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

July 16, 2007
April 27, 2013
May 2007
August 2009   (final data collection date for primary outcome measure)
Myocardial perfusion determined by CMR [ Time Frame: 3 days ] [ Designated as safety issue: No ]
Myocardial perfusion determined by CMR [ Time Frame: 3 days ]
Complete list of historical versions of study NCT00502528 on ClinicalTrials.gov Archive Site
  • 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 ]
  • Final infarct size determined by CMR [ Time Frame: 3 days/ 6 months ]
  • Left ventricular function determined by CMR [ Time Frame: 3 days/ 6 months ]
  • Plasma NT-BNP [ Time Frame: 30 days/ 6 months ]
  • Area under the curve of CK-MB levels estimating infarct size [ Time Frame: 3 days ]
  • ECG ST-segment resolution [ Time Frame: 1 hour ]
  • markers of inflammation [ Time Frame: 24 hours/ 30 days ]
  • major adverse cardiac events (MACE) (cardiovascular death, re-hospitalization for unstable angina and AMI, hospitalization for worsening heart failure) [ Time Frame: 30 days ]
  • Liver function [ Time Frame: 24hours/ 3 days/ 30 days ]
  • Event free survival [ Time Frame: 6 months ]
  • Remodeling determined by MRT [ Time Frame: 6 months ]
Not Provided
Not Provided
 
Endothelin Receptor Blockade in Acute ST-elevation Myocardial Infarction
Endothelin Receptor Blockade in Acute ST-elevation Myocardial Infarction

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.

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.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
ST-Elevation Myocardial Infarction
  • Drug: Placebo
    Peri-interventional
    Other Name: sodium salt
  • Drug: BQ-123
    Peri-interventional
    Other Name: Cyclo(-D-Trp-D-Asp-Pro-D-Val-Leu) sodium salt
  • Placebo Comparator: 1
    Placebo
    Intervention: Drug: Placebo
  • Active Comparator: 2
    BQ-123
    Intervention: Drug: BQ-123
Adlbrecht C, Andreas M, Redwan B, Distelmaier K, Mascherbauer J, Kaider A, Wolzt M, Tilea IA, Neunteufl T, Delle-Karth G, Maurer G, Lang IM. Systemic endothelin receptor blockade in ST-segment elevation acute coronary syndrome protects the microvasculature: a randomised pilot study. EuroIntervention. 2012 Apr;7(12):1386-95. doi: 10.4244/EIJV7I12A218.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
57
August 2012
August 2009   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Austria
 
NCT00502528
BQ123AMI12/06
Yes
Irene Lang, Medical University of Vienna
Medical University of Vienna
Not Provided
Principal Investigator: Irene M Lang, MD Medical University of Vienna
Medical University of Vienna
April 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP