Effect of Additional Treatment With EXenatide in Patients With an Acute Myocardial Infarction (the EXAMI Trial)

The recruitment status of this study is unknown because the information has not been verified recently.
Verified January 2010 by VU University Medical Center.
Recruitment status was  Recruiting
Sponsor:
Information provided by:
VU University Medical Center
ClinicalTrials.gov Identifier:
NCT01254123
First received: November 29, 2010
Last updated: December 3, 2010
Last verified: January 2010
  Purpose

Myocardial infarction (MI) causes loss of myocytes and may lead to loss of ventricular function, morbidity and mortality. The most effective therapy is early reperfusion of the ischemic myocardium by percutaneous coronary intervention (PCI). Reperfusion limits myocardial ischaemic necrosis, but also induces inflammation, oxidative stress and calcium overload: a process referred to as reperfusion injury leading to necrosis and apotosis. Glucagon Like Peptide-1 (GLP-1) is an incretin hormone that has shown to activate anti-apoptotic enzymes, reducing reperfusion injury. GLP-1 agonists have been demonstrated to be cardioprotective in several animal studies and in a single small non-randomized clinical study. In this pilot study we will assess the safety and efficacy of GLP-1 receptor agonist Exenatide infusion compared to placebo in patients with an acute myocardial infarction undergoing primary PCI.

A total of 40 patients will be included in this single centre prospective randomised placebo controlled two-arm pilot study. Patients who are to undergo a primary PCI for a first acute ST elevation myocardial infarction are randomly assigned to placebo or Exenatide 5ug bolus in 30 minutes, followed by a continuous Exenatide infusion of 20ug/ 24 hours for 72 hours. Blood samples are obtained for assessment of enzymatic infarct size and Exenatide levels. Side effects of Exenatide are stringently monitored. Cardiac function will be measured using Cardiac Magnetic Resonance Imaging (CMRI) and 3D echocardiography at 1 week and 4 months post MI. Infarct size will be assessed by means of the final infarct size at 4 months post MI as a percentage of the area at risk at 1 week post MI. Furthermore we will compare the RNA profile of both groups.


Condition Intervention Phase
Patients With a First Acute Myocardial Infarction to be Treated With Primary Percutaneous Coronary Intervention (PCI).
Drug: Exenatide infusion
Drug: Placebo infusion.
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind
Primary Purpose: Treatment
Official Title: Effect of Additional Treatment With EXenatide in Patients With an Acute Myocardial Infarction (the EXAMI Trial)

Resource links provided by NLM:


Further study details as provided by VU University Medical Center:

Primary Outcome Measures:
  • Safety of GLP-1 receptor agonist Exenatide infusion compared to placebo in patients with an acute myocardial infarction undergoing primary PCI [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Infarct size, assessed by means of the final infarct size at 4 months post myocardial infarction (CMRI) as a percentage of the area at risk at 1 week post myocardial infarction (T2 weighed CMRI). [ Designated as safety issue: No ]
  • Regional myocardial function based on a MRI segmental analysis at 1 weeek and at 4 months post myocardial infarction. [ Designated as safety issue: No ]
  • Global left ventricular ejection fraction (EF), Left Ventricular End Systolic Volume (LVESV), Left Ventricular End Diastolic Volume (LVEDV) at 1 week and at 4 months post myocardial infarction measured by Cardiac MRI. [ Designated as safety issue: No ]
  • Regional myocardial function assessed by 2D and 3D echocardiography at 1 week and at 4 months post myocardial infarction. [ Designated as safety issue: No ]
  • Global left ventricular EF, LVESV, LVEDV at 1 week and at 4 months post myocardial infarction measured by 2D and 3D echocardiography. [ Designated as safety issue: No ]
  • Angiographic parameters as Trombolysis In Myocardial Infarction (TIMI) frame count and TIMI blush grade after PCI. [ Designated as safety issue: No ]
  • The occurrence within 4 months of a Major Adverse Cardiac Event (MACE) defined as cardiac death, myocardial infarction, coronary bypass grafting, or a repeat PCI . [ Designated as safety issue: Yes ]
  • Side effects of exenatide [ Designated as safety issue: Yes ]
  • Serum-glucose levels during the first 72 hours. [ Designated as safety issue: Yes ]

Estimated Enrollment: 40
Study Start Date: November 2009
Arms Assigned Interventions
Active Comparator: Exenatide Drug: Exenatide infusion

On arrival to our cardiac care unit (CCU) and after informed consent patients will be randomized to Exenatide infusion or Placebo infusion. Patients in the Exenatide group will immediately be treated be with Exenatide iv, 5ug bolus in 30 minutes, followed by a continuous Exenatide infusion of 20ug/ 24 hours.

Exenatide preparation: Byetta injection pens containing 1,2 ml (concentration 0,25 mg/ml; 60 doses of 5 μg) will be obtained. 3 doses (15 μg) will be diluted in 49 ml saline and 1 ml Human Serum Albumen (Cealb 200g/L, 10ml) to get a total of 50 ml containing 15 μg exenatide (or 300 ng exenatide / ml). A 50cc syringe will be placed in a pump system that is connected with a cannula in the patient's vein. The infusionrate will be 33,3 ml/hr for the first 30 minutes, followed by an infusion rate of 2,8 ml/hr for 72 hours. New 50cc syringes will be made every 8 hours.

Placebo Comparator: Placebo Drug: Placebo infusion.

On arrival to our cardiac care unit (CCU) and after informed consent patients will be randomized to Exenatide infusion or Placebo infusion. Patients in the placebo group will immediately be treated with placebo infusion.

Placebo preparation: 49ml saline and 1ml Human Serum Albumen (Cealb 200g/L, 10ml) to get a total of 50 ml will be placed in a 50cc syringe and placed in a pump system that is connected with a cannula in the patient's vein. The infusionrate will be 33,3 ml/hr for the first 30 minutes, followed by an infusion rate of 2,8 ml/hr for 72 hours. New 50cc syringes will be made every 8 hours.


  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • >18 and < 80 years of age
  • First myocardial infarction
  • ST elevation of more than one mm in at least 2 separate leads on the electrocardiogram (ECG)
  • Delay between onset of sustained chestpain and PCI < 6 hours.

Exclusion Criteria:

  • Cardiac rhythm is other than normal sinus rhythm.
  • Patient in Killip class 3 or 4 of heart failure
  • Cardiogenic shock defined as sustained systolic blood pressure ≤ 80mmHg despite fluid hydration.
  • Post cardiac resuscitation
  • Need for intra aortic balloon counterpulsation therapy
  • The patient is unable to hold his/her breath for up to 20 seconds due to age or concomitant illness
  • No former PCI performed
  • No recanalisation achieved of the occluded coronary artery
  • Culprit not in segment 1,2,3,6,7,11,12,13 of the coronary artery
  • No definite culprit
  • More than one occluded vessel, or a more than 70% stenosis by visual assessment in a non-culprit vessel.
  • TIMI 3 flow in culprit lesion at presentation
  • Decreased renal function eGFR < 30ml/min
  • Any contraindication for MRI ie: implanted electronic devices such as pacemakers, internal defibrillators, neurostimulators, implanted drug infusion devices, cochlear implants, cerebrovascular clips, claustrophobia. previous vascular surgery: aneurysm clip, carotid artery vascular clamp, aortic clips, venous umbrella spinal/intra-ventricular shunts
  • Metal fragments in eye, head, ear, skin or shoulder.
  • Swann-Ganz catheter.
  • Known pre-existing left ventricular dysfunction measured by any technique (ejection fraction < 45% prior to current admission for myocardial infarction)
  • Prior myocardial infarction
  • Prior coronary artery bypass grafting
  • Moderate to severe cardiac valve disease
  • Stroke or transient ischemic attack within the previous 24 hours
  • Serious known concomitant disease with a life expectancy of less than one year
  • Follow up impossible
  • Previous participation in a trial within the previous 30 days
  • Known type I Diabetes Mellitus
  • Known type II Diabetes Mellitus
  • Pregnancy and/or lactation
  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: NCT01254123

Contacts
Contact: Y. Appelman, Dr. 0031204442441 Y.Appelman@vumc.nl

Locations
Netherlands
VU Medical Center Recruiting
Amsterdam, Netherlands, 1081 HV
Contact: Yolande Appelman, Dr.    0031204442441    Y.Appelman@vumc.nl   
Principal Investigator: Yolande Appelman, Dr.         
Sponsors and Collaborators
VU University Medical Center
Investigators
Principal Investigator: Yolande Appelman, Dr. Dept. of Cardiology VU Medical Center
  More Information

No publications provided by VU University Medical Center

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
ClinicalTrials.gov Identifier: NCT01254123     History of Changes
Other Study ID Numbers: NL28593.029.09
Study First Received: November 29, 2010
Last Updated: December 3, 2010
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by VU University Medical Center:
Glucagon Like Peptide-1
Exenatide
myocardial infarction
MRI
PCI

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

ClinicalTrials.gov processed this record on October 19, 2014