Endothelin Receptor Blockade in Acute ST-elevation Myocardial Infarction

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Irene Lang, Medical University of Vienna
ClinicalTrials.gov Identifier:
NCT00502528
First received: July 16, 2007
Last updated: April 27, 2013
Last verified: April 2013
  Purpose

Background and Objective: Acute coronary syndrome is characterized by compromised blood flow at the epicardial and microvascular levels. The aim of the present study is to investigate the effect of ET-receptor blockade by BQ-123 on myocardial perfusion and infarct size as an adjunct to PCI-reperfusion therapy in patients with STEMI.

Patients are randomized to receive periinterventional intravenous BQ-123 or placebo.


Condition Intervention Phase
ST-Elevation Myocardial Infarction
Drug: Placebo
Drug: BQ-123
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Endothelin Receptor Blockade in Acute ST-elevation Myocardial Infarction

Resource links provided by NLM:


Further study details as provided by Medical University of Vienna:

Primary Outcome Measures:
  • Myocardial perfusion determined by CMR [ Time Frame: 3 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Final infarct size determined by CMR [ Time Frame: 3 days ] [ Designated as safety issue: No ]
  • Left ventricular function determined by CMR [ Time Frame: 3 days/ 6 months (6-months Remodeling-substudy) ] [ Designated as safety issue: No ]
  • Plasma NT-BNP [ Time Frame: 30 days/ 6 months (6-months substudy) ] [ Designated as safety issue: No ]
  • Enzymatic infarct size (CK levels) [ Time Frame: 3 days ] [ Designated as safety issue: No ]
  • ECG ST-segment resolution [ Time Frame: 1 hour ] [ Designated as safety issue: No ]
  • Markers of inflammation [ Time Frame: 24 hours/ 30 days ] [ Designated as safety issue: No ]
  • Major adverse cardiac events (MACE) (cardiovascular death, re-hospitalization for unstable angina and AMI, hospitalization for worsening heart failure) [ Time Frame: 30 days ] [ Designated as safety issue: Yes ]
  • Liver function [ Time Frame: 24hours/ 3 days/ 30 days ] [ Designated as safety issue: Yes ]
  • Event free survival [ Time Frame: 6 months (6-months substudy) ] [ Designated as safety issue: Yes ]
  • Holter ECG [ Time Frame: 3 days / 30 days (EP-substudy) ] [ Designated as safety issue: Yes ]

Enrollment: 57
Study Start Date: May 2007
Study Completion Date: August 2012
Primary Completion Date: August 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: 1
Placebo
Drug: Placebo
Peri-interventional
Other Name: sodium salt
Active Comparator: 2
BQ-123
Drug: BQ-123
Peri-interventional
Other Name: Cyclo(-D-Trp-D-Asp-Pro-D-Val-Leu) sodium salt

Detailed Description:

Background and Objective: Acute coronary syndrome is characterized by compromised blood flow at the epicardial and microvascular levels. We have previously shown that thrombectomy in ST-elevation myocardial infarction (STEMI) accelerates ST-segment resolution, possibly by preventing distal embolization. Therefore, we analyzed the vasoconstrictor concentration of acute coronary thrombi, and found high concentrations of endothelin (ET) which correlated with the magnitude of ST-segment resolution within one hour of percutaneous coronary intervention (PCI). Furthermore, ET-receptor blockade by tezosentan significantly repressed vasoconstriction in an in-vitro model using porcine coronary artery rings incubated with coronary thrombus homogenates extracted from STEMI patients.

The aim of the present study is to investigate the effect of ET-receptor blockade by BQ-123 on myocardial perfusion and infarct size as an adjunct to PCI-reperfusion therapy in patients with STEMI.

Methods: Fifty eligible patients will be randomized to receive periinterventional intravenous BQ-123 or placebo. The primary endpoint of the study will be microvascular function evaluated by cardiac magnetic resonance tomography.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • STEMI patients (defined as: Evidence of ischemic chest pain for >30 minutes within <12 hours and new ST-segment elevation for ≥2 mm in two or more contiguous electrocardiographic leads or in case of a true posterior infarction reciprocal ST-segment depressions in in V1 and V2 >1mm and/or elevated serum creatine phosphokinase or twofold elevation of troponin-T), aged 18 years and above, who undergo primary percutaneous revascularization (PCI) and have confirmed initial TIMI 0 or 1 in the infarct related coronary artery.

Exclusion Criteria:

  • Significant liver disease
  • Thrombolytic therapy
  • History of prior myocardial infarction
  • Current atrial fibrillation
  • History of congestive heart failure
  • History of migraine headache
  • Significant valvular heart disease, primary myocardial disease
  • Cardiogenic shock (sRR <90mmHg or need for inotropic support)
  • Child-bearing potential
  • Inability to read, understand and sign the informed consent
  • Life expectancy <3y
  • Prior organ transplantation
  • Medication with konazoles, ritonavir, rifampicin and sulfonyl-urea derivatives
  • Participation in another clinical study
  • Metal implants contraindicating CMR
  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: NCT00502528

Locations
Austria
Medical University of Vienna
Vienna, Vienna-Austria, Austria, 1090
Sponsors and Collaborators
Medical University of Vienna
Investigators
Principal Investigator: Irene M Lang, MD Medical University of Vienna
  More Information

Publications:
Responsible Party: Irene Lang, PI, Medical University of Vienna
ClinicalTrials.gov Identifier: NCT00502528     History of Changes
Other Study ID Numbers: BQ123AMI12/06
Study First Received: July 16, 2007
Last Updated: April 27, 2013
Health Authority: Austria: Agency for Health and Food Safety

Keywords provided by Medical University of Vienna:
Infarction
Endothelin
Perfusion

Additional relevant MeSH terms:
Infarction
Myocardial Infarction
Cardiovascular Diseases
Heart Diseases
Ischemia
Myocardial Ischemia
Necrosis
Pathologic Processes
Vascular Diseases

ClinicalTrials.gov processed this record on October 23, 2014