A multicenter, randomized, double-blind, parallel group, active-controlled study to evaluate the efficacy and safety of both aliskiren monotherapy and aliskiren/enalapril combination therapy compared to enalapril monotherapy, on morbidity and mortality in patients with chronic heart failure (NYHA Class II - IV) - ND

Conditions: chronic heart failure
MedDRA version: 9.1Level: LLTClassification code 10045917Term: Unspecified hypertensive heart disease with congestive heart failure

Registration Number: EUCTR2008-004104-31-IT

Lead Sponsor: OVARTIS FARMA

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 7046

Inclusion Criteria

Inclusion criteria Patients eligible for inclusion in this study have to fulfill all of the following criteria: 1. Outpatients ≥ 18 years of age, male or female. 2. Patients with a diagnosis of chronic heart failure (NYHA Class II ? IV): LVEF ≤ 35% at visit 1 (local measurement, within the past 6 months assessed by echocardiography, MUGA, CT scan, MRI or ventricular angiography) Elevated BNP at visit 1: BNP ≥ 150 pg/ml (according to local measurement). OR BNP ≥ 100 pg/ml (according to local measurement) and unplanned hospitalization for HF within the last 12 months prior to visit 1. 3. Patients must be treated with an ACE inhibitor at a stable dose (enalapril 10 mg daily at least or any other ACE inhibitor, e.g. ramipril, quinapril, lisinopril, fosinopril, perindopril, trandolapril; based on equivalent doses described in Table 4-1: Dose equivalence guidance table of ACEi`s) for at least 4 weeks prior to visit 1. 4. Patients must be treated with a beta blocker, unless contraindicated or not tolerated, at a stable dose for at least 4 weeks prior to visit 1 (for patients not on target dose, according to local guidelines, or in absence of that medication, the reason should be documented). 5. Written informed consent to participate in the study and ability to comply with all requirements.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

Exclusion criteria Patients with any of the following will be excluded from participation in the study: 1. History of hypersensitivity to any of the study drugs including history or allergy to ACEi?s as well as known or suspected contraindications to the study drugs or previous history of intolerance to high doses of ACEi?s during up-titration process. 2. Patients treated concomitantly with both ARB and aldosterone antagonist in addition to study drug at visit 1. 3. Current acute decompensated HF (defined as an acute exacerbation of a chronic heart failure status manifested by typical signs and symptoms of HF like dyspnea, fatigue etc, that may require IV therapy with diuretics, vasodilators and/or inotropic drugs). 4. Symptomatic hypotension and/or less than 95 mmHg SBP at visit 1 and/or less than 90 mmHg SBP at visit 4. 5. Acute coronary syndrome, stroke, transient ischemic attack, cardiac, carotid or major vascular surgery, percutaneous coronary intervention (PCI) or carotid angioplasty, within the past 3 months prior to visit 1. 6. Coronary or carotid artery disease likely to require surgical or percutaneous intervention within the 6 months after visit 1. 7. Right heart failure due to severe pulmonary disease. 8. Diagnosis of peripartum or chemotherapy induced cardiomyopathy within the 12 months prior to visit 1. 9. Patients with a history of heart transplant or who are on a transplant list or with LVAD (left ventricular assistance device). 10. Documented ventricular arrhythmia with syncopal episodes within past 3 months, prior to visit 1, that is untreated. 11. Documented history of ventricular tachycardia or ventricular fibrillation without ICD producing significant hemodynamic consequences or considered life-threatening within the 3 months prior to visit 1. 12. Treatment with Vaughn Williams Type Ic anti-arrhythmic agents. 13. Symptomatic bradycardia, or second or third degree heart block without a pacemaker. 14. Implantation of a CRT (cardiac resynchronization therapy) device within the prior 3 months from visit 1 or intent to implant a CRT device. 15. Presence of hemodynamically significant mitral and /or aortic valve disease, except mitral regurgitation secondary to left ventricular dilatation. 16. Presence of hemodynamically significant obstructive lesions of left ventricular outflow tract, including aortic stenosis. 17. 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: Any history of pancreatic injury, pancreatitis or evidence of impaired pancreatic function/injury as indicated by, e.g. abnormal lipase or amylase. Primary liver disease considered to be life threatening. Renal disease likely to be life threatening or eGFR < 40 ml/min/1.73m2 as calculated by the MDRD formula at visit 1 or eGFR < 35 ml/min/1.73m2 as calculated by the MDRD formula at visit 4 or decrease of eGFR of more than 25% from visit 1 to visit 4. (according to local laboratory measurement). Current duodenal or gastric ulcers, or gastrointestinal/rectal bleeding during the 3 months prior to visit 1. Current treatment with cholestyramine and colestipol resins at visit 1. 18. Serum potassium ≥ 5.0 mmol/L at visit 1 or ≥ 5.2 mmol/L at visit 4 (according to local laboratory measurement). please see protocol

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The co-primary objectives of this study are to test if aliskiren monotherapy is superior or at least non-inferior to enalapril monotherapy and/or to test if aliskiren/enalapril combination is superior to enalapril monotherapy in delaying time to first occurrence of either cardiovascular death or heart failure hospitalization in patients with chronic heart failure (NYHA Class II - IV).;Secondary Objective: To evaluate whether, aliskiren monotherapy and/or the combination of aliskiren/enalapril is superior to enalapril monotherapy in reducing the BNP level from baseline to predefined timepoint. To evaluate whether, aliskiren monotherapy and/or the combination of aliskiren/enalapril is superior to enalapril monotherapy in improving the clinical summary score (assessed by KCCQ) from baseline to predefined timepoint.;Primary end point(s): The primary efficacy endpoint consists of the following components: Cardiovascular death Heart failure hospitalization

Secondary Outcome Measures

Name	Time	Method

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