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

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

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.

Study Overview

• Status: Unknown
• Conditions: Extracorporeal Circulation; Hemofiltration
• Intervention / Treatment: Device: Cytosorb Adsorber

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.

• Study Type: Interventional
• Enrollment (Anticipated): 80
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Germany
  • Bavaria
    • Nuremberg, Bavaria, Germany, 90471
      • Klinikum Nürnberg - Nuremberg Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years to 85 years (Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment; CPB with Cytosorb	Device: Cytosorb Adsorber; Cytokine adsorption during CPB
No Intervention: Control; CPB without Cytosorb (Control)

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality	Impact of intraoperative Cytokine adsorption on postoperative patient course	28 days

Collaborators and Investigators

• Sponsor: Klinikum Nürnberg
• Collaborators: CytoSorbents, Inc

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Anticipated): May 1, 2017
• Primary Completion (Anticipated): May 1, 2019
• Study Completion (Anticipated): May 1, 2019

Study Registration Dates

• First Submitted: June 16, 2015
• First Submitted That Met QC Criteria: March 31, 2017
• First Posted (Actual): April 7, 2017

Study Record Updates

• Last Update Posted (Actual): April 7, 2017
• Last Update Submitted That Met QC Criteria: March 31, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Other Study ID Numbers: 1_15B

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No