Endothelin Receptor Blockade in Acute ST-elevation Myocardial Infarction

ST-Elevation Myocardial Infarction Clinical Trial

Official title:

Endothelin Receptor Blockade in Acute ST-elevation Myocardial Infarction

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00502528
• Other study ID #: BQ123AMI12/06
• Status: Completed
• Phase: Phase 2
• First received: July 16, 2007
• Last updated: April 27, 2013
• Start date: May 2007
• Est. completion date: August 2012

Study information

• Verified date: April 2013
• Source: Medical University of Vienna
• Contact: n/a
• Is FDA regulated: No
• Health authority: Austria: Agency for Health and Food Safety
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 57
• Est. completion date: August 2012
• Est. primary completion date: August 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Infarction
• Myocardial Infarction
• ST-Elevation Myocardial Infarction

Intervention

Drug:
• Placebo
Peri-interventional
• BQ-123
Peri-interventional

Locations

Country	Name	City	State
Austria	Medical University of Vienna	Vienna	Vienna-Austria

Sponsors (1)

Lead Sponsor	Collaborator
Medical University of Vienna

Country where clinical trial is conducted

Austria, 

References & Publications (1)

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 microvasculatur — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Myocardial perfusion determined by CMR		3 days	No
Secondary	Final infarct size determined by CMR		3 days	No
Secondary	Left ventricular function determined by CMR		3 days/ 6 months (6-months Remodeling-substudy)	No
Secondary	Plasma NT-BNP		30 days/ 6 months (6-months substudy)	No
Secondary	Enzymatic infarct size (CK levels)		3 days	No
Secondary	ECG ST-segment resolution		1 hour	No
Secondary	Markers of inflammation		24 hours/ 30 days	No
Secondary	Major adverse cardiac events (MACE) (cardiovascular death, re-hospitalization for unstable angina and AMI, hospitalization for worsening heart failure)		30 days	Yes
Secondary	Liver function		24hours/ 3 days/ 30 days	Yes
Secondary	Event free survival		6 months (6-months substudy)	Yes
Secondary	Holter ECG		3 days / 30 days (EP-substudy)	Yes