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

This study is currently recruiting participants.
Verified February 2014 by Novartis
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT00853658
First received: February 26, 2009
Last updated: February 19, 2014
Last verified: February 2014
  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 monotherapy
Drug: Aliskiren monotherapy
Drug: Aliskiren / Enalapril combination therapy
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).

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Delaying time to first occurrence of either cardiovascular death or heart failure hospitalization in patients with chronic heart failure [ Time Frame: 4 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Reduction in the BNP level from baseline to predefined timepoint [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Improvement in the clinical summary score (assessed by KCCQ) from baseline to predefined timepoint. [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Estimated Enrollment: 7041
Study Start Date: March 2009
Estimated Study Completion Date: November 2015
Estimated Primary Completion Date: November 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1
Enalapril monotherapy -10 mg
Drug: Enalapril monotherapy
Enalapril monotherapy -10 mg
Experimental: 2
Aliskiren monotherapy
Drug: Aliskiren monotherapy
Aliskiren monotherapy-150 mg titrated to 300 mg
Experimental: 3
Aliskiren / Enalapril combination therapy-150 mg/10 mg titrated to 300 mg/ 10 mg
Drug: Aliskiren / Enalapril combination therapy
Aliskiren / Enalapril combination therapy- 150 mg/10 mg titrated to 300 mg/ 10 mg

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients with a diagnosis of chronic heart failure (NYHA Class II - IV):

    • LVEF ≤ 35% at visit 1. (local measurement, measured within the past 6 months assessed by echocardiogram, MUGA, CT scan, MRI or ventricular angiography)
    • Elevated BNP at visit 1: BNP ≥ 150 pg/ml (according to local measurement).
    • BNP ≥ 100 pg/ml (according to local measurement) and unplanned hospitalization with HF within the last 12 months prior visit 1.
  • 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 as described in the dose equivalence guidance table of ACEi's) for at least 4 weeks prior to visit 1

Exclusion Criteria:

  • 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.
  • Patients treated concomitantly with both ARB and aldosterone antagonist in addition to study drug at visit 1.
  • Current acute decompensated HF.
  • Symptomatic hypotension and/or less than 95 mmHg SBP at visit 1 and/or less than 90 mmHg at visit 4.
  • Renal disease likely to be life threatening or eGFR < 40 ml/min/1.73m2 as measured by the MDRD formula at visit 1 and eGFR < 35 ml/min/1.73m2 as measured 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).
  • Serum potassium ≥ 5.0 mmol/L at visit 1 or ≥ 5.2 mmol/L at visit 4 (according to local laboratory measurement).
  • 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.
  • Coronary or carotid artery disease likely to require surgical or percutaneous intervention within the 6 months after visit 1.
  • Right heart failure due to severe pulmonary disease
  • Other protocol-defined inclusion/exclusion criteria may apply
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00853658

Contacts
Contact: Novartis Pharmaceuticals 1-888-669-6682
Contact: Novartis Pharmaceuticals

  Show 1029 Study Locations
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT00853658     History of Changes
Other Study ID Numbers: CSPP100F2301, 2008-004104-31
Study First Received: February 26, 2009
Last Updated: February 19, 2014
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
Pharmacologic Actions
Antihypertensive Agents
Cardiovascular Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on April 17, 2014