Endothelin Receptor Blockade in Acute ST-elevation Myocardial Infarction
Primary Purpose
ST-Elevation Myocardial Infarction
Status
Completed
Phase
Phase 2
Locations
Austria
Study Type
Interventional
Intervention
Placebo
BQ-123
Sponsored by
About this trial
This is an interventional treatment trial for ST-Elevation Myocardial Infarction focused on measuring Infarction, Endothelin, Perfusion
Eligibility 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
Sites / Locations
- Medical University of Vienna
Arms of the Study
Arm 1
Arm 2
Arm Type
Placebo Comparator
Active Comparator
Arm Label
1
2
Arm Description
Placebo
BQ-123
Outcomes
Primary Outcome Measures
Myocardial perfusion determined by CMR
Secondary Outcome Measures
Final infarct size determined by CMR
Left ventricular function determined by CMR
Plasma NT-BNP
Enzymatic infarct size (CK levels)
ECG ST-segment resolution
Markers of inflammation
Major adverse cardiac events (MACE) (cardiovascular death, re-hospitalization for unstable angina and AMI, hospitalization for worsening heart failure)
Liver function
Event free survival
Holter ECG
Full Information
NCT ID
NCT00502528
First Posted
July 16, 2007
Last Updated
April 27, 2013
Sponsor
Medical University of Vienna
1. Study Identification
Unique Protocol Identification Number
NCT00502528
Brief Title
Endothelin Receptor Blockade in Acute ST-elevation Myocardial Infarction
Official Title
Endothelin Receptor Blockade in Acute ST-elevation Myocardial Infarction
Study Type
Interventional
2. Study Status
Record Verification Date
April 2013
Overall Recruitment Status
Completed
Study Start Date
May 2007 (undefined)
Primary Completion Date
August 2009 (Actual)
Study Completion Date
August 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Medical University of Vienna
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
ST-Elevation Myocardial Infarction
Keywords
Infarction, Endothelin, Perfusion
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
57 (Actual)
8. Arms, Groups, and Interventions
Arm Title
1
Arm Type
Placebo Comparator
Arm Description
Placebo
Arm Title
2
Arm Type
Active Comparator
Arm Description
BQ-123
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
sodium salt
Intervention Description
Peri-interventional
Intervention Type
Drug
Intervention Name(s)
BQ-123
Other Intervention Name(s)
Cyclo(-D-Trp-D-Asp-Pro-D-Val-Leu) sodium salt
Intervention Description
Peri-interventional
Primary Outcome Measure Information:
Title
Myocardial perfusion determined by CMR
Time Frame
3 days
Secondary Outcome Measure Information:
Title
Final infarct size determined by CMR
Time Frame
3 days
Title
Left ventricular function determined by CMR
Time Frame
3 days/ 6 months (6-months Remodeling-substudy)
Title
Plasma NT-BNP
Time Frame
30 days/ 6 months (6-months substudy)
Title
Enzymatic infarct size (CK levels)
Time Frame
3 days
Title
ECG ST-segment resolution
Time Frame
1 hour
Title
Markers of inflammation
Time Frame
24 hours/ 30 days
Title
Major adverse cardiac events (MACE) (cardiovascular death, re-hospitalization for unstable angina and AMI, hospitalization for worsening heart failure)
Time Frame
30 days
Title
Liver function
Time Frame
24hours/ 3 days/ 30 days
Title
Event free survival
Time Frame
6 months (6-months substudy)
Title
Holter ECG
Time Frame
3 days / 30 days (EP-substudy)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Irene M Lang, MD
Organizational Affiliation
Medical University of Vienna
Official's Role
Principal Investigator
Facility Information:
Facility Name
Medical University of Vienna
City
Vienna
State/Province
Vienna-Austria
ZIP/Postal Code
1090
Country
Austria
12. IPD Sharing Statement
Citations:
PubMed Identifier
22522549
Citation
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.
Results Reference
result
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Endothelin Receptor Blockade in Acute ST-elevation Myocardial Infarction
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