Cytokine Removal in Cardiopulmonary Bypass Patients (CytoSorb)

• ClinicalTrials.gov Identifier: NCT01879176
• Recruitment Status: Completed
• First Posted: June 17, 2013
• Results First Posted: January 10, 2017
• Last Update Posted: February 23, 2017
• Sponsor: Medical University of Vienna
• Collaborator: CytoSorbents, Inc
• Information provided by (Responsible Party): Dr. Martin Bernardi, Medical University of Vienna

Tracking Information

• First Submitted Date: June 7, 2013
• First Posted Date: June 17, 2013
• Results First Submitted Date: April 30, 2016
• Results First Posted Date: January 10, 2017
• Last Update Posted Date: February 23, 2017
• Study Start Date: August 2013
• Actual Primary Completion Date: May 2015 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: November 10, 2016): IL-6 [ Time Frame: 1. Preoperative 2. Before CBP 3. After CPB 4. 2 hours after CPB 5. 24 hours 6. 48 hours 7. 120 hours ]
• Original Primary Outcome Measures (submitted: June 13, 2013): Evolution of cytokines IL-1β, IL-6, IL-18, TNF-α, IL-10 [ Time Frame: 1. At induction of anaesthesia 2. Start CBP 3. At the end of CPB 4. 2 hours 5. 24 hours 6. 48 hours 7. 120 - 168 hours ]
• Current Secondary Outcome Measures: Not Provided

Original Secondary Outcome Measures (submitted: June 13, 2013)

• Serum CRP changes [ Time Frame: 1. At induction of anaesthesia 2. Start CBP 3. At the end of CPB 4. 2 hours 5. 24 hours 6. 48 hours 7. 120 - 168 hours ]
• ex vivo LPS induced TNF-α production [ Time Frame: 1. At induction of anaesthesia 2. Start CBP 3. At the end of CPB 4. 2 hours 5. 24 hours 6. 48 hours 7. 120 - 168 hours ]

• Current Other Pre-specified Outcome Measures: Not Provided

Original Other Pre-specified Outcome Measures (submitted: June 13, 2013)

• Drug treatment [ Time Frame: 1. At induction of anaesthesia 2. Start CBP 3. At the end of CPB 4. 2 hours 5. 24 hours 6. 48 hours 7. 120 - 168 hours ]
  • Vasopressor dose
  • Insulin dose
• Volemic status [ Time Frame: 1. At induction of anaesthesia 2. Start CBP 3. At the end of CPB 4. 2 hours 5. 24 hours 6. 48 hours 7. 120 - 168 hours ]
  • Need of fluid components (crystalloid, colloid solutions)
  • Need of blood products (erythrocytes, fresh frozen plasma, platelets)
  • Body impedance
  • Body weight
• Changes in procalcitonin, albumin, fibrinogen and total blood count [ Time Frame: 1. At induction of anaesthesia 2. Start CBP 3. At the end of CPB 4. 2 hours 5. 24 hours 6. 48 hours 7. 120 - 168 hours ]
• • Length of ICU stay [ Time Frame: participants will be followed for the duration of ICU stay ]
• 30 days mortality [ Time Frame: at day 30 ]

Descriptive Information

• Brief Title: Cytokine Removal in Cardiopulmonary Bypass Patients
• Official Title: Effect of Cytokine Removal in Cardiopulmonary Bypass Patients Using the Cytosorb ™ Filter

Brief Summary

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.

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
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Single (Participant); Primary Purpose: Treatment
• Condition: Elective Cardiac Surgical Interventions

Intervention

Device: CytoSorb

Other Names:

• Polymer Based Adsorption Systems
• ISO 13485:2003

Study Arms

• 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 .
  Intervention: Device: CytoSorb
• No Intervention: Control
  No filter will be installed on the CPB machine.

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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: May 18, 2015): 46
• Original Estimated Enrollment (submitted: June 13, 2013): 40
• Actual Study Completion Date: May 2015
• Actual Primary Completion Date: May 2015 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Austria

Administrative Information

• NCT Number: NCT01879176
• Other Study ID Numbers: 1095/2013
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Dr. Martin Bernardi, Medical University of Vienna
• Original Responsible Party: Same as current
• Current Study Sponsor: Medical University of Vienna
• Original Study Sponsor: Same as current
• 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

• PRS Account: Medical University of Vienna
• Verification Date: January 2017