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

Primary Purpose

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

Status

Unknown status

Phase

Phase 3

Locations

Netherlands

Study Type

Interventional

Intervention

Exenatide infusion

Placebo infusion.

About this trial

This is an interventional treatment trial for Patients With a First Acute Myocardial Infarction to be Treated With Primary Percutaneous Coronary Intervention (PCI). focused on measuring Glucagon Like Peptide-1, Exenatide, myocardial infarction, MRI, PCI

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

VU Medical CenterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Exenatide

Placebo

Arm Description

Outcomes

Primary Outcome Measures

Safety of GLP-1 receptor agonist Exenatide infusion compared to placebo in patients with an acute myocardial infarction undergoing primary PCI

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).

Regional myocardial function based on a MRI segmental analysis at 1 weeek and at 4 months post myocardial infarction.

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.

Regional myocardial function assessed by 2D and 3D echocardiography at 1 week and at 4 months post myocardial infarction.

Global left ventricular EF, LVESV, LVEDV at 1 week and at 4 months post myocardial infarction measured by 2D and 3D echocardiography.

Angiographic parameters as Trombolysis In Myocardial Infarction (TIMI) frame count and TIMI blush grade after PCI.

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 .

Side effects of exenatide

Serum-glucose levels during the first 72 hours.

Full Information

NCT ID

NCT01254123

First Posted

November 29, 2010

Last Updated

December 3, 2010

Sponsor

Amsterdam UMC, location VUmc

1. Study Identification

Unique Protocol Identification Number

NCT01254123

Brief Title

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

Acronym

EXAMI

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

January 2010

Overall Recruitment Status

Unknown status

Study Start Date

November 2009 (undefined)

Primary Completion Date

undefined (undefined)

Study Completion Date

undefined (undefined)

3. Sponsor/Collaborators

Name of the Sponsor

Amsterdam UMC, location VUmc

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

Keywords

Glucagon Like Peptide-1, Exenatide, myocardial infarction, MRI, PCI

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

Single

Allocation

Randomized

Enrollment

40 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Exenatide

Arm Type

Active Comparator

Arm Title

Placebo

Arm Type

Placebo Comparator

Intervention Type

Drug

Intervention Name(s)

Exenatide infusion

Intervention Description

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

Intervention Name(s)

Placebo infusion.

Intervention Description

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.

Primary Outcome Measure Information:

Title

Safety of GLP-1 receptor agonist Exenatide infusion compared to placebo in patients with an acute myocardial infarction undergoing primary PCI

Secondary Outcome Measure Information:

Title

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).

Title

Regional myocardial function based on a MRI segmental analysis at 1 weeek and at 4 months post myocardial infarction.

Title

Regional myocardial function assessed by 2D and 3D echocardiography at 1 week and at 4 months post myocardial infarction.

Title

Global left ventricular EF, LVESV, LVEDV at 1 week and at 4 months post myocardial infarction measured by 2D and 3D echocardiography.

Title

Angiographic parameters as Trombolysis In Myocardial Infarction (TIMI) frame count and TIMI blush grade after PCI.

Title

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 .

Title

Side effects of exenatide

Title

Serum-glucose levels during the first 72 hours.

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

Eligibility 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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Y. Appelman, Dr.

Phone

0031204442441

Y.Appelman@vumc.nl

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Yolande Appelman, Dr.

Organizational Affiliation

Dept. of Cardiology VU Medical Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

VU Medical Center

City

Amsterdam

ZIP/Postal Code

1081 HV

Country

Netherlands

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Yolande Appelman, Dr.

Phone

0031204442441

Y.Appelman@vumc.nl

First Name & Middle Initial & Last Name & Degree

Yolande Appelman, Dr.

12. IPD Sharing Statement

Citations:

PubMed Identifier

28286967

Citation

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.

Results Reference

derived

PubMed Identifier

22067476

Citation

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.

Results Reference

derived

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

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