EMPRES: Exenatide for Myocardial Protection During Reperfusion Study

Sponsor

University Health Network, Toronto (Other)

Overall Status

Unknown status

CT.gov ID

NCT01938235

Collaborator

AstraZeneca (Industry)

198

Enrollment

Locations

Arms

Duration (Months)

19.8

Patients Per Site

0.4

Patients Per Site Per Month

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Myocardial Infarction	Drug: Exenatide Drug: Placebo	Phase 2

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

198 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Feb 1, 2014

Anticipated Primary Completion Date :

Jul 1, 2017

Anticipated Study Completion Date :

Jan 1, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Drug: Exenatide Intravenous bolus and 24-hour infusion of exenatide Other Names: Byetta
Placebo Comparator: 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*.	Drug: Placebo Intravenous bolus and 24-hour infusion of placebo

Arm

Intervention/Treatment

Experimental: 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.

Drug: Exenatide

Intravenous bolus and 24-hour infusion of exenatide

Other Names:

Byetta

Placebo Comparator: 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*.

Drug: Placebo

Intravenous bolus and 24-hour infusion of placebo

Outcome Measures

Primary Outcome Measures

Ratio of final infarct size at 3 months over area at risk at 72 hours post randomization (using cMRI) [3 months]

Secondary Outcome Measures

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)]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Foothills Medical Centre	Calgary	Alberta	Canada	T2N 4Z6
2	Royal Alexandra Hospital	Edmonton	Alberta	Canada	T5H 3V9
3	University of Alberta Hospital	Edmonton	Alberta	Canada	T6G 2B7
4	Hamilton Health Sciences - General Site	Hamilton	Ontario	Canada	L8L 2X2
5	London Health Sciences Centre	London	Ontario	Canada	N6A 5A5
6	Southlake Regional Health Centre	Newmarket	Ontario	Canada	L3Y 2P7
7	Sunnybrook Health Sciences Centre	Toronto	Ontario	Canada	M4N 3M5
8	St. Michael's Hospital	Toronto	Ontario	Canada	M5B 1W8
9	Toronto General Hospital, University Health Network	Toronto	Ontario	Canada	M5G 2C4
10	Institut universitaire de cardiologie et de pneumologie de Quebec (Hopital Laval)	Quebec City	Quebec	Canada	G1V 4G5

Sponsors and Collaborators

University Health Network, Toronto
AstraZeneca

Investigators

Study Chair: Vladimir Dzavik, MD, University Health Network, Toronto

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Vladimír Džavík, Director, Research and Innovation in Interventional Cardiology and Cardiac Intensive Care, Division of Cardiology, University Health Network, Toronto

ClinicalTrials.gov Identifier:

NCT01938235

Other Study ID Numbers:

MB001-001
9427-D0416-21C

First Posted:

Sep 10, 2013

Last Update Posted:

Aug 5, 2016

Last Verified:

Aug 1, 2016

Individual Participant Data (IPD) Sharing Statement:

Undecided

Plan to Share IPD:

Undecided

Keywords provided by Vladimír Džavík, Director, Research and Innovation in Interventional Cardiology and Cardiac Intensive Care, Division of Cardiology, University Health Network, Toronto

Myocardial infarction

Percutaneous coronary intervention

Reperfusion injury

Exenatide

Magnetic resonance imaging

Additional relevant MeSH terms:

Myocardial Infarction

Infarction

Exenatide

Study Results

No Results Posted as of Aug 5, 2016