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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT00853658
First received: February 26, 2009
Last updated: October 3, 2016
Last verified: October 2016
  Purpose
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.

Condition Intervention Phase
Chronic Heart Failure
Drug: Enalapril
Drug: Aliskiren
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: 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). The Study is Also Known as Aliskiren Trial of Minimizing OutcomeS in Patients With HEart Failure (ATMOSPHERE).

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Number of Participants That Had First Occurrence of the Composite Endpoint, Which is Defined as Either Cardiovascular (CV) Death or Heart Failure (HF) Hospitalization [ Time Frame: up to End of Study (78 months) ] [ Designated as safety issue: No ]
    Number of participants that had first occurrence of the composite endpoint, which is defined as either CV death or HF hospitalization due to HF.


Secondary Outcome Measures:
  • Change From Baseline to Month 12 for the Kansas City Cardiomyopathy Questionnaire (KCCQ) Clinical Summary Score [ Time Frame: Baseline, Month 12 ] [ Designated as safety issue: No ]
    Change from baseline to Month 12 for the Kansas City Cardiomyopathy Questionnaire (KCCQ) clinical summary score. KCCQ is a 23-item, self-administered instrument that quantifies physical function, symptoms (frequency, severity and recent change), social function, self-efficacy and knowledge, and quality of life. KCCQ clinical summary score is a composite assessment of physical limitations and total symptom scores. Scores are transformed to a range of 0-100, in which higher scores reflect better health status.

  • All Cause Death [ Time Frame: up to end of study (78 months) ] [ Designated as safety issue: No ]
    Number of patients - All-cause death. All-cause death is common in Heart Failure HF patients this measures how many patients had this event.


Enrollment: 7064
Study Start Date: March 2009
Study Completion Date: October 2015
Primary Completion Date: October 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Combination Aliskiren / Enalapril
Aliskiren / Enalapril combination therapy-150 mg/10 mg titrated to 300 mg/ 10 mg film-coated tablets and administered orally.
Drug: Enalapril
Enalapril 10 mg film-coated tablet and administered orally.
Drug: Aliskiren
Aliskiren 150 mg titrated to 300 mg film-coated tablet and administered orally.
Other Name: SPP100
Experimental: Aliskiren
Aliskiren monotherapy - 150 mg titrated to 300 mg film-coated tablets and administered orally.
Drug: Aliskiren
Aliskiren 150 mg titrated to 300 mg film-coated tablet and administered orally.
Other Name: SPP100
Active Comparator: Enalapril
Enalapril monotherapy -10 mg film-coated tablet and administered orally.
Drug: Enalapril
Enalapril 10 mg film-coated tablet and administered orally.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00853658

  Show 808 Study Locations
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT00853658     History of Changes
Other Study ID Numbers: CSPP100F2301  2008-004104-31 
Study First Received: February 26, 2009
Results First Received: October 3, 2016
Last Updated: October 3, 2016
Health Authority: United States: Food and Drug Administration
Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
Australia: National Health and Medical Research Council
Austria: Federal Office for Safety in Health Care
Belgium: Federal Agency for Medicinal Products and Health Products
Brazil: Ministry of Health
Canada: Health Canada
China: Food and Drug Administration
Colombia: INVIMA Instituto Nacional de Vigilancia de Medicamentos y Alimentos
Costa Rica: Ethics Committee
Estonia: The State Agency of Medicine
Czech Republic: State Institute for Drug Control
Denmark: Danish Medicines Agency
Finland: Finnish Medicines Agency
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices
Greece: National Organization of Medicines
Hungary: National Institute of Pharmacy
Iceland: Icelandic Medicines Control Agency
India: Central Drugs Standard Control Organization
Ireland: Medical Ethics Research Committee
Italy: National Institute of Health
Japan: Pharmaceuticals and Medical Devices Agency
Korea: Food and Drug Administration
Latvia: State Agency of Medicines
Lithuania: State Medicine Control Agency - Ministry of Health
Netherlands: Medicines Evaluation Board (MEB)
Norway: Norwegian Medicines Agency
Peru: General Directorate of Pharmaceuticals, Devices, and Drugs
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Portugal: National Pharmacy and Medicines Institute
Romania: National Medicines Agency
Russia: Ministry of Health of the Russian Federation
Slovakia: State Institute for Drug Control
South Africa: Medicines Control Council
Spain: Spanish Agency of Medicines
Sweden: Medical Products Agency
Switzerland: Swissmedic
Taiwan: Department of Health
Thailand: Ministry of Public Health
Turkey: Ethics Committee
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Venezuela: Ministry of Health and Social Development

Keywords provided by Novartis:
Chronic Heart Failure
Cardiovascular death
CHF hospitalization
morbi-mortality trial
outcome study
endpoint driven
plasma renin activity
renin angiotensin aldosterone system
direct renin inhibitors
BNP
KCCQ
eGFR
(NYHA class II to IV) with elevated
BNP and reduced LVEF

Additional relevant MeSH terms:
Heart Failure
Heart Diseases
Cardiovascular Diseases
Enalapril
Enalaprilat
Angiotensin-Converting Enzyme Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antihypertensive Agents

ClinicalTrials.gov processed this record on January 14, 2017