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Sponsored by: |
Vanderbilt University |
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Information provided by: | Vanderbilt University |
ClinicalTrials.gov Identifier: | NCT00868855 |
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 |
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Coronary Artery Disease |
Drug: Bradykinin |
Phase I |
Study Type: | Interventional |
Study Design: | Diagnostic, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety Study |
Official Title: | The Intracoronary Tissue-Type Plasminogen Activator (t-PA) Release Predicts Major Adverse Cardiac Events in Patients With Non-Critical Coronary Artery Disease |
Enrollment: | 16 |
Study Start Date: | December 2003 |
Estimated Primary Completion Date: | December 2010 (Final data collection date for primary outcome measure) |
Arms | Assigned Interventions |
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1: Experimental
Bradykinin
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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.
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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).
Ages Eligible for Study: | 18 Years and older |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Exclusion Criteria:
United States, Tennessee | |
Vanderbilt University Medical Center | |
Nashville, Tennessee, United States, 37232 |
Principal Investigator: | Douglas Vaughn, MD | Northwestern University |
Responsible Party: | Northwestern University ( Douglas Vaughn, MD ) |
Study ID Numbers: | IRB# 030473, NHLBI Grant 5P5OHL081009-02 |
Study First Received: | March 19, 2009 |
Last Updated: | March 24, 2009 |
ClinicalTrials.gov Identifier: | NCT00868855 History of Changes |
Health Authority: | United States: Food and Drug Administration |
Coronary Artery Disease |
Arterial Occlusive Diseases Vasodilator Agents Heart Diseases Bradykinin Myocardial Ischemia Vascular Diseases Tissue Plasminogen Activator Fibrinolytic Agents |
Ischemia Arteriosclerosis Cardiovascular Agents Coronary Disease Fibrin Modulating Agents Plasminogen Coronary Artery Disease |
Arterial Occlusive Diseases Vasodilator Agents Heart Diseases Molecular Mechanisms of Pharmacological Action Bradykinin Myocardial Ischemia Hematologic Agents Vascular Diseases Tissue Plasminogen Activator Fibrinolytic Agents |
Arteriosclerosis Cardiovascular Agents Pharmacologic Actions Coronary Disease Fibrin Modulating Agents Therapeutic Uses Cardiovascular Diseases Plasminogen Coronary Artery Disease |