Extracorporeal Elimination of Cytokines Following Abdominal-thoracic Esophagectomy

Study Overview
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Brief Summary
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This study evaluates the effect of extracorporeal removal of inflammatory mediators on the systemic inflammation reaction of patients admitted to the intensive care unit following elective esophagectomy. Half of the participants will be treated with an adsorption device (CytoSorbents Adsorber), while the other half will be treated according to standard care. Significant reductions of interleukin-6 plasma concentration, SOFA score and catecholamine dosage in the intervention group are expected.

Detailed Description
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Radical esophagectomy combined with extensive lymphadenectomy for esophageal cancer is one of the most invasive surgical procedures. Even with progress made in surgical technique and postoperative management the rate of short- and long term complications remains high. The surgical trauma invariably causes liberation and activation of inflammatory mediators and danger associated molecular patterns, which in turn result in a pronounced systemic inflammatory reaction, leading to multiorgan dysfunction including adult respiratory distress syndrome (ARDS) in many patients. The subsequent counter regulation of the immune system induces immune paralysis, which is followed by infectious complications and increases the probability of severe sepsis. Moreover, severe systemic inflammation causes capillary leakage, resulting in impaired wound healing and endangered anastomoses. Therefore, it seems that early and effective measures against the excessive production of mediators and cytokines are indicated without impairment of the innate and adaptive immune response as it would be expected with the administration of e.g. steroids. Instead, the removal of an excessive amount of circulating cytokines might be a desirable method having shown its effectivity in the therapy of septic shock in the past. The aim of this study is to demonstrate the effectiveness of extracorporeal cytokine removal to dampen the systemic inflammatory response following abdominal-thoracic esophagectomy.

Official Title
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Extracorporeal Elimination of Cytokines Following Abdominal-thoracic Esophagectomy - a Randomized Study (EXCESS)

Conditions
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Inflammation

Intervention / Treatment
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* Device: CytoSorb cytokine elimination


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: abdominal-thoracic esophagectomy with radical lymphadenectomy post operative admission to ICU age >= 18 yrs written informed consent Exclusion Criteria: Participation in another interventional trial pregnancy or lactation systemic medication with high dose steroids and/or immunosuppressants and/or radiotherapy during the last 3 months known diseases of the immune system (benign and malign) contraindications for extracorporeal therapy Thrombocytopenia < 50*10^9/l therapy limitations (DNR), moribund status missing informed consent

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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Standard Care<br>intensive care therapy according to international standards and following local SOPs, including fluid therapy, mechanical ventilation, catecholamine therapy and other pharmacotherapy as required | |
| Experimental: CytoSorb<br>all of the above, plus extracorporeal hemadsorption therapy (CytoSorbents Adsorber cartridge) using continuous veno-venous hemofiltration (citrate anticoagulation) CytoSorb cytokine elimination | Device: CytoSorb cytokine elimination<br>* Hemoperfusion using continuous veno-venous hemofiltration (citrate regional anticoagulation) with CytoSorb cytokine elimination over a period of 48h immediately following admission to the intensive care unit<br>* Other names: hemadsorption;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of interleukin-6 plasma levels | Change of interleukin-6 plasma levels | 72 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in SOFA Score | decrease of >= 2 score points in the intervention group | 120 hours | 
| Change of catecholamine dose | decrease of >= 0.1 µg/kg/min catecholamine dosage to achieve MAP > 65 mmHg in intervention group | 48 hours | 
| Fluid intake | reduction of fluid intake to maintain MAP > 65 mmHg of >= 1000 ml/24h in intervention group | 120 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Esophagectomy Inflammation Hemoperfusion Cytokines