Removal of Cytokines in Patients Undergoing Cardiac Surgery With CPB

Extracorporeal Circulation Clinical Trial

— REMOTE  

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT03104179
• Other study ID #: 1_15B
• Status: Not yet recruiting
• Phase: N/A
• First received: June 16, 2015
• Last updated: March 31, 2017
• Start date: May 2017
• Est. completion date: May 2019

Study information

• Verified date: March 2017
• Source: Klinikum Nürnberg
• Contact: Giuseppe Santarpino, MD
• Phone: +4909113985441
• Email: giuseppe.santarpino[@]klinikum-nuernberg.de
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 80
• Est. completion date: May 2019
• Est. primary completion date: May 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 65 Years to 85 Years

Eligibility

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

Related Conditions & MeSH terms

• Extracorporeal Circulation
• Hemofiltration

Intervention

Device:
• Cytosorb Adsorber
Cytokine adsorption during CPB

Locations

Country	Name	City	State
Germany	Klinikum Nürnberg - Nuremberg Hospital	Nuremberg	Bavaria

Sponsors (2)

Lead Sponsor	Collaborator
Klinikum Nürnberg	CytoSorbents, Inc

Country where clinical trial is conducted

Germany, 

References & Publications (5)

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. — View 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. Review. — View 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. — View Citation

Levy JH, Tanaka KA. Inflammatory response to cardiopulmonary bypass. Ann Thorac Surg. 2003 Feb;75(2):S715-20. Review. — View Citation

Peng ZY, Wang HZ, Carter MJ, Dileo MV, Bishop JV, Zhou FH, Wen XY, Rimmelé 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Mortality	Impact of intraoperative Cytokine adsorption on postoperative patient course	28 days
Primary	Cytokine levels following CPB	Evaluation of cytokine adsorber effect on cytokine levels intra- and post	72 hours
Secondary	Intra- and postoperative catecholamine dosages	Impact of intraoperative Cytokine adsorption on hemodynamic stability	until ICU discharge, expected average 4 days
Secondary	postoperative renal failure necessitating RRT	Impact of intraoperative Cytokine adsorption on postoperative organ function	until ICU discharge, expected average 4 days
Secondary	Level of ferritin	Impact of intraoperative Cytokine adsorption on iron metabolism	72 hours
Secondary	Level of transferrin	Impact of intraoperative Cytokine adsorption on iron metabolism	72 hours
Secondary	Level of haptoglobin	Impact of intraoperative Cytokine adsorption on iron metabolism	72 hours
Secondary	Length of ICU stay	Impact of intraoperative Cytokine adsorption on postoperative patient course	until discharge from ICU, expected average 4 days
Secondary	Length of hospital stay	Impact of intraoperative Cytokine adsorption on postoperative patient course	up to hospital discharge, expected average 14 days