Tissue-Type Plasminogen Activator (t-PA) Release Predicts Major Adverse Cardiac Events (MACE) in Patients With Non-Critical Coronary Artery Disease

This study is enrolling participants by invitation only.
Sponsor:
Information provided by:
Vanderbilt University
ClinicalTrials.gov Identifier:
NCT00868855
First received: March 19, 2009
Last updated: March 24, 2009
Last verified: March 2009
  Purpose

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.


Condition Intervention Phase
Coronary Artery Disease
Drug: Bradykinin
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Diagnostic
Official Title: The Intracoronary Tissue-Type Plasminogen Activator (t-PA) Release Predicts Major Adverse Cardiac Events in Patients With Non-Critical Coronary Artery Disease

Resource links provided by NLM:


Further study details as provided by Vanderbilt University:

Primary Outcome Measures:
  • Mortality [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]

Enrollment: 16
Study Start Date: December 2003
Estimated Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Bradykinin
Drug: Bradykinin
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.
Other Name: Bachem Distribution Services GmbH-Bradykinin

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).

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age >18 year old male and female patients
  2. All patients are referred for elective cardiac catheterization based on clinical indication
  3. Cath shows mild or moderate (<70% stenosis) CAD that does not require mechanical intervention

Exclusion Criteria:

  1. Severe stenosis requires intervention.
  2. Significant left main coronary artery disease (>40%).
  3. Acute MI or acute coronary syndrome with enzyme elevation or ischemic EKG changes
  4. Patients with severe left ventricular dysfunction (EF<35%)
  5. Prior history of myocardial infarction
  6. History of stroke within 3 months.
  7. Recent history of thrombolytic
  8. History of coronary intervention within previous 6 months.
  9. Patients with history of coronary spasm
  10. Patients with congestive heart failure (class III and IV).
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00868855

Locations
United States, Tennessee
Vanderbilt University Medical Center
Nashville, Tennessee, United States, 37232
Sponsors and Collaborators
Vanderbilt University
Investigators
Principal Investigator: Douglas Vaughn, MD Northwestern University
  More Information

No publications provided

Responsible Party: Douglas Vaughn, MD, Northwestern University
ClinicalTrials.gov Identifier: NCT00868855     History of Changes
Other Study ID Numbers: IRB# 030473, NHLBI Grant 5P5OHL081009-02
Study First Received: March 19, 2009
Last Updated: March 24, 2009
Health Authority: United States: Food and Drug Administration

Keywords provided by Vanderbilt University:
Coronary Artery Disease

Additional relevant MeSH terms:
Coronary Artery Disease
Myocardial Ischemia
Coronary Disease
Heart Diseases
Cardiovascular Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Plasminogen
Tissue Plasminogen Activator
Bradykinin
Kininogens
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Cardiovascular Agents
Therapeutic Uses
Hematologic Agents
Vasodilator Agents
Cysteine Proteinase Inhibitors
Protease Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on September 22, 2014