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

NCT ID: NCT01254123

Last Updated: 2010-12-06

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE3

Total Enrollment

40 participants

Study Classification

INTERVENTIONAL

Study Start Date

2009-11-30

Brief Summary

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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.

Detailed Description

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Conditions

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Patients With a First Acute Myocardial Infarction to be Treated With Primary Percutaneous Coronary Intervention (PCI).

Keywords

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Glucagon Like Peptide-1 Exenatide myocardial infarction MRI PCI

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Study Groups

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Exenatide

Group Type ACTIVE_COMPARATOR

Exenatide infusion

Intervention Type DRUG

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

Group Type PLACEBO_COMPARATOR

Placebo infusion.

Intervention Type DRUG

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.

Interventions

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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.

Intervention Type 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.

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Amsterdam UMC, location VUmc

OTHER

Sponsor Role lead

Principal Investigators

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Yolande Appelman, Dr.

Role: PRINCIPAL_INVESTIGATOR

Dept. of Cardiology VU Medical Center

Locations

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VU Medical Center

Amsterdam, , Netherlands

Site Status RECRUITING

Countries

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Netherlands

Central Contacts

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Y. Appelman, Dr.

Role: CONTACT

Phone: 0031204442441

Email: [email protected]

Facility Contacts

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Yolande Appelman, Dr.

Role: primary

References

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Huang M, Wei R, Wang Y, Su T, Li Q, Yang X, Chen X. Protective effect of glucagon-like peptide-1 agents on reperfusion injury for acute myocardial infarction: a meta-analysis of randomized controlled trials. Ann Med. 2017 Nov;49(7):552-561. doi: 10.1080/07853890.2017.1306653. Epub 2017 Mar 31.

Reference Type DERIVED
PMID: 28286967 (View on PubMed)

Scholte M, Timmers L, Bernink FJ, Denham RN, Beek AM, Kamp O, Diamant M, Horrevoets AJ, Niessen HW, Chen WJ, van Rossum AC, van Royen N, Doevendans PA, Appelman Y. Effect of additional treatment with EXenatide in patients with an Acute Myocardial Infarction (EXAMI): study protocol for a randomized controlled trial. Trials. 2011 Nov 8;12:240. doi: 10.1186/1745-6215-12-240.

Reference Type DERIVED
PMID: 22067476 (View on PubMed)

Other Identifiers

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NL28593.029.09

Identifier Type: -

Identifier Source: org_study_id