Clinical trial NCT01938235: Exenatide for Myocardial Protection During Reperfusion Study
Official title: Exenatide for Myocardial Protection During Reperfusion Study: A Double-blind, Placebo-controlled Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Myocardial Infarction
Keywords: Myocardial infarction
Percutaneous coronary intervention
Reperfusion injury
Exenatide
Magnetic resonance imaging
Lead sponsor: University Health Network, Toronto
Sponsor class: OTHER
Collaborators: name: AstraZeneca
First posted: 2013-09-10
Enrollment: 198
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Ratio of final infarct size at 3 months over area at risk at 72 hours post randomization (using cMRI)
timeFrame: 3 months
Secondary outcomes:
measure: Left ventricular global and regional LV systolic ejection fraction
timeFrame: 72 hours
measure: Left ventricular global and regional LV systolic ejection fraction
timeFrame: 3 months
measure: Left ventricular volume
timeFrame: 72 hours
measure: Left ventricular volume
timeFrame: 3 months
measure: Infarct size/area of risk (measured by cMRI)
timeFrame: 3 months
measure: Myocardial enzyme levels (troponin I and CK-MB)
timeFrame: 24 hours
measure: ST segment elevation resolution (measured by ECG)
timeFrame: 1 hour
measure: ST segment elevation resolution (measured by ECG)
timeFrame: 24 hours
measure: ST segment elevation resolution (measured by ECG)
timeFrame: 72 hours
measure: ST segment elevation resolution (measured by ECG)
timeFrame: 3 months
measure: Angiographic myocardial blush score
timeFrame: At the time of the PCI procedure
measure: Serum glucose concentration
timeFrame: Baseline
measure: Serum glucose concentration
timeFrame: 8 hours
measure: Serum glucose concentration
timeFrame: 16 hours
measure: Serum glucose concentration
timeFrame: 24 hours
measure: Serum glucose concentration
timeFrame: 72 hours
measure: Inflammatory marker levels (interleukin-6, interleukin-10, TNF-alpha)
timeFrame: 24 hours
measure: NT-proBNP blood levels
timeFrame: 24 hours
measure: Death
timeFrame: 3 months
measure: Myocardial infarction (heart attack)
timeFrame: 3 months
measure: Measure of extent of heart failure (NYHA classification)
timeFrame: 72 hours
measure: Measure of extent of heart failure (NYHA classification)
timeFrame: 3 months
measure: Major adverse cardiac events (defined as a combined outcome of death, recurrent myocardial infarction, stroke, and unplanned repeat revascularization)
timeFrame: 6 months
measure: Death
timeFrame: 6 months
measure: Recurrent myocardial infarction (heart attack)
timeFrame: 6 months
measure: Stroke
timeFrame: 6 months
measure: Unplanned repeat revascularization
timeFrame: 6 months
measure: Development of heart failure
timeFrame: 6 months
measure: Cardiogenic shock
timeFrame: During index hospitalization (up to 6 months)
measure: Blood glucose < 3.0 mmol/L
timeFrame: During index hospitalization (up to 6 months)
measure: Hypotension (defined as SBP <90 mmHg)
timeFrame: During index hospitalization (up to 6 months)
Other outcomes:
Locations:
city: Calgary
country: Canada
facility: Foothills Medical Centre
state: Alberta
city: Edmonton
country: Canada
facility: Royal Alexandra Hospital
state: Alberta
city: Edmonton
country: Canada
facility: University of Alberta Hospital
state: Alberta
city: Hamilton
country: Canada
facility: Hamilton Health Sciences - General Site
state: Ontario
city: London
country: Canada
facility: London Health Sciences Centre
state: Ontario
city: Newmarket
country: Canada
facility: Southlake Regional Health Centre
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Centre
state: Ontario
city: Toronto
country: Canada
facility: St. Michael's Hospital
state: Ontario
city: Toronto
country: Canada
facility: Toronto General Hospital, University Health Network
state: Ontario
city: Quebec City
country: Canada
facility: Institut universitaire de cardiologie et de pneumologie de Quebec (Hopital Laval)
state: Quebec
Study officials:
affiliation: University Health Network, Toronto
name: Vladimir Dzavik, MD
role: STUDY_CHAIR
References: