Myocardial Infarction
Conditions
Keywords
Myocardial infarction, Percutaneous coronary intervention, Reperfusion injury, Exenatide, Magnetic resonance imaging
Brief summary
This study aims to assess the effect of exenatide on myocardial injury in patients undergoing emergent percutaneous coronary intervention (PCI) for ST segment elevation myocardial infarction or heart attack (STEMI).
Detailed description
This is a Phase II randomized, double-blind, placebo-controlled study of patients with STEMI. Those who agree to participate will be immediately randomized to one of two groups: a 24-h infusion of exenatide; or a 24 h infusion of placebo. We will assess the ability of exenatide to reduce ischemic injury. This study will serve as safety evaluation study as well as a pilot for a larger multicentre trial powered for clinical outcomes.
Interventions
DRUGExenatide
Intravenous bolus and 24-hour infusion of exenatide
DRUGPlacebo
Intravenous bolus and 24-hour infusion of placebo
Sponsors
AstraZeneca
University Health Network, Toronto
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Admission for primary PCI for STEMI, with enrollment within 12 hours of onset of symptoms. STEMI will be defined as typical ECG changes (ST segment elevation ≥1mm in 2 or more limb leads, or ≥2mm in 2 or more precordial leads, or new onset LBBB) associated with acute chest pain or an elevation of cardiac enzymes. * Antegrade TIMI 0 or 1 prior to PCI in the infarct-related artery * Age ≥18 years
Exclusion criteria
* Symptomatic hypoglycemia (serum glucose \<3.3 µmol/L; 60 mg/dl) * Diabetes mellitus requiring insulin therapy * Diabetic ketoacidosis * Coronary anatomy warranting emergent coronary artery bypass graft surgery * Mechanical complication of STEMI (ventricular septal rupture, free wall rupture, acute severe mitral regurgitation) * Need for hemodialysis * Malignancy, HIV, or central nervous system disorder * Cardiopulmonary resuscitation \>15 min and compromised level of consciousness. * Cardiogenic shock * Current participation in any research study involving investigational drugs or devices * Inability to give informed consent * Inability to safely undergo cMRI (presence of cardiac pacemaker, implanted cardiac defibrillator, aneurysm clips, carotid artery vascular clamp, neurostimulator, implanted drug infusion device, bone growth/fusion stimulator, cochlear, otologic, or ear implant, severe claustrophobia) * Women of childbearing potential who are known to be pregnant or lactating or who have a positive pregnancy test on admission * History of pancreatitis * Known end stage renal failure or known eGFR \<30 mL/min * Currently taking exenatide (Byetta, Bydureon), liraglutide (Victoza), or any other GLP-1 agonist
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Ratio of final infarct size at 3 months over area at risk at 72 hours post randomization (using cMRI) | 3 months |
Secondary
| Measure | Time frame |
|---|---|
| NT-proBNP blood levels | 24 hours |
| Death | 3 months |
| Myocardial infarction (heart attack) | 3 months |
| Measure of extent of heart failure (NYHA classification) | 72 hours |
| Angiographic myocardial blush score | At the time of the PCI procedure |
| Serum glucose concentration | Baseline |
| Left ventricular global and regional LV systolic ejection fraction | 72 hours |
| Left ventricular volume | 72 hours |
| Infarct size/area of risk (measured by cMRI) | 3 months |
| Inflammatory marker levels (interleukin-6, interleukin-10, TNF-alpha) | 24 hours |
| ST segment elevation resolution (measured by ECG) | 1 hour |
| Major adverse cardiac events (defined as a combined outcome of death, recurrent myocardial infarction, stroke, and unplanned repeat revascularization) | 6 months |
| Recurrent myocardial infarction (heart attack) | 6 months |
| Stroke | 6 months |
| Unplanned repeat revascularization | 6 months |
| Development of heart failure | 6 months |
| Cardiogenic shock | During index hospitalization (up to 6 months) |
| Blood glucose < 3.0 mmol/L | During index hospitalization (up to 6 months) |
| Hypotension (defined as SBP <90 mmHg) | During index hospitalization (up to 6 months) |
| Myocardial enzyme levels (troponin I and CK-MB) | 24 hours |
Countries
Canada
Contacts
Primary ContactVal Panzov, MD
Backup ContactMelissa Giamou, BSc
Outcome results
None listed