Clinical trial NCT03104179: Removal of Cytokines in Patients Undergoing Cardiac Surgery With CPB
Official title: Removal of Cytokines in Patients Undergoing Cardiac Surgery With CPB (The REMOTE Study)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Extracorporeal Circulation
Hemofiltration
Lead sponsor: Klinikum Nürnberg
Sponsor class: OTHER
Collaborators: name: CytoSorbents, Inc
First posted: 2017-04-07
Enrollment: 80
Sex: ALL
Minimum age (years): 65
Maximum age (years): 85
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Cytokine levels following CPB
timeFrame: 72 hours
Secondary outcomes:
measure: Intra- and postoperative catecholamine dosages
timeFrame: until ICU discharge, expected average 4 days
measure: postoperative renal failure necessitating RRT
timeFrame: until ICU discharge, expected average 4 days
measure: Level of ferritin
timeFrame: 72 hours
measure: Level of transferrin
timeFrame: 72 hours
measure: Level of haptoglobin
timeFrame: 72 hours
measure: Length of ICU stay
timeFrame: until discharge from ICU, expected average 4 days
measure: Length of hospital stay
timeFrame: up to hospital discharge, expected average 14 days
Other outcomes:
measure: Mortality
timeFrame: 28 days
Locations:
city: Nuremberg
country: Germany
facility: Klinikum Nürnberg - Nuremberg Hospital
state: Bavaria
Study officials:
References:
citation: Levy JH, Tanaka KA. Inflammatory response to cardiopulmonary bypass. Ann Thorac Surg. 2003 Feb;75(2):S715-20. doi: 10.1016/s0003-4975(02)04701-x.
citation: Allan CK, Newburger JW, McGrath E, Elder J, Psoinos C, Laussen PC, del Nido PJ, Wypij D, McGowan FX Jr. The relationship between inflammatory activation and clinical outcome after infant cardiopulmonary bypass. Anesth Analg. 2010 Nov;111(5):1244-51. doi: 10.1213/ANE.0b013e3181f333aa. Epub 2010 Sep 9.
citation: Bellomo R, Auriemma S, Fabbri A, D'Onofrio A, Katz N, McCullough PA, Ricci Z, Shaw A, Ronco C. The pathophysiology of cardiac surgery-associated acute kidney injury (CSA-AKI). Int J Artif Organs. 2008 Feb;31(2):166-78. doi: 10.1177/039139880803100210.
citation: Blomquist S, Gustafsson V, Manolopoulos T, Pierre L. Clinical experience with a novel endotoxin adsorbtion device in patients undergoing cardiac surgery. Perfusion. 2009 Jan;24(1):13-7. doi: 10.1177/0267659109106730.
citation: Peng ZY, Wang HZ, Carter MJ, Dileo MV, Bishop JV, Zhou FH, Wen XY, Rimmele T, Singbartl K, Federspiel WJ, Clermont G, Kellum JA. Acute removal of common sepsis mediators does not explain the effects of extracorporeal blood purification in experimental sepsis. Kidney Int. 2012 Feb;81(4):363-9. doi: 10.1038/ki.2011.320. Epub 2011 Sep 14.