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) - ATMOSPHERE
- Conditions
- chronic heart failure (NYHA Class II - IV)MedDRA version: 13.1Level: LLTClassification code 10008908Term: Chronic heart failureSystem Organ Class: 10007541 - Cardiac disorders
- Registration Number
- EUCTR2008-004104-31-GR
- Lead Sponsor
- ovartis Pharma Services AG
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 7046
1. Patients = 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 or NT-proBNP at visit 1:
BNP = 150 pg/ml (or BNP = 100 pg/ml and unplanned hospitalization for HF within the last 12 months prior to visit 1) (according to local measurement)
OR
NT-proBNP = 600 pg/ml (or NT-proBNP = 400 pg/ml and unplanned hospitalization for HF within the last 12 months prior to visit 1) (according to local measurement).
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)
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years)
F.1.3.1 Number of subjects for this age range
For full list, please refer to the protocol.
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. Patients with atrial fibrillation or other significant cardiac rhythm abnormality will be excluded as this makes it difficult to acquire quality pulse waves for analysis.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method