Ulinastatin's Anti-inflammatory Reaction in Cardiac Surgery

Cardiovascular Disease Clinical Trial

— ulistin  

Official title:

Effect of Ulinastatin on Postoperative Systemic Inflammatory Response in Cardiac Surgery

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01518569
• Other study ID #: KUH1160040
• Status: Completed
• Phase: Phase 4
• First received: January 20, 2012
• Last updated: January 25, 2012
• Start date: March 2008
• Est. completion date: August 2008

Study information

• Verified date: January 2012
• Source: Konkuk University Medical Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: Korea: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 26
• Est. completion date: August 2008
• Est. primary completion date: June 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 25 Years to 75 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Cardiovascular Disease
• Cardiovascular Diseases

Intervention

Drug:
• ulinastatin
ulinastatin 5000 unit/kg iv before the initiation of CPB
• placebo
placebo (the same amount of normal saline) iv before the initiation of CPB

Locations

Country	Name	City	State
Korea, Republic of	Konkuk University Medical Center	Seoul

Sponsors (1)

Lead Sponsor	Collaborator
Konkuk University Medical Center

Country where clinical trial is conducted

Korea, Republic of, 

References & Publications (2)

Hill GE. Cardiopulmonary bypass-induced inflammation: is it important? J Cardiothorac Vasc Anesth. 1998 Apr;12(2 Suppl 1):21-5. Review. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	bactericidal permeability increasing protein		5-30 min before the end of anesthesia	No
Primary	interleukin-6		5-30 min before the end of anesthesia	No
Primary	tumor necrosis factorTNF-a		5-30 min before the end of anesthesia	No
Secondary	Creatine kinase-MB		before anesthesia, 24 hour after the end of anesthesia	No
Secondary	troponin I		before anesthesia, 24 hour after the end of anesthesia	No
Secondary	C-reactive protein		before anesthesia, 24 hour after the end of anesthesia	No
Secondary	serum creatinine		before anesthesia, 24 hour after the end of anesthesia	No
Secondary	PaO2/FiO2 ratio		before anesthesia, 24 hour after the end of anesthesia	No