E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Acute decompensated heart failure |
|
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 | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10000803 |
E.1.2 | Term | Acute heart failure |
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 |
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. |
|
E.2.2 | Secondary objectives of the trial |
Key secondary objective:
To test whether aliskiren in addition to standard therapy delays the time to first occurrence of either cardiovascular death or heart failure (HF) re-hospitalization, within 12 months, in patients experiencing acute decompensated heart failure.
For other secondary endpoints and full details on endpoints please refer to protocol. |
|
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 12 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 or NT-proBNP ≥1600 pg/ml) measured locally at Visit 1.
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 |
|
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. Subjects with refractory, end stage heart failure defined as patients requiring ventricular assist devices (LVAD, IABP or any type of mechanical support), continued treatment with positive intravenous inotropic therapy or hospice care.
8. Unstable angina or coronary artery disease likely to require coronary artery bypass graft (CABG) or percutaneous transluminal coronary angioplasty (PTCA) before randomization.
9. Sustained ventricular arrhythmia with syncopal episodes within past 3 months that is untreated
10. Presence of hemodynamically significant mitral stenosis or mitral regurgitation, except mitral regurgitation secondary to left ventricular dilatation
11. Presence of hemodynamically significant obstructive lesions of left ventricular outflow tract, including aortic stenosis
12. Persistent systolic blood pressure < 110 mm Hg
13. Stroke within the past 3 months
14. Primary liver disease considered to be life threatening
15. Serum potassium > 5.0 mEq/L (5.0 mmol/L) at Visit 2
16. Severe hyponatremia < 130 meq/l at Visit 2
17. Renal disease with eGFR < 40 ml/min/1.73m2 (as measured by the MDRD formula) at Visit 2 |
|
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. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
Key secondary endpoint:
• Cardiovascular death
• HF re-hospitalization
Other secondary endpoints:
• Cardiovascular death
• HF re-hospitalization
• Non-fatal MI
• Non-fatal Stroke
• Sudden death with resuscitation |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
key and other secondary endpoint: 1, 6 and 12 months |
|
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 Mortality trial |
|
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
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) | 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.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 17 |
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 | 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 |
|
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 | |
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 |