E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
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 |
• Evaluate the overall safety and tolerability of aliskiren 150 mg when given in addition to standard therapy in hypertensive patients with stable heart failure. |
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E.2.2 | Secondary objectives of the trial |
• Evaluate the efficacy of aliskiren on N-terminal pro-brain natriuretic peptide when added to standard therapy in hypertensive patients with stable heart failure. • Evaluate the efficacy of aliskiren on brain natriuretic when added to standard therapy in hypertensive patients with stable heart failure. • Evaluate the efficacy of aliskiren on aldosterone when added to standard therapy in hypertensive patients with stable heart failure. • Evaluate the effect of aliskiren on improvement in signs and symptoms of heart failure and change in NYHA classification from baseline to study end. • Evaluate the effect of aliskiren on cardiac hemodynamics as assessed by echocardiography at baseline and end of study. • Evaluate the blood pressure lowering effect (change from baseline in MSSBP and MSDBP) of aliskiren 150 mg in hypertensive patients with stable heart failure.
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
• Outpatients 18 years of age and older. • Male or female patients are eligible. Female patients must be either post-menopausal for one year, surgically sterile, or using effective contraceptive methods such as oral contraceptives, barrier method with spermicide or an intrauterine device. • Patients with history or current diagnosis of essential hypertension • Patients with stable heart failure (NYHA Class II-IV), for at least 1 month prior to Visit 1. Patients must be on a stable dosage regimen of heart failure medications which may consist of the following: either an ACE inhibitor OR an ARB, and a beta blocker for the 1 month period prior to Visit 1. For patients not on either an ACE inhibitor OR an ARB, and a beta blocker at entry the reason (e.g., patient is intolerant of these medications or the absence of a clinical indication) should be documented. The use of digoxin and diuretics as background therapy for heart failure is allowed. • Patients with a BNP > 150 pg/ml (43 pmol/L) at Visit 1. • Patients with documented sinus rhythm at Visit 1. • Patients who are eligible and 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).
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E.4 | Principal exclusion criteria |
• Patients with stable heart failure who require treatment with both an ACE inhibitor and an ARB • Patients who previously entered an aliskiren study and who qualified to be randomized or enrolled into the active drug treatment period. • History or evidence of a secondary form of hypertension • Right heart failure due to pulmonary disease. • Diagnosis of postpartum cardiomyopathy. • Hemodynamically significant mitral stenosis or lesions of the left ventricular outflow tract including aortic stenosis or hypertrophic obstructive cardiomyopathy. • Secondary forms of cardiomyopathy such as restrictive cardiomyopathy or infective cardiomyopathy (e.g., Chagas’ disease). • Patients with a history of heart transplant or who are on a transplant list (life expectancy < 6 months at time of entry into the study). • Persistent sitting systolic blood pressure < 90 mm Hg. • Unstable angina or coronary artery disease likely to require coronary artery bypass graft (CABG) or PTCA during the 14 weeks of the trial. Patients with angina pectoris requiring pharmacological therapy are allowed entry into the study. • History of myocardial infarction, coronary bypass surgery, or any percutaneous coronary intervention (PCI) during the 6 months prior to Visit 1. • Second or third degree heart block without a pacemaker. • Patients with chronic atrial fibrillation. • Patients with an ICD or pacemaker where patient uses pacemaker > 20% of the time. • Patients with a biventricular pacemaker or biventricular ICD. • Episode(s) of ventricular tachycardia or another severe arrhythmia producing significant hemodynamic consequences or considered life-threatening within 3 months of Visit 1. • Patients who require treatment with Vaughn Williams Type 1 or 3 anti-arrhythmic agents within 30 days prior to Visit 1 or who may require them anytime during the study are to be excluded (note: the use of amiodarone is permitted if the patient has been on a stable does for at least 30 days prior to Visit 1). • Transient ischemic cerebral attack or cerebral vascular accident during the 6 months prior to Visit 1. • Patients with active or unstable bronchospasm or asthma (patients must be on stable regimen of respiratory medications for 1 month prior to Visit 1). • Serum potassium ≥ 5.1 mEq/L (5.1 mmol/L) at Visit 1. • 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 Visit 1. • Currently active gastritis, duodenal or gastric ulcers, or gastrointestinal/rectal bleeding during the 3 months prior to Visit 1. • Any history of pancreatic injury, 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: SGOT or SGPT values exceeding 3 x ULN at Visit 1, a history of hepatic encephalopathy, a history of esophageal varices, or a history of portocaval shunt. • Evidence of renal impairment as determined by any one of the following: serum creatinine > 2.0 mg/dL (177 umol/L) at Visit 1, a history of dialysis, or a history of nephrotic syndrome. • Current treatment with cholestyramine and colestipol resins. • History of malignancy including leukemia and lymphoma (but not basal cell skin cancer) within the past five years. • History or evidence of drug or alcohol abuse within the last 12 months. • Pregnant or nursing women. • Any surgical or medical condition, which 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. • History of noncompliance to medical regimens or unwillingness to comply with the study protocol. • Any condition that in the opinion of the investigator or the Novartis medical monitor would jeopardize the evaluation of efficacy or safety. • Participation in any investigational drug trial within one month of Visit 1. • Persons directly involved in the execution of this protocol.
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E.5 End points |
E.5.1 | Primary end point(s) |
Evaluate the overall safety and tolerability of aliskiren 150 mg when given in addition to standard therapy in hypertensive patients with stable heart failure |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Information not present in EudraCT |
E.6.2 | Prophylaxis | Information not present in EudraCT |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Information not present in EudraCT |
E.6.7 | Pharmacodynamic | Information not present in EudraCT |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | Information not present in EudraCT |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Information not present in EudraCT |
E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
E.6.13 | Others | Information not present in EudraCT |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Information not present in EudraCT |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Information not present in EudraCT |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | Information not present in EudraCT |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | Information not present in EudraCT |
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 | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| Information not present in EudraCT |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.5 | The trial involves multiple Member States | Yes |
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 | Information not present in EudraCT |
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 |
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E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
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
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 15 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 15 |