Efficacy and Safety of Aliskiren and Aliskiren/Enalapril Combination on Morbi-mortality in Patients With Chronic Heart Failure - Full Text View

Sponsor:	Novartis
Information provided by:	Novartis
ClinicalTrials.gov Identifier:	NCT00853658

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 III

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:

MedlinePlus related topics: Heart Failure

Drug Information available for: Enalapril Enalapril maleate Enalaprilat Aliskiren

U.S. FDA Resources

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 Primary Completion Date:	March 2013 (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

862-778-8300

Show 41 Study Locations

Sponsors and Collaborators

Novartis

More Information

No publications provided

Responsible Party:	External Affairs, Novartis Pharmaceuticals
ClinicalTrials.gov Identifier:	NCT00853658 History of Changes
Other Study ID Numbers:	CSPP100F2301
Study First Received:	February 26, 2009
Last Updated:	May 19, 2011
Health Authority:	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: State 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 - French Health Products Safety Agency; 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 and Social Development 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; United States: Food and Drug Administration; 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 February 09, 2012