Role of Endothelin in Microvascular Dysfunction Following PCI for NSTEMI

NCT00586820 | Completed Phase 2 Results DMC

• 1 other identifier: 859-05
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

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.

Conditions

Myocardial Reperfusion Injury

Keywords

Coronary Atherosclerosis; Microvascular Dysfunction; Non-ST Elevation Myocardial Infarction

Outcome Measures

Primary Outcomes (1)

• 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.

  immediately following PCI procedure

Secondary Outcomes (1)

• Percent Change in Creatinine Kinase Isoenzyme Muscle/Brain Type (CK-MB) From Immediately Pre-PCI to 8 and 16 Hours Post-PCI

  immediately pre-PCI, 8 hours post-PCI, 16 hours post-PCI

Study Arms (2)

BQ-123

EXPERIMENTAL

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

Drug: BQ-123

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

BQ-123 DRUG

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).

BQ-123

Placebo DRUG

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

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• Systemic hypotension (systolic \<90 mmHg)
• Heart failure or known ejection fraction \< 30%
• Left main disease
• Culprit lesion is in a saphenous vein graft
• % 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

Sponsors & Collaborators

• Mayo Clinic: lead

Study Sites (1)

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Related Publications (1)

• 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.

  PMID: 27547429 DERIVED

MeSH Terms

Conditions

Myocardial Reperfusion Injury; Coronary Artery Disease; Non-ST Elevated Myocardial Infarction

Interventions

cyclo(Trp-Asp-Pro-Val-Leu)

Condition Hierarchy (Ancestors)

Cardiomyopathies; Heart Diseases; Cardiovascular Diseases; Myocardial Ischemia; Vascular Diseases; Reperfusion Injury; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Coronary Disease; Arteriosclerosis; Arterial Occlusive Diseases; Myocardial Infarction; Infarction; Ischemia; Necrosis

Results Point of Contact

• Title: Dr. Amir Lerman
• Organization: Mayo Clinic

lerman.amir@mayo.edu

507-255-6670

Study Officials

• Abhiram Prasad, M.D.

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine, College of Medicine

Study Record Dates

• First Submitted: December 21, 2007
• First Posted: January 7, 2008
• Study Start: May 1, 2005
• Primary Completion: January 1, 2012
• Study Completion: January 1, 2012
• Last Updated: July 4, 2014
• Results First Posted: July 4, 2014

Record last verified: 2014-06

Locations

US (1)