Exenatide for Myocardial Protection During Reperfusion Study (EMPRES)

University Health Network, Toronto

Status and phase: Unknown; Phase 2

Conditions: Myocardial Infarction

Treatments: Drug: Placebo; Drug: Exenatide

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT01938235

9427-D0416-21C (Other Identifier)

MB001-001

Details and patient eligibility

About

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).

Full 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.

Enrollment: 198 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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198 participants in 2 patient groups, including a placebo group

Exenatide

Experimental group

Description:

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.

Treatment:

Drug: Exenatide

Placebo

Placebo Comparator group

Description:

o Placebo bolus over 30 min followed by placebo infusion at 'Rate 1' for 1.5 h, followed by 'Rate 2' for 22 hours\*.

Treatment:

Drug: Placebo