A 36 week, multicenter, randomized, double-blind, placebo- controlled, parallel-group, pilot study to evaluate the efficacy and safety of aliskiren on the prevention of left ventricular remodeling in high risk post-AMI patients when added to optimized standard therapy

• Register: EUCTR
• Last refreshed on: 10 July 2015
• Main ID: EUCTR2006-001704-37-CZ
• Date of registration: 17/05/2007
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma Services AG
• Public title: A 36 week, multicenter, randomized, double-blind, placebo- controlled, parallel-group, pilot study to evaluate the efficacy and safety of aliskiren on the prevention of left ventricular remodeling in high risk post-AMI patients when added to optimized standard therapy
• Scientific title: A 36 week, multicenter, randomized, double-blind, placebo- controlled, parallel-group, pilot study to evaluate the efficacy and safety of aliskiren on the prevention of left ventricular remodeling in high risk post-AMI patients when added to optimized standard therapy
• Date of first enrolment: 10/07/2007
• Target sample size: 800
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2006-001704-37
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no

Countries of recruitment

Belgium, Czech Republic, Denmark, Germany, Hungary, Italy, Netherlands, Sweden, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
1. Male or female patients 18 years and older.
2. Patients within 7-42 days of an acute myocardial infarction associated with left
ventricular systolic dysfunction prior to Visit 1 (see below). A qualifying myocardial
infarction will require each of the following:
• Typical clinical presentation consistent with myocardial infarction (i.e., chest pain,
shortness of breath)
• Elevation of cardiac markers (any of the following will fulfill the requirement for
an increase in cardiac markers):
• Both total CK and CK-MB are above the upper limit of normal (ULN) and either
total CK or CK-MB are at least twice the upper limit of normal (2xULN)
• CK-MB is elevated to at least twice the upper limit of normal (2xULN) when
total CK is not available, and is confirmed by an accompanying Troponin T or I
level at least three times the upper limit of normal (3xULN)
• Total CK is elevated to at least twice the upper limit of normal (2xULN) when
CK-MB is not available, or to above the ULN if confirmed by an accompanying
Troponin T or I level at least three times the upper limit of normal (3xULN)
• Troponin T or I level is at least five times the upper limit of normal (5xULN) and
neither total CK nor CK-MB are available.
• Typical ECG changes, including evolving ST-segment or T-wave changes in two
or more contiguous ECG leads, the development of new pathological Q/QS
waves in two or more contiguous ECG leads, or the development of new left
bundle branch block.
3. Documented left ventricular systolic dysfunction associated with the qualifying
acute myocardial infarction obtained as a clinical study at least 5 days after the
qualifying MI but prior to Visit 1. Systolic dysfunction will be defined by at least
one of the following criteria:
• Echocardiography: left ventricular ejection fraction (LVEF) = 40%
• Radionuclide ventriculography: LVEF = 40%
• Ventricular contrast angiography: LVEF = 35%.
4. Patients must be on stable doses of the following concomitant medications for at
least 2 weeks prior to Visit 1 unless contraindicated due to intolerance:
• A Beta-blocker
• An Anti-platelet agent
• A Statin
5. An evidence-based dose of an Angiotensin Converting Enzyme Inhibitor (ACEI) or
Angiotensin Receptor Blocker (ARB) but not both.
6. Patients who are eligible, able to participate in the study, and who consent to do
so after the purpose and nature of the investigation has been clearly explained to
them (written informed consent).
7. Qualifying Echocardiogram:
• Patients who fulfill the screening inclusion and exclusion criteria will have a
qualifying echocardiogram performed and transmitted to the Echo Core
Laboratory. To be eligible for randomization, patients must fulfill the following
criteria by the core laboratory:
• Acceptable image quality
• Confirmed LVEF = 45%
• Qualifying Myocardial Infarct Percentage = 20% (akinetic or dyskinetic segment
length as percent of total cavity perimeter).
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
For full list, please see protocol.

1. Patients requiring both ACEI and ARB combination therapy at V1 or any time
during the study.
2. Hypertrophic cardiomyopathies due to etiologies other than hypertension (i.e.,
idiopathic or valvular).
3. Severe refractory hypertension defined as MSSBP = 180 mmHg and/or MSDBP =
110 mmHg) at Visit 2.
4. Hemodynamically significant stenotic or obstructive valvular, subvalvular or
supravalvular lesions.
5. Secondary forms of cardiomyopathy such as restrictive cardiomyopathy or
infective cardiomyopathy (e.g., Chagas’ disease).
6. Cardiogenic shock or systolic BP < 100 mmHg within the 24 hours prior to Visit 2.
7. Estimated Glomerular Filtration Rate (eGFR) < 30 ml/min/1.73m2 using the MDRD
formula at Visit 1.
8. Stroke or transient ischemic event (TIA) within 6 months of Study Visit 1.
9. Serum potassium = 5.1 mEq/L, or dehydration at Study Visit 1.
10. Significant valvular cardiovascular disease expected to lead to cardiac surgery
during the course of the study.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Hypertension

Intervention(s)

Product Name: Aliskiren
Product Code: SPP100A
Pharmaceutical Form: Film-coated tablet
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Product Name: Aliskiren
Product Code: SPP100A
Pharmaceutical Form: Film-coated tablet
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Primary end point(s): The primary efficacy variable is the change in left ventricular end systolic volume (LVESV) as assessed by echocardiography, from baseline to end of study.

Secondary Objective: For full list, refer to protocol

To evaluate the effect of aliskiren compared to placebo on:
• a composite outcome of CV death, hospitalization for heart failure, or a reduction
in ejection fraction greater than 6 units (absolute percentage points)
• a composite outcome of time to CV death, hospitalization for heart failure,
recurrent myocardial infarction, stroke or resuscitated sudden death
• change in left ventricular ejection fraction (LVEF) between baseline and end of
study
Exploratory Objectives:
To evaluate the effect of aliskiren compared to placebo on:
• renal function as measured by change in estimated glomerular filtration rate
(eGFR), cystatin C, and urinary albumin creatinine ration (uacr) from baseline to
end of study (in a subset of patients)
• other biological markers relevant to the pathophysiology of remodeling and other
outcomes after myocardial infarction (in a subset of patients)

Main Objective: To demonstrate that aliskiren 300 mg, in addition to standard therapy, has superior efficacy compared to placebo in reducing the primary index of adverse cardiac remodeling (defined as the change in LVESV from baseline to end of study) in patients after high risk acute myocardial infarction.

Secondary ID(s)

2006-001704-37-NL

CSPP100A2340