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

July 3, 2014 updated by: Amir Lerman, Mayo Clinic

Role of Endothelin in Microvascular Dysfunction Following Percutaneous Coronary Intervention for Non-ST Elevation Myocardial Infarction

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

23

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Average Peak Velocity (APV) Immediately Following Percutaneous Coronary Intervention (PCI)
Time Frame: immediately following PCI procedure
Coronary microvascular blood flow will be assessed following successful PCI by measuring APV in the culprit vessel using Doppler echocardiography.
immediately following PCI procedure

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
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.
immediately pre-PCI, 8 hours post-PCI, 16 hours post-PCI

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Mayo Clinic

Investigators

  • Principal Investigator: Abhiram Prasad, M.D., Mayo Clinic

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2005

Primary Completion (Actual)

January 1, 2012

Study Completion (Actual)

January 1, 2012

Study Registration Dates

First Submitted

December 21, 2007

First Submitted That Met QC Criteria

January 4, 2008

First Posted (Estimate)

January 7, 2008

Study Record Updates

Last Update Posted (Estimate)

July 4, 2014

Last Update Submitted That Met QC Criteria

July 3, 2014

Last Verified

June 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 859-05

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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