Patients With a First Acute Myocardial Infarction to be Treated With Primary Percutaneous Coronary Intervention (PCI).Phase 3EXAMINCT01254123
Effect of Additional Treatment With EXenatide in Patients With an Acute Myocardial Infarction (the EXAMI Trial)
A Phase 3 study testing Exenatide infusion in people with Patients With a First Acute Myocardial Infarction to be Treated With Primary Percutaneous Coronary Intervention (PCI)., run by Amsterdam UMC, location VUmc at 1 site in Netherlands.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Patients With a First Acute Myocardial Infarction to be Treated With Primary Percutaneous Coronary Intervention (PCI).
- What is being tested?
- Exenatide infusion
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 40 participants
- Where
- 1 siteNetherlands
- Study dates
- Nov 2009to not given
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- >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.
Who cannot join
- 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
Show all 27Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
Netherlands1 site, 1 recruiting
- Recruiting
VU Medical Center
Amsterdam, 1081 HV
Yolande Appelman, Dr., 0031204442441, Y.Appelman@vumc.nl
Yolande Appelman, Dr.
About this study
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.
- Being tested
- Exenatide infusion, Placebo infusion.
- Keywords
- Glucagon Like Peptide-1, Exenatide, myocardial infarction, MRI, PCI
- Medical subject headings
- Myocardial Infarction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Exenatide infusionDrug
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 infusion.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.
| Study group | Role | What they receive |
|---|---|---|
| Exenatide | Active comparator | Not described Receives: Drug: Exenatide infusion |
| Placebo | Placebo comparator | Not described Receives: Drug: Placebo infusion. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety of GLP-1 receptor agonist Exenatide infusion compared to placebo in patients with an acute myocardial infarction undergoing primary PCI
Secondary outcomes (9)
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.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Dec 2010 (estimated)
- Study startNov 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Patients With a First Acute Myocardial Infarction to be Treated With Primary Percutaneous Coronary Intervention (PCI).Studies of the same condition, open and under way.
- More trials run by Amsterdam UMC, location VUmcThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Amsterdam UMC, location VUmc
- Sponsor type
- University, hospital or other
- Investigators
- Yolande Appelman, Dr., Principal investigator, Dept. of Cardiology VU Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01254123
- Sponsor's protocol ID
- NL28593.029.09
- Acronym
- EXAMI
- Status last verified
- Jan 2010
- First submitted
- 29 Nov 2010
- Last updated
- 6 Dec 2010
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 28286967Scholte 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.
PubMed 22067476
Study at a glance
From the registry record, last updated by the sponsor on 6 Dec 2010. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Additional Treatment With EXenatide in Patients With an Acute Myocardial Infarction (the EXAMI Trial)
- ClinicalTrials.gov ID
- NCT01254123
- Acronym / sponsor ID
- EXAMI / NL28593.029.09
- Keywords
- Glucagon Like Peptide-1, Exenatide, myocardial infarction, MRI, PCI
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- Amsterdam UMC, location VUmcUniversity, hospital or other
- Study start
- Nov 2009
- First posted
- 6 Dec 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Exenatide | Active comparator | Drug: Exenatide infusion |
| Placebo | Placebo comparator | Drug: Placebo infusion. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- >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.
Key exclusion criteria (27 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Exenatide infusionOn 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. | Drug | Exenatide |
| 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. | Drug | Placebo |
Primary outcome
Safety of GLP-1 receptor agonist Exenatide infusion compared to placebo in patients with an acute myocardial infarction undergoing primary PCI
9 secondary outcomes
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.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Dec 2010.
- Derived from this study: PubMed 28286967Huang 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.
- Derived from this study: PubMed 22067476Scholte 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.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Yolande Appelman, Dr. principal investigator
Dept. of Cardiology VU Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Exenatide infusion in people with Patients With a First Acute Myocardial Infarction to be Treated With Primary Percutaneous Coronary Intervention (PCI)., run by Amsterdam UMC, location VUmc at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 6 Dec 2010. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Y. Appelman, Dr. (0031204442441, Y.Appelman@vumc.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety of GLP-1 receptor agonist Exenatide infusion compared to placebo in patients with an acute myocardial infarction undergoing primary PCI. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01254123, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Dec 2010.