Exenatide for Myocardial Protection During Reperfusion Study

Study Overview
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Brief Summary
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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
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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.

Official Title
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Exenatide for Myocardial Protection During Reperfusion Study: A Double-blind, Placebo-controlled Trial

Conditions
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Myocardial Infarction

Intervention / Treatment
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* Drug: Exenatide
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Exenatide<br>o Exenatide at a dose of 1.5 µg IV over 30 min followed by 1.2 µg/hr IV for 1.5 h (Rate1), followed by 1.9 µg/hr IV* for 22 h (Rate 2) *Once the creatinine clearance is available, if the value is <60 mL/min, the rate at 2 hours will be maintained at Rate 1 for the duration of the infusion. If the value becomes available after the 2-hour point, and the rate has already been changed to Rate 2, the infusion will be titrated back down to Rate 1 if the creatinine clearance is <60 mL/min. If the creatinine clearance is <30 mL/min, the infusion will be discontinued and the patient will otherwise continue with all study procedures. A bolus administration of study medication is initiated preferably prior to reperfusion, or, if not possible, up to 30 minutes after the start of reperfusion to avoid delays in door-to-door balloon times. | Drug: Exenatide<br>* Intravenous bolus and 24-hour infusion of exenatide<br>* Other names: Byetta;|
| Placebo Comparator: Placebo<br>o Placebo bolus over 30 min followed by placebo infusion at 'Rate 1' for 1.5 h, followed by 'Rate 2' for 22 hours*. | Drug: Placebo<br>* Intravenous bolus and 24-hour infusion of placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ratio of final infarct size at 3 months over area at risk at 72 hours post randomization (using cMRI) |  | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Left ventricular global and regional LV systolic ejection fraction |  | 72 hours | 
| Left ventricular global and regional LV systolic ejection fraction |  | 3 months | 
| Left ventricular volume |  | 72 hours | 
| Left ventricular volume |  | 3 months | 
| Infarct size/area of risk (measured by cMRI) |  | 3 months | 
| Myocardial enzyme levels (troponin I and CK-MB) |  | 24 hours | 
| ST segment elevation resolution (measured by ECG) |  | 1 hour | 
| ST segment elevation resolution (measured by ECG) |  | 24 hours | 
| ST segment elevation resolution (measured by ECG) |  | 72 hours | 
| ST segment elevation resolution (measured by ECG) |  | 3 months | 
| Angiographic myocardial blush score |  | At the time of the PCI procedure | 
| Serum glucose concentration |  | Baseline | 
| Serum glucose concentration |  | 8 hours | 
| Serum glucose concentration |  | 16 hours | 
| Serum glucose concentration |  | 24 hours | 
| Serum glucose concentration |  | 72 hours | 
| Inflammatory marker levels (interleukin-6, interleukin-10, TNF-alpha) |  | 24 hours | 
| 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 | 
| Measure of extent of heart failure (NYHA classification) |  | 3 months | 
| Major adverse cardiac events (defined as a combined outcome of death, recurrent myocardial infarction, stroke, and unplanned repeat revascularization) |  | 6 months | 
| Death |  | 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) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Myocardial infarction, Percutaneous coronary intervention, Reperfusion injury, Exenatide, Magnetic resonance imaging