Clinical trial NCT03145441: Intraoperative Use of Extracorporeal Cytokine Adsorption During Orthotopic Heart Transplantation
Official title: The Impact of Pre-emptive Intraoperative Use of Extracorporeal Cytokine Adsorption During Orthotopic Heart Transplantation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Cardiac Transplantation
Cardiopulmonary Bypass
Lead sponsor: Semmelweis University
Sponsor class: OTHER
First posted: 2017-05-09
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Early postoperative hemodynamic instability
timeFrame: 24-48 hours
measure: Postoperative vasoplegia syndrome
timeFrame: 24-48 hours
measure: Cytokine and complement levels
timeFrame: 24-48 hours
Secondary outcomes:
measure: Inflammatory reaction
timeFrame: 24-48 hours
measure: Mechanical ventilation
timeFrame: up to 6 months
measure: Hospital stay
timeFrame: up to 6 months
measure: Length of survival
timeFrame: 1 year
measure: Medical circulatory support
timeFrame: 72 hours
measure: Perioperative complications
timeFrame: up to 1 month
measure: The incidence of early rejection
timeFrame: 1 month
Other outcomes:
Locations:
city: Budapest
country: Hungary
facility: Semmelweis University
Study officials:
References:
citation: 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.
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. doi: 10.1097/01.CCM.0000291646.34815.BB.
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.