Tissue-Type Plasminogen Activator (t-PA) Release Predicts Major Adverse Cardiac Events (MACE) in Patients With Non-critical Coronary Artery Disease
Primary Purpose
Coronary Artery Disease
Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Bradykinin
Sponsored by
About this trial
This is an interventional diagnostic trial for Coronary Artery Disease focused on measuring Coronary Artery Disease
Eligibility Criteria
Inclusion Criteria:
- Age >18 year old male and female patients
- All patients are referred for elective cardiac catheterization based on clinical indication
- Cath shows mild or moderate (<70% stenosis) CAD that does not require mechanical intervention
Exclusion Criteria:
- Severe stenosis requires intervention.
- Significant left main coronary artery disease (>40%).
- Acute MI or acute coronary syndrome with enzyme elevation or ischemic EKG changes
- Patients with severe left ventricular dysfunction (EF<35%)
- Prior history of myocardial infarction
- History of stroke within 3 months.
- Recent history of thrombolytic
- History of coronary intervention within previous 6 months.
- Patients with history of coronary spasm
- Patients with congestive heart failure (class III and IV).
Sites / Locations
- Vanderbilt University Medical Center
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
1
Arm Description
Bradykinin
Outcomes
Primary Outcome Measures
Mortality
Secondary Outcome Measures
Full Information
NCT ID
NCT00868855
First Posted
March 19, 2009
Last Updated
December 11, 2017
Sponsor
Vanderbilt University
1. Study Identification
Unique Protocol Identification Number
NCT00868855
Brief Title
Tissue-Type Plasminogen Activator (t-PA) Release Predicts Major Adverse Cardiac Events (MACE) in Patients With Non-critical Coronary Artery Disease
Official Title
The Intracoronary Tissue-type Plasminogen Activator (t-PA) Release Predicts Major Adverse Cardiac Events in Patients With Non-critical Coronary Artery Disease
Study Type
Interventional
2. Study Status
Record Verification Date
December 2017
Overall Recruitment Status
Terminated
Why Stopped
poor enrollment
Study Start Date
December 2003 (undefined)
Primary Completion Date
December 2010 (Actual)
Study Completion Date
December 2010 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Vanderbilt University
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Coronary artery disease is the leading cause of death in USA. Contemporary cardiac care has substantially reduced mortality and morbidity in patients with severe coronary artery disease. However, patients with mild to moderate coronary artery stenosis (<70% stenosis) often present in the future with life threatening acute coronary syndrome which carries significant mortality and morbidity. It is difficult to predict outcomes in these patients before the events because the lack of complete understanding of the mechanisms underlying acute coronary syndrome and the lack of reliable markers that will predict major adverse cardiac events (MACE). Tissue-type plasminogen activator (t-PA) is released from endothelial cells and a major factor that prevent thrombosis in the coronary artery, the cause of acute coronary syndrome. Endothelial dysfunction impairs t-PA release. Therefore, we hypothesize that patients with impaired coronary artery t-PA release will have significantly higher risk for future MACE due to intrinsic fibrinolytic dysfunction that leads to increased thrombosis risk.
To test this hypothesis, we will determine whether intrinsic endothelial fibrinolytic dysfunction predicts MACE in patients with non-significant CAD. The study will measure t-PA release mediated by bradykinin, a major mediator for t-PA release. This will involve infusion of bradykinin into left main coronary artery of individuals who have undergone routine cardiac catheterization (clinically indicated). We will take blood samples from the coronary sinus and measure t-PA and plasminogen activator inhibitor-1 antigen and activity levels.
Detailed Description
Tissue-type Plasminogen Activator (tPA) is a protein in the blood which breaks down clots and plays an important role in preventing myocardial infarction. It is produced by the endothelial cell lining of the blood vessels. Previous studies demonstrate that t-PA is released in response to the hormones bradykinin and acetylcholine. Impaired t-PA release upon bradykinin stimulation may indicate endothelial dysfunction that leads to the development of acute coronary syndrome. In this project, we will determine whether impaired t-PA release can predict future occurrence of acute coronary syndrome. The study will involve individuals getting routine left heart cardiac catheterizations (indication for cardiac catheterization is solely based on clinical indication). Prior to the procedure, patient will have two blood samples (5 ml each) collected from their forearm before and after 2 minutes blood pressure cuff inflation on their arm. After routine diagnostic cardiac catheterization and there is no severe coronary artery stenosis (<70% stenosis), research protocol will be initiated. Study includes infusion with increasing doses of bradykinin into their left main coronary artery, and sample small amounts of blood from their coronary sinus (15 ml total).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Coronary Artery Disease
Keywords
Coronary Artery Disease
7. Study Design
Primary Purpose
Diagnostic
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
16 (Actual)
8. Arms, Groups, and Interventions
Arm Title
1
Arm Type
Experimental
Arm Description
Bradykinin
Intervention Type
Drug
Intervention Name(s)
Bradykinin
Other Intervention Name(s)
Bachem Distribution Services GmbH-Bradykinin
Intervention Description
Bradykinin, 0.2 ug - 2ug/minute, one time intracoronary infusion over 6 minutes. Drug (bradykinin) will be infused into the left main coronary artery via diagnostic catheter (JL4) at an escalating rate of 0.2, 0.6, 2 g/ml (1ml/min). A 5F Multipurpose catheter will be advanced to coronary sinus for blood sampling.
Primary Outcome Measure Information:
Title
Mortality
Time Frame
5 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age >18 year old male and female patients
All patients are referred for elective cardiac catheterization based on clinical indication
Cath shows mild or moderate (<70% stenosis) CAD that does not require mechanical intervention
Exclusion Criteria:
Severe stenosis requires intervention.
Significant left main coronary artery disease (>40%).
Acute MI or acute coronary syndrome with enzyme elevation or ischemic EKG changes
Patients with severe left ventricular dysfunction (EF<35%)
Prior history of myocardial infarction
History of stroke within 3 months.
Recent history of thrombolytic
History of coronary intervention within previous 6 months.
Patients with history of coronary spasm
Patients with congestive heart failure (class III and IV).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Douglas Vaughn, MD
Organizational Affiliation
Northwestern University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Vanderbilt University Medical Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Tissue-Type Plasminogen Activator (t-PA) Release Predicts Major Adverse Cardiac Events (MACE) in Patients With Non-critical Coronary Artery Disease
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