Exenatide for Myocardial Protection During Reperfusion Study
- Registration Number
- NCT01938235
- Lead Sponsor
- University Health Network, Toronto
- 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.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 198
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo o Placebo bolus over 30 min followed by placebo infusion at 'Rate 1' for 1.5 h, followed by 'Rate 2' for 22 hours\*. Exenatide Exenatide 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.
- Primary Outcome Measures
Name Time Method Ratio of final infarct size at 3 months over area at risk at 72 hours post randomization (using cMRI) 3 months
- Secondary Outcome Measures
Name Time Method Left ventricular volume 3 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) Left ventricular global and regional LV systolic ejection fraction 3 months Myocardial enzyme levels (troponin I and CK-MB) 24 hours Angiographic myocardial blush score At the time of the PCI procedure Serum glucose concentration 72 hours Inflammatory marker levels (interleukin-6, interleukin-10, TNF-alpha) 24 hours NT-proBNP blood levels 24 hours Death 6 months Infarct size/area of risk (measured by cMRI) 3 months ST segment elevation resolution (measured by ECG) 3 months Myocardial infarction (heart attack) 3 months 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 Recurrent myocardial infarction (heart attack) 6 months Stroke 6 months
Trial Locations
- Locations (10)
Institut universitaire de cardiologie et de pneumologie de Quebec (Hopital Laval)
🇨🇦Quebec City, Quebec, Canada
Toronto General Hospital, University Health Network
🇨🇦Toronto, Ontario, Canada
Southlake Regional Health Centre
🇨🇦Newmarket, Ontario, Canada
Sunnybrook Health Sciences Centre
🇨🇦Toronto, Ontario, Canada
St. Michael's Hospital
🇨🇦Toronto, Ontario, Canada
London Health Sciences Centre
🇨🇦London, Ontario, Canada
University of Alberta Hospital
🇨🇦Edmonton, Alberta, Canada
Royal Alexandra Hospital
🇨🇦Edmonton, Alberta, Canada
Foothills Medical Centre
🇨🇦Calgary, Alberta, Canada
Hamilton Health Sciences - General Site
🇨🇦Hamilton, Ontario, Canada