Ulinastatin's Anti-inflammatory Reaction in Cardiac Surgery (ulistin)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Tae-Yop Kim, MD PhD, Konkuk University Medical Center
ClinicalTrials.gov Identifier:
NCT01518569
First received: January 20, 2012
Last updated: January 25, 2012
Last verified: January 2012
  Purpose

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.


Condition Intervention Phase
Cardiovascular Disease
Drug: ulinastatin
Drug: placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Prevention
Official Title: Effect of Ulinastatin on Postoperative Systemic Inflammatory Response in Cardiac Surgery

Resource links provided by NLM:


Further study details as provided by Konkuk University Medical Center:

Primary Outcome Measures:
  • bactericidal permeability increasing protein [ Time Frame: 5-30 min before the end of anesthesia ] [ Designated as safety issue: No ]
  • interleukin-6 [ Time Frame: 5-30 min before the end of anesthesia ] [ Designated as safety issue: No ]
  • tumor necrosis factorTNF-α [ Time Frame: 5-30 min before the end of anesthesia ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Creatine kinase-MB [ Time Frame: before anesthesia, 24 hour after the end of anesthesia ] [ Designated as safety issue: No ]
  • troponin I [ Time Frame: before anesthesia, 24 hour after the end of anesthesia ] [ Designated as safety issue: No ]
  • C-reactive protein [ Time Frame: before anesthesia, 24 hour after the end of anesthesia ] [ Designated as safety issue: No ]
  • serum creatinine [ Time Frame: before anesthesia, 24 hour after the end of anesthesia ] [ Designated as safety issue: No ]
  • PaO2/FiO2 ratio [ Time Frame: before anesthesia, 24 hour after the end of anesthesia ] [ Designated as safety issue: No ]

Enrollment: 26
Study Start Date: March 2008
Study Completion Date: August 2008
Primary Completion Date: June 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: placebo
normal saline, same amount, iv
Drug: placebo
placebo (the same amount of normal saline) iv before the initiation of CPB
Other Name: normall saline
Active Comparator: ulinastatin
5000 unit/kg iv
Drug: ulinastatin
ulinastatin 5000 unit/kg iv before the initiation of CPB
Other Name: ulistin

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

Ages Eligible for Study:   25 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01518569

Locations
Korea, Republic of
Konkuk University Medical Center
Seoul, Korea, Republic of, 143-729
Sponsors and Collaborators
Konkuk University Medical Center
  More Information

Publications:
Responsible Party: Tae-Yop Kim, MD PhD, Professor of Anesthesiology, Konkuk University Medical Center
ClinicalTrials.gov Identifier: NCT01518569     History of Changes
Other Study ID Numbers: KUH1160040
Study First Received: January 20, 2012
Last Updated: January 25, 2012
Health Authority: Korea: Food and Drug Administration

Keywords provided by Konkuk University Medical Center:
ulinastatin
systemic inflammation
cardiac surgery
cardiopulmonary bypass

Additional relevant MeSH terms:
Cardiovascular Diseases
Inflammation
Pathologic Processes
Urinastatin
Trypsin Inhibitors
Serine Proteinase Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 23, 2014