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

• Register: EUCTR
• Last refreshed on: 7 January 2013
• Main ID: EUCTR2006-001704-37-IT
• Date of registration: 10/11/2008
• Prospective Registration: No
• Primary sponsor: NOVARTIS FARMA
• Public title: A 36-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group study to evaluate the efficacy and safety of aliskiren on the prevention of left ventricular remodeling in high risk post-acute myocardial infarction patients when added to optimized standard therapy
• Scientific title: A 36-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group study to evaluate the efficacy and safety of aliskiren on the prevention of left ventricular remodeling in high risk post-acute myocardial infarction patients when added to optimized standard therapy
• Date of first enrolment: 26/10/2006
• 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: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2

Countries of recruitment

Belgium, 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: 0
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:
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. 11.Unstable angina requiring intervention between Visit 1 and Visit 2. 12.Any coronary artery revascularization procedure within 7 days prior to Visit 1. 13.Planned or anticipated elective CABG, PCI, CRT, LVAD or cardiac transplant after the patient is enrolled into the study. 14.Current abuse or recent history of alcohol or other drug substance abuse (past 12 months). 15.Significant non-cardiovascular illness or condition likely to result in death prior to trial completion, e.g., major organ transplant (life expectancy < 1 year). 16.Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of study drugs including, but not limited to, any of the following: ? History of major gastrointestinal tract surgery such as gastrectomy, gastroenterostomy, or bowel resection. ? Currently active or previously active inflammatory bowel disease during the 12 months prior to Study Visit 1. ? Currently active gastritis, duodenal or gastric ulcers, or gastrointestinal/rectal bleeding during the 3 months prior to Study Visit 1. ? Current pancreatitis or evidence of impaired pancreatic function/injury as indicated by abnormal lipase or amylase. ? Evidence of hepatic disease as determined by any one of the following: AST or ALT values exceeding 3 x ULN at Study Visit 1, a history of hepatic encephalopathy, a history of esophageal varices, or a history of portocaval shunt. ? Current treatment with cholestyramine and colestipol resins. 17.Any surgical or medical condition that in the opinion of the investigator may place the patient at higher risk from his/her participation in the study or is likely to prevent the patient from complying with the requirements of the study or completing the study. 18.History of noncompliance to medical regimens or unwillingness to comply with the study protocol. 19.Any condition that in the opinion of the investigator or the Novartis medical monitor would jeopardize the evaluation of efficacy or safety. 20.Persons directly involved in the execution of this protocol. 21.Use of other investigational drugs within 30 days or 5 half-lives prior to Visit 1, whichever is longer. 22.Known or suspected contraindications to or history of hypersensitivity to any of the study drugs or to drugs belonging to the same therapeutic class (e.g., renin inhibitors) as the study drug. 23.History of malignancy of any organ system, treated or untreated, within the past 5 years whether or not there is evidence of local rec

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

Health Condition(s) or Problem(s) studied

ACUTE MYOCARDIAL INFARCT
MedDRA version: 14.1 Level: PT Classification code 10000891 Term: Acute myocardial infarction System Organ Class: 10007541 - Cardiac disorders

Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

Intervention(s)

Product Name: aliskiren
Product Code: CSPP100A
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Aliskiren
CAS Number: 173335-58-2
Current Sponsor code: SPP100A
Concentration unit: mg milligram(s)
Concentration number: 150-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Product Name: aliskiren
Product Code: CSPP100A
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Renin-inhibitors
Concentration unit: mg milligram(s)
Concentration number: 75-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Secondary Objective: The secondary objectives of this trial are to evaluate the effect of aliskiren compared to placebo on: ? a composite outcome of CV death, hospitalization for heart failure, or a reduction in left ventricular ejection fraction greater than 6 units (absolute percentage points) ? a composite outcome of CV death, hospitalization for heart failure, recurrent myocardial infarction, stroke or resuscitated sudden death ? change in left ventricular end-diastolic volume (LVEDV) between baseline and end of study ? change in left ventricular ejection fraction (LVEF) between baseline and end of study ? Right ventricular (RV) and left ventricular (LV) volumes, LVEF, and myocardial infarct related scarring as determined by contrast enhanced cardiac magnetic resonance imaging (MRI) (in a subset of patients) ? overall safety and tolerability in combination with standard therapy in patients post acute myocardial infarction.

Main Objective: ? 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.

Primary end point(s): The primary efficacy endpoint will be change in left ventricular end systolic volume (LVESV), from baseline to end of study. Ventricular volumes will be assessed utilizing Simpson's rule from the apical 4 and 2-chamber views.

Secondary ID(s)

CSPP100A2340

2006-001704-37-NL