Exenatide for Myocardial Protection During Reperfusion Study (EMPRES)

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2014 by University Health Network, Toronto
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
Vlad Dzavik, University Health Network, Toronto
ClinicalTrials.gov Identifier:
NCT01938235
First received: August 29, 2013
Last updated: February 5, 2014
Last verified: February 2014
  Purpose

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 Intervention Phase
Myocardial Infarction
Drug: Exenatide
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Exenatide for Myocardial Protection During Reperfusion Study: A Double-blind, Placebo-controlled Trial

Resource links provided by NLM:


Further study details as provided by University Health Network, Toronto:

Primary Outcome Measures:
  • Ratio of final infarct size at 3 months over area at risk at 72 hours post randomization (using cMRI) [ Time Frame: 3 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Left ventricular global and regional LV systolic ejection fraction [ Time Frame: 72 hours ] [ Designated as safety issue: No ]
  • Left ventricular global and regional LV systolic ejection fraction [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  • Left ventricular volume [ Time Frame: 72 hours ] [ Designated as safety issue: No ]
  • Left ventricular volume [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  • Infarct size/area of risk (measured by cMRI) [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  • Myocardial enzyme levels (troponin I and CK-MB) [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
  • ST segment elevation resolution (measured by ECG) [ Time Frame: 1 hour ] [ Designated as safety issue: No ]
  • ST segment elevation resolution (measured by ECG) [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
  • ST segment elevation resolution (measured by ECG) [ Time Frame: 72 hours ] [ Designated as safety issue: No ]
  • ST segment elevation resolution (measured by ECG) [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  • Angiographic myocardial blush score [ Time Frame: At the time of the PCI procedure ] [ Designated as safety issue: No ]
  • Serum glucose concentration [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
  • Serum glucose concentration [ Time Frame: 72 hours ] [ Designated as safety issue: No ]
  • Glucose blood concentration (measured with point-of-care device) [ Time Frame: Every 2 hours for 24 hours post-PCI procedure ] [ Designated as safety issue: No ]
  • Inflammatory marker levels (interleukin-6, IL-10, TNF-alpha) [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
  • Inflammatory cell activation (neutrophil phagocytosis, chemotaxis, superoxide production) [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
  • Inflammatory cell activation (neutrophil phagocytosis, chemotaxis, superoxide production) [ Time Frame: 72 hours ] [ Designated as safety issue: No ]
  • NT-proBNP blood levels [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
  • Death [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  • Myocardial infarction (heart attack) [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  • Measure of extent of heart failure (NYHA classification) [ Time Frame: 72 hours ] [ Designated as safety issue: No ]
  • Measure of extent of heart failure (NYHA classification) [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  • Major adverse cardiac events (defined as a combined outcome of death, recurrent myocardial infarction, stroke, and unplanned repeat revascularization) [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
  • Death [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
  • Recurrent myocardial infarction (heart attack) [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
  • Stroke [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
  • Unplanned repeat revascularization [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
  • Development of heart failure [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
  • Cardiogenic shock [ Time Frame: During index hospitalization (up to 6 months) ] [ Designated as safety issue: Yes ]
  • Blood glucose < 3.0 mmol/L [ Time Frame: During index hospitalization (up to 6 months) ] [ Designated as safety issue: Yes ]
  • Hypotension (defined as SBP <90 mmHg) [ Time Frame: During index hospitalization (up to 6 months) ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 198
Study Start Date: February 2014
Estimated Study Completion Date: October 2015
Estimated Primary Completion Date: July 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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), or

*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 Name: 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

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Admission for primary PCI for STEMI 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. For non-anterior MI: ST-segment elevation = 1mm in 2 or more limb leads and at least one of the following high-risk characteristics: systolic blood pressure < 100 mm Hg, heart rate > 100 bpm, Killip class II or III, ST-segment depression ≥ 2 mm in the anterior leads, or ST-segment elevation ≥ 1 mm in right-sided lead V4 (V4R)
  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01938235

Contacts
Contact: Val Panzov, MD 416-864-6060 ext 7125 panzovV@smh.ca
Contact: Melissa Giamou, BSc 416-864-6060 ext 7889 giamoum@smh.ca

Locations
Canada, Ontario
University Health Network, Toronto General Hospital Not yet recruiting
Toronto, Ontario, Canada, M5G 2C4
University Health Network Recruiting
Toronto, Ontario, Canada, M5G 2C4
Principal Investigator: Vladimir Dzavik, MD         
Sponsors and Collaborators
University Health Network, Toronto
Bristol-Myers Squibb
Investigators
Study Chair: Vladimir Dzavik, MD University Health Network, Toronto
  More Information

No publications provided

Responsible Party: Vlad Dzavik, Deputy Head, Division of Cardiology, University Health Network, Toronto
ClinicalTrials.gov Identifier: NCT01938235     History of Changes
Other Study ID Numbers: MB001-001, 9427-D0416-21C
Study First Received: August 29, 2013
Last Updated: February 5, 2014
Health Authority: Canada: Health Canada

Keywords provided by University Health Network, Toronto:
Myocardial infarction
Percutaneous coronary intervention
Reperfusion injury
Exenatide
Magnetic resonance imaging

Additional relevant MeSH terms:
Infarction
Myocardial Infarction
Ischemia
Pathologic Processes
Necrosis
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Vascular Diseases
Exenatide
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists

ClinicalTrials.gov processed this record on September 16, 2014