Endothelin-Receptor Blockade in Coronary Heart Disease

Sponsor

Medical University of Vienna (Other)

Overall Status

Completed

CT.gov ID

NCT00427232

Collaborator

(none)

Enrollment

Location

Duration (Months)

0.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Endothelin is a hormon that causes acute and chronic narrowing of heart vessels. The purpose of this study is to assess whether suppression of this activity by using two types of receptor antagonists can reduce this effect and thus improve blood supply of the heart muscle.

Condition or Disease	Intervention/Treatment	Phase
Coronary Vessels Endothelins Vascular Resistance	Drug: BQ-123 and BQ-788	Phase 1

Detailed Description

Endothelin (ET) is the most potent vasoconstrictor known and plays a major role in the development of coronary artery disease as well as in acute vasoconstriction. This effect is mainly mediated by the vascular ET-A receptor, whereas the ET-B receptor mediates vasodilation and cleavage of ET. Currently, there are both selective ET-A antagonists and non-selective ET-A and ET-B antagonists under investigation. The aim of the study is to test the effect of ET-receptor blockade on the vasoreagibility of epicardial and intramyocardial coronary arteries in patients undergoing cardiac catheterization. We randomly use the selective ET-A receptor BQ-123 (Group A) and the combination of BQ-123 and the ET-B receptor antagonist BQ-788 (Group B). The tested infusion will be applied selectively into the assessed coronary artery by a special infusion catheter. To evaluate the morphometric changes we use quantitative coronary angiography to measure the diameter of the coronary artery before and after intracoronary infusion of the tested substances. Furthermore we will use Pressure Wire to measure the hemodynamic conditions before and after infusion, thus evaluating the epicardial and the intramyocardial blood perfusion.

Comparison: Coronary artery diameter as measured by quantitative angiography (minimal lumen diameter) and parameters indicative of epicardial and intramyocardial blood flow as determined by Pressure Wire (fractional flow reserver, coronary flow reserve, intramyocardial resistance) before and after ET-antagonist infusion will be compared.

Study Design

Study Type:

Interventional

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double

Primary Purpose:

Diagnostic

Official Title:

Selective and Non-Selective Endothelin-Receptor Blockade in Coronary Artey Disease

Study Start Date :

May 1, 2003

Study Completion Date :

Aug 1, 2006

Outcome Measures

Primary Outcome Measures

minimal lumen diameter measured directly after infusion of the ET-antagonist(s) []

Secondary Outcome Measures

fractional flow reserve, coronary flow reserve, intramyocardial resistance measured directly after infusion of the ET-antagonist(s) []

Eligibility Criteria

Criteria

Ages Eligible for Study:

19 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

coronary artey disease
stable angina pectoris
male and post-menopausal female patients
age above 19 years
able and willing to conform to the requirements of the study
provided written informed consent

Exclusion Criteria:

severe focal coronary stenosis
visually calcified stenosis
aorto-ostial lesion location and unprotected left main stenosis
pre-menopausal female patients
diabetes mellitus
unstable angina pectoris and/or acute Q-wave myocardial infarctaion within the past 72 hours
current vasoactive medication
previous percutaneous transluminal revascularization at the site of the target lesion
lesion which has extremely angulated segments >90%
vessel with escessive tortuosity of the proximal segment
severe hypotension
severely reduced left ventricular function
severe carotid stenosis
patients with pace maker
patients with elevated liver enzymes
patients simultaneously participating in another device or drug study
inability of unwillingness to comply with the study protocol