E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10011949 |
E.1.2 | Term | Decompensation cardiac |
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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 |
To test whether aliskiren in addition to standard therapy delays the time to first occurrence of either cardiovascular death or heart failure re-hospitalization within 6 months, in patients experiencing acute decompensated heart failure. |
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E.2.2 | Secondary objectives of the trial |
To test whether aliskiren in addition to standard therapy delays the time to first occurrence of either cardiovascular death or heart failure re-hospitalization, through end of study, in patients experiencing acute decompensated heart failure. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patients eligible for inclusion in this study have to fulfill all of the following criteria: 1. Patient hospitalized with a primary diagnosis of worsening heart failure &#8805; 18 years of age, male or female. 2. Patients with a diagnosis of acute heart failure expressed by symptoms (dyspnea or fatigability - NYHA Class III-IV) and signs of fluid overload (i.e. jugular venous distension, edema or positive rales auscultation or pulmonary congestion on chest x-ray) at the time of hospitalization. LVEF < 40% (measured within the last 6 months). Hospitalization for ADHF and remain stabilized for at least 6 hours (defined as SBP &#8805; 110 mm Hg after acute decompensated episode) and did not receive IV vasodilators (other than nitrates) and/or IV inotropic drugs at anytime from ADHF presentation to time of randomization. 3. Elevated BNP at Visit 1 (BNP &#8805; 400 pg/ml) (measured locally) 4. Patients with a history of chronic heart failure on standard therapy defined as requiring HF treatment for at least 30 days before the current hospitalization. (NYHA Class II IV) 5. Written informed consent to participate in the study. 6. Ability to comply with all study requirements |
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E.4 | Principal exclusion criteria |
1. Patients that required any use of IV vasodilators (except nitrates), and/or any IV inotropic therapy from the time of presentation for worsening HF to randomization 2. Concomitant use of ACEI and ARB at randomization 3. Right heart failure due to pulmonary disease 4. Diagnosis of postpartum cardiomyopathy 5. Myocardial infarction or cardiac surgery, including percutaneous transluminal coronary angioplasty (PTCA), within past 3 months. 6. Patients with a history of heart transplant or who are on a transplant list 7. Unstable angina or coronary artery disease likely to require coronary artery bypass graft (CABG) or percutaneous transluminal coronary angioplasty (PTCA) before randomization. 8. Sustained ventricular arrhythmia with syncopal episodes within past 3 months that is untreated 9. Presence of hemodynamically significant mitral stenosis or mitral regurgitation, except mitral regurgitation secondary to left ventricular dilatation 10. Presence of hemodynamically significant obstructive lesions of left ventricular outflow tract, including aortic stenosis 11. Persistent systolic blood pressure < 110 mm Hg 12. Stroke within the past 3 months 13. Primary liver disease considered to be life threatening 14. Serum potassium > 5.0 mEq/L (5.0 mmol/L) at Visit 2 (measured locally) 15. Severe hyponatremia < 130 meq/l at Visit 2 (measured locally) 16. Renal disease or eGFR < 40 ml/min/1.73m2 (as measured by the MDRD formula) at Visit 2 (measured locally) 17. History or presence of any other diseases (i.e. including malignancies) with a life expectancy of < 3 years 18. Prior (defined as less then 30 days from randomization) or current double-blind treatment in CHF trials or participation in an investigational drug study within the past 30 days 19. History of hypersensitivity to any of the study medications or to medications belonging to the same therapeutic class as the study medications 20. Any condition that in the opinion of the investigator or medical monitor would jeopardize the evaluation of efficacy or safety 21. History of noncompliance to medical regimens and patients who are considered potentially unreliable 22. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive Human Chorionic Gonadotropin (hCG) laboratory test (> 5 mIU/ml) 23. Women of child-bearing potential (WOCBP), defined as all women physiologically capable of becoming pregnant, including women whose career, lifestyle, or sexual orientation precludes intercourse with a male partner and women whose partners have been sterilized by vasectomy or other means, UNLESS they meet the following definition of post-menopausal: 12 months of natural (spontaneous) amenorrhea or 6 months of spontaneous amenorrhea with serum Follicle Stimulating Hormone (FSH) levels > 40 mIU/m or 6 weeks post surgical bilateral oophorectomy with or without hysterectomy OR are using one or more of the following acceptable methods of contraception: surgical sterilization (e.g., bilateral tubal ligation), hormonal contraception (implantable, patch, and oral), and double-barrier methods (if accepted by local regulatory authority and ethics committee). Reliable contraception should be maintained throughout the study and for 7 days after study drug discontinuation 24. Treatment with any of the following drugs within the past 3 months prior to Visit 1: Chronic intermittent intravenous inotrope therapy Direct renin inhibitor including aliskiren |
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary and secondary efficacy endpoints The primary efficacy endpoint consists of the following components: Cardiovascular death HF hospitalization |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
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) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
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 | 30 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 482 |
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 | 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
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 3 |