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

August 29, 2013
February 5, 2014
February 2014
July 2015   (final data collection date for primary outcome measure)
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 ]
Same as current
Complete list of historical versions of study NCT01938235 on ClinicalTrials.gov Archive Site
  • 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 ]
Same as current
Not Provided
Not Provided
 
Exenatide for Myocardial Protection During Reperfusion Study
Exenatide for Myocardial Protection During Reperfusion Study: A Double-blind, Placebo-controlled Trial

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).

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.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Myocardial Infarction
  • Drug: Exenatide
    Intravenous bolus and 24-hour infusion of exenatide
    Other Name: Byetta
  • Drug: Placebo
  • 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.

    Intervention: Drug: Exenatide
  • 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*.
    Intervention: Drug: Placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
198
October 2015
July 2015   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact: Val Panzov, MD 416-864-6060 ext 7125 panzovV@smh.ca
Contact: Melissa Giamou, BSc 416-864-6060 ext 7889 giamoum@smh.ca
Canada
 
NCT01938235
MB001-001, 9427-D0416-21C
Yes
Vlad Dzavik, University Health Network, Toronto
University Health Network, Toronto
Bristol-Myers Squibb
Study Chair: Vladimir Dzavik, MD University Health Network, Toronto
University Health Network, Toronto
February 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP