| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
cardiovacular disease,
functional hypertension,
|
|
| E.1.1.1 | Medical condition in easily understood language |
| srdeční choroby, vysoký krevní tlak |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 14.0 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10020772 |
| E.1.2 | Term | Hypertension |
| E.1.2 | System Organ Class | 10047065 - Vascular disorders |
|
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 14.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10007648 |
| E.1.2 | Term | Cardiovascular disease, unspecified |
| E.1.2 | System Organ Class | 10007541 - Cardiac disorders |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
1. To determine whether treatment with an aliskiren-based regimen (in part combined with amlodipine or hydrochlorothiazide) compared to a non-aliskiren based regimen, both on top of non-study blood pressure lowering agents where applicable, reduces the risks of major cardiovascular events (composite of cardiovascular death, non-fatal MI, non-fatal stroke and significant heart failure)
2. To determine whether intensified therapy with aliskiren plus an additional BP lowering drug (amlodipine or hydrochlorothiazide) compared to placebo, both on top of non-study blood pressure lowering agents where applicable, reduces the risk of major cardiovascular events
|
|
| E.2.2 | Secondary objectives of the trial |
To determine whether treatment with an aliskiren-based regimen compared to non-aliskiren based regimen:
1. Prevents decline in the ability to perform everyday activities independently (key secondary objective)
2. Prevents decline in renal function
3. Reduces total mortality
|
|
| E.2.3 | Trial contains a sub-study | Yes |
| E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Two focused sub-studies will be conducted in order to obtain more detailed information about mechanisms of disease and treatment benefit. These substudies will be conducted concurrently with the main study, in a subset of patients at selected centres. Descriptions of these substudies are included in the appendices to the protocol.
1. Magnetic resonance imaging (MRI) substudy evaluating serial changes in brain structure to document silent infarcts and white matter lesions, and to relate these to changes in cognition.
For more informations please see Appendix E of the study protocol.
2. Ambulatory blood pressure substudy
For more informations please see Appendix Fof the study protocol.
|
|
| E.3 | Principal inclusion criteria |
The study will enrol elderly people with SBP 130 to 159 mmHg (at Visit 1), and 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
a) Previous myocardial infarction or
b) 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
c) Multi-vessel PCI, or
d) Multi-vessel coronary artery bypass graft (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
a) Previous limb bypass surgery or percutaneous transluminal angioplasty, or
b) Previous limb or foot amputation, or
c) 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
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):
a) History of dyslipidemia, defined as low-density lipoproteins (LDL) cholesterol > 3.5 mmol/L (135 mg/dL) or high-density lipoprotein (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
b) History of current or recent smoking (regular tobacco use within 5 years)
c) Abdominal adiposity defined as waist/hip ratio ≥ 0.90 in women and ≥ 0.95 in men
d) 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
e) Renal dysfunction: eGFR< 60 ml/min/1.73m2, but > 30 ml/min/1.73m2 (Modification of diet in renal disease [MDRD] formula) and/or microalbuminurea/macroalbuminurea
f) Clinical evidence of LVH
3. Men and women aged ≥ 70 years if they do not have any of the above (primary prevention)
|
|
| E.4 | Principal 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
2. Contraindications to aliskiren, amlodipine or hydrochlorothiazide
3. Use of both thiazide diuretic and amlodipine or another calcium channel blocker
Patients on only one of these two classes of drugs are eligible
4. Uncontrolled hypertension (systolic blood pressure ≥ 160 mmHg and/or diastolic
blood pressure ≥ 100 mmHg)
5. Symptomatic heart failure, requiring the use of loop diuretics
6. Hemodynamically significant primary valvular or outflow tract obstruction (e.g. aortic or mitral valve stenosis, asymmetric septal hypertrophy, malfunctioning prosthetic valve)
7. Constrictive pericarditis
8. Complex congenital heart disease
9. Acute stroke < 3 months or TIA ≤ 7 days before informed consent
10. Acute coronary syndrome < 1 months before informed consent
For a complete list of exclusion criteria, please refer to protocol. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary end points are the composite of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, and significant heart failure. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
1. Decline in ability to perform everyday activities independently.
2. Renal dysfunction (Primary outcome: end-stage renal disease [ESRD] requiring dialysis or transplantation or doubling of serum creatinine and reaching an eGFR < 45 ml/min/1.73 m2)
3. Total mortality |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | Yes |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | Yes |
| E.8.2.3.1 | Comparator description |
|
| E.8.2.4 | Number of treatment arms in the trial | 4 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 60 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Argentina |
| Brazil |
| Canada |
| Chile |
| China |
| Colombia |
| India |
| Israel |
| Korea, Republic of |
| Malaysia |
| Philippines |
| Russian Federation |
| South Africa |
| Turkey |
| Ukraine |
| United States |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 6 |
| E.8.9.1 | In the Member State concerned months | 3 |
| E.8.9.1 | In the Member State concerned days | 26 |
| E.8.9.2 | In all countries concerned by the trial years | 6 |
| E.8.9.2 | In all countries concerned by the trial months | 3 |
| E.8.9.2 | In all countries concerned by the trial days | 26 |
Print
