Clinical trial NCT02606799: Extracorporeal Elimination of Cytokines Following Abdominal-thoracic Esophagectomy
Official title: Extracorporeal Elimination of Cytokines Following Abdominal-thoracic Esophagectomy - a Randomized Study (EXCESS)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Inflammation
Keywords: Esophagectomy Inflammation Hemoperfusion Cytokines
Lead sponsor: Universitätsklinikum Hamburg-Eppendorf
Sponsor class: OTHER
Collaborators: name: CytoSorbents, Inc
First posted: 2015-11-17
Enrollment: 5
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Change of interleukin-6 plasma levels
timeFrame: 72 hours
Secondary outcomes:
measure: Change in SOFA Score
timeFrame: 120 hours
measure: Change of catecholamine dose
timeFrame: 48 hours
measure: Fluid intake
timeFrame: 120 hours
Other outcomes:
Locations:
city: Hamburg
country: Germany
facility: University Medical Center Hamburg-Eppendorf
Study officials:
affiliation: University Medical Center Hamburg-Eppendorf, Dep. of Critical Care
name: Axel Nierhaus, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Panagiotou A, Gaiao S, Cruz DN. Extracorporeal therapies in sepsis. J Intensive Care Med. 2013 Sep-Oct;28(5):281-95. doi: 10.1177/0885066611425759. Epub 2011 Oct 25.
citation: Bruenger F, Kizner L, Weile J, Morshuis M, Gummert JF. First successful combination of ECMO with cytokine removal therapy in cardiogenic septic shock: a case report. Int J Artif Organs. 2015 Feb;38(2):113-6. doi: 10.5301/ijao.5000382. Epub 2015 Feb 3.
citation: Kellum JA, Song M, Venkataraman R. Hemoadsorption removes tumor necrosis factor, interleukin-6, and interleukin-10, reduces nuclear factor-kappaB DNA binding, and improves short-term survival in lethal endotoxemia. Crit Care Med. 2004 Mar;32(3):801-5. doi: 10.1097/01.ccm.0000114997.39857.69.
citation: Basu R, Pathak S, Goyal J, Chaudhry R, Goel RB, Barwal A. Use of a novel hemoadsorption device for cytokine removal as adjuvant therapy in a patient with septic shock with multi-organ dysfunction: A case study. Indian J Crit Care Med. 2014 Dec;18(12):822-4. doi: 10.4103/0972-5229.146321.
citation: Mitzner SR, Gloger M, Henschel J, Koball S. Improvement of hemodynamic and inflammatory parameters by combined hemoadsorption and hemodiafiltration in septic shock: a case report. Blood Purif. 2013;35(4):314-5. doi: 10.1159/000351206. Epub 2013 Jul 31. No abstract available.