Role of Endothelin in Microvascular Dysfunction Following PCI for NSTEMI (BQ-123)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Amir Lerman, Mayo Clinic
ClinicalTrials.gov Identifier:
NCT00586820
First received: December 21, 2007
Last updated: July 3, 2014
Last verified: June 2014
  Purpose

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.

Non-ST segment elevation myocardial infarction (NSTEMI) is one type of heart attack. It is defined as the development of heart muscle necrosis results from an acute interruption of blood supply to a part of the heart which is demonstrated by an elevation of cardiac markers Creatinine Kinase Isoenzyme Muscle/Brain Type (CK-MB) in the blood and the absence of ST-segment elevation in ECG (electrocardiography). ST-segment is a portion of ECG, its elevation indicates full thickness damage of heart muscle. Absence of ST-segment elevation in NSTEMI indicates partial thickness damage of heart muscle occurs. Therefore, NSTEMI is less severe type of heart attack compared to STEMI (ST-segment elevation myocardial infarction) in which full thickness damage of heart muscle occurs.


Condition Intervention Phase
Myocardial Reperfusion Injury
Drug: BQ-123
Drug: Placebo
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 Non-ST Elevation Myocardial Infarction

Resource links provided by NLM:


Further study details as provided by Mayo Clinic:

Primary Outcome Measures:
  • Average Peak Velocity (APV) Immediately Following Percutaneous Coronary Intervention (PCI) [ Time Frame: immediately following PCI procedure ] [ Designated as safety issue: No ]
    Coronary microvascular blood flow will be assessed following successful PCI by measuring APV in the culprit vessel using Doppler echocardiography.


Secondary Outcome Measures:
  • Percent Change in Creatinine Kinase Isoenzyme Muscle/Brain Type (CK-MB) From Immediately Pre-PCI to 8 and 16 Hours Post-PCI [ Time Frame: immediately pre-PCI, 8 hours post-PCI, 16 hours post-PCI ] [ Designated as safety issue: No ]
    CK-MB is a cardiac marker that can demonstrate the development of heart muscle necrosis resulting from an acute interruption of blood supply to a part of the heart. CK-MB is measured by a blood test.


Enrollment: 23
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
Experimental: BQ-123
BQ-123 will be infused at 300 nmol/min for 20 minutes prior to percutaneous coronary intervention (PCI).
Drug: BQ-123
BQ-123 is a cyclic peptide consisting of five amino acids. BQ-123 will be infused at 300 nmol/min for 20 minutes prior to percutaneous coronary intervention (PCI).
Placebo Comparator: Placebo
Subjects randomized to the placebo arm will receive a placebo infusion (saline) for 20 minutes prior to PCI.
Drug: Placebo
Subjects randomized to the placebo arm will receive a placebo infusion (saline) for 20 minutes prior to PCI.

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.

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 a selective endothelin type A receptor antagonist (BQ-123), 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:

  • Age ≥ 18 years
  • 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:

  • 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, or renal disorders
  • Pregnancy or lactation
  • Federal Medical Center inmates
  • Inability or unwillingness to provide informed consent
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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: Amir Lerman, Professor of Medicine, College of Medicine, Mayo Clinic
ClinicalTrials.gov Identifier: NCT00586820     History of Changes
Other Study ID Numbers: 859-05
Study First Received: December 21, 2007
Results First Received: April 21, 2014
Last Updated: July 3, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Mayo Clinic:
Coronary Atherosclerosis
Microvascular Dysfunction
Non-ST Elevation Myocardial Infarction

Additional relevant MeSH terms:
Myocardial Infarction
Myocardial Reperfusion Injury
Reperfusion Injury
Wounds and Injuries
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Vascular Diseases
Cardiomyopathies
Postoperative Complications
Pathologic Processes
Cyclo(Trp-Asp-Pro-Val-Leu)
Antihypertensive Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 14, 2014