Dysfunctions of organ function are often connected with increased mortality, prolonged mechanical ventilation , septic complications, increased catecholamine dosages and prolonged length of ICU stay. Use of cytokine adsorption within the extracorporeal circuit during CBP can affect the circulating cytokine levels during and after CPB and lead to a diminished inflammatory response, acute phase reaction as well as reduction of organ failure.

Detailed Description
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In a lot of cases during cardiac surgery cardiopulmonary bypass initiates SIRS due to release of cytokines during immunological response. They are induced by different types of inductors ( intrinsic and extrinsic). High levels of inflammation markers like TNF-a, IL 6 and IL 10 as well as TGF-ß are detectable after 2 hours of surgery. Beside the inflammation acute phase parameters like fibrinogen, ferritin are increased. These changes lead to rheology impairments. These strong reactions lead to dysfunction of different organs possibly culminating in a multi organ failure. There is a correlation between amounts of cytokines and mortality. Often AKI occurs after CPB with a rate of about 30%. Dysfunctions of organ function are often connected with increased mortality, prolonged mechanical ventilation , septic complications, increased catecholamine dosages and prolonged length of ICU stay. Use of cytokine adsorption within the extracorporeal circuit during CBP can affect the circulating cytokine levels during and after CPB and lead to a diminished inflammatory response, acute phase reaction as well as reduction of organ failure. Official Title: Removal of Cytokines in patients undergoing cardiac surgery with CPB ( The REMOTE Study) Study type: Interventional Study design: randomized, controlled Endpoint Classification: Efficacy study Interventional Model: Parallel assignment Masking: Single blinding ( Subject) Primary purpose: Treatment Patients who have an elective cardiac surgery with an expected CPB duration > 75 min ( e.g. valve surgery, CABG, combined procedures, redo) will be enrolled into the study after a giving informed consent. Selection of patients are directed by randomization. Patient which drop out will be replaced.

Official Title
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Removal of Cytokines in Patients Undergoing Cardiac Surgery With CPB (The REMOTE Study)

Conditions
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Extracorporeal Circulation, Hemofiltration

Intervention / Treatment
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* Device: Cytosorb Adsorber


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Elective cardiac surgery with CPB Signed informed consent CPB time > 75 min. Comorbidities: diabetes mellitus CHF, NYHA class 1 and 2 liver dysfunction (1, 2) kidney dysfunction (1, 2) hypertension arteriosclerosis Exclusion Criteria: Age < 65 years Declined informed consent Planed temperature < 32 C Emergency surgery Preexisting renal replacement therapy Preexisting kidney transplantation Administration of immunosuppressants like steroids AIDS with CD 4 < 200/ Participation in other trials

Ages Eligible for Study
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Minimum Age: 65 Years
Maximum Age: 85 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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment<br>CPB with Cytosorb | Device: Cytosorb Adsorber<br>* Cytokine adsorption during CPB<br>|
| No Intervention: Control<br>CPB without Cytosorb (Control) | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cytokine levels following CPB | Evaluation of cytokine adsorber effect on cytokine levels intra- and post | 72 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Intra- and postoperative catecholamine dosages | Impact of intraoperative Cytokine adsorption on hemodynamic stability | until ICU discharge, expected average 4 days | 
| postoperative renal failure necessitating RRT | Impact of intraoperative Cytokine adsorption on postoperative organ function | until ICU discharge, expected average 4 days | 
| Level of ferritin | Impact of intraoperative Cytokine adsorption on iron metabolism | 72 hours | 
| Level of transferrin | Impact of intraoperative Cytokine adsorption on iron metabolism | 72 hours | 
| Level of haptoglobin | Impact of intraoperative Cytokine adsorption on iron metabolism | 72 hours | 
| Length of ICU stay | Impact of intraoperative Cytokine adsorption on postoperative patient course | until discharge from ICU, expected average 4 days | 
| Length of hospital stay | Impact of intraoperative Cytokine adsorption on postoperative patient course | up to hospital discharge, expected average 14 days |