Ignite Creation Date:
2024-05-05 @ 11:47 AM
Last Modification Date:
2024-10-26 @ 9:13 AM
Study NCT ID:
NCT00125645
Status:
COMPLETED
Last Update Posted:
2018-05-08
First Post:
2005-07-29
Brief Title:
Left Ventricular Function After Acute Myocardial Infarction AMI Treatment With Angiotensin 2-Receptor Blockade GLOBAL-Study
Sponsor:
University of Southern Denmark
Organization:
University of Southern Denmark
Study Overview
Official Title:
Global Left Ventricular Function After Acute Myocardial Infarction Treatment With the Angiotensin 2-Receptor Blocker Irbesartan
Status:
COMPLETED
Status Verified Date:
2007-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The purpose of this study is to compare changes in global left ventricular LV function after 3 months of treatment with irbesartan compared with usual care in patients with acute myocardial infarction a wall motion score 13 EF040 and signs of diastolic dysfunction The hypothesis is that an angiotensin 2-receptor inhibitor will improve global left ventricular function
Detailed Description:
Study objectives
Primary Objective
To compare the change in global LV function assessed with myocardial performance index MPI after 3 months treatment with irbesartan compared to usual care in patients admitted to hospital with acute myocardial infarction wall motion score index 13 LVEF 040 and MPI 055
Secondary Objectives
To compare irbesartan added to an ACE-inhibitor compared to usual care in patients with AMI WMSI 13 and MPI 055
To compare LV diastolic function assessed by pulse wave and color M-mode Doppler echocardiography and left atrial size after treatment with irbesartan compared to usual care in AMI and
WMSI 13 and MPI 055 and
WMSI 13 and MPI 055
To compare change in WMSI after treatment with irbesartan compared to usual care in patients with AMI and
WMSI 13 and MPI 055 and
WMSI 13 and MPI 055
Tertiary Objectives
To assess the effects of irbesartan versus usual care on neurohormonal activation and glucose metabolism optional
Study Design
A Danish multicenter randomized prospective trial with PROBE-design
Study Drug
Patients will be randomized to receive either irbesartan 300 mg once daily or usual care
Duration of Therapy
Irbesartan 300 mg daily for 3 months after hospital discharge for acute myocardial infarction
Patients should receive standard medical therapy including revascularisation as appropriate
Expected Number of Patients
200 patients with AMI WMSI 13 and MPI 055 100 patients in the irbesartan group and 100 in the usual care group The patients will be included in the analysis of the primary endpoint Further approximately 100 patients with AMI WMSI 13 and MPI 055 treated with an ACE-inhibitor would be part of the secondary endpoints
Main Inclusion Criteria
Patients admitted to hospital with clinical symptoms of acute myocardial infarction andor electrocardiographic signs of AMI and a documented elevation in cardiac markers troponin T or I or elevation of cardiac enzymes creatinine kinase MB
Myocardial performance index MPI 055 determined by echocardiography prior to randomization
Be randomized within 7 days of AMI in or out patient
Written informed consent
Main Exclusion Criteria
Age 18 years
Any contraindications to angiotensin 2-receptor blocker
In patients with WMSI 13 treatment with ACE-inhibitor or angiotensin 2-receptor blockers
In patients with WMSI 13 no initiated or planned treatment with an ACE-inhibitor Treatment with an ACE-inhibitor must be started within 7 days
Pregnancy or women of childbearing potential who are not using an effective method of contraception
Other comorbid conditions that would influence the study
Currently receiving an experimental study-drug
Study Medication
Irbesartan 300 mg once daily which can be reduced to 150 mg at the discretion of the treating physician With a dose less than 150 mg patients will be excluded from analysis
Mode of Administration
The drugs will be given unblinded but with blinded assessment of the endpoints
Evaluation Criteria
Primary Outcome
Change in MPI in patients with WMSI 13 treated with either irbesartan or usual care
Secondary Outcomes
Change in MPI in patients with WMSI 13 on an ACE-inhibitor treated with either irbesartan or usual care
Change in left ventricular diastolic function pulse wave and color M-mode echocardiography and left atrial size in patients with WMSI 13 or 13
Change in LV systolic function WMSI and LVEF in patients with WMSI 13 or WMSI 13
Tertiary Outcomes
Changes in neurohormonal activation and glucose metabolism optional
Definitions of Objectives
Myocardial Performance Index
MPI is calculated as the sum of the isovolumetric relaxation and contraction times divided by ejection time this is measured from mitral inflow and left ventricular outflow recording obtained by pulse wave Doppler echocardiography
LV Diastolic Function
Assessment of mitral inflow curve E- and A-wave and deceleration time of the E-wave
Color M-mode
Assessment of the flow propagation velocity
Left atrial size measured by single plane volume in a four chamber view
Systolic Function
Wall motion score index LV is divided into 16 segments which are scored based on myocardial thickening and endocardial excursion 3 hyperkinesis 2 normokinesis 1 hypokinesis 0 akinesis and -1 paradoxical motion WMSI is calculated by dividing the sum of scores by the number of segments analyzed
LV ejection fraction is obtained by multiplying WMSI by 30
Neurohormonal activation is assessed by pro-NT-BNP and glycemic control is assessed by an oral glucose tolerance test during hospitalisation and after 3 months in patients without known diabetes mellitus optional
Statistical Considerations
Population Analyzed All randomized patients will be in the study for the planned treatment period of 3 months but only patients on 150 mg irbesartan will be analyzed according to the primary endpoint
Sample Size Consideration The primary study objective is to show that irbesartan will improve MPI more than usual care after 3 months treatment in patients with AMI WMSI 13 and MPI 055
Furthermore patients with reduced LV function WMSI 13 and with reduced global LV function MPI 055 will be included in the study and irbesartan will be added to an ACE-inhibitor compared to usual care This patient will be included in the secondary objectives and therefore no sample size estimation has been performed 100 patients are estimated to be enrolled in this study group and will be used for descriptive purposes
It is assumed that MPI has a normal distribution in the study population and from previous populations of patients with AMI it is found that MPIs have a mean value of 055 SD 020 in patients with WMSI 13 based on an estimated change in MPI of 20 in the irbesartan group a total of approximately 200 patients are needed for the study
Duration of Treatment and Observations
Treatment
Patients will receive irbesartan 300 mg daily at least 150 mg per day for 3 months treatment
The primary observation period will be 3 months corresponding to the treatment period but vital status or hospitalisation will be noted after 6 and 12 months
Primary Objective
To compare the change in global LV function assessed with myocardial performance index MPI after 3 months treatment with irbesartan compared to usual care in patients admitted to hospital with acute myocardial infarction wall motion score index 13 LVEF 040 and MPI 055
Secondary Objectives
To compare irbesartan added to an ACE-inhibitor compared to usual care in patients with AMI WMSI 13 and MPI 055
To compare LV diastolic function assessed by pulse wave and color M-mode Doppler echocardiography and left atrial size after treatment with irbesartan compared to usual care in AMI and
WMSI 13 and MPI 055 and
WMSI 13 and MPI 055
To compare change in WMSI after treatment with irbesartan compared to usual care in patients with AMI and
WMSI 13 and MPI 055 and
WMSI 13 and MPI 055
Tertiary Objectives
To assess the effects of irbesartan versus usual care on neurohormonal activation and glucose metabolism optional
Study Design
A Danish multicenter randomized prospective trial with PROBE-design
Study Drug
Patients will be randomized to receive either irbesartan 300 mg once daily or usual care
Duration of Therapy
Irbesartan 300 mg daily for 3 months after hospital discharge for acute myocardial infarction
Patients should receive standard medical therapy including revascularisation as appropriate
Expected Number of Patients
200 patients with AMI WMSI 13 and MPI 055 100 patients in the irbesartan group and 100 in the usual care group The patients will be included in the analysis of the primary endpoint Further approximately 100 patients with AMI WMSI 13 and MPI 055 treated with an ACE-inhibitor would be part of the secondary endpoints
Main Inclusion Criteria
Patients admitted to hospital with clinical symptoms of acute myocardial infarction andor electrocardiographic signs of AMI and a documented elevation in cardiac markers troponin T or I or elevation of cardiac enzymes creatinine kinase MB
Myocardial performance index MPI 055 determined by echocardiography prior to randomization
Be randomized within 7 days of AMI in or out patient
Written informed consent
Main Exclusion Criteria
Age 18 years
Any contraindications to angiotensin 2-receptor blocker
In patients with WMSI 13 treatment with ACE-inhibitor or angiotensin 2-receptor blockers
In patients with WMSI 13 no initiated or planned treatment with an ACE-inhibitor Treatment with an ACE-inhibitor must be started within 7 days
Pregnancy or women of childbearing potential who are not using an effective method of contraception
Other comorbid conditions that would influence the study
Currently receiving an experimental study-drug
Study Medication
Irbesartan 300 mg once daily which can be reduced to 150 mg at the discretion of the treating physician With a dose less than 150 mg patients will be excluded from analysis
Mode of Administration
The drugs will be given unblinded but with blinded assessment of the endpoints
Evaluation Criteria
Primary Outcome
Change in MPI in patients with WMSI 13 treated with either irbesartan or usual care
Secondary Outcomes
Change in MPI in patients with WMSI 13 on an ACE-inhibitor treated with either irbesartan or usual care
Change in left ventricular diastolic function pulse wave and color M-mode echocardiography and left atrial size in patients with WMSI 13 or 13
Change in LV systolic function WMSI and LVEF in patients with WMSI 13 or WMSI 13
Tertiary Outcomes
Changes in neurohormonal activation and glucose metabolism optional
Definitions of Objectives
Myocardial Performance Index
MPI is calculated as the sum of the isovolumetric relaxation and contraction times divided by ejection time this is measured from mitral inflow and left ventricular outflow recording obtained by pulse wave Doppler echocardiography
LV Diastolic Function
Assessment of mitral inflow curve E- and A-wave and deceleration time of the E-wave
Color M-mode
Assessment of the flow propagation velocity
Left atrial size measured by single plane volume in a four chamber view
Systolic Function
Wall motion score index LV is divided into 16 segments which are scored based on myocardial thickening and endocardial excursion 3 hyperkinesis 2 normokinesis 1 hypokinesis 0 akinesis and -1 paradoxical motion WMSI is calculated by dividing the sum of scores by the number of segments analyzed
LV ejection fraction is obtained by multiplying WMSI by 30
Neurohormonal activation is assessed by pro-NT-BNP and glycemic control is assessed by an oral glucose tolerance test during hospitalisation and after 3 months in patients without known diabetes mellitus optional
Statistical Considerations
Population Analyzed All randomized patients will be in the study for the planned treatment period of 3 months but only patients on 150 mg irbesartan will be analyzed according to the primary endpoint
Sample Size Consideration The primary study objective is to show that irbesartan will improve MPI more than usual care after 3 months treatment in patients with AMI WMSI 13 and MPI 055
Furthermore patients with reduced LV function WMSI 13 and with reduced global LV function MPI 055 will be included in the study and irbesartan will be added to an ACE-inhibitor compared to usual care This patient will be included in the secondary objectives and therefore no sample size estimation has been performed 100 patients are estimated to be enrolled in this study group and will be used for descriptive purposes
It is assumed that MPI has a normal distribution in the study population and from previous populations of patients with AMI it is found that MPIs have a mean value of 055 SD 020 in patients with WMSI 13 based on an estimated change in MPI of 20 in the irbesartan group a total of approximately 200 patients are needed for the study
Duration of Treatment and Observations
Treatment
Patients will receive irbesartan 300 mg daily at least 150 mg per day for 3 months treatment
The primary observation period will be 3 months corresponding to the treatment period but vital status or hospitalisation will be noted after 6 and 12 months
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 2612 | None | None | None |