A Randomized Controlled Trial of Aliskiren in the Prevention of Major Cardiovascular Events in Elderly People

Condition(s) targeted: Cardiovascular Events

Intervention: Aliskiren and Amlodipine or HCTZ (Drug); Aliskiren (Drug); Amlodipine or HCTZ (Drug); Placebo (Drug)

Phase: Phase 3

Status: Recruiting

Sponsored by: Novartis

Official(s) and/or principal investigator(s):
Novartis Pharmaceuticals, Study Director, Affiliation: Novartis Pharmaceuticals

This study will provide new information regarding the role of aliskiren (with or without additional therapy with a diuretic or a CCB) in elderly individuals (≥ 65 years) with SBP 130 to 159 mmHg, in preventing major CV events and on global measures of physical, executive and cognitive function.

Official title: A Randomized Controlled Trial of Aliskiren in the Prevention of Major Cardiovascular Events in Elderly People

Study design: Allocation: Randomized, Intervention Model: Factorial Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Primary outcome: Reduction in risk of major cardiovascular events (composite of CV death, non-fatal MI, non-fatal stroke and significant heart failure)

Secondary outcome:

Prevention of decline in the ability to perform everyday activities independently

Prevention of decline in renal function.

Reduction of total mortality

Minimum age: 65 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

Systolic blood pressure 130 - 159 mmHg with any one of the following (1, 2 or 3):

1. Men and women aged ≥ 65 years if they have at least one of the following: (secondary prevention) Coronary heart disease

- Previous myocardial infarction or

- Stable angina or unstable angina with documented multi-vessel coronary artery

disease, > 50% stenosis in at least 2 major coronary arteries on coronary angiography, or positive stress test (ECG or nuclear perfusion scintogram), or

- Multi-vessel PCI, or

- Multi-vessel CABG surgery > 4 years prior to informed consent, or with recurrent

angina or ischemia following surgery Stroke/TIA Previous documented stroke or documented TIA < 1 year before informed consent Peripheral artery disease

- Previous limb bypass surgery or percutaneous transluminal angioplasty, or

- Previous limb or foot amputation, or

- History of intermittent claudication, with an ankle: arm BP ratio ≤ 0. 80 on at

least one side, or significant peripheral artery stenosis (> 50%) documented by angiography or non-invasive testing Diabetes mellitus High-risk diabetics with evidence of end-organ damage

2. Men and women aged ≥ 65 years with no history of CVD, and with at least 1 CV risk factor (primary prevention):

- History of dyslipidemia, defined as LDL cholesterol > 3. 5 mmol/L (135 mg/dL) or

HDL< 1. 3 mmol/L (50 mg/dL) in women or < 1. 0 mmol/L (39 mg/dL) in men or total cholesterol/HDL ratio > 5

- History of current or recent smoking (regular tobacco use within 5 years)

- Abdominal adiposity defined as waist/hip ratio ≥ 0. 90 in women and ≥ 0. 95 in men

- History of dysglycemia defined as impaired fasting glucose (IFG - fasting plasma

glucose 5. 6 to 6. 9 mmol/L [101 to 124 mg/dL]), or impaired glucose tolerance

(IGT - fasting plasma glucose < 7 mmol/L [126 mg/dL] but 2 hour glucose 7. 8 to

11. 0 mmol/L [140 to 198 mg/dL]) or type 2 diabetes

- Renal dysfunction: eGFR< 60 ml/min/1. 73m2 but > 30 ml/min/1. 73m2 (MDRD formula)

and/or microalbuminurea/macroalbuminurea

- Clinical evidence of left ventricular hypertrophy

3. Men and women aged ≥ 70 years if they do not have any of the above (primary prevention)

Exclusion Criteria:

1. Current treatment with aliskiren, an ACE-inhibitor, an ARB or an aldosterone antagonist and unable to discontinue this therapy in those without clinical vascular disease. Individuals with CVD or type 2 diabetes and/or renal dysfunction may receive an ACE-inhibitor or an ARB, but not both, contraindications to aliskiren, amlodipine or hydrochlorothiazide.

2. Use of both thiazide diuretic and amlodipine or another calcium channel blocker Patients on only one of these two classes of drugs are eligible

3. Uncontrolled hypertension (systolic blood pressure ≥ 160 mmHg and/or diastolic blood pressure ≥ 100 mmHg)

4. Symptomatic heart failure, requiring the use of loop diuretics

5. Hemodynamically significant primary valvular or outflow tract obstruction (e. g. aortic or mitral valve stenosis, asymmetric septal hypertrophy, malfunctioning prosthetic valve). Constrictive pericarditis. Complex congenital heart disease.

6. Acute stroke < 3 months or TIA ≤ 7 days before informed consent, acute coronary syndrome < 1 months before informed consent

7. Planned cardiac surgery or angioplasty < 3 months after informed consent or having had the procedure < 3 months before informed consent

8. Severe renal impairment eGFR ≤ 30 ml/min/1. 73m2 (MDRD formula); known renal artery stenosis ; serum potassium ≥ 5. 3 mmol/L

9. Chronic liver disease (i. e. cirrhosis, esophageal varices, portocaval shunt or persistent hepatitis) or abnormal liver function, i. e., alanine transaminase (ALT) or AST > 3x upper limit of normal (ULN)

10. Concurrent treatment with cyclosporine or quinidine; chronic use of non-steroidal anti-inflammatory drug (NSAIDs) or cyclooxygenase-2 (COX 2) inhibitors in patients with eGFR < 60 ml/min/1. 73m2 (MDRD formula)

11. History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years regardless of whether there is evidence of local recurrence or metastases

12. Other serious condition(s) likely to interfere with study participation or with the ability to complete the study. Significant psychiatric illness, senility, dementia, alcohol or substance abuse, which could impair the ability to provide informed consent and to adhere to the study procedures

Investigative Site, Ciudad de Autonoma de Buenos Aires, Argentina; Not yet recruiting
Novartis, Phone: 862-778-8300

Investigative Site, São José do Rio Preto, Brazil; Not yet recruiting
Novartis, Phone: 862-778-8300

Investigative Site, Toronto, Canada; Not yet recruiting
Novartis, Phone: 862-778-8300

Investigative Site, Osorno, Chile; Not yet recruiting
Novartis, Phone: 862-778-8300

Investigative Site, Barranquilla, Colombia; Not yet recruiting
Novartis, Phone: 862-778-8300

Investigative Site, Prague, Czech Republic; Not yet recruiting
Novartis, Phone: 862-778-8300

Investigative Site, Erlangen, Germany; Not yet recruiting
Novartis, Phone: 862-778-8300

Investigative Site, Budapest, Hungary; Recruiting
Novartis, Phone: 862-778-8300

Investigative Site, Mumbai, India; Not yet recruiting
Novartis, Phone: 862-778-8300

Investigative Site, Galway, Ireland; Not yet recruiting
Novartis, Phone: 862-778-8300

Investigative Site, Batu caves, Malaysia; Not yet recruiting
Novartis, Phone: 862-778-8300

Investigative Site, Leiderdorp, Netherlands; Not yet recruiting
Novartis, Phone: 862-778-8300

Investigative Site, Quezon City, Philippines; Not yet recruiting
Novartis, Phone: 862-778-8300

Investigative Sites, Moscow, Russian Federation; Not yet recruiting
Novartis, Phone: 862-778-8300

Investigative Site, Cape Town, South Africa; Not yet recruiting
Novartis, Phone: 862-778-8300

Investigative Site, Valencia, Spain; Not yet recruiting
Novartis, Phone: 862-778-8300

Investigative Site, Stockholm, Sweden; Not yet recruiting
Novartis, Phone: 862-778-8300

Investigative Site, Istanbul, Turkey; Not yet recruiting
Novartis, Phone: 862-778-8300

Investigative Site, Kyiv, Ukraine; Not yet recruiting
Novartis, Phone: 862-778-8300

Investigative Site, Portland, Oregon 97201, United States; Not yet recruiting
Novartis, Phone: 862-778-8300

Starting date: December 2010
Last updated: August 17, 2011