Cytokine Removal in Cardiopulmonary Bypass Patients (CytoSorb)

Effect of Cytokine Removal in Cardiopulmonary Bypass Patients Using the Cytosorb ™ Filter

Cardiopulmonary bypass (CPB) surgery initiates a systemic inflammatory response induced by extrinsic (e.g. anesthesia, contact activation within the extracorporeal circuit, endotoxemia) and intrinsic (e.g. tissue damage, endothelial cell activation, ischemia-reperfusion injury of myocardium) factors. Monocytes are important players in systemic inflammation and the main producers of pro- and antiinflammatory cytokines. Monocytes activated by the extracorporeal circuit lead to a dysregulation of inflammatory homeostasis, increased levels of proinflammatory plasma mediators such as TNF-a, IL-1β, IL-6 and IL-18 are joined by antiinflammatory cytokines such as IL-10. This strong inflammatory response induces post surgical monocyte immunosuppression which is indicated by an impaired production of ex vivo LPS induced TNF-a production. Also malfunction of the peripheral circulation with increased lactate levels, pronounced fluid accumulation, increased need of vasopressors and cerebral dysfunction are observed. All of these factors may delay weaning from the ventilator, recovery of organ functions and discharge from ICU. Thus measures to decrease the inflammatory process have the potential to improve the perioperative course.

Use of cytokine adsorbing circuit during CBP has an effect on circulation cytokine levels for the first 36 hours after surgery and induces a decreased inflammatory response for up to 3 days post surgery.

Study Overview

• Status: Completed
• Conditions: Elective Cardiac Surgical Interventions
• Intervention / Treatment: Device: CytoSorb

Detailed Description

Patients, who have an elective cardiac surgical intervention with an expected CBP duration >120 minutes (e.g.: valve surgery, coronary artery bypass graft (CABG), combined procedures) will be enrolled to the study after given informed consent.

Patients, who decline will be asked to collect their secondary outcome data to create a "real - life" group and increase the number of patients in the control group. In this "real - life" group no additional blood samples will be taken.

• Study Type: Interventional
• Enrollment (Actual): 46
• Phase: Phase 3

Contacts and Locations

Study Locations

• Austria
  • Vienna, Austria, 1090
    • Divison of Cardiothoracic Anaesthesia and Intensive Care, Medical University of Vienna

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• elective cardiac surgical intervention with an expected CBP duration >120 minutes

Exclusion Criteria:

• Emergency procedures
• Heart transplantation
• Elective left ventricular assist device (LVAD) implantation
• Pulmonary thromendarterectomy
• Declined informed consent
• Serum creatinine > 2mg/dl
• Body mass index < 18
• Age < 18 years
• Pregnant woman
• Receiving chemotherapy or diagnosed with any disease state (e.g., AIDS) that has produced leukopenia
• Receiving antileukocyte drugs
• Receiving TNF-α Blockers, immunosuppressive drugs (e.g. tocilizumab)
• CRP > 2mg/dl
• History of Stroke
• Bilirubin >2mg/dl

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: CytoSorb; For the intervention group, the CytoSorb filter will be installed on the CPB machine in a parallel circuit to the body circulation. The flow through the filter will be driven by a roller pump with 200ml.min-1 .	Device: CytoSorb; Other Names: Polymer Based Adsorption Systems; ISO 13485:2003
No Intervention: Control; No filter will be installed on the CPB machine.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
IL-6	1. Preoperative 2. Before CBP 3. After CPB 4. 2 hours after CPB 5. 24 hours 6. 48 hours 7. 120 hours

Collaborators and Investigators

• Sponsor: Medical University of Vienna
• Collaborators: CytoSorbents, Inc
• Investigators: Study Director: Michael Hiesmayr, MD, Medical University of Vienna; Principal Investigator: Martin H Bernardi, MD, Medical University of Vienna; Study Chair: Harald Rinösl, MD, Medical University of Vienna; Study Chair: Friedrich Hoffelner, General Hospital of Vienna; Study Director: Andreas Spittler, MD, Medical University of Vienna; Study Chair: Dominik Wiedemann, MD, Medical University of Vienna; Study Chair: Philipp Opfermann, MD, Medical University of Vienna

Publications and helpful links

General Publications

• Bernardi MH, Rinoesl H, Dragosits K, Ristl R, Hoffelner F, Opfermann P, Lamm C, Preissing F, Wiedemann D, Hiesmayr MJ, Spittler A. Effect of hemoadsorption during cardiopulmonary bypass surgery - a blinded, randomized, controlled pilot study using a novel adsorbent. Crit Care. 2016 Apr 9;20:96. doi: 10.1186/s13054-016-1270-0.
• Wisgrill L, Lamm C, Hell L, Thaler J, Berger A, Weiss R, Weber V, Rinoesl H, Hiesmayr MJ, Spittler A, Bernardi MH. Influence of hemoadsorption during cardiopulmonary bypass on blood vesicle count and function. J Transl Med. 2020 May 15;18(1):202. doi: 10.1186/s12967-020-02369-x.

Study record dates

Study Major Dates

• Study Start: August 1, 2013
• Primary Completion (Actual): May 1, 2015
• Study Completion (Actual): May 1, 2015

Study Registration Dates

• First Submitted: June 7, 2013
• First Submitted That Met QC Criteria: June 13, 2013
• First Posted (Estimate): June 17, 2013

Study Record Updates

• Last Update Posted (Actual): February 23, 2017
• Last Update Submitted That Met QC Criteria: January 9, 2017
• Last Verified: January 1, 2017

More Information

Terms related to this study

• Other Study ID Numbers: 1095/2013

Plan for Individual participant data (IPD)

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