Efficacy and Safety of Aliskiren and Aliskiren/Enalapril Combination on Morbidity-mortality in Patients With Chronic Heart Failure (ATMOSPHERE)

Novartis

Status and phase: Completed; Phase 3

Conditions: Chronic Heart Failure

Treatments: Drug: Enalapril; Drug: Aliskiren

Study type: Interventional

Funder types: Industry

Identifiers

NCT00853658

CSPP100F2301

2008-004104-31 (EudraCT Number)

Details and patient eligibility

About

The study will evaluate the efficacy and safety of both aliskiren monotherapy and aliskiren/enalapril combination therapy as compared to enalapril monotherapy, on morbidity and mortality in patients with chronic heart failure (NYHA Class II - IV.

Enrollment: 7,064 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria

Patients eligible for inclusion in this study had to fulfill all of the following criteria:

1. Patients ≥ 18 years of age, male or female.

2. Patients with a diagnosis of chronic heart failure (NYHA

   Class II - IV):

   1. LVEF ≤ 35% at Visit 1 (local measurement, within the past 6 months assessed by echocardiography, multiple uptake gated acquisition scan (MUGA), computerized tomography(CT) scan, magnetic resonance imaging (MRI) or ventricular angiography)
   2. 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 had to be treated with an ACEI at a stable dose enalapril 10 mg daily at least or any other ACEI, e.g. ramipril, quinapril, lisinopril, fosinopril, perindopril, trandolapril; based on equivalent doses, for at least 4 weeks prior to Visit 1

4. Patients had to 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.

Exclusion Criteria

Patients with any of the following were to be excluded from participation in the study:

1. History of hypersensitivity to any of the study drugs including history or allergy to ACEIs as well as known or suspected contraindications to the study drugs or previous history of intolerance to high doses of ACEIs during up- titration process.
2. Patients treated concomitantly with both an ARB and an 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 systolic blood pressure (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. Patients with Diabetes Mellitus.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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7,064 participants in 3 patient groups

Combination Aliskiren / Enalapril

Experimental group

Description:

Aliskiren / Enalapril combination therapy-150 mg/10 mg titrated to 300 mg/ 10 mg film-coated tablets and administered orally.

Treatment:

Drug: Aliskiren

Drug: Enalapril

Aliskiren

Experimental group

Description:

Aliskiren monotherapy - 150 mg titrated to 300 mg film-coated tablets and administered orally.

Treatment:

Drug: Aliskiren

Enalapril

Active Comparator group

Description:

Enalapril monotherapy -10 mg film-coated tablet and administered orally.

Treatment:

Drug: Enalapril