Role of Endothelin in Microvascular Dysfunction Following PCI for NSTEMI (BQ123)
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Purpose
Background: Percutaneous coronary intervention (PCI) for acute coronary syndromes frequently fails to restore myocardial perfusion despite establishing epicardial vessel patency. Endothelin-1 (ET-1) is a potent vasoconstrictor and its expression is increased in atherosclerotic coronary arteries. Our hypothesis is that increased activity of the endogenous endothelin system contributes to microvascular dysfunction, and adjunctive therapy with an endothelin receptor antagonist will result in improved microvascular blood flow.
Aims: The aims of the study are to assess in patients with non ST-elevation myocardial infarction, whether: 1) PCI causes an increase in coronary blood ET-1 level; 2) an endothelin receptor antagonist acutely improves coronary microvascular blood flow following PCI, Methods: The study is a prospective, double blind, placebo-controlled trial to assess the efficacy of BQ 123, a selective endothelin type A receptor antagonist, as adjunctive therapy for PCI for patients with non ST elevation myocardial infarction. Simultaneous aorta and coronary sinus blood samples will be obtained for ET-1 levels before and following the completion of PCI. Coronary microvascular blood flow will be assessed following successful PCI by measuring coronary flow reserve (primary endpoint) in the culprit vessel using a Doppler wire. Additional measures of microvascular flow will include TIMI frame count and Myocardial Blush Grade. The parameters will be compared between the BQ-123 and placebo treated patients.
| Condition | Intervention | Phase |
|---|---|---|
|
Microvascular Dysfunction Related to PCI |
Drug: BQ123 |
Phase 2 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator) Primary Purpose: Treatment |
| Official Title: | Role of Endothelin in Microvascular Dysfunction Following Percutaneous Coronary Intervention for NonST Elevation Myocardial Infarction |
- Primary endpoint: coronary flow reserve (CFR) [ Time Frame: immediately following PCI ] [ Designated as safety issue: No ]
- Secondary Endpoints: coronary sinus ET-1 levels before and after PCI [ Time Frame: Immediately pre and post PCI ] [ Designated as safety issue: No ]
- Post PCI: diastolic deceleration time from the coronary Doppler signal, TIMI frame count, myocardial blush grade [ Time Frame: Immediately post PCI ] [ Designated as safety issue: No ]
| Enrollment: | 24 |
| Study Start Date: | May 2005 |
| Study Completion Date: | January 2012 |
| Primary Completion Date: | January 2012 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Placebo Comparator: control
After randomization, patients will receive drug or placebo prior to PCI
|
Drug: BQ123
The control group will receive placebo rather than another vasodilator in order to specifically elucidate the role of the endogenous endothelin system. The Treatment group will receive an intracoronary infusion of either 300 nmol/min of BQ-123
|
|
Active Comparator: treatment
After randomization, patients will receive drug or placebo prior to PCI
|
Drug: BQ123
The control group will receive placebo rather than another vasodilator in order to specifically elucidate the role of the endogenous endothelin system. The Treatment group will receive an intracoronary infusion of either 300 nmol/min of BQ-123
|
Detailed Description:
Our hypothesis is that the endogenous endothelin system contributes to microvascular dysfunction and impaired myocardial reperfusion following successful PCI for non ST-elevation MI, and that endothelin receptor antagonism will improve microvascular flow. The study will provide new insight into the humoral regulation of the microcirculation in patients presenting with acute coronary syndromes. To address our hypothesis, three specific aims are proposed in patients with non ST elevation MI:
Aim 1: Assess whether there is ET-1 release into the coronary circulation following PCI.
Aim 2: Assess the acute effect of BQ-123, an endothelin receptor antagonist, on coronary microvascular blood flow immediately following PCI.
General methods: This section describes our approach to investigating the specific aims. The study is a prospective, double blind, placebo-controlled trial to assess the efficacy of BQ 123, a selective endothelin type A receptor antagonist, as adjunctive therapy for PCI for non ST elevation MI. The control group will receive placebo rather than another vasodilator in order to specifically elucidate the role of the endogenous endothelin system.
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Patients will be eligible for randomization if they meet the following criteria: Age ≥ 18 years, and a clinical diagnosis of unstable angina or non ST-elevation myocardial infarction , and requiring clinically indicated PCI for the management of non ST elevation acute coronary syndrome.
Exclusion Criteria:
- Patients will be ineligible for the study if one or more of the following conditions exist: systemic hypotension (systolic <90 mmHg), heart failure or known ejection fraction < 30%, left main disease, culprit lesion is in a saphenous vein graft, 100% occlusion of the culprit vessel or culprit is an ostial right coronary stenosis, currently enrolled in other active cardiovascular investigational studies, severe endocrine, hepatic, renal, disorders, pregnancy or lactation, inability to provide consent, Federal Medical Center inmates, inability or unwillingness to provide informed consent
Contacts and Locations More Information
Additional Information:
No publications provided
| Responsible Party: | Abhiram Prasad, Professor of Medicine, College of Medicine, Mayo Clinic |
| ClinicalTrials.gov Identifier: | NCT00586820 History of Changes |
| Other Study ID Numbers: | 859-05, BQ123 |
| Study First Received: | December 21, 2007 |
| Last Updated: | June 13, 2012 |
| Health Authority: | United States: Food and Drug Administration |
Keywords provided by Mayo Clinic:
|
coronary atherosclerosis Microvascular dysfunction NonST elevation MI |
Additional relevant MeSH terms:
|
Myocardial Infarction Myocardial Ischemia Heart Diseases Cardiovascular Diseases Vascular Diseases |
Cyclo(Trp-Asp-Pro-Val-Leu) Antihypertensive Agents Cardiovascular Agents Therapeutic Uses Pharmacologic Actions |
ClinicalTrials.gov processed this record on May 19, 2013