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

NCT00868855 | Terminated Phase 1 DMC

• 2 other identifiers: IRB# 0304735P5OHL081009-02
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

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.

Conditions

Coronary Artery Disease

Keywords

Coronary Artery Disease

Outcome Measures

Primary Outcomes (1)

• Mortality

  5 years

Study Arms (1)

1

EXPERIMENTAL

Bradykinin

Drug: Bradykinin

Interventions

Bradykinin DRUG

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.

Also known as: Bachem Distribution Services GmbH-Bradykinin

1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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).

Sponsors & Collaborators

• Vanderbilt University: lead

Study Sites (1)

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

MeSH Terms

Conditions

Coronary Artery Disease

Interventions

Bradykinin

Condition Hierarchy (Ancestors)

Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases

Intervention Hierarchy (Ancestors)

Kinins; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Neuropeptides; Oligopeptides; Proteins; Nerve Tissue Proteins; Autacoids; Inflammation Mediators; Biological Factors

Study Officials

• Douglas Vaughn, MD

  Northwestern University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 19, 2009
• First Posted: March 25, 2009
• Study Start: December 1, 2003
• Primary Completion: December 1, 2010
• Study Completion: December 1, 2010
• Last Updated: December 13, 2017

Record last verified: 2017-12

Locations

US (1)