E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Acute decompensated heart failure |
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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 | 10000803 |
E.1.2 | Term | Acute heart failure |
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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. To test whether aliskiren in addition to standard therapy reduces time to first cardiovascular event (define as cardiovascular death, HF hospitalization, non-fatal MI, non-fatal stroke, sudden death with resuscitation) in patients hospitalized for an acute heart failure (HF) event when stabilized. To test whether aliskiren in addition to standard therapy reduces the time to all cause mortality in patients hospitalized for an acute HF event within 6 months and through end of study. To test whether aliskiren reduces in addition to standard therapy the BNP level in patients hospitalized for an acute HF event at 1 month and 6 months. To test whether, aliskiren therapy improves Quality of Life at 1month, 6 month and end of study).
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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 ≥ 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 ≥ 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 ≥ 400 pg/ml) 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 15. Severe hyponatremia < 130 meq/l at Visit 2 16. Renal disease or eGFR < 40 ml/min/1.73m2 (as measured by the MDRD formula) at Visit 2
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy variable is time to first cardiovascular death or heart failure hospitalization. The primary composite endpoint will be derived based on the adjudicated events. |
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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 | 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 | Yes |
E.6.13.1 | Other scope of the trial description |
Morbidity and Moratlity trial |
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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 | 6 |
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 | 0 |
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 |
E.8.9.2 | In all countries concerned by the trial days | 0 |