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


Tracking Information

Start Date  ICMJEMarch 2009
Estimated Primary Completion DateMarch 2013   (final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE 
 (submitted: February 27, 2009)
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 ]
Original Primary Outcome Measures  ICMJESame as current
Change HistoryComplete list of historical versions of study NCT00853658 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE 
 (submitted: February 27, 2009)
  • 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 ]
Original Secondary Outcome Measures  ICMJESame as current

Descriptive Information

Brief Title  ICMJEEfficacy and Safety of Aliskiren and Aliskiren/Enalapril Combination on Morbi-mortality in Patients With Chronic Heart Failure
Official Title  ICMJEA 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).
Brief Summary

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.

Detailed Description 
Study PhasePhase III
Study Type  ICMJEInterventional
Study Design  ICMJETreatment, Randomized, Double Blind (Subject, Caregiver, Investigator), Parallel Assignment
Condition  ICMJEChronic Heart Failure
Intervention  ICMJE
  • Drug: Enalapril monotherapy
    Enalapril monotherapy -10 mg
  • Drug: Aliskiren monotherapy
    Aliskiren monotherapy-150 mg titrated to 300 mg
  • Drug: Aliskiren / Enalapril combination therapy
    Aliskiren / Enalapril combination therapy- 150 mg/10 mg titrated to 300 mg/ 10 mg
Study Arms / Comparison Groups
  • 1: Active Comparator
    Enalapril monotherapy -10 mg
    Intervention: Drug: Enalapril monotherapy
  • 2: Experimental
    Aliskiren monotherapy
    Intervention: Drug: Aliskiren monotherapy
  • 3: Experimental
    Aliskiren / Enalapril combination therapy-150 mg/10 mg titrated to 300 mg/ 10 mg
    Intervention: Drug: Aliskiren / Enalapril combination therapy

Recruitment Information

Estimated Enrollment  ICMJE7041
Completion Date 
Estimated Primary Completion DateMarch 2013   (final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
GenderBoth
Ages18 Years and older
Accepts Healthy VolunteersNo
Contacts  ICMJE
Contact: Novartis862-778-8300
Location Countries  ICMJEUnited States,   Argentina,   Australia,   Belgium,   Canada,   China,   Colombia,   Costa Rica,   Czech Republic,   Denmark,   Estonia,   Finland,   France,   Germany,   Greece,   Hungary,   Iceland,   India,   Ireland,   Italy,   Japan,   Korea, Republic of,   Latvia,   Lithuania,   Netherlands,   Norway,   Peru,   Poland,   Portugal,   Romania,   Russian Federation,   Slovakia,   South Africa,   Spain,   Sweden,   Switzerland,   Taiwan,   Thailand,   Turkey,   United Kingdom,   Venezuela

Administrative Information

NCT ID  ICMJENCT00853658
Responsible PartyExternal Affairs, Novartis Pharmaceuticals
Study ID Numbers  ICMJECSPP100F2301
Study Sponsor  ICMJENovartis
Collaborators  ICMJE 
Investigators  ICMJE 
Information Provided ByNovartis