A Comparison Of Outcomes In Patients In New York Heart Association (NYHA) Class II Heart Failure When Treated With Eplerenone Or Placebo In Addition To Standard Heart Failure Medicines

Heart Failure Clinical Trial

— EMPHASIS-HF  

Official title:

The Effect Of Eplerenone Versus Placebo On Cardiovascular Mortality And Heart Failure Hospitalization In Subjects With NYHA Class II Chronic Systolic Heart Failure

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00232180
• Other study ID #: A6141079
• Status: Completed
• Phase: Phase 3
• Start date: March 2006
• Est. completion date: January 2012

Study information

• Verified date: December 2020
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

In an earlier study, eplerenone was shown to improve survival in patients who had heart failure immediately following a heart attack. However, it is not known how patients with established mild-to-moderate heart failure (NYHA Class II), who have the additional risk of sudden death, will respond if treated with eplerenone. In this trial, eplerenone plus standard heart failure medicines is being compared to placebo plus standard heart failure medicines in terms of an additional ability to prolong life and prevent re-hospitalizations for worsening heart failure in these patients. The Data Safety Monitoring Committee (DSMC) observed during its conduct of the protocol-specified second interim analysis on the 6th of May, 2010 that the efficacy of eplerenone had met the pre-specified stopping rules in the protocol. As a result of the discussion between the DSMC and the Executive Steering Committee (ESC), the ESC recommended that EMPHASIS-HF should be terminated, Based on the convincing efficacy and the consideration that it would be unethical not to offer this treatment to patients, the ESC recommended that all the patients in the trial should be transferred to open-label eplerenone. The Open Label Extension eplerenone arm will last for 12 months. Eplerenone is not currently approved for the indication studied in this patient population. On May 26, 2010, further enrollment into EMPHASIS-HF was stopped. The amendment is considered to be the most appropriate way to ensure that all the subjects who participated in the double-blind phase of the EMPHASIS-HF trial can be offered treatment with eplerenone

Recruitment information / eligibility

• Status: Completed
• Enrollment: 2743
• Est. completion date: January 2012
• Est. primary completion date: May 2010
• Accepts healthy volunteers: No
• Gender: All
• Age group: 55 Years and older

Eligibility

Inclusion Criteria:

• History (Hx) of chronic systolic heart failure of ischemic or non-ischemic etiology of at least 4 weeks duration; Currently, New York Heart Association (NYHA) functional Class II and on optimal dose, or maximally tolerated dose of standard heart failure medicines (advisable to include ACE-I/ARBs; beta-blockers) and diuretics if indicated for fluid overload. Should have participated in the double-blind phase of the EMPHASIS-HF trial

Exclusion Criteria:

• Severe chronic systolic heart failure symptomatic at rest despite optimal medical therapy; estimated glomerular filtration rate (eGFR) <30 ml/min/1.73m2.

Related Conditions & MeSH terms

• Heart Failure

Intervention

Drug:
• Eplerenone
Eplerenone administered on top of background standard heart failure therapy

Locations

Country	Name	City	State
Argentina	Pfizer Investigational Site	Buenos Aires
Argentina	Pfizer Investigational Site	Cordoba
Argentina	Pfizer Investigational Site	Moron	Pcia. De Buenos Aires
Australia	Pfizer Investigational Site	Brisbane	Queensland
Australia	Pfizer Investigational Site	Concord	New South Wales
Australia	Pfizer Investigational Site	Launceston	Tasmania
Belgium	Pfizer Investigational Site	Antwerpen
Belgium	Pfizer Investigational Site	Bonheiden
Belgium	Pfizer Investigational Site	Eupen
Belgium	Pfizer Investigational Site	Genk
Belgium	Pfizer Investigational Site	Hasselt
Belgium	Pfizer Investigational Site	Huy
Belgium	Pfizer Investigational Site	La Louvière
Belgium	Pfizer Investigational Site	Lanaken
Belgium	Pfizer Investigational Site	Leuven
Belgium	Pfizer Investigational Site	Overpelt
Belgium	Pfizer Investigational Site	Yvoir
Canada	Pfizer Investigational Site	Hamilton	Ontario
Canada	Pfizer Investigational Site	Hamilton	Ontario
Canada	Pfizer Investigational Site	London	Ontario
Canada	Pfizer Investigational Site	Montreal	Quebec
Canada	Pfizer Investigational Site	Montreal	Quebec
Canada	Pfizer Investigational Site	Montreal	Quebec
Canada	Pfizer Investigational Site	Quebec
Canada	Pfizer Investigational Site	Sherbrooke	Quebec
Canada	Pfizer Investigational Site	St-Charles Borromee	Quebec
Canada	Pfizer Investigational Site	St-georges (Beauce)	Quebec
Czechia	Pfizer Investigational Site	Brno
Czechia	Pfizer Investigational Site	Brno
Czechia	Pfizer Investigational Site	Hradec Kralove
Czechia	Pfizer Investigational Site	Ostrava
Czechia	Pfizer Investigational Site	Plzen
Czechia	Pfizer Investigational Site	Plzen
Czechia	Pfizer Investigational Site	Praha 1
Czechia	Pfizer Investigational Site	Praha 1
Czechia	Pfizer Investigational Site	Praha 10
Czechia	Pfizer Investigational Site	Praha 2
Czechia	Pfizer Investigational Site	Praha 6
Czechia	Pfizer Investigational Site	Pribram
France	Pfizer Investigational Site	Angers Cedex 01
France	Pfizer Investigational Site	Brest
France	Pfizer Investigational Site	Cergy-Pontoise
France	Pfizer Investigational Site	Chateauroux
France	Pfizer Investigational Site	Creteil	Cedex
France	Pfizer Investigational Site	Gap	Cedex
France	Pfizer Investigational Site	Gap CEDEX
France	Pfizer Investigational Site	Nantes Cedex 01
France	Pfizer Investigational Site	Nice CEDEX 1
France	Pfizer Investigational Site	Nîmes
France	Pfizer Investigational Site	Paris CEDEX 13
France	Pfizer Investigational Site	St-Amand-Montrond
France	Pfizer Investigational Site	Strasbourg
France	Pfizer Investigational Site	Strasbourg
France	Pfizer Investigational Site	Toulouse	Cedex 4
France	Pfizer Investigational Site	Valenciennes
Germany	Pfizer Investigational Site	Bad Nauheim
Germany	Pfizer Investigational Site	Bad Rothenfelde
Germany	Pfizer Investigational Site	Berlin
Germany	Pfizer Investigational Site	Berlin
Germany	Pfizer Investigational Site	Berlin
Germany	Pfizer Investigational Site	Berlin
Germany	Pfizer Investigational Site	Dortmund
Germany	Pfizer Investigational Site	Duisburg
Germany	Pfizer Investigational Site	Essen
Germany	Pfizer Investigational Site	Frankfurt/Main
Germany	Pfizer Investigational Site	Goettingen
Germany	Pfizer Investigational Site	Hagen
Germany	Pfizer Investigational Site	Halle
Germany	Pfizer Investigational Site	Hannover
Germany	Pfizer Investigational Site	Homburg/Saar
Germany	Pfizer Investigational Site	Koeln
Germany	Pfizer Investigational Site	Leipzig
Germany	Pfizer Investigational Site	Ludwigshafen
Germany	Pfizer Investigational Site	Luebeck
Greece	Pfizer Investigational Site	Athens	Attika
Greece	Pfizer Investigational Site	Athens
Greece	Pfizer Investigational Site	Athens
Greece	Pfizer Investigational Site	Athens
Greece	Pfizer Investigational Site	Athens
Greece	Pfizer Investigational Site	Haidari	Attiki
Greece	Pfizer Investigational Site	Thessaloniki
Greece	Pfizer Investigational Site	Thessaloniki
Greece	Pfizer Investigational Site	Thessaloniki
Hong Kong	Pfizer Investigational Site	Chai Wan
Hong Kong	Pfizer Investigational Site	Pokfulam
Hong Kong	Pfizer Investigational Site	Shatin NT
Hungary	Pfizer Investigational Site	Budapest
Hungary	Pfizer Investigational Site	Budapest
Hungary	Pfizer Investigational Site	Budapest
Hungary	Pfizer Investigational Site	Debrecen
Hungary	Pfizer Investigational Site	Mosonmagyarovar
Hungary	Pfizer Investigational Site	Siófok
Hungary	Pfizer Investigational Site	Szeged
India	Pfizer Investigational Site	Bangalore	Karnataka
India	Pfizer Investigational Site	Bangalore	Karnataka
India	Pfizer Investigational Site	Chennai	Tamil Nadu
India	Pfizer Investigational Site	Coimbatore	Tamil Nadu
India	Pfizer Investigational Site	Hyderabad	Andhra Pradesh
India	Pfizer Investigational Site	Hyderabad	Andhra Pradesh
India	Pfizer Investigational Site	Lucknow	Uttar Pradesh
India	Pfizer Investigational Site	Ludhiana	Punjab
India	Pfizer Investigational Site	Pune	Maharshtra
Ireland	Pfizer Investigational Site	Cork
Ireland	Pfizer Investigational Site	Dublin
Ireland	Pfizer Investigational Site	Dublin
Ireland	Pfizer Investigational Site	Galway
Italy	Pfizer Investigational Site	Bergamo (BG)
Italy	Pfizer Investigational Site	Catania
Italy	Pfizer Investigational Site	Catania
Italy	Pfizer Investigational Site	Firenze
Italy	Pfizer Investigational Site	Mestre - Zelardino (VE)
Italy	Pfizer Investigational Site	Milano
Italy	Pfizer Investigational Site	Modena
Italy	Pfizer Investigational Site	Napoli
Italy	Pfizer Investigational Site	Padova
Italy	Pfizer Investigational Site	Palermo
Italy	Pfizer Investigational Site	Parma
Italy	Pfizer Investigational Site	Piacenza
Italy	Pfizer Investigational Site	Roma
Italy	Pfizer Investigational Site	Sassari
Italy	Pfizer Investigational Site	Trieste
Italy	Pfizer Investigational Site	Venezia
Korea, Republic of	Pfizer Investigational Site	Republic Of Korea	Korea
Korea, Republic of	Pfizer Investigational Site	Suwon
Korea, Republic of	Pfizer Investigational Site	Taegu
Mexico	Pfizer Investigational Site	Aguascalientes	Aguacalientes
Mexico	Pfizer Investigational Site	Aguascalientes
Mexico	Pfizer Investigational Site	Chihuahua
Mexico	Pfizer Investigational Site	Guadalajara	Jalisco
Mexico	Pfizer Investigational Site	Mexico	DF
Mexico	Pfizer Investigational Site	San Luis Potosi
Mexico	Pfizer Investigational Site	Zapopan	Jalisco
Netherlands	Pfizer Investigational Site	's-Hertogenbosch
Netherlands	Pfizer Investigational Site	Alkmaar
Netherlands	Pfizer Investigational Site	Apeldoorn
Netherlands	Pfizer Investigational Site	Apeldoorn
Netherlands	Pfizer Investigational Site	Arnhem
Netherlands	Pfizer Investigational Site	Breda
Netherlands	Pfizer Investigational Site	Deventer
Netherlands	Pfizer Investigational Site	Dordrecht
Netherlands	Pfizer Investigational Site	Dordrecht
Netherlands	Pfizer Investigational Site	Eindhoven
Netherlands	Pfizer Investigational Site	Groningen
Netherlands	Pfizer Investigational Site	Heerlen
Netherlands	Pfizer Investigational Site	Veldhoven
Netherlands	Pfizer Investigational Site	Velp
Netherlands	Pfizer Investigational Site	Zwolle
Poland	Pfizer Investigational Site	Gdansk
Poland	Pfizer Investigational Site	Krakow
Poland	Pfizer Investigational Site	Lodz
Poland	Pfizer Investigational Site	Piotrkow Trybunalski
Poland	Pfizer Investigational Site	Poznan
Poland	Pfizer Investigational Site	Stalowa Wola
Poland	Pfizer Investigational Site	Szczecin
Poland	Pfizer Investigational Site	Warszawa
Poland	Pfizer Investigational Site	Warszawa
Poland	Pfizer Investigational Site	Warszawa
Portugal	Pfizer Investigational Site	Almada
Portugal	Pfizer Investigational Site	Amadora
Portugal	Pfizer Investigational Site	Coimbra
Portugal	Pfizer Investigational Site	Guilhufe - PNF	Penafiel
Portugal	Pfizer Investigational Site	Linda-a-Velha
Portugal	Pfizer Investigational Site	Lisboa
Portugal	Pfizer Investigational Site	Lisboa
Portugal	Pfizer Investigational Site	Oliveira de Azemeis
Portugal	Pfizer Investigational Site	Portalegre
Portugal	Pfizer Investigational Site	Porto
Portugal	Pfizer Investigational Site	Vila Franca de Xira
Portugal	Pfizer Investigational Site	Vila Real
Russian Federation	Pfizer Investigational Site	Moscow
Russian Federation	Pfizer Investigational Site	Moscow
Russian Federation	Pfizer Investigational Site	Novosibirsk
Russian Federation	Pfizer Investigational Site	S-Petersburg
Russian Federation	Pfizer Investigational Site	S-Petersburg
Russian Federation	Pfizer Investigational Site	Saint-Petersburg
Russian Federation	Pfizer Investigational Site	Saint-Petersburg
Russian Federation	Pfizer Investigational Site	Voronezh
Russian Federation	Pfizer Investigational Site	Yaroslavl
Singapore	Pfizer Investigational Site	Singapore
Singapore	Pfizer Investigational Site	Singapore
Slovakia	Pfizer Investigational Site	Bratislava
Slovakia	Pfizer Investigational Site	Bratislava
Slovakia	Pfizer Investigational Site	Bratislava
Slovakia	Pfizer Investigational Site	Bratislava
Slovakia	Pfizer Investigational Site	Bratislava
Slovakia	Pfizer Investigational Site	Levice
Slovakia	Pfizer Investigational Site	Liptovsky Mikulas
Slovakia	Pfizer Investigational Site	Nitra
Slovakia	Pfizer Investigational Site	Trencin
South Africa	Pfizer Investigational Site	Bloemfontein
South Africa	Pfizer Investigational Site	Cape Town
South Africa	Pfizer Investigational Site	Cape Town
South Africa	Pfizer Investigational Site	Congella
South Africa	Pfizer Investigational Site	Johannesburg
South Africa	Pfizer Investigational Site	Kwazulu Natal
South Africa	Pfizer Investigational Site	Soweto	Johannesburg
Spain	Pfizer Investigational Site	Almeria
Spain	Pfizer Investigational Site	Barakaldo	Vizcaya
Spain	Pfizer Investigational Site	Barcelona
Spain	Pfizer Investigational Site	Cordoba
Spain	Pfizer Investigational Site	Malaga
Spain	Pfizer Investigational Site	Santiago de Compostela	LA Coruña
Sweden	Pfizer Investigational Site	Angelholm
Sweden	Pfizer Investigational Site	Bollnas
Sweden	Pfizer Investigational Site	Falun
Sweden	Pfizer Investigational Site	Goteborg
Sweden	Pfizer Investigational Site	Goteborg
Sweden	Pfizer Investigational Site	Göteborg
Sweden	Pfizer Investigational Site	Göteborg
Sweden	Pfizer Investigational Site	Halmstad
Sweden	Pfizer Investigational Site	Hässleholm
Sweden	Pfizer Investigational Site	Lindesberg
Sweden	Pfizer Investigational Site	Linkoping
Sweden	Pfizer Investigational Site	Lulea
Sweden	Pfizer Investigational Site	Molndal
Sweden	Pfizer Investigational Site	Skelleftea
Sweden	Pfizer Investigational Site	Varberg
Sweden	Pfizer Investigational Site	Vaxjo
Ukraine	Pfizer Investigational Site	Dnipropetrovsk
Ukraine	Pfizer Investigational Site	Dnipropetrovsk
Ukraine	Pfizer Investigational Site	Dnipropetrovsk
Ukraine	Pfizer Investigational Site	Donetsk
Ukraine	Pfizer Investigational Site	Donetsk
Ukraine	Pfizer Investigational Site	Kharkiv
Ukraine	Pfizer Investigational Site	Kharkiv
Ukraine	Pfizer Investigational Site	Kiev
Ukraine	Pfizer Investigational Site	Kyiv
Ukraine	Pfizer Investigational Site	Kyiv
Ukraine	Pfizer Investigational Site	Lviv
Ukraine	Pfizer Investigational Site	Lviv
Ukraine	Pfizer Investigational Site	Odessa
Ukraine	Pfizer Investigational Site	Odessa
Ukraine	Pfizer Investigational Site	Simferopol	Crimea
Ukraine	Pfizer Investigational Site	Uzhgorod
Ukraine	Pfizer Investigational Site	Zaporizhzhia
United Arab Emirates	Pfizer Investigational Site	Abu Dhabi
United Arab Emirates	Pfizer Investigational Site	Dubai	UAE
United Kingdom	Pfizer Investigational Site	Belfast	Northern Ireland
United Kingdom	Pfizer Investigational Site	Belfast
United Kingdom	Pfizer Investigational Site	Coventry
United Kingdom	Pfizer Investigational Site	Edinburgh
United Kingdom	Pfizer Investigational Site	Glasgow
United Kingdom	Pfizer Investigational Site	Glasgow
United Kingdom	Pfizer Investigational Site	Glasgow	Strathclyde
United Kingdom	Pfizer Investigational Site	Harrow
United Kingdom	Pfizer Investigational Site	Knutsford	Cheshire
United Kingdom	Pfizer Investigational Site	Larbert
United Kingdom	Pfizer Investigational Site	Macclesfield
United Kingdom	Pfizer Investigational Site	Macclesfield	Cheshire
United Kingdom	Pfizer Investigational Site	Manchester
United Kingdom	Pfizer Investigational Site	Milton Keynes
United Kingdom	Pfizer Investigational Site	Sheffield
United Kingdom	Pfizer Investigational Site	Southend-on-Sea
United Kingdom	Pfizer Investigational Site	Torquay
United States	Pfizer Investigational Site	Albany	New York
United States	Pfizer Investigational Site	Annapolis	Maryland
United States	Pfizer Investigational Site	Bangor	Maine
United States	Pfizer Investigational Site	Baton Rouge	Louisiana
United States	Pfizer Investigational Site	Beaver	Pennsylvania
United States	Pfizer Investigational Site	Boston	Massachusetts
United States	Pfizer Investigational Site	Bridgeport	Connecticut
United States	Pfizer Investigational Site	Cincinnati	Ohio
United States	Pfizer Investigational Site	Cincinnati	Ohio
United States	Pfizer Investigational Site	Colorado Springs	Colorado
United States	Pfizer Investigational Site	Columbia	Maryland
United States	Pfizer Investigational Site	Cumberland	Rhode Island
United States	Pfizer Investigational Site	Dallas	Texas
United States	Pfizer Investigational Site	Dallas	Texas
United States	Pfizer Investigational Site	Daytona Beach	Florida
United States	Pfizer Investigational Site	Doylestown	Pennsylvania
United States	Pfizer Investigational Site	Gainesville	Florida
United States	Pfizer Investigational Site	Germantown	Tennessee
United States	Pfizer Investigational Site	Hartford	Connecticut
United States	Pfizer Investigational Site	Indianapolis	Indiana
United States	Pfizer Investigational Site	Indianapolis	Indiana
United States	Pfizer Investigational Site	Jupiter	Florida
United States	Pfizer Investigational Site	Knoxville	Tennessee
United States	Pfizer Investigational Site	Leetsdale	Pennsylvania
United States	Pfizer Investigational Site	Loma Linda	California
United States	Pfizer Investigational Site	Louisville	Kentucky
United States	Pfizer Investigational Site	Louisville	Kentucky
United States	Pfizer Investigational Site	Louisville	Kentucky
United States	Pfizer Investigational Site	Madison	Wisconsin
United States	Pfizer Investigational Site	Manchester	New Hampshire
United States	Pfizer Investigational Site	Melbourne	Florida
United States	Pfizer Investigational Site	Merced	California
United States	Pfizer Investigational Site	Minneapolis	Minnesota
United States	Pfizer Investigational Site	MN	Minnesota
United States	Pfizer Investigational Site	Oklahoma City	Oklahoma
United States	Pfizer Investigational Site	Oklahoma City	Oklahoma
United States	Pfizer Investigational Site	Omaha	Nebraska
United States	Pfizer Investigational Site	Omaha	Nebraska
United States	Pfizer Investigational Site	Omaha	Nebraska
United States	Pfizer Investigational Site	Phoenix	Arizona
United States	Pfizer Investigational Site	Pittsburgh	Pennsylvania
United States	Pfizer Investigational Site	Pittsburgh	Pennsylvania
United States	Pfizer Investigational Site	Plano	Texas
United States	Pfizer Investigational Site	Rochester	New York
United States	Pfizer Investigational Site	Rochester	New York
United States	Pfizer Investigational Site	Rockford	Illinois
United States	Pfizer Investigational Site	Spokane	Washington
United States	Pfizer Investigational Site	Stockton	California
United States	Pfizer Investigational Site	Tupelo	Mississippi
United States	Pfizer Investigational Site	Tupelo	Mississippi
United States	Pfizer Investigational Site	Washington	District of Columbia
Venezuela	Pfizer Investigational Site	Caracas	Distrito Capital
Venezuela	Pfizer Investigational Site	Caracas	Estado Miranda
Venezuela	Pfizer Investigational Site	Caracas	Estado Miranda

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer's Upjohn has merged with Mylan to form Viatris Inc.

Countries where clinical trial is conducted

United States,  Venezuela,  Argentina,  Australia,  Belgium,  Canada,  Czechia,  France,  Germany,  Greece,  Hong Kong,  Hungary,  India,  Ireland,  Italy,  Korea, Republic of,  Mexico,  Netherlands,  Poland,  Portugal,  Russian Federation,  Singapore,  Slovakia,  South Africa,  Spain,  Sweden,  Ukraine,  United Arab Emirates,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With First Occurrence of Cardiovascular (CV) Mortality or Hospitalization Due to Heart Failure (HF) (Adjudicated): Up to Cut-off Date	CV mortality is defined as death due to heart failure, myocardial infarction, cardiac arrhythmia, stroke or cerebral vascular accident (CVA), other CV cause (such as aneurysm or pulmonary embolism). Hospitalization due to HF is defined as an overnight stay, or longer, in a hospital environment (emergency room, observation unit or in-patient care, or similar facility including admission to a day care facility) due to HF as the primary reason for hospitalization as determined by the endpoint committee adjudicator.	Baseline (30 March 2006) up to 50 months (cut-off date: 25 May 2010)
Primary	Number of Participants With First Occurrence of Cardiovascular (CV) Mortality or Hospitalization Due to Heart Failure (HF) (Adjudicated)	CV mortality is defined as death due to heart failure, myocardial infarction, cardiac arrhythmia, stroke or cerebral vascular accident (CVA), other CV cause (such as aneurysm or pulmonary embolism). Hospitalization due to HF is defined as an overnight stay, or longer, in a hospital environment (emergency room, observation unit or in-patient care, or similar facility including admission to a day care facility) due to HF as the primary reason for hospitalization as determined by the endpoint committee adjudicator.	Baseline (30 March 2006) up to 59.5 months (complete DB phase: 18 March 2011)
Secondary	Number of Participants With First Occurrence of All-Cause Mortality or Heart Failure (HF) Hospitalization (Adjudicated)	Death due to any cause or first of occurrence HF hospitalization. HF hospitalization is defined as an overnight stay, or longer, in a hospital environment (emergency room, observation unit or in-patient care, or similar facility including admission to a day care facility) due to HF as the primary reason for hospitalization as determined by the endpoint committee adjudicator.	Baseline (30 March 2006) up to 50 months (cut-off date: 25 May 2010), 59.5 months (complete DB phase: 18 March 2011)
Secondary	Number of Participants With First Occurrence of All-Cause Mortality (Adjudicated)	Death due to any cause.	Baseline (30 March 2006) up to 50 months (cut-off date: 25 May 2010), 59.5 months (complete DB phase: 18 March 2011)
Secondary	Number of Participants With First Occurrence of Cardiovascular (CV) Mortality (Adjudicated)	CV mortality is defined as death due to heart failure, myocardial infarction, cardiac arrhythmia, stroke or cerebral vascular accident (CVA), other CV cause (such as aneurysm or pulmonary embolism).	Baseline (30 March 2006) up to 50 months (cut-off date: 25 May 2010), 59.5 months (complete DB phase: 18 March 2011)
Secondary	Number of Participants With First Occurrence of All-Cause Hospitalization (Adjudicated)	Hospitalization due to any cause is defined as an overnight stay, or longer, in a hospital environment (emergency room, observation unit or in-patient care, or similar facility including admission to a day care facility).	Baseline (30 March 2006) up to 50 months (cut-off date: 25 May 2010), 59.5 months (complete DB phase: 18 March 2011)
Secondary	Number of Participants With First Occurrence of Heart Failure (HF) Hospitalization (Adjudicated)	First occurrence of HF hospitalization. Hospitalization due to HF is defined as an overnight stay, or longer, in a hospital environment (emergency room, observation unit or in-patient care, or similar facility including admission to a day care facility) due to HF as the primary reason for hospitalization as determined by the endpoint committee adjudicator.	Baseline (30 March 2006) up to 50 months (cut-off date: 25 May 2010), 59.5 months (complete DB phase: 18 March 2011)
Secondary	Number of Participants With First Occurrence of All-Cause Mortality or All-Cause Hospitalization (Adjudicated)	Death due to any cause or hospitalization due to any cause. Hospitalization due to any cause is defined as an overnight stay, or longer, in a hospital environment (emergency room, observation unit or in-patient care, or similar facility including admission to a day care facility).	Baseline (30 March 2006) up to 50 months (cut-off date: 25 May 2010), 59.5 months (complete DB phase: 18 March 2011)
Secondary	Number of Participants With First Occurrence Of Heart Failure (HF) Mortality or Heart Failure (HF) Hospitalization (Adjudicated)	Death due to HF or first occurrence of HF hospitalization. Hospitalization due to HF is defined as an overnight stay, or longer, in a hospital environment (emergency room, observation unit or in-patient care, or similar facility including admission to a day care facility) due to HF as the primary reason for hospitalization as determined by the endpoint committee adjudicator.	Baseline (30 March 2006) up to 50 months (cut-off date: 25 May 2010), 59.5 months (complete DB phase: 18 March 2011)
Secondary	Number of Participants With First Occurrence of Cardiovascular (CV) Hospitalization (Adjudicated)	First occurrence of CV hospitalization. CV hospitalization is defined as hospitalization due to HF (first or subsequent), acute myocardial infarction, angina pectoris (unstable), cardiac arrhythmia (atrial fibrillation [AF], atrial flutter, supraventricular arrhythmias, or ventricular arrhythmias), stroke/CVA, other CV reasons (such as hypotension or peripheral vascular disease), implantation of a cardioverter defibrillator (ICD), or cardiac resynchronization therapy (CRT) with CV event as the primary reason for hospitalization as determined by endpoint committee adjudicator.	Baseline (30 March 2006) up to 50 months (cut-off date: 25 May 2010), 59.5 months (complete DB phase: 18 March 2011)
Secondary	Number of Participants With First Occurrence of Fatal or Non-fatal Myocardial Infarction (Adjudicated)		Baseline (30 March 2006) up to 50 months (cut-off date: 25 May 2010), 59.5 months (complete DB phase: 18 March 2011)
Secondary	Number of Participants With First Occurrence of Fatal or Non-fatal Stroke (Adjudicated)		Baseline (30 March 2006) up to 50 months (cut-off date: 25 May 2010), 59.5 months (complete DB phase: 18 March 2011)
Secondary	Number of Participants With First Occurrence of Implantation of Cardiac Defibrillator (ICD) (Adjudicated)	First occurrence of implantation of cardiac defibrillator (ICD). ICD is an electronic device capable of monitoring the heart rhythm. When the heart is beating normally, the device remains inactive. If the heart develops a life-threatening tachycardia, the ICD delivers electrical shocks to the heart to terminate the abnormal rhythm and return the heart rhythm to normal.	Baseline (30 March 2006) up to 50 months (cut-off date: 25 May 2010), 59.5 months (complete DB phase: 18 March 2011)
Secondary	Number of Participants With First Occurrence of Implantation of Resynchronization Device (Cardiac Resynchronization Therapy [CRT]) (Adjudicated)	First occurrence of implantation of resynchronization device. CRT is use of a specialized pacemaker to re-coordinate the action of the right and left ventricles in heart failure.	Baseline (30 March 2006) up to 50 months (cut-off date: 25 May 2010), 59.5 months (complete DB phase: 18 March 2011)
Secondary	Number of Participants With First Occurrence of Hospitalization Due to Worsening Renal Function (Adjudicated)	First occurrence of hospitalization due to worsening renal function. Hospitalization due to worsening renal function is defined as an overnight stay, or longer, in a hospital environment (emergency room, observation unit or in-patient care, or similar facility including admission to a day care facility) due to worsening renal function as the primary reason for hospitalization as determined by endpoint committee adjudicator. Worsening renal function is defined as doubling of serum creatinine level from baseline level.	Baseline (30 March 2006) up to 50 months (cut-off date: 25 May 2010), 59.5 months (complete DB phase: 18 March 2011)
Secondary	Number of Participants With First Occurrence of Hospitalization Due to Hyperkalemia (Adjudicated)	First occurrence of hospitalization due to hyperkalemia. Hospitalization due to hyperkalemia is defined as an overnight stay, or longer, in a hospital environment (emergency room, observation unit or in-patient care, or similar facility including admission to a day care facility) due to hyperkalemia as the primary reason for hospitalization as determined by endpoint committee adjudicator. Hyperkalemia is defined as serum potassium level greater than (>) 5.5 milliequivalents per liter (mEq/L).	Baseline (30 March 2006) up to 50 months (cut-off date: 25 May 2010), 59.5 months (complete DB phase: 18 March 2011)
Secondary	Number of Participants With New Onset Atrial Fibrillation or Flutter	New onset of atrial fibrillation or flutter is defined as the diagnosis of atrial fibrillation or flutter in a participant after randomization, where atrial fibrillation was not present before randomization.	Baseline (30 March 2006) up to 50 months (cut-off date: 25 May 2010), 59.5 months (complete DB phase: 18 March 2011)
Secondary	Number of Participants With New Onset Diabetes Mellitus (DM)	The definition of new onset diabetes mellitus is the diagnosis of diabetes mellitus in a participant after randomization, when DM was not present before randomization.	Baseline (30 March 2006) up to 50 months (cut-off date: 25 May 2010), 59.5 months (complete DB phase: 18 March 2011)

External Links

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