Role of Endothelin in Microvascular Dysfunction Following PCI for NSTEMI (BQ123)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Abhiram Prasad, Mayo Clinic
ClinicalTrials.gov Identifier:
NCT00586820
First received: December 21, 2007
Last updated: June 13, 2012
Last verified: June 2012
  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

Resource links provided by NLM:


Further study details as provided by Mayo Clinic:

Primary Outcome Measures:
  • Primary endpoint: coronary flow reserve (CFR) [ Time Frame: immediately following PCI ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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
Criteria

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
Please refer to this study by its ClinicalTrials.gov identifier: NCT00586820

Locations
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Mayo Clinic
Investigators
Principal Investigator: Abhiram Prasad, M.D. Mayo Clinic
  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 April 16, 2014