Clinical trial NCT01518569: Ulinastatin's Anti-inflammatory Reaction in Cardiac Surgery
Official title: Effect of Ulinastatin on Postoperative Systemic Inflammatory Response in Cardiac Surgery
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Cardiovascular Disease
Keywords: ulinastatin
systemic inflammation
cardiac surgery
cardiopulmonary bypass
Lead sponsor: Konkuk University Medical Center
Sponsor class: OTHER
First posted: 2012-01-26
Enrollment: 26
Sex: ALL
Minimum age (years): 25
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The purpose of the present study is to determine whether ulinastatin, urinary anti-trypsin inhibitor, attenuates cardiopulmonary bypass (CPB)-activated systemic inflammatory response in cardiac surgery with CPB.

Serial measurements and analysis of several inflammatory cytokines (bactericidal permeability increasing protein, interleukin-6, tumor necrosis factor-α)as well as markers of cardiac injury, renal impairment and oxygenation profile will be performed to determine ulinastatin's efficacy.

Detailed description: Applying aortic cross-clamp (ACC) and cardiopulmonary bypass (CPB) for cardiac surgery produces variable systemic inflammatory reactions. As a common complication of those reactions, pulmonary dysfunction, which usually indicated by postoperative hypoxemia, is frequently associated with cardiac surgery employing CPB and has been used as a major predictor of morbidity and mortality.

Circulating humoral and cellular factors are involved in the development of the systemic inflammatory reactions including organ dysfunction. So far, many studies analyzed the concentration of inflammatory marker (cytokine) to determine the degree of systemic inflammatory responses in various conditions.

Ulinastatin has anti-inflammatory activity and suppresses the infiltration of neutrophils. Previous studies suggested ulinastatin's cytoprotective effect against ischemia-reperfusion injury in major organs and its inhibition of inflammatory marker production.

The purpose of the present study is to determine ulinastatin's possible protective efficacy of in attenuating CPB-activated systemic inflammatory response regarding postoperative cardiac, renal and pulmonary dysfunction in cardiac surgery with CPB. Serial measurements and analysis of several inflammatory cytokines, such as bactericidal permeability increasing protein (BPI), interleukin (IL)-6, tumor necrosis factor (TNF)-α, as well as markers of cardiac injury, renal impairment and oxygenation profile, such as creatine kinase-MB (CK-MB), troponin I (TnI), C-reactive protein (CRP), arterial O2 tension /inspired O2 fraction (PaO2/FiO2 ratio), will be performed to this purpose.

Eligibility criteria: Inclusion Criteria:

* elective cardiac surgery employing CPB

Exclusion Criteria:

* urgent/emergency surgery,
* previous heart surgery,
* combined CABG and valve surgery,
* age \> 75 yrs,
* left ventricular ejection fraction \< 0.45,
* diabetes treated with insulin,
* active gastropathic disorder,
* treatment for chronic obstructive pulmonary disease,
* preoperative use of steroids
* postoperative re-operation due to bleeding control
* pre and postoperative renal replacement therapy
* left ventricular assist device implantation

Primary outcomes:
measure: bactericidal permeability increasing protein
timeFrame: 5-30 min before the end of anesthesia
measure: interleukin-6
timeFrame: 5-30 min before the end of anesthesia
measure: tumor necrosis factorTNF-α
timeFrame: 5-30 min before the end of anesthesia
Secondary outcomes:
measure: Creatine kinase-MB
timeFrame: before anesthesia, 24 hour after the end of anesthesia
measure: troponin I
timeFrame: before anesthesia, 24 hour after the end of anesthesia
measure: C-reactive protein
timeFrame: before anesthesia, 24 hour after the end of anesthesia
measure: serum creatinine
timeFrame: before anesthesia, 24 hour after the end of anesthesia
measure: PaO2/FiO2 ratio
timeFrame: before anesthesia, 24 hour after the end of anesthesia
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Konkuk University Medical Center
Study officials:
References:
citation: Nakanishi K, Takeda S, Sakamoto A, Kitamura A. Effects of ulinastatin treatment on the cardiopulmonary bypass-induced hemodynamic instability and pulmonary dysfunction. Crit Care Med. 2006 May;34(5):1351-7. doi: 10.1097/01.CCM.0000215110.55899.AE.
citation: Hill GE. Cardiopulmonary bypass-induced inflammation: is it important? J Cardiothorac Vasc Anesth. 1998 Apr;12(2 Suppl 1):21-5.