The primary objective is to determine whether additional treatment with exenatide in patients with acute myocardial infarction and treated with primary PCI, leads to a more preserved left ventricular function, compared to placebo in addition to…
ID
Source
Brief title
Condition
- Heart failures
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Infarct size measured as the final infarct size on Delayed Enhancement (DE) MRI
at 4 months as a percentage of the area at risk on T2 weighed MRI at 3-7 days.
Secondary outcome
The difference between all treatment groups in:
-Myocardial infarct size as measured by serum CKmb release during the first 72
hours after PCI.
-Regional myocardial function based on a MRI segmental analysis at 3-7 days
and at 4 months.
-Global left ventricular ejection fraction, Left Ventricular End Systolic
Volume (LVESV), Left Ventricular End Diastolic Volume (LVEDV) at 3-7 days and
at 4 months measured by MRI.
-Presence and extent of microvascular obstruction measured by DE MRI 3-7 days
after PCI.
-Global left ventricular ejection fraction, LVESV, LVEDV at 2-7 days and at 4
months measured by Echocardiography.
-Global left ventricular ejection fraction measured by strain echocardiography.
-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 .
-Repeat PCI in the infarct related artery during 4 months follow up.
-Serum-glucose levels during the first 72 hours.
-Side effects of exenatide
-Angiographic parameters as Trombolysis In Myocardial Infarction (TIMI) frame
count and TIMI blush grade after PCI
-SPECT data after PCI. Comparison with MRI perfusion defects
-Resistance measurements by ComboWire
Background summary
Myocardial infarction causes loss of myocytes and may lead to loss of
ventricular function, morbidity and mortality. It is well known that
preservation of myocytes during myocardial infarction will affect the infarct
size and prognosis. The most effective therapy is early reperfusion of the
ischemic myocardium by percutaneous coronary intervention (PCI). Reperfusion
limits myocardial ischemic necrosis, however, it also results in accelerated
apoptosis due to calcium overload, inflammation and oxidative stress; a
phenomenon referred to as reperfusion injury. Therefore, large myocardial
infarctions still occur despite adequate reperfusion therapy. Glucagon-like
peptide (GLP)-1 is a gut incretin hormone, which is released by the gut in
response to nutrient intake. It facilitates glucose induced insulin release,
and therefore, analogues of GLP-1 are now being used for the treatment of
diabetes. Furthermore, GLP-1 has been demonstrated to possess anti-apoptotic
properties that may protect the heart against ischaemia - reperfusion injury.
Multiple in vitro and in vivo animal studies showed evidence for this
hypothesis. So far only one study tested GLP-1 infusion during acute myocardial
infarction in human patients and showed improvement of left ventricular
function when using GLP-1 infusion in addition to primary PCI alone. Another
recent clinical study (2011) demonstrated that additional treatment with the
GLP-1 receptor agonist exenetide in patient with an acute myocardial infarction
undergoing PCI improves mycardial salvage. Because it concerns only one study,
more research is required to confirm the results. In this randomized study we
will assess the additional effect of exenatide on left ventricular function
after acute myocardial infarction treated with primary percutaneous coronary
intervention (PCI) compared to placebo. Magnetic Resonance Imaging (MRI) will
be used to asses left ventricular function during admission and at 4 months
follow up.
Study objective
The primary objective is to determine whether additional treatment with
exenatide in patients with acute myocardial infarction and treated with primary
PCI, leads to a more preserved left ventricular function, compared to placebo
in addition to primary PCI.
Study design
A prospective randomized placebo controlled two-arm study.
After informed consent has been obtained patients are randomized to the
following 2 groups: (1) PCI and placebo (2) PCI and exenatide infusion started
before PCI and continued for 72 hours after PCI. ComboWire measurements will be
performed in all patients after PCI. SPECT will be performed in all patients
after PCI. MRI measurements are performed in all patiens 3 to 7 days after PCI
and at 4 months. Echocardiography is performed in all patients 2-7 days after
PCI and at 4 months. Close glucose control is performed from hospital admission
until discharge and if indicated also after discharge.
Intervention
Administration of exenatide (exenatide group) or placebo (placebogroup) in
addition to standard treatment of acute myocardial infarction by PCI.
Study burden and risks
-during exenatide treatment there is a small risk of developing hypoglycaemia.
Therefore bloodglucose levels will be strictly monitored.
-during exenatide treatment patients might suffer from side effects like
nausea.
-during admission and at 4 months follow up echocardiography and CMR will be
performed.
Small radiation dose with 1 SPECT investigations ± 3,5 mSv
Boelelaan 1117
Amsterdam 1081 HV
NL
Boelelaan 1117
Amsterdam 1081 HV
NL
Listed location countries
Age
Inclusion criteria
-First myocardial infarction
-ST elevation of at least 0,1mV in at least 2 contiguous leads
- > 18 years of age
- Delay between onset of sustained chestpain and PCI < 6 hours
Exclusion criteria
-Diabetes type I or II
-Heartfailure (Kilip III or IV)
-No definite Culprit
-More than one occluded vessel, or a more than 70% stenosis by visual assessment in a non-culprit vessel.
-No recanalisation achieved of the occluded coronary artery
-Decreased renal function eGFR < 30ml/min
-Any contraindication for MRI
- TIMI 2 or 3 flow in culprit lesion at presentation
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2009-014272-21-NL |
| CCMO | NL28593.029.09 |