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

Primary Purpose

Myocardial Reperfusion Injury

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
BQ-123
Placebo
Sponsored by
Mayo Clinic
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Myocardial Reperfusion Injury focused on measuring Coronary Atherosclerosis, Microvascular Dysfunction, Non-ST Elevation Myocardial Infarction

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Mayo Clinic

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

BQ-123

Placebo

Arm Description

BQ-123 will be infused at 300 nmol/min for 20 minutes prior to percutaneous coronary intervention (PCI).

Subjects randomized to the placebo arm will receive a placebo infusion (saline) for 20 minutes prior to PCI.

Outcomes

Primary Outcome Measures

Average Peak Velocity (APV) Immediately Following Percutaneous Coronary Intervention (PCI)
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
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.

Full Information

First Posted
December 21, 2007
Last Updated
July 3, 2014
Sponsor
Mayo Clinic
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1. Study Identification

Unique Protocol Identification Number
NCT00586820
Brief Title
Role of Endothelin in Microvascular Dysfunction Following PCI for NSTEMI
Acronym
BQ-123
Official Title
Role of Endothelin in Microvascular Dysfunction Following Percutaneous Coronary Intervention for Non-ST Elevation Myocardial Infarction
Study Type
Interventional

2. Study Status

Record Verification Date
June 2014
Overall Recruitment Status
Completed
Study Start Date
May 2005 (undefined)
Primary Completion Date
January 2012 (Actual)
Study Completion Date
January 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Mayo Clinic

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Myocardial Reperfusion Injury
Keywords
Coronary Atherosclerosis, Microvascular Dysfunction, Non-ST Elevation Myocardial Infarction

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
23 (Actual)

8. Arms, Groups, and Interventions

Arm Title
BQ-123
Arm Type
Experimental
Arm Description
BQ-123 will be infused at 300 nmol/min for 20 minutes prior to percutaneous coronary intervention (PCI).
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Subjects randomized to the placebo arm will receive a placebo infusion (saline) for 20 minutes prior to PCI.
Intervention Type
Drug
Intervention Name(s)
BQ-123
Intervention Description
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).
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Subjects randomized to the placebo arm will receive a placebo infusion (saline) for 20 minutes prior to PCI.
Primary Outcome Measure Information:
Title
Average Peak Velocity (APV) Immediately Following Percutaneous Coronary Intervention (PCI)
Description
Coronary microvascular blood flow will be assessed following successful PCI by measuring APV in the culprit vessel using Doppler echocardiography.
Time Frame
immediately following PCI procedure
Secondary Outcome Measure Information:
Title
Percent Change in Creatinine Kinase Isoenzyme Muscle/Brain Type (CK-MB) From Immediately Pre-PCI to 8 and 16 Hours Post-PCI
Description
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.
Time Frame
immediately pre-PCI, 8 hours post-PCI, 16 hours post-PCI

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Abhiram Prasad, M.D.
Organizational Affiliation
Mayo Clinic
Official's Role
Principal Investigator
Facility Information:
Facility Name
Mayo Clinic
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
27547429
Citation
Guddeti RR, Prasad A, Matsuzawa Y, Aoki T, Rihal C, Holmes D, Best P, Lennon RJ, Lerman LO, Lerman A. Role of endothelin in microvascular dysfunction following percutaneous coronary intervention for non-ST elevation acute coronary syndromes: a single-centre randomised controlled trial. Open Heart. 2016 Aug 4;3(2):e000428. doi: 10.1136/openhrt-2016-000428. eCollection 2016.
Results Reference
derived
Links:
URL
http://clinicaltrials.mayo.edu
Description
Mayo Clinic Clinical Trials

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Role of Endothelin in Microvascular Dysfunction Following PCI for NSTEMI

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