Intraoperative Use of Extracorporeal Cytokine Adsorption During Orthotopic Heart Transplantation

Cardiopulmonary Bypass Clinical Trial

Official title:

The Impact of Pre-emptive Intraoperative Use of Extracorporeal Cytokine Adsorption During Orthotopic Heart Transplantation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03145441
• Other study ID #: SU-AITK/VM-2017/1
• Status: Completed
• Phase: N/A
• Start date: April 9, 2018
• Est. completion date: December 31, 2021

Study information

• Verified date: September 2022
• Source: Semmelweis University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

There are several factors initiating cytokine storm and dysregulated systemic inflammatory response during cardiac transplantation. This may lead to serious perioperative complications: circulatory collapse, respiratory insufficiency, acute renal and liver failure, multi-organ dysfunction etc.

On the other hand the high level of cytokines may play an important role in the development of graft rejection which is still a relevant problem in this patient group.

There are some new data showing that the use of extracorporeal cytokine adsorber during long cardiopulmonary bypass time (>120min) may be beneficial to prevent SIRS (Systemic Inflammatory Response Syndrome) with decreasing the level of cytokines in patients undergoing elective cardiac surgery. However there is lack of data and studies regarding the effect of extracorporeal cytokine adsorption during cardiac transplantation.

The aim of the study is to investigate the effect of extracorporeal cytokine adsorber built in the cardiopulmonary bypass circle during heart transplantation. The hypothesis is that removal of cytokines during heart transplantation prevents the development of extreme systemic inflammatory response, hemodynamic collapse dominated by vasoplegia, and contribute to reduce the incidence of severe perioperative complications and early graft rejection.

Description:

Patients undergoing cardiac transplantation will be enrolled in the study after giving a written, signed informed consent.

The participants will be randomized into two groups:

• intervention group (30 patients): a cytokine adsorber (CytoSorb®) will be installed into the cardiopulmonary bypass circle during the operation

• control group (30 patients): no cytokine adsorber will be used during cardiopulmonary bypass

The investigators will collect demographic, clinical and laboratory data about patients before, during and after the operation.

The the use of vasopressors and inotropes in the perioperative period, length of mechanical ventilation, ICU and hospital stay, and incidence of perioperative complications, early cellular or humoral graft rejection, and survival will be documented.

The level of cytokines (IL-1, IL-6, IL-10, IL-17, tumor necrosis factor-alfa) and complements before, during and after the use of cardiopulmonary bypass will be determined if the investigators find relevant difference between the two groups in clinical variables.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: December 31, 2021
• Est. primary completion date: December 31, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• patients undergoing heart transplantation

• no medical or mechanical circulatory support straight before transplantation

• age > 18 years

Exclusion Criteria:

• age < 18 years

• septic condition (controlled infection) before transplantation

• prolonged hospital stay straight before transplantation

• use of positive inotropes or vasopressors straight before transplantation

• use of mechanical circulatory support straight before transplantation

• acute liver or kidney failure straight before transplantation

• high urgency transplantation

• retransplantation

• the patient declines participating in the study

Related Conditions & MeSH terms

• Cardiac Transplantation
• Cardiopulmonary Bypass

Intervention

Device:
• CytoSorb®
CytoSorb® is a biocompatible, high adsorptive polymer indicated in conditions where cytokine levels are extremely elevated.

Locations

Country	Name	City	State
Hungary	Semmelweis University	Budapest

Sponsors (1)

Lead Sponsor	Collaborator
Semmelweis University

Country where clinical trial is conducted

Hungary, 

References & Publications (3)

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. — View Citation

Kellum JA, Venkataraman R, Powner D, Elder M, Hergenroeder G, Carter M. Feasibility study of cytokine removal by hemoadsorption in brain-dead humans. Crit Care Med. 2008 Jan;36(1):268-72. — View Citation

Liang TB, Yu ZY, Zheng SS. [Expression of non-T cell derived cytokines in acute rejection after heart transplantation: experiment with mouse model]. Zhonghua Yi Xue Za Zhi. 2006 Jan 3;86(1):26-30. Chinese. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Early postoperative hemodynamic instability	Hemodynamic instability described by Vasoactive Inotropic Score and calculated for the first two postoperative days.; Vasoactive Inotropic Score is considered as 'high' if values = 30 points, representing higher risk for worse outcomes.	24-48 hours
Primary	Postoperative vasoplegia syndrome	Severity of postoperative vasoplegia based on criteria of vasoplegia syndrome: Norepinephrine reqirements = 0.3 µg/kg/min AND arginine vasopressin requirements at any dose	24-48 hours
Primary	Cytokine and complement levels	Level of pro- and anti-inflammatory cytokines (IL-1, IL-6, IL-10, IL-17, tumor necrosis factor-alfa) and complements immediately after induction of anesthesia, before initiation of cardiopulmonary bypass (CPB), 2 hours after initiation of CPB, at termination of CPB, 6-12-24 hours after initiation of CPB	24-48 hours
Secondary	Inflammatory reaction	Level of C reactive protein (CRP), white blood cells and procalcitonin immediately after induction of anesthesia, before initiation of cardiopulmonary bypass (CPB), 2 hours after initiation of CPB, at termination of CPB, 6-12-24 hours after initiation of CPB	24-48 hours
Secondary	Mechanical ventilation	Length of mechanical ventilation	up to 6 months
Secondary	Hospital stay	Length of ICU and hospital stay	up to 6 months
Secondary	Length of survival	Length of survival after heart transplantation	1 year
Secondary	Medical circulatory support	Use and dosage of vasopressors and inotropes immediately after induction of anesthesia, before initiation of cardiopulmonary bypass (CPB), 2 hours after initiation of CPB, at termination of CPB, 6-12-24 hours after initiation of CPB, on 2nd and 3rd postoperative day	72 hours
Secondary	Perioperative complications	Incidence of perioperative complications after heart transplantation during ICU stay (sepsis, SIRS, respiratory failure, acute renal failure, acute liver failure, postoperative cognitive dysfunction, graft failure)	up to 1 month
Secondary	The incidence of early rejection	The incidence of early (< 1 month) cellular or humoral rejection after heart transplantation	1 month