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Trial record 21 of 112 for:    EPLERENONE

Clinical Study Of Eplerenone In Japanese Patients With Chronic Heart Failure (J-EMPHASIS-HF)

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ClinicalTrials.gov Identifier: NCT01115855
Recruitment Status : Completed
First Posted : May 4, 2010
Results First Posted : October 27, 2016
Last Update Posted : October 27, 2016
Sponsor:
Information provided by (Responsible Party):
Pfizer

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Heart Failure
Interventions Drug: Eplerenone
Drug: Placebo
Enrollment 221
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Eplerenone Placebo
Hide Arm/Group Description Participants with estimated glomerular filtration rate (eGFR) greater than or equal to (>=) 50 milliliter per minute divided by 1.73 squared meter (mL/min/1.73m^2) received eplerenone 25 milligram (mg) tablet once daily up to Week 4 and participants with eGFR 30 to less than (<) 50 mL/min/1.73m^2 received eplerenone 25 mg tablet every other day up to Week 4. . From Week 4 onward, the dose of eplerenone was limited to 50 mg once daily for participants with eGFR >=50 mL/min/1.73 m^2 and 25 mg once daily for participants with eGFR 30 to <50 mL/min/1.73 m^2 up to Month 48. Participants with eGFR >=50 mL/min/1.73m^2 received placebo matched with eplerenone tablet orally once daily from up to Week 4 and participants with eGFR 30 to <50 mL/min/1.73m^2 received placebo matched with eplerenone tablet every other day up to Week 4. From Week 4 onward, all participants received placebo matched with eplerenone tablet once daily up to Month 48.
Period Title: Overall Study
Started 111 110
Completed 75 74
Not Completed 36 36
Reason Not Completed
Adverse Event             16             18
Death             6             5
Lab Abnormality             1             1
Protocol Violation             0             1
Withdrawal by Subject             5             5
Other             8             6
Arm/Group Title Eplerenone Placebo Total
Hide Arm/Group Description Participants with eGFR >=50 mL/min/1.73m^2 received eplerenone 25 mg tablet once daily up to Week 4 and participants with eGFR 30 to < 50 mL/min/1.73m^2 received eplerenone 25 mg tablet every other day up to Week 4. From Week 4 onward, the dose of eplerenone was limited to 50 mg once daily for participants with eGFR >=50 mL/min/1.73 m^2 and 25 mg once daily for participants with eGFR 30 to <50 mL/min/1.73 m^2 up to Month 48. Participants with eGFR >=50 mL/min/1.73m^2 received placebo matched with eplerenone tablet orally once daily from up to Week 4 and participants with eGFR 30 to <50 mL/min/1.73m^2 received placebo matched with eplerenone tablet every other day up to Week 4. From Week 4 onward, all participants received placebo matched with eplerenone tablet once daily up to Month 48. Total of all reporting groups
Overall Number of Baseline Participants 111 110 221
Hide Baseline Analysis Population Description
Full analysis set included all randomized participants.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 111 participants 110 participants 221 participants
69.0  (8.7) 68.4  (7.7) 68.7  (8.2)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 111 participants 110 participants 221 participants
Female
26
  23.4%
19
  17.3%
45
  20.4%
Male
85
  76.6%
91
  82.7%
176
  79.6%
1.Primary Outcome
Title Number of Participants With First Occurrence of Cardiovascular (CV) Mortality or Hospitalization Due to Heart Failure (HF)
Hide Description CV mortality was defined as any death due to HF, myocardial infarction, cardiac arrhythmia, stroke or cerebral vascular accident, other CV cause (such as aneurysm or pulmonary embolism). Hospitalization due to HF was 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. Hazard ratio of Eplerenone versus placebo for first occurrence of the event was obtained from a Cox proportional hazards model.
Time Frame Randomization up to the date when the last enrolled participant had been followed up for 1 year (up to 1744 days)
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set included all randomized participants.
Arm/Group Title Eplerenone Placebo
Hide Arm/Group Description:
Participants with eGFR >=50 mL/min/1.73m^2 received eplerenone 25 mg tablet once daily up to Week 4 and participants with eGFR 30 to < 50 mL/min/1.73m^2 received eplerenone 25 mg tablet every other day up to Week 4. From Week 4 onward, the dose of eplerenone was limited to 50 mg once daily for participants with eGFR >=50 mL/min/1.73 m^2 and 25 mg once daily for participants with eGFR 30 to <50 mL/min/1.73 m^2 up to Month 48.
Participants with eGFR >=50 mL/min/1.73m^2 received placebo matched with eplerenone tablet orally once daily from up to Week 4 and participants with eGFR 30 to <50 mL/min/1.73m^2 received placebo matched with eplerenone tablet every other day up to Week 4. From Week 4 onward, all participants received placebo matched with eplerenone tablet once daily up to Month 48.
Overall Number of Participants Analyzed 111 110
Measure Type: Number
Unit of Measure: participants
33 36
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Eplerenone, Placebo
Comments Cox Proportional Hazard Model with baseline New York Heart Association (NYHA) cohort (II, III/IV) and baseline eGFR (30-<50 ml/min/1.73 m^2, >=50 ml/min/1.73 m^2) covariates.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.85
Confidence Interval (2-Sided) 95%
0.53 to 1.36
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Number of Participants With First Occurrence of Cardiovascular (CV) Mortality, Hospitalization Due to Heart Failure (HF), or Addition/Increase of Heart Failure (HF) Medication
Hide Description CV mortality was defined as any death due to HF, myocardial infarction, cardiac arrhythmia, stroke or cerebral vascular accident, other CV cause (such as aneurysm or pulmonary embolism). Hospitalization due to HF was 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. Addition/ increase of HF medications was defined as administration of new HF medication or increase of 50 percentage (%) or more in dose of HF medication for >= 3 days. Hazard ratio of Eplerenone versus placebo for first occurrence of the event was obtained from a Cox proportional hazards model.
Time Frame Randomization up to the date when the last enrolled participant had been followed up for 1 year (up to 1744 days)
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set included all randomized participants.
Arm/Group Title Eplerenone Placebo
Hide Arm/Group Description:
Participants with eGFR >=50 mL/min/1.73m^2 received eplerenone 25 mg tablet once daily up to Week 4 and participants with eGFR 30 to < 50 mL/min/1.73m^2 received eplerenone 25 mg tablet every other day up to Week 4. From Week 4 onward, the dose of eplerenone was limited to 50 mg once daily for participants with eGFR >=50 mL/min/1.73 m^2 and 25 mg once daily for participants with eGFR 30 to <50 mL/min/1.73 m^2 up to Month 48.
Participants with eGFR >=50 mL/min/1.73m^2 received placebo matched with eplerenone tablet orally once daily from up to Week 4 and participants with eGFR 30 to <50 mL/min/1.73m^2 received placebo matched with eplerenone tablet every other day up to Week 4. From Week 4 onward, all participants received placebo matched with eplerenone tablet once daily up to Month 48.
Overall Number of Participants Analyzed 111 110
Measure Type: Number
Unit of Measure: participants
42 45
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Eplerenone, Placebo
Comments Cox Proportional Hazard Model with baseline NYHA cohort (II, III/IV) and baseline eGFR (30­-<50 ml/min/1.73 m^2, >­=50 ml/min/1.73 m^2) covariates.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.86
Confidence Interval (2-Sided) 95%
0.56 to 1.31
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Number of Participants With With First Occurrence of All-Cause Mortality
Hide Description All-cause mortality was defined as any CV mortality, Non-CV mortality, including malignant tumor, pulmonary disease and trauma.CV mortality was defined as death due to HF, myocardial infarction, cardiac arrhythmia, stroke or cerebral vascular accident, other CV cause (such as aneurysm or pulmonary embolism). Mortality during treatment, within 30 days of treatment discontinuation and after 30 days of discontinuation was reported. Hazard ratio of Eplerenone versus placebo for first occurrence of the event was obtained from a Cox proportional hazards model.
Time Frame Randomization up to the date when the last enrolled participant had been followed up for 1 year (up to 1744 days)
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set included all randomized participants.
Arm/Group Title Eplerenone Placebo
Hide Arm/Group Description:
Participants with eGFR >=50 mL/min/1.73m^2 received eplerenone 25 mg tablet once daily up to Week 4 and participants with eGFR 30 to < 50 mL/min/1.73m^2 received eplerenone 25 mg tablet every other day up to Week 4. From Week 4 onward, the dose of eplerenone was limited to 50 mg once daily for participants with eGFR >=50 mL/min/1.73 m^2 and 25 mg once daily for participants with eGFR 30 to <50 mL/min/1.73 m^2 up to Month 48.
Participants with eGFR >=50 mL/min/1.73m^2 received placebo matched with eplerenone tablet orally once daily from up to Week 4 and participants with eGFR 30 to <50 mL/min/1.73m^2 received placebo matched with eplerenone tablet every other day up to Week 4. From Week 4 onward, all participants received placebo matched with eplerenone tablet once daily up to Month 48.
Overall Number of Participants Analyzed 111 110
Measure Type: Number
Unit of Measure: participants
During treatment 6 5
Within 30 days of treatment discontinuation 1 1
After 30 days of treatment discontinuation 10 4
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Eplerenone, Placebo
Comments Cox Proportional Hazard Model with baseline NYHA cohort (II, III/IV) and baseline eGFR (30­-<50 ml/min/1.73 m^2, >­=50 ml/min/1.73 m^2) covariates.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.77
Confidence Interval (2-Sided) 95%
0.81 to 3.87
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Number of Participants With With First Occurrence of Cardiovascular Mortality
Hide Description CV mortality was defined as death due to HF, myocardial infarction, cardiac arrhythmia, stroke or cerebral vascular accident, other CV cause (such as aneurysm or pulmonary embolism). Hazard ratio of Eplerenone versus placebo for first occurrence of the event was obtained from a Cox proportional hazards model.
Time Frame Randomization up to the date when the last enrolled participant had been followed up for 1 year (up to 1744 days)
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set included all randomized participants.
Arm/Group Title Eplerenone Placebo
Hide Arm/Group Description:
Participants with eGFR >=50 mL/min/1.73m^2 received eplerenone 25 mg tablet once daily up to Week 4 and participants with eGFR 30 to < 50 mL/min/1.73m^2 received eplerenone 25 mg tablet every other day up to Week 4. From Week 4 onward, the dose of eplerenone was limited to 50 mg once daily for participants with eGFR >=50 mL/min/1.73 m^2 and 25 mg once daily for participants with eGFR 30 to <50 mL/min/1.73 m^2 up to Month 48.
Participants with eGFR >=50 mL/min/1.73m^2 received placebo matched with eplerenone tablet orally once daily from up to Week 4 and participants with eGFR 30 to <50 mL/min/1.73m^2 received placebo matched with eplerenone tablet every other day up to Week 4. From Week 4 onward, all participants received placebo matched with eplerenone tablet once daily up to Month 48.
Overall Number of Participants Analyzed 111 110
Measure Type: Number
Unit of Measure: participants
14 6
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Eplerenone, Placebo
Comments Cox Proportional Hazard Model with baseline NYHA cohort (II, III/IV) and baseline eGFR (30-­<50 ml/min/1.73 m^2, >­=50 ml/min/1.73 m^2) covariates.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 2.40
Confidence Interval (2-Sided) 95%
0.92 to 6.24
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Number of Participants With First Occurrence of All-cause Hospitalization
Hide Description All cause hospitalization included all hospitalizations as CV hospitalization, which was defined as any hospitalization due to CV events including HF, myocardial infarction, arrhythmia, angina pectoris and non-CV hospitalizations which was defined as any hospitalization due to non-CV events including renal dysfunction, hyperkalaemia, malignant tumor and pulmonary disease. Hazard ratio of Eplerenone versus placebo for first occurrence of the event was obtained from a Cox proportional hazards model.
Time Frame Randomization up to the date when the last enrolled participant had been followed up for 1 year (up to 1744 days)
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set included all randomized participants.
Arm/Group Title Eplerenone Placebo
Hide Arm/Group Description:
Participants with eGFR >=50 mL/min/1.73m^2 received eplerenone 25 mg tablet once daily up to Week 4 and participants with eGFR 30 to < 50 mL/min/1.73m^2 received eplerenone 25 mg tablet every other day up to Week 4. From Week 4 onward, the dose of eplerenone was limited to 50 mg once daily for participants with eGFR >=50 mL/min/1.73 m^2 and 25 mg once daily for participants with eGFR 30 to <50 mL/min/1.73 m^2 up to Month 48.
Participants with eGFR >=50 mL/min/1.73m^2 received placebo matched with eplerenone tablet orally once daily from up to Week 4 and participants with eGFR 30 to <50 mL/min/1.73m^2 received placebo matched with eplerenone tablet every other day up to Week 4. From Week 4 onward, all participants received placebo matched with eplerenone tablet once daily up to Month 48.
Overall Number of Participants Analyzed 111 110
Measure Type: Number
Unit of Measure: participants
45 58
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Eplerenone, Placebo
Comments Cox Proportional Hazard Model with baseline NYHA cohort (II, III/IV) and baseline eGFR (30­-<50 ml/min/1.73 m^2, >­=50 ml/min/1.73 m^2) covariates.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.65
Confidence Interval (2-Sided) 95%
0.44 to 0.97
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Number of Participants With First Occurrence of Hospitalization Due to Heart Failure (HF)
Hide Description Hospitalization due to HF was 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. Hazard ratio of Eplerenone versus placebo for first occurrence of the event was obtained from a Cox proportional hazards model.
Time Frame Randomization up to the date when the last enrolled participant had been followed up for 1 year (up to 1744 days)
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set included all randomized participants.
Arm/Group Title Eplerenone Placebo
Hide Arm/Group Description:
Participants with eGFR >=50 mL/min/1.73m^2 received eplerenone 25 mg tablet once daily up to Week 4 and participants with eGFR 30 to < 50 mL/min/1.73m^2 received eplerenone 25 mg tablet every other day up to Week 4. From Week 4 onward, the dose of eplerenone was limited to 50 mg once daily for participants with eGFR >=50 mL/min/1.73 m^2 and 25 mg once daily for participants with eGFR 30 to <50 mL/min/1.73 m^2 up to Month 48.
Participants with eGFR >=50 mL/min/1.73m^2 received placebo matched with eplerenone tablet orally once daily from up to Week 4 and participants with eGFR 30 to <50 mL/min/1.73m^2 received placebo matched with eplerenone tablet every other day up to Week 4. From Week 4 onward, all participants received placebo matched with eplerenone tablet once daily up to Month 48.
Overall Number of Participants Analyzed 111 110
Measure Type: Number
Unit of Measure: participants
27 33
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Eplerenone, Placebo
Comments Cox Proportional Hazard Model with baseline NYHA cohort (II, III/IV) and baseline eGFR (30­-<50 ml/min/1.73 m^2, >­=50 ml/min/1.73 m^2) covariates.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.75
Confidence Interval (2-Sided) 95%
0.45 to 1.25
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Number of Participants With First Occurrence of All-cause Mortality or All-cause Hospitalization
Hide Description All cause hospitalization included all hospitalizations as CV hospitalization, which was defined as any hospitalization due to CV events including HF, myocardial infarction, arrhythmia, angina pectoris and non-CV hospitalizations which was defined as any hospitalization due to non-CV events including renal dysfunction, hyperkalaemia, malignant tumor and pulmonary disease. All-cause mortality was defined as any CV mortality, Non-CV mortality, including malignant tumor, pulmonary disease and trauma.CV mortality was defined as death due to HF, myocardial infarction, cardiac arrhythmia, stroke or cerebral vascular accident, other CV cause (such as aneurysm or pulmonary embolism). Hazard ratio of Eplerenone versus placebo for first occurrence of the event was obtained from a Cox proportional hazards model.
Time Frame Randomization up to the date when the last enrolled participant had been followed up for 1 year (up to 1744 days)
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set included all randomized participants.
Arm/Group Title Eplerenone Placebo
Hide Arm/Group Description:
Participants with eGFR >=50 mL/min/1.73m^2 received eplerenone 25 mg tablet once daily up to Week 4 and participants with eGFR 30 to < 50 mL/min/1.73m^2 received eplerenone 25 mg tablet every other day up to Week 4. From Week 4 onward, the dose of eplerenone was limited to 50 mg once daily for participants with eGFR >=50 mL/min/1.73 m^2 and 25 mg once daily for participants with eGFR 30 to <50 mL/min/1.73 m^2 up to Month 48.
Participants with eGFR >=50 mL/min/1.73m^2 received placebo matched with eplerenone tablet orally once daily from up to Week 4 and participants with eGFR 30 to <50 mL/min/1.73m^2 received placebo matched with eplerenone tablet every other day up to Week 4. From Week 4 onward, all participants received placebo matched with eplerenone tablet once daily up to Month 48.
Overall Number of Participants Analyzed 111 110
Measure Type: Number
Unit of Measure: participants
48 61
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Eplerenone, Placebo
Comments Cox Proportional Hazard Model with baseline NYHA cohort (II, III/IV) and baseline eGFR (30-­<50 ml/min/1.73 m^2, >­=50 ml/min/1.73 m^2) covariates.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.66
Confidence Interval (2-Sided) 95%
0.45 to 0.97
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Number of Participants With First Occurrence of Heart Failure (HF) Mortality or Heart Failure (HF) Hospitalization
Hide Description HF mortality was defined as any death due to HF. Hospitalization due to HF was 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. Hazard ratio of Eplerenone versus placebo for first occurrence of the event was obtained from a Cox proportional hazards model.
Time Frame Randomization up to the date when the last enrolled participant had been followed up for 1 year (up to 1744 days)
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set included all randomized participants.
Arm/Group Title Eplerenone Placebo
Hide Arm/Group Description:
Participants with eGFR >=50 mL/min/1.73m^2 received eplerenone 25 mg tablet once daily up to Week 4 and participants with eGFR 30 to < 50 mL/min/1.73m^2 received eplerenone 25 mg tablet every other day up to Week 4. From Week 4 onward, the dose of eplerenone was limited to 50 mg once daily for participants with eGFR >=50 mL/min/1.73 m^2 and 25 mg once daily for participants with eGFR 30 to <50 mL/min/1.73 m^2 up to Month 48.
Participants with eGFR >=50 mL/min/1.73m^2 received placebo matched with eplerenone tablet orally once daily from up to Week 4 and participants with eGFR 30 to <50 mL/min/1.73m^2 received placebo matched with eplerenone tablet every other day up to Week 4. From Week 4 onward, all participants received placebo matched with eplerenone tablet once daily up to Month 48.
Overall Number of Participants Analyzed 111 110
Measure Type: Number
Unit of Measure: participants
29 33
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Eplerenone, Placebo
Comments Cox Proportional Hazard Model with baseline NYHA cohort (II, III/IV) and baseline eGFR (30-­<50 ml/min/1.73 m^2, >=­50 ml/min/1.73 m^2) covariates.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.81
Confidence Interval (2-Sided) 95%
0.49 to 1.33
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Number of Participants With First Occurrence of Cardiovascular (CV) Hospitalization
Hide Description CV hospitalization, which was defined as any hospitalization due to CV events including HF, myocardial infarction, arrhythmia, angina pectoris. Hazard ratio of Eplerenone versus placebo for first occurrence of the event was obtained from a Cox proportional hazards model.
Time Frame Randomization up to the date when the last enrolled participant had been followed up for 1 year (up to 1744 days)
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set included all randomized participants.
Arm/Group Title Eplerenone Placebo
Hide Arm/Group Description:
Participants with eGFR >=50 mL/min/1.73m^2 received eplerenone 25 mg tablet once daily up to Week 4 and participants with eGFR 30 to < 50 mL/min/1.73m^2 received eplerenone 25 mg tablet every other day up to Week 4. From Week 4 onward, the dose of eplerenone was limited to 50 mg once daily for participants with eGFR >=50 mL/min/1.73 m^2 and 25 mg once daily for participants with eGFR 30 to <50 mL/min/1.73 m^2 up to Month 48.
Participants with eGFR >=50 mL/min/1.73m^2 received placebo matched with eplerenone tablet orally once daily from up to Week 4 and participants with eGFR 30 to <50 mL/min/1.73m^2 received placebo matched with eplerenone tablet every other day up to Week 4. From Week 4 onward, all participants received placebo matched with eplerenone tablet once daily up to Month 48.
Overall Number of Participants Analyzed 111 110
Measure Type: Number
Unit of Measure: participants
35 44
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Eplerenone, Placebo
Comments Cox Proportional Hazard Model with baseline NYHA cohort (II, III/IV) and baseline eGFR (30­-<50 ml/min/1.73 m^2, >­=50 ml/min/1.73 m^2) covariates.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.70
Confidence Interval (2-Sided) 95%
0.45 to 1.10
Estimation Comments [Not Specified]
10.Secondary Outcome
Title Number of Participants With First Occurrence of Addition/Increase of Heart Failure (HF) Medication Due to Heart Failure (HF) Worsening
Hide Description Addition/ increase of HF medications was defined as administration of new HF medication or increase of 50 percent or more in dose of HF medication for >= 3 days. Hazard ratio of Eplerenone versus placebo for first occurrence of the event was obtained from a Cox proportional hazards model.
Time Frame Randomization up to the date when the last enrolled participant had been followed up for 1 year (up to 1744 days)
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set included all randomized participants.
Arm/Group Title Eplerenone Placebo
Hide Arm/Group Description:
Participants with eGFR >=50 mL/min/1.73m^2 received eplerenone 25 mg tablet once daily up to Week 4 and participants with eGFR 30 to < 50 mL/min/1.73m^2 received eplerenone 25 mg tablet every other day up to Week 4. From Week 4 onward, the dose of eplerenone was limited to 50 mg once daily for participants with eGFR >=50 mL/min/1.73 m^2 and 25 mg once daily for participants with eGFR 30 to <50 mL/min/1.73 m^2 up to Month 48.
Participants with eGFR >=50 mL/min/1.73m^2 received placebo matched with eplerenone tablet orally once daily from up to Week 4 and participants with eGFR 30 to <50 mL/min/1.73m^2 received placebo matched with eplerenone tablet every other day up to Week 4. From Week 4 onward, all participants received placebo matched with eplerenone tablet once daily up to Month 48.
Overall Number of Participants Analyzed 111 110
Measure Type: Number
Unit of Measure: participants
38 43
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Eplerenone, Placebo
Comments Cox Proportional Hazard Model with baseline NYHA cohort (II, III/IV) and baseline eGFR (30-­<50 ml/min/1.73 m^2, >­=50 ml/min/1.73 m^2) covariates.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.83
Confidence Interval (2-Sided) 95%
0.53 to 1.28
Estimation Comments [Not Specified]
11.Secondary Outcome
Title Number of Participants With First Occurrence of Fatal/Non-Fatal Stroke
Hide Description Hazard ratio of Eplerenone versus placebo for first occurrence of the event was obtained from a Cox proportional hazards model.
Time Frame Randomization up to the date when the last enrolled participant had been followed up for 1 year (up to 1744 days)
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set included all randomized participants.
Arm/Group Title Eplerenone Placebo
Hide Arm/Group Description:
Participants with eGFR >=50 mL/min/1.73m^2 received eplerenone 25 mg tablet once daily up to Week 4 and participants with eGFR 30 to < 50 mL/min/1.73m^2 received eplerenone 25 mg tablet every other day up to Week 4. From Week 4 onward, the dose of eplerenone was limited to 50 mg once daily for participants with eGFR >=50 mL/min/1.73 m^2 and 25 mg once daily for participants with eGFR 30 to <50 mL/min/1.73 m^2 up to Month 48.
Participants with eGFR >=50 mL/min/1.73m^2 received placebo matched with eplerenone tablet orally once daily from up to Week 4 and participants with eGFR 30 to <50 mL/min/1.73m^2 received placebo matched with eplerenone tablet every other day up to Week 4. From Week 4 onward, all participants received placebo matched with eplerenone tablet once daily up to Month 48.
Overall Number of Participants Analyzed 111 110
Measure Type: Number
Unit of Measure: participants
3 4
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Eplerenone, Placebo
Comments Cox Proportional Hazard Model with baseline NYHA cohort (II, III/IV) and baseline eGFR (30-­<50 ml/min/1.73 m^2, >­=50 ml/min/1.73 m^2) covariates.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.79
Confidence Interval (2-Sided) 95%
0.18 to 3.53
Estimation Comments [Not Specified]
12.Secondary Outcome
Title Number of Participants With First Occurrence of Fatal/Non-Fatal Myocardial Infarction (MI)
Hide Description Hazard ratio of Eplerenone versus placebo for first occurrence of the event was obtained from a Cox proportional hazards model.
Time Frame Randomization up to the date when the last enrolled participant had been followed up for 1 year (up to 1744 days)
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set included all randomized participants.
Arm/Group Title Eplerenone Placebo
Hide Arm/Group Description:
Participants with eGFR >=50 mL/min/1.73m^2 received eplerenone 25 mg tablet once daily up to Week 4 and participants with eGFR 30 to < 50 mL/min/1.73m^2 received eplerenone 25 mg tablet every other day up to Week 4. From Week 4 onward, the dose of eplerenone was limited to 50 mg once daily for participants with eGFR >=50 mL/min/1.73 m^2 and 25 mg once daily for participants with eGFR 30 to <50 mL/min/1.73 m^2 up to Month 48.
Participants with eGFR >=50 mL/min/1.73m^2 received placebo matched with eplerenone tablet orally once daily from up to Week 4 and participants with eGFR 30 to <50 mL/min/1.73m^2 received placebo matched with eplerenone tablet every other day up to Week 4. From Week 4 onward, all participants received placebo matched with eplerenone tablet once daily up to Month 48.
Overall Number of Participants Analyzed 111 110
Measure Type: Number
Unit of Measure: participants
1 1
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Eplerenone, Placebo
Comments Cox Proportional Hazard Model with baseline NYHA cohort (II, III/IV) and baseline eGFR (30-­<50 ml/min/1.73 m^2, >­=50 ml/min/1.73 m^2) covariates.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.11
Confidence Interval (2-Sided) 95%
0.07 to 17.85
Estimation Comments [Not Specified]
13.Secondary Outcome
Title Number of Participants With First Occurrence of New Onset Atrial Fibrillation/Flutter
Hide Description New onset of atrial fibrillation or flutter was defined as the diagnosis of atrial fibrillation or flutter in a participant after randomization. Hazard ratio of Eplerenone versus placebo for first occurrence of the event was obtained from a Cox proportional hazards model.
Time Frame Randomization up to the date when the last enrolled participant had been followed up for 1 year (up to 1744 days)
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set included all randomized participants.
Arm/Group Title Eplerenone Placebo
Hide Arm/Group Description:
Participants with eGFR >=50 mL/min/1.73m^2 received eplerenone 25 mg tablet once daily up to Week 4 and participants with eGFR 30 to < 50 mL/min/1.73m^2 received eplerenone 25 mg tablet every other day up to Week 4. From Week 4 onward, the dose of eplerenone was limited to 50 mg once daily for participants with eGFR >=50 mL/min/1.73 m^2 and 25 mg once daily for participants with eGFR 30 to <50 mL/min/1.73 m^2 up to Month 48.
Participants with eGFR >=50 mL/min/1.73m^2 received placebo matched with eplerenone tablet orally once daily from up to Week 4 and participants with eGFR 30 to <50 mL/min/1.73m^2 received placebo matched with eplerenone tablet every other day up to Week 4. From Week 4 onward, all participants received placebo matched with eplerenone tablet once daily up to Month 48.
Overall Number of Participants Analyzed 111 110
Measure Type: Number
Unit of Measure: participants
4 2
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Eplerenone, Placebo
Comments Cox Proportional Hazard Model with baseline NYHA cohort (II, III/IV) and baseline eGFR (30-­<50 ml/min/1.73 m^2, >­=50 ml/min/1.73 m^2) covariates.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 2.11
Confidence Interval (2-Sided) 95%
0.39 to 11.56
Estimation Comments [Not Specified]
14.Secondary Outcome
Title Number of Participants With First Occurrence of New Onset Diabetes Mellitus
Hide Description New onset diabetes mellitus was defined as the diagnosis of diabetes mellitus in a participant after randomization. Hazard ratio of Eplerenone versus placebo for first occurrence of the event was obtained from a Cox proportional hazards model.
Time Frame Randomization up to the date when the last enrolled participant had been followed up for 1 year (up to 1744 days)
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set included all randomized participants.
Arm/Group Title Eplerenone Placebo
Hide Arm/Group Description:
Participants with eGFR >=50 mL/min/1.73m^2 received eplerenone 25 mg tablet once daily up to Week 4 and participants with eGFR 30 to < 50 mL/min/1.73m^2 received eplerenone 25 mg tablet every other day up to Week 4. From Week 4 onward, the dose of eplerenone was limited to 50 mg once daily for participants with eGFR >=50 mL/min/1.73 m^2 and 25 mg once daily for participants with eGFR 30 to <50 mL/min/1.73 m^2 up to Month 48.
Participants with eGFR >=50 mL/min/1.73m^2 received placebo matched with eplerenone tablet orally once daily from up to Week 4 and participants with eGFR 30 to <50 mL/min/1.73m^2 received placebo matched with eplerenone tablet every other day up to Week 4. From Week 4 onward, all participants received placebo matched with eplerenone tablet once daily up to Month 48.
Overall Number of Participants Analyzed 111 110
Measure Type: Number
Unit of Measure: participants
1 2
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Eplerenone, Placebo
Comments Cox Proportional Hazard Model with baseline NYHA cohort (II, III/IV) and baseline eGFR (30­-<50 ml/min/1.73 m^2, >­=50 ml/min/1.73 m^2) covariates.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.51
Confidence Interval (2-Sided) 95%
0.05 to 5.66
Estimation Comments [Not Specified]
15.Secondary Outcome
Title Number of Participants With First Occurrence of Hospitalisation Due to Worsening Renal Function
Hide Description Hospitalization due to worsening renal function (as per physician’s decision) was 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. Hazard ratio of Eplerenone versus placebo for first occurrence of the event was obtained from a Cox proportional hazards model.
Time Frame Randomization up to the date when the last enrolled participant had been followed up for 1 year (up to 1744 days)
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set included all randomized participants.
Arm/Group Title Eplerenone Placebo
Hide Arm/Group Description:
Participants with eGFR >=50 mL/min/1.73m^2 received eplerenone 25 mg tablet once daily up to Week 4 and participants with eGFR 30 to < 50 mL/min/1.73m^2 received eplerenone 25 mg tablet every other day up to Week 4. From Week 4 onward, the dose of eplerenone was limited to 50 mg once daily for participants with eGFR >=50 mL/min/1.73 m^2 and 25 mg once daily for participants with eGFR 30 to <50 mL/min/1.73 m^2 up to Month 48.
Participants with eGFR >=50 mL/min/1.73m^2 received placebo matched with eplerenone tablet orally once daily from up to Week 4 and participants with eGFR 30 to <50 mL/min/1.73m^2 received placebo matched with eplerenone tablet every other day up to Week 4. From Week 4 onward, all participants received placebo matched with eplerenone tablet once daily up to Month 48.
Overall Number of Participants Analyzed 111 110
Measure Type: Number
Unit of Measure: participants
2 2
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Eplerenone, Placebo
Comments Cox Proportional Hazard Model with baseline NYHA cohort (II, III/IV) and baseline eGFR (30-­<50 ml/min/1.73 m^2, >­=50 ml/min/1.73 m^2) covariates.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.13
Confidence Interval (2-Sided) 95%
0.16 to 8.04
Estimation Comments [Not Specified]
16.Secondary Outcome
Title Number of Participants With First Occurrence of Hospitalization for Hyperkalemia
Hide Description Hospitalization due to hyperkalemia (as per physician’s decision) was 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. Hazard ratio of Eplerenone versus placebo for first occurrence of the event was obtained from a Cox proportional hazards model.
Time Frame Randomization up to the date when the last enrolled participant had been followed up for 1 year (up to 1744 days)
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set included all randomized participants.
Arm/Group Title Eplerenone Placebo
Hide Arm/Group Description:
Participants with eGFR >=50 mL/min/1.73m^2 received eplerenone 25 mg tablet once daily up to Week 4 and participants with eGFR 30 to < 50 mL/min/1.73m^2 received eplerenone 25 mg tablet every other day up to Week 4. From Week 4 onward, the dose of eplerenone was limited to 50 mg once daily for participants with eGFR >=50 mL/min/1.73 m^2 and 25 mg once daily for participants with eGFR 30 to <50 mL/min/1.73 m^2 up to Month 48.
Participants with eGFR >=50 mL/min/1.73m^2 received placebo matched with eplerenone tablet orally once daily from up to Week 4 and participants with eGFR 30 to <50 mL/min/1.73m^2 received placebo matched with eplerenone tablet every other day up to Week 4. From Week 4 onward, all participants received placebo matched with eplerenone tablet once daily up to Month 48.
Overall Number of Participants Analyzed 111 110
Measure Type: Number
Unit of Measure: participants
0 0
17.Secondary Outcome
Title Change From Baseline in Plasma Concentration of Brain Natriuretic Peptide at Months 5, 9, 13, 17, 21, 25, 29, 33, 37, 42, 48 and Final Visit
Hide Description [Not Specified]
Time Frame Baseline, Months 5,9,13,17,21,25,29,33,37,42,48, Final Visit (up to Month 48)
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set included all randomized participants. Here, ‘n’ signifies those participants who were evaluable at specified time point for each arm, respectively.
Arm/Group Title Eplerenone Placebo
Hide Arm/Group Description:
Participants with eGFR >=50 mL/min/1.73m^2 received eplerenone 25 mg tablet once daily up to Week 4 and participants with eGFR 30 to < 50 mL/min/1.73m^2 received eplerenone 25 mg tablet every other day up to Week 4. From Week 4 onward, the dose of eplerenone was limited to 50 mg once daily for participants with eGFR >=50 mL/min/1.73 m^2 and 25 mg once daily for participants with eGFR 30 to <50 mL/min/1.73 m^2 up to Month 48.
Participants with eGFR >=50 mL/min/1.73m^2 received placebo matched with eplerenone tablet orally once daily from up to Week 4 and participants with eGFR 30 to <50 mL/min/1.73m^2 received placebo matched with eplerenone tablet every other day up to Week 4. From Week 4 onward, all participants received placebo matched with eplerenone tablet once daily up to Month 48.
Overall Number of Participants Analyzed 111 110
Mean (Standard Deviation)
Unit of Measure: picogram/milliliter (pg/ml)
Baseline (n=111,110) 469.29  (375.43) 435.61  (391.49)
Change at Month 5 (n=105,106) -169.75  (424.40) -36.36  (413.73)
Change at Month 9 (n=99,104) -208.54  (405.74) -76.23  (442.47)
Change at Month 13 (n=95,101) -258.66  (395.05) -93.99  (409.87)
Change at Month 17 (n=81,82) -242.92  (431.59) -69.74  (535.05)
Change at Month 21 (n=72,73) -241.33  (429.24) -57.31  (515.76)
Change at Month 25 (n=63,63) -249.76  (473.68) -83.99  (506.79)
Change at Month 29 (n=53,48) -269.07  (502.78) -95.33  (350.51)
Change at Month 33 (n=45,40) -228.84  (575.05) -43.98  (500.78)
Change at Month 37 (n=40,33) -211.86  (597.30) -73.73  (626.13)
Change at Month 42 (n=30,26) -155.65  (320.44) -22.31  (689.26)
Change at Month 48 (n=16,16) -200.85  (357.51) -122.33  (450.87)
Change at Final Visit (n=109,110) -149.75  (473.95) -57.45  (509.85)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Eplerenone, Placebo
Comments Change from baseline at Month 5 : Mixed effect model of repeated measurements with covariates of the treatment, Week, interaction between treatment and week, baseline NYHA cohort (II, III/IV), baseline eGFR (30-<50 ml/min/1.73 m^2, >=50 ml/min/1.73 m^2) and baseline value.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Square Mean Difference
Estimated Value -102.93
Confidence Interval (2-Sided) 95%
-195.92 to -9.94
Parameter Dispersion
Type: Standard Error of the mean
Value: 47.13
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Eplerenone, Placebo
Comments Change from baseline at Month 9 :Mixed effect model of repeated measurements with covariates of the treatment, Week, interaction between treatment and week, baseline NYHA cohort (II, III/IV), baseline eGFR (30-<50 ml/min/1.73 m^2, >=50 ml/min/1.73 m^2) and baseline value.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Square Mean Difference
Estimated Value -95.77
Confidence Interval (2-Sided) 95%
-184.51 to -7.04
Parameter Dispersion
Type: Standard Error of the mean
Value: 44.54
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Eplerenone, Placebo
Comments Change from baseline at Month 13 : Mixed effect model of repeated measurements with covariates of the treatment, Week, interaction between treatment and week, baseline NYHA cohort (II, III/IV), baseline eGFR (30-<50 ml/min/1.73 m^2, >=50 ml/min/1.73 m^2) and baseline value.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Square Mean Difference
Estimated Value -125.09
Confidence Interval (2-Sided) 95%
-195.50 to -54.68
Parameter Dispersion
Type: Standard Error of the mean
Value: 35.15
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Eplerenone, Placebo
Comments Change from baseline at Month 17 :Mixed effect model of repeated measurements with covariates of the treatment, Week, interaction between treatment and week, baseline NYHA cohort (II, III/IV), baseline eGFR (30-<50 ml/min/1.73 m^2, >=50 ml/min/1.73 m^2) and baseline value.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Square Mean Difference
Estimated Value -31.94
Confidence Interval (2-Sided) 95%
-232.77 to -31.11
Parameter Dispersion
Type: Standard Error of the mean
Value: 51.12
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Eplerenone, Placebo
Comments Change from baseline at Month 21 : Mixed effect model of repeated measurements with covariates of the treatment, Week, interaction between treatment and week, baseline NYHA cohort (II, III/IV), baseline eGFR (30-<50 ml/min/1.73 m^2, >=50 ml/min/1.73 m^2) and baseline value.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Square Mean Difference
Estimated Value -132.39
Confidence Interval (2-Sided) 95%
-240.94 to -23.84
Parameter Dispersion
Type: Standard Error of the mean
Value: 52.77
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Eplerenone, Placebo
Comments Change from baseline at Month 25 :Mixed effect model of repeated measurements with covariates of the treatment, Week, interaction between treatment and week, baseline NYHA cohort (II, III/IV), baseline eGFR (30-<50 ml/min/1.73 m^2, >=50 ml/min/1.73 m^2) and baseline value.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Square Mean Difference
Estimated Value -117.18
Confidence Interval (2-Sided) 95%
-221.49 to -12.87
Parameter Dispersion
Type: Standard Error of the mean
Value: 51.76
Estimation Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Eplerenone, Placebo
Comments Change from baseline at Month 29 :Mixed effect model of repeated measurements with covariates of the treatment, Week, interaction between treatment and week, baseline NYHA cohort (II, III/IV), baseline eGFR (30-<50 ml/min/1.73 m^2, >=50 ml/min/1.73 m^2) and baseline value.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Square Mean Difference
Estimated Value -101.50
Confidence Interval (2-Sided) 95%
-267.36 to 64.36
Parameter Dispersion
Type: Standard Error of the mean
Value: 61.05
Estimation Comments [Not Specified]
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Eplerenone, Placebo
Comments Change from baseline at Month 33 : Mixed effect model of repeated measurements with covariates of the treatment, Week, interaction between treatment and week, baseline NYHA cohort (II, III/IV), baseline eGFR (30-<50 ml/min/1.73 m^2, >=50 ml/min/1.73 m^2) and baseline value.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Square Mean Difference
Estimated Value -110.78
Confidence Interval (2-Sided) 95%
-307.49 to 85.93
Parameter Dispersion
Type: Standard Error of the mean
Value: 92.42
Estimation Comments [Not Specified]
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Eplerenone, Placebo
Comments Change from baseline at Month 37 : Mixed effect model of repeated measurements with covariates of the treatment, Week, interaction between treatment and week, baseline NYHA cohort (II, III/IV), baseline eGFR (30-<50 ml/min/1.73 m^2, >=50 ml/min/1.73 m^2) and baseline value.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Square Mean Difference
Estimated Value -119.62
Confidence Interval (2-Sided) 95%
-2137.82 to 1898.59
Parameter Dispersion
Type: Standard Error of the mean
Value: 158.84
Estimation Comments [Not Specified]
Show Statistical Analysis 10 Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Eplerenone, Placebo
Comments Change from baseline at Month 42 : Mixed effect model of repeated measurements with covariates of the treatment, Week, interaction between treatment and week, baseline NYHA cohort (II, III/IV), baseline eGFR (30-<50 ml/min/1.73 m^2, >=50 ml/min/1.73 m^2) and baseline value.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Square Mean Difference
Estimated Value -144.60
Confidence Interval (2-Sided) 90%
-2692.95 to 2403.76
Parameter Dispersion
Type: Standard Error of the mean
Value: 200.56
Estimation Comments [Not Specified]
Show Statistical Analysis 11 Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Eplerenone, Placebo
Comments Change from baseline at Month 48 :Mixed effect model of repeated measurements with covariates of the treatment, Week, interaction between treatment and week, baseline NYHA cohort (II, III/IV), baseline eGFR (30-<50 ml/min/1.73 m^2, >=50 ml/min/1.73 m^2) and baseline value.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Square Mean Difference
Estimated Value -77.26
Confidence Interval (2-Sided) 95%
-2131.88 to 1977.37
Parameter Dispersion
Type: Standard Error of the mean
Value: 966.09
Estimation Comments [Not Specified]
Show Statistical Analysis 12 Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Eplerenone, Placebo
Comments Change from baseline at Month 13 : ANCOVA with treatment effect and covariates of the NYHA cohort (II, III/IV), baseline eGFR (30-<50 ml/min/1.73 m^2, >=50 ml/min/1.73 m^2) and baseline value.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Square Mean Difference
Estimated Value -102.30
Confidence Interval (2-Sided) 95%
-172.61 to -32.00
Parameter Dispersion
Type: Standard Error of the mean
Value: 35.67
Estimation Comments [Not Specified]
18.Secondary Outcome
Title Change From Baseline in Plasma Concentration of Serum N-terminal Pro-Brain Natriuretic Peptide (NT-proBNP) at Months 5, 9, 13, 17, 21, 25, 29, 33, 37, 42, 48 and Final Visit
Hide Description [Not Specified]
Time Frame Baseline, Months 5, 9, 13, 17, 21 ,25, 29, 33, 37, 42, 48 and Final Visit (up to Month 48)
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set included all randomized participants. Here, ‘n’ signifies those participants who were evaluable at specified time point for each arm, respectively.
Arm/Group Title Eplerenone Placebo
Hide Arm/Group Description:
Participants with eGFR >=50 mL/min/1.73m^2 received eplerenone 25 mg tablet once daily up to Week 4 and participants with eGFR 30 to < 50 mL/min/1.73m^2 received eplerenone 25 mg tablet every other day up to Week 4. From Week 4 onward, the dose of eplerenone was limited to 50 mg once daily for participants with eGFR >=50 mL/min/1.73 m^2 and 25 mg once daily for participants with eGFR 30 to <50 mL/min/1.73 m^2 up to Month 48.
Participants with eGFR >=50 mL/min/1.73m^2 received placebo matched with eplerenone tablet orally once daily from up to Week 4 and participants with eGFR 30 to <50 mL/min/1.73m^2 received placebo matched with eplerenone tablet every other day up to Week 4. From Week 4 onward, all participants received placebo matched with eplerenone tablet once daily up to Month 48.
Overall Number of Participants Analyzed 111 110
Mean (Standard Deviation)
Unit of Measure: pg/mL
Baseline (n=111,110) 2635.78  (2143.64) 2354.31  (1874.30)
Change at Month 5 (n=105,106) -770.51  (2172.88) -205.18  (1801.42)
Change at Month 9 (n=99,104) -884.76  (2265.57) -425.47  (1883.54)
Change at Month 13 (n=95,101) -1066.86  (2088.51) -452.02  (1878.98)
Change at Month 17 (n=81,82) -1126.96  (2384.14) -109.59  (3380.42)
Change at Month 21 (n=72,73) -957.86  (2601.47) -250.85  (2508.01)
Change at Month 25 (n=63,63) -453.57  (4894.51) -128.02  (2627.01)
Change at Month 29 (n=53,48) -1013.83  (3167.91) -187.08  (2524.52)
Change at Month 33 (n=45,40) -168.36  (5404.82) 434.35  (5134.98)
Change at Month 37 (n=40,33) -9.64  (5188.24) 171.21  (5081.43)
Change at Month 42 (n=30,26) -246.77  (4753.87) 928.35  (6494.32)
Change at Month 48 (n=16,16) -970.71  (4833.60) -450.69  (1487.78)
Change at Final Visit (n=109,110) -177.00  (3780.44) 296.35  (3823.59)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Eplerenone, Placebo
Comments Change from baseline at Month 5 :Mixed effect model of repeated measurements with covariates of the treatment, Week, interaction between treatment and week, baseline NYHA cohort (II, III/IV), baseline eGFR (30-<50 ml/min/1.73 m^2, >=50 ml/min/1.73 m^2) and baseline value.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Square Mean Difference
Estimated Value -364.65
Confidence Interval (2-Sided) 95%
-1863.06 to 1133.76
Parameter Dispersion
Type: Standard Error of the mean
Value: 763.83
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Eplerenone, Placebo
Comments Change from baseline at Month 9 : Mixed effect model of repeated measurements with covariates of the treatment, Week, interaction between treatment and week, baseline NYHA cohort (II, III/IV), baseline eGFR (30-<50 ml/min/1.73 m^2, >=50 ml/min/1.73 m^2) and baseline value.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Square Mean Difference
Estimated Value -247.14
Confidence Interval (2-Sided) 95%
-1642.43 to 1148.14
Parameter Dispersion
Type: Standard Error of the mean
Value: 711.26
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Eplerenone, Placebo
Comments Change from baseline at Month 13 : Mixed effect model of repeated measurements with covariates of the treatment, Week, interaction between treatment and week, baseline NYHA cohort (II, III/IV), baseline eGFR (30-<50 ml/min/1.73 m^2, >=50 ml/min/1.73 m^2) and baseline value.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Square Mean Difference
Estimated Value -370.14
Confidence Interval (2-Sided) 95%
-1742.51 to 1002.22
Parameter Dispersion
Type: Standard Error of the mean
Value: 699.58
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Eplerenone, Placebo
Comments Change from baseline at Month 17 : Mixed effect model of repeated measurements with covariates of the treatment, Week, interaction between treatment and week, baseline NYHA cohort (II, III/IV), baseline eGFR (30-<50 ml/min/1.73 m^2, >=50 ml/min/1.73 m^2) and baseline value.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Square Mean Difference
Estimated Value -664.09
Confidence Interval (2-Sided) 95%
-141189.93 to 139861.75
Parameter Dispersion
Type: Standard Error of the mean
Value: 11059.62
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Eplerenone, Placebo
Comments Change from baseline at Month 21 :Mixed effect model of repeated measurements with covariates of the treatment, Week, interaction between treatment and week, baseline NYHA cohort (II, III/IV), baseline eGFR (30-<50 ml/min/1.73 m^2, >=50 ml/min/1.73 m^2) and baseline value.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Square Mean Difference
Estimated Value -414.99
Confidence Interval (2-Sided) 95%
-39445.52 to 38615.54
Parameter Dispersion
Type: Standard Error of the mean
Value: 3071.77
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Eplerenone, Placebo
Comments Change from baseline at Month 25 : Mixed effect model of repeated measurements with covariates of the treatment, Week, interaction between treatment and week, baseline NYHA cohort (II, III/IV), baseline eGFR (30-<50 ml/min/1.73 m^2, >=50 ml/min/1.73 m^2) and baseline value.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Square Mean Difference
Estimated Value 23.86
Confidence Interval (2-Sided) 95%
-21649.89 to 21697.60
Parameter Dispersion
Type: Standard Error of the mean
Value: 10794.85
Estimation Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Eplerenone, Placebo
Comments Change from baseline at Month 29 : Mixed effect model of repeated measurements with covariates of the treatment, Week, interaction between treatment and week, baseline NYHA cohort (II, III/IV), baseline eGFR (30-<50 ml/min/1.73 m^2, >=50 ml/min/1.73 m^2) and baseline value.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Square Mean Difference
Estimated Value -245.23
Confidence Interval (2-Sided) 95%
-85358.69 to 84868.22
Parameter Dispersion
Type: Standard Error of the mean
Value: 6698.57
Estimation Comments [Not Specified]
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Eplerenone, Placebo
Comments Change from baseline at Month 33 : Mixed effect model of repeated measurements with covariates of the treatment, Week, interaction between treatment and week, baseline NYHA cohort (II, III/IV), baseline eGFR (30-<50 ml/min/1.73 m^2, >=50 ml/min/1.73 m^2) and baseline value.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Square Mean Difference
Estimated Value 170.49
Confidence Interval (2-Sided) 95%
-21375.69 to 21716.66
Parameter Dispersion
Type: Standard Error of the mean
Value: 10730.38
Estimation Comments [Not Specified]
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Eplerenone, Placebo
Comments Change from baseline at Month 37 : Mixed effect model of repeated measurements with covariates of the treatment, Week, interaction between treatment and week, baseline NYHA cohort (II, III/IV), baseline eGFR (30-<50 ml/min/1.73 m^2, >=50 ml/min/1.73 m^2) and baseline value.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Square Mean Difference
Estimated Value -58.77
Confidence Interval (2-Sided) 95%
-30160.25 to 30042.70
Parameter Dispersion
Type: Standard Error of the mean
Value: 12765.30
Estimation Comments [Not Specified]
Show Statistical Analysis 10 Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Eplerenone, Placebo
Comments Change from baseline at Month 42 : Mixed effect model of repeated measurements with covariates of the treatment, Week, interaction between treatment and week, baseline NYHA cohort (II, III/IV), baseline eGFR (30-<50 ml/min/1.73 m^2, >=50 ml/min/1.73 m^2) and baseline value.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Square Mean Difference
Estimated Value -212.25
Confidence Interval (2-Sided) 90%
-22723.82 to 22299.33
Parameter Dispersion
Type: Standard Error of the mean
Value: 11073.11
Estimation Comments [Not Specified]
Show Statistical Analysis 11 Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Eplerenone, Placebo
Comments Change from baseline at Month 48 : Mixed effect model of repeated measurements with covariates of the treatment, Week, interaction between treatment and week, baseline NYHA cohort (II, III/IV), baseline eGFR (30-<50 ml/min/1.73 m^2, >=50 ml/min/1.73 m^2) and baseline value.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Square Mean Difference
Estimated Value -80.16
Confidence Interval (2-Sided) 95%
-146026.28 to 145865.96
Parameter Dispersion
Type: Standard Error of the mean
Value: 11486.21
Estimation Comments [Not Specified]
Show Statistical Analysis 12 Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Eplerenone, Placebo
Comments Change from baseline at Month 13 : ANCOVA with treatment effect and covariates of the NYHA cohort (II, III/IV), baseline eGFR (30-<50 ml/min/1.73 m^2, >=50 ml/min/1.73 m^2) and baseline value.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Square Mean Difference
Estimated Value -187.72
Confidence Interval (2-Sided) 95%
-662.67 to 287.23
Parameter Dispersion
Type: Standard Error of the mean
Value: 240.96
Estimation Comments [Not Specified]
19.Secondary Outcome
Title Change From Baseline in Left Ventricular Ejection Fraction (LVEF) at Months 5, 9, 13, 17, 21, 25, 29, 33, 37, 42, 48 and Final Visit
Hide Description LVEF was calculated based on end-diastolic volume measured by two-dimensional echocardiography.
Time Frame Baseline, Months 5, 9, 13, 17, 21, 25, 29, 33, 37, 42, 48, Final Visit (up to Month 48)
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set included all randomized participants. Here, ‘n’ signifies those participants who were evaluable at specified time point for each arm, respectively.
Arm/Group Title Eplerenone Placebo
Hide Arm/Group Description:
Participants with eGFR >=50 mL/min/1.73m^2 received eplerenone 25 mg tablet once daily up to Week 4 and participants with eGFR 30 to < 50 mL/min/1.73m^2 received eplerenone 25 mg tablet every other day up to Week 4. From Week 4 onward, the dose of eplerenone was limited to 50 mg once daily for participants with eGFR >=50 mL/min/1.73 m^2 and 25 mg once daily for participants with eGFR 30 to <50 mL/min/1.73 m^2 up to Month 48.
Participants with eGFR >=50 mL/min/1.73m^2 received placebo matched with eplerenone tablet orally once daily from up to Week 4 and participants with eGFR 30 to <50 mL/min/1.73m^2 received placebo matched with eplerenone tablet every other day up to Week 4. From Week 4 onward, all participants received placebo matched with eplerenone tablet once daily up to Month 48.
Overall Number of Participants Analyzed 111 110
Mean (Standard Deviation)
Unit of Measure: percentage of LVEF
Baseline (n=111,110) 25.64  (4.95) 26.64  (3.97)
Change at Month 5 (n=105,106) 5.98  (8.87) 4.01  (7.59)
Change at Month 9 (n=99,104) 33.89  (10.64) 31.37  (9.19)
Change at Month 13 (n=94,101) 9.62  (9.70) 4.86  (10.13)
Change at Month 17 (n=81,82) 11.36  (11.45) 5.50  (10.74)
Change at Month 21 (n=72,73) 12.73  (12.04) 6.37  (11.88)
Change at Month 25 (n=63,64) 12.18  (12.18) 6.60  (10.94)
Change at Month 29 (n=53,48) 11.95  (12.28) 6.45  (12.83)
Change at Month 33 (n=45,39) 13.67  (13.94) 5.20  (10.19)
Change at Month 37 (n=40,33) 13.34  (14.59) 7.18  (10.49)
Change at Month 42 (n=30,26) 12.15  (14.38) 5.13  (10.36)
Change at Month 48 (n=16,16) 10.18  (16.02) 8.41  (11.51)
Change at Final Visit (n=109,110) 9.50  (12.03) 5.99  (11.04)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Eplerenone, Placebo
Comments Change from baseline at Month 5 : Mixed effect model of repeated measurements with covariates of the treatment, Week, interaction between treatment and week, baseline NYHA cohort (II, III/IV), baseline eGFR (30-<50 ml/min/1.73 m^2, >=50 ml/min/1.73 m^2) and baseline value.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Square Mean Difference
Estimated Value 1.71
Confidence Interval (2-Sided) 95%
-0.55 to 3.96
Parameter Dispersion
Type: Standard Error of the mean
Value: 1.14
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Eplerenone, Placebo
Comments Change from baseline at Month 9 : Mixed effect model of repeated measurements with covariates of the treatment, Week, interaction between treatment and week, baseline NYHA cohort (II, III/IV), baseline eGFR (30-<50 ml/min/1.73 m^2, >=50 ml/min/1.73 m^2) and baseline value.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Square Mean Difference
Estimated Value 2.74
Confidence Interval (2-Sided) 95%
0.07 to 5.42
Parameter Dispersion
Type: Standard Error of the mean
Value: 1.36
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Eplerenone, Placebo
Comments Change from baseline at Month 13 : Mixed effect model of repeated measurements with covariates of the treatment, Week, interaction between treatment and week, baseline NYHA cohort (II, III/IV), baseline eGFR (30-<50 ml/min/1.73 m^2, >=50 ml/min/1.73 m^2) and baseline value.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Square Mean Difference
Estimated Value 3.86
Confidence Interval (2-Sided) 95%
1.11 to 6.60
Parameter Dispersion
Type: Standard Error of the mean
Value: 1.39
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Eplerenone, Placebo
Comments Change from baseline at Month 17 : Mixed effect model of repeated measurements with covariates of the treatment, Week, interaction between treatment and week, baseline NYHA cohort (II, III/IV), baseline eGFR (30-<50 ml/min/1.73 m^2, >=50 ml/min/1.73 m^2) and baseline value.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Square Mean Difference
Estimated Value 4.86
Confidence Interval (2-Sided) 95%
1.81 to 7.90
Parameter Dispersion
Type: Standard Error of the mean
Value: 1.54
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Eplerenone, Placebo
Comments Change from baseline at Month 21 : Mixed effect model of repeated measurements with covariates of the treatment, Week, interaction between treatment and week, baseline NYHA cohort (II, III/IV), baseline eGFR (30-<50 ml/min/1.73 m^2, >=50 ml/min/1.73 m^2) and baseline value.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Square Mean Difference
Estimated Value 5.65
Confidence Interval (2-Sided) 95%
2.36 to 8.94
Parameter Dispersion
Type: Standard Error of the mean
Value: 1.67
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Eplerenone, Placebo
Comments Change from baseline at Month 25 :Mixed effect model of repeated measurements with covariates of the treatment, Week, interaction between treatment and week, baseline NYHA cohort (II, III/IV), baseline eGFR (30-<50 ml/min/1.73 m^2, >=50 ml/min/1.73 m^2) and baseline value.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Square Mean Difference
Estimated Value 3.44
Confidence Interval (2-Sided) 95%
0.12 to 6.75
Parameter Dispersion
Type: Standard Error of the mean
Value: 1.68
Estimation Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Eplerenone, Placebo
Comments Change from baseline at Month 29 : Mixed effect model of repeated measurements with covariates of the treatment, Week, interaction between treatment and week, baseline NYHA cohort (II, III/IV), baseline eGFR (30-<50 ml/min/1.73 m^2, >=50 ml/min/1.73 m^2) and baseline value.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Square Mean Difference
Estimated Value 3.60
Confidence Interval (2-Sided) 95%
-0.06 to 7.25
Parameter Dispersion
Type: Standard Error of the mean
Value: 1.85
Estimation Comments [Not Specified]
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Eplerenone, Placebo
Comments Change from baseline at Month 33 :Mixed effect model of repeated measurements with covariates of the treatment, Week, interaction between treatment and week, baseline NYHA cohort (II, III/IV), baseline eGFR (30-<50 ml/min/1.73 m^2, >=50 ml/min/1.73 m^2) and baseline value.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Square Mean Difference
Estimated Value 4.65
Confidence Interval (2-Sided) 95%
0.86 to 8.44
Parameter Dispersion
Type: Standard Error of the mean
Value: 1.92
Estimation Comments [Not Specified]
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Eplerenone, Placebo
Comments Change from baseline at Month 37 : Mixed effect model of repeated measurements with covariates of the treatment, Week, interaction between treatment and week, baseline NYHA cohort (II, III/IV), baseline eGFR (30-<50 ml/min/1.73 m^2, >=50 ml/min/1.73 m^2) and baseline value.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Square Mean Difference
Estimated Value 3.85
Confidence Interval (2-Sided) 95%
0.02 to 7.68
Parameter Dispersion
Type: Standard Error of the mean
Value: 1.94
Estimation Comments [Not Specified]
Show Statistical Analysis 10 Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Eplerenone, Placebo
Comments Change from baseline at Month 42 : Mixed effect model of repeated measurements with covariates of the treatment, Week, interaction between treatment and week, baseline NYHA cohort (II, III/IV), baseline eGFR (30-<50 ml/min/1.73 m^2, >=50 ml/min/1.73 m^2) and baseline value.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Square Mean Difference
Estimated Value 4.67
Confidence Interval (2-Sided) 90%
0.08 to 9.25
Parameter Dispersion
Type: Standard Error of the mean
Value: 2.31
Estimation Comments [Not Specified]
Show Statistical Analysis 11 Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Eplerenone, Placebo
Comments Change from baseline at Month 48 : Mixed effect model of repeated measurements with covariates of the treatment, Week, interaction between treatment and week, baseline NYHA cohort (II, III/IV), baseline eGFR (30-<50 ml/min/1.73 m^2, >=50 ml/min/1.73 m^2) and baseline value.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Square Mean Difference
Estimated Value 4.13
Confidence Interval (2-Sided) 95%
-1.82 to 10.07
Parameter Dispersion
Type: Standard Error of the mean
Value: 2.98
Estimation Comments [Not Specified]
Show Statistical Analysis 12 Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Eplerenone, Placebo
Comments Change from baseline at Month 13 : ANCOVA with treatment effect and covariates of the NYHA cohort (II, III/IV), baseline eGFR (30-<50 ml/min/1.73 m^2, >=50 ml/min/1.73 m^2) and baseline value.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Square Mean Difference
Estimated Value 3.18
Confidence Interval (2-Sided) 95%
0.56 to 5.80
Parameter Dispersion
Type: Standard Error of the mean
Value: 1.33
Estimation Comments [Not Specified]
20.Secondary Outcome
Title Change From Baseline in Urine Albumin-to-Creatinine Ratio at Months 5, 9, 13, 17, 21, 25, 29, 33, 37, 42, 48 and Final Visit
Hide Description [Not Specified]
Time Frame Baseline, Months 5, 9, 13, 17, 21, 25, 29, 33, 37, 42, 48, Final Visit (up to Month 48)
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set included all randomized participants. Here, ‘n’ signifies those participants who were evaluable at specified time point for each arm, respectively.
Arm/Group Title Eplerenone Placebo
Hide Arm/Group Description:
Participants with eGFR >=50 mL/min/1.73m^2 received eplerenone 25 mg tablet once daily up to Week 4 and participants with eGFR 30 to < 50 mL/min/1.73m^2 received eplerenone 25 mg tablet every other day up to Week 4. From Week 4 onward, the dose of eplerenone was limited to 50 mg once daily for participants with eGFR >=50 mL/min/1.73 m^2 and 25 mg once daily for participants with eGFR 30 to <50 mL/min/1.73 m^2 up to Month 48.
Participants with eGFR >=50 mL/min/1.73m^2 received placebo matched with eplerenone tablet orally once daily from up to Week 4 and participants with eGFR 30 to <50 mL/min/1.73m^2 received placebo matched with eplerenone tablet every other day up to Week 4. From Week 4 onward, all participants received placebo matched with eplerenone tablet once daily up to Month 48.
Overall Number of Participants Analyzed 111 110
Mean (Standard Deviation)
Unit of Measure: microgram per gram creatinine (mg/gCr)
Baseline (n=111,108) 169.82  (787.32) 154.93  (366.44)
Change at Month 5 (n=104,103) -21.14  (359.53) 46.23  (377.56)
Change at Month 9 (n=98,101) -11.10  (249.68) 23.79  (362.35)
Change at Month 13 (n=94,98) -41.56  (322.12) -19.04  (253.57)
Change at Month 17 (n=80,82) -13.66  (247.48) 79.28  (530.74)
Change at Month 21 (n=72,73) -63.65  (498.00) 28.84  (431.48)
Change at Month 25 (n=62,63) 17.17  (489.08) 30.08  (350.86)
Change at Month 29 (n=50,47) 18.51  (454.75) -4.58  (504.53)
Change at Month 33 (n=43,39) -47.07  (506.66) -3.38  (417.43)
Change at Month 37 (n=39,33) -80.21  (743.85) 34.20  (393.95)
Change at Month 42 (n=27,25) -162.18  (921.61) -29.95  (187.19)
Change at Month 48 (n=16,16) -303.19  (1211.28) -41.03  (113.70)
Change at Final Visit (n=109,110) -29.30  (597.07) -31.56  (271.71)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Eplerenone, Placebo
Comments Change from baseline at Month 5: Mixed effect model of repeated measurements with covariates of the treatment, Week, interaction between treatment and week, baseline NYHA cohort (II, III/IV), baseline eGFR (30-<50 ml/min/1.73 m^2, >=50 ml/min/1.73 m^2) and baseline value.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Square Mean Difference
Estimated Value -61.53
Confidence Interval (2-Sided) 95%
-186.44 to 63.37
Parameter Dispersion
Type: Standard Error of the mean
Value: 59.75
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Eplerenone, Placebo
Comments Change from baseline at Month 9 : Mixed effect model of repeated measurements with covariates of the treatment, Week, interaction between treatment and week, baseline NYHA cohort (II, III/IV), baseline eGFR (30-<50 ml/min/1.73 m^2, >=50 ml/min/1.73 m^2) and baseline value.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Square Mean Difference
Estimated Value -24.94
Confidence Interval (2-Sided) 95%
-131.27 to 81.39
Parameter Dispersion
Type: Standard Error of the mean
Value: 54.20
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Eplerenone, Placebo
Comments Change from baseline at Month 13 :Mixed effect model of repeated measurements with covariates of the treatment, Week, interaction between treatment and week, baseline NYHA cohort (II, III/IV), baseline eGFR (30-<50 ml/min/1.73 m^2, >=50 ml/min/1.73 m^2) and baseline value.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Square Mean Difference
Estimated Value -12.57
Confidence Interval (2-Sided) 95%
-97.28 to 72.13
Parameter Dispersion
Type: Standard Error of the mean
Value: 43.18
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Eplerenone, Placebo
Comments Change from baseline at Month 17 :Mixed effect model of repeated measurements with covariates of the treatment, Week, interaction between treatment and week, baseline NYHA cohort (II, III/IV), baseline eGFR (30-<50 ml/min/1.73 m^2, >=50 ml/min/1.73 m^2) and baseline value.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Square Mean Difference
Estimated Value -78.47
Confidence Interval (2-Sided) 95%
-221.25 to 64.31
Parameter Dispersion
Type: Standard Error of the mean
Value: 72.78
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Eplerenone, Placebo
Comments Change from baseline at Month 21 : Mixed effect model of repeated measurements with covariates of the treatment, Week, interaction between treatment and week, baseline NYHA cohort (II, III/IV), baseline eGFR (30-<50 ml/min/1.73 m^2, >=50 ml/min/1.73 m^2) and baseline value.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Square Mean Difference
Estimated Value -79.63
Confidence Interval (2-Sided) 95%
-211.88 to 52.63
Parameter Dispersion
Type: Standard Error of the mean
Value: 67.42
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Eplerenone, Placebo
Comments Change from baseline at Month 25 : Mixed effect model of repeated measurements with covariates of the treatment, Week, interaction between treatment and week, baseline NYHA cohort (II, III/IV), baseline eGFR (30-<50 ml/min/1.73 m^2, >=50 ml/min/1.73 m^2) and baseline value.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Square Mean Difference
Estimated Value 19.35
Confidence Interval (2-Sided) 95%
-230.01 to 268.71
Parameter Dispersion
Type: Standard Error of the mean
Value: 88.95
Estimation Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Eplerenone, Placebo
Comments Change from baseline at Month 29: Mixed effect model of repeated measurements with covariates of the treatment, Week, interaction between treatment and week, baseline NYHA cohort (II, III/IV), baseline eGFR (30-<50 ml/min/1.73 m^2, >=50 ml/min/1.73 m^2) and baseline value.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Square Mean Difference
Estimated Value -21.05
Confidence Interval (2-Sided) 95%
-194.21 to 152.11
Parameter Dispersion
Type: Standard Error of the mean
Value: 88.27
Estimation Comments [Not Specified]
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Eplerenone, Placebo
Comments Change from baseline at Month 33: Mixed effect model of repeated measurements with covariates of the treatment, Week, interaction between treatment and week, baseline NYHA cohort (II, III/IV), baseline eGFR (30-<50 ml/min/1.73 m^2, >=50 ml/min/1.73 m^2) and baseline value.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Square Mean Difference
Estimated Value -40.79
Confidence Interval (2-Sided) 95%
-197.55 to 115.97
Parameter Dispersion
Type: Standard Error of the mean
Value: 79.91
Estimation Comments [Not Specified]
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Eplerenone, Placebo
Comments Change from baseline at Month 37 : Mixed effect model of repeated measurements with covariates of the treatment, Week, interaction between treatment and week, baseline NYHA cohort (II, III/IV), baseline eGFR (30-<50 ml/min/1.73 m^2, >=50 ml/min/1.73 m^2) and baseline value.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Square Mean Difference
Estimated Value -44.48
Confidence Interval (2-Sided) 95%
-247.11 to 158.15
Parameter Dispersion
Type: Standard Error of the mean
Value: 103.29
Estimation Comments [Not Specified]
Show Statistical Analysis 10 Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Eplerenone, Placebo
Comments Change from baseline at Month 42 : Mixed effect model of repeated measurements with covariates of the treatment, Week, interaction between treatment and week, baseline NYHA cohort (II, III/IV), baseline eGFR (30-<50 ml/min/1.73 m^2, >=50 ml/min/1.73 m^2) and baseline value.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Square Mean Difference
Estimated Value -27.69
Confidence Interval (2-Sided) 90%
-238.31 to 182.93
Parameter Dispersion
Type: Standard Error of the mean
Value: 107.06
Estimation Comments [Not Specified]
Show Statistical Analysis 11 Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Eplerenone, Placebo
Comments Change from baseline at Month 48: Mixed effect model of repeated measurements with covariates of the treatment, Week, interaction between treatment and week, baseline NYHA cohort (II, III/IV), baseline eGFR (30-<50 ml/min/1.73 m^2, >=50 ml/min/1.73 m^2) and baseline value.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Square Mean Difference
Estimated Value -31.46
Confidence Interval (2-Sided) 95%
-221.17 to 158.24
Parameter Dispersion
Type: Standard Error of the mean
Value: 96.48
Estimation Comments [Not Specified]
Show Statistical Analysis 12 Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Eplerenone, Placebo
Comments Change from baseline at Month 13 :ANCOVA with treatment effect and covariates of the NYHA cohort (II, III/IV), baseline eGFR (30-<50 ml/min/1.73 m^2, >=50 ml/min/1.73 m^2) and baseline value.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Square Mean Difference
Estimated Value -2.04
Confidence Interval (2-Sided) 95%
-58.91 to 54.83
Parameter Dispersion
Type: Standard Error of the mean
Value: 28.85
Estimation Comments [Not Specified]
21.Secondary Outcome
Title Number of Participants With Change From Baseline in New York Heart Association (NYHA) Classification at Weeks 1, 4, Months 2, 3, 4, 5, 9, 13, 17 21, 25, 29, 33, 37, 42, 48 and Final Visit
Hide Description NYHA: classified as ‘class I’ (participants with cardiac disease but without resulting limitations of physical activity), ‘class II’ (participants with cardiac disease resulting in slight limitation of physical activity), ‘class III’ (participants with cardiac disease resulting in marked limitation of physical activity), ‘class IV’ (participants with cardiac disease resulting in inability to carry on any physical activity without discomfort). Participants with change from baseline were classified as ‘improved' (positive change), ‘no change’ or ‘worsened' (negative change).
Time Frame Baseline, Weeks 1, 4, Months 2, 3, 4, 5, 9, 13, 17, 21, 25, 29, 33, 37, 42, 48 and Final Visit (up to Month 48)
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set included all randomized participants. Here, ‘n’ signifies those participants who were evaluable at specified time point for each arm, respectively.
Arm/Group Title Eplerenone Placebo
Hide Arm/Group Description:
Participants with eGFR >=50 mL/min/1.73m^2 received eplerenone 25 mg tablet once daily up to Week 4 and participants with eGFR 30 to < 50 mL/min/1.73m^2 received eplerenone 25 mg tablet every other day up to Week 4. From Week 4 onward, the dose of eplerenone was limited to 50 mg once daily for participants with eGFR >=50 mL/min/1.73 m^2 and 25 mg once daily for participants with eGFR 30 to <50 mL/min/1.73 m^2 up to Month 48.
Participants with eGFR >=50 mL/min/1.73m^2 received placebo matched with eplerenone tablet orally once daily from up to Week 4 and participants with eGFR 30 to <50 mL/min/1.73m^2 received placebo matched with eplerenone tablet every other day up to Week 4. From Week 4 onward, all participants received placebo matched with eplerenone tablet once daily up to Month 48.
Overall Number of Participants Analyzed 111 110
Measure Type: Number
Unit of Measure: participants
Week 1 (n=111, 110) : Improved 4 2
Week 1 (n=111, 110) : Unchanged 107 107
Week 1 (n=111, 110) : Worse 0 1
Week 4 (n=111, 108) : Improved 10 14
Week 4 (n=111, 108) : Unchanged 101 92
Week 4 (n=111, 108) : Worse 0 2
Month 2 (n=109, 109) : Improved 15 14
Month 2 (n=109, 109) : Unchanged 94 95
Month 2 (n=109, 109) : Worse 0 0
Month 3 (n=106, 107) : Improved 18 16
Month 3 (n=106, 107) : Unchanged 88 91
Month 3 (n=106, 107) : Worse 0 0
Month 4 (n=106, 106) : Improved 22 20
Month 4 (n=106, 106) : Unchanged 82 86
Month 4 (n=106, 106) : Worse 2 0
Month 5 (n=104, 106) : Improved 24 22
Month 5 (n=104, 106) : Unchanged 76 83
Month 5 (n=104, 106) : Worse 4 1
Month 9 (n=99, 105) : Improved 27 20
Month 9 (n=99, 105) : Unchanged 71 81
Month 9 (n=99, 105) : Worse 1 4
Month 13 (n=94, 102) : Improved 31 19
Month 13 (n=94, 102) : Unchanged 62 82
Month 13 (n=94, 102) : Worse 1 1
Month 17 (n=81, 82) : Improved 25 18
Month 17 (n=81, 82) : Unchanged 55 61
Month 17 (n=81, 82) : Worse 1 3
Month 21 (n=72, 73) : Improved 21 19
Month 21 (n=72, 73) : Unchanged 50 51
Month 21 (n=72, 73) : Worse 1 3
Month 25 (n=63, 64) : Improved 23 14
Month 25 (n=63, 64) : Unchanged 38 48
Month 25 (n=63, 64) : Worse 2 2
Month 29 (n=53, 48) : Improved 17 12
Month 29 (n=53, 48) : Unchanged 36 35
Month 29 (n=53, 48) : Worse 0 1
Month 33 (n=46, 39) : Improved 14 10
Month 33 (n=46, 39) : Unchanged 31 27
Month 33 (n=46, 39) : Worse 1 2
Month 37 (n=40, 33) : Improved 12 10
Month 37 (n=40, 33) : Unchanged 28 22
Month 37 (n=40, 33) : Worse 0 1
Month 42 (n=30, 26) : Improved 7 7
Month 42 (n=30, 26) : Unchanged 23 18
Month 42 (n=30, 26) : Worse 0 1
Month 48 (n=16, 16) : Improved 2 6
Month 48 (n=16, 16) : Unchanged 14 9
Month 48 (n=16, 16) : Worse 0 1
Final Visit (n=111, 110) : Improved 25 26
Final Visit (n=111, 110) : Unchanged 80 80
Final Visit (n=111, 110) : Worse 6 4
22.Secondary Outcome
Title Change From Baseline in Specific Activity Scale (SAS) Score at Week 4, Months 2, 3, 4, 5, 9, 13, 17 21, 25, 29, 33, 37, 42, 48 and Final Visit
Hide Description Specific activity scale was estimated by pre-specified questionnaire (for different activities) to assess the exercise capability of the participants. Answers provided by participants were transformed in terms of number of metabolic equivalents (METs).1 MET was defined as the amount of oxygen consumed while sitting at rest and is equal to 3.5 ml oxygen per kg body weight* minute. Scale ranged from 1 (less than (<) 2 METs) = lowest level of exercise tolerance to 6 (>=8METs) = highest level of tolerance and higher score indicated more tolerance.
Time Frame Baseline, Week 4, Months 5, 9, 13, 17, 21, 25, 29, 33, 37, 42, 48, Final Visit (up to Month 48)
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set included all randomized participants. Here, ‘n’ signifies those participants who were evaluable at specified time point for each arm, respectively.
Arm/Group Title Eplerenone Placebo
Hide Arm/Group Description:
Participants with eGFR >=50 mL/min/1.73m^2 received eplerenone 25 mg tablet once daily up to Week 4 and participants with eGFR 30 to < 50 mL/min/1.73m^2 received eplerenone 25 mg tablet every other day up to Week 4. From Week 4 onward, the dose of eplerenone was limited to 50 mg once daily for participants with eGFR >=50 mL/min/1.73 m^2 and 25 mg once daily for participants with eGFR 30 to <50 mL/min/1.73 m^2 up to Month 48.
Participants with eGFR >=50 mL/min/1.73m^2 received placebo matched with eplerenone tablet orally once daily from up to Week 4 and participants with eGFR 30 to <50 mL/min/1.73m^2 received placebo matched with eplerenone tablet every other day up to Week 4. From Week 4 onward, all participants received placebo matched with eplerenone tablet once daily up to Month 48.
Overall Number of Participants Analyzed 111 110
Mean (Standard Deviation)
Unit of Measure: metabolic equivalents (METs)
Baseline (n=111,110) 4.85  (1.51) 4.89  (1.54)
Change at Week 4 (n= 111,108) 0.15  (0.79) 0.27  (1.08)
Change at Month 5 (n=104,106) 0.46  (1.15) 0.33  (1.19)
Change at Month 9 (n=99,104) 0.41  (1.16) 0.37  (1.39)
Change at Month 13 (n=94,102) 0.52  (1.18) 0.44  (1.45)
Change at Month 17 (n=81,82) 0.46  (1.38) 0.47  (1.81)
Change at Month 21 (n=72,73) 0.34  (1.33) 0.59  (1.64)
Change at Month 25 (n=63,63) 0.48  (1.08) 0.63  (1.72)
Change at Month 29 (n=53,48) 0.42  (1.14) 0.65  (1.56)
Change at Month 33 (n=46,40) 0.37  (1.28) 0.51  (1.80)
Change at Month 37 (n=40,33) 0.53  (1.47) 0.68  (1.39)
Change at Month 42 (n=30,26) 0.39  (1.70) 0.47  (1.83)
Change at Month 48 (n=16,16) -0.13  (1.57) 0.64  (1.59)
Change at Final Visit (n=111,110) 0.14  (1.56) 0.25  (1.65)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Eplerenone, Placebo
Comments Change from baseline at Month 5 : Mixed effect model of repeated measurements with covariates of the treatment, Week, interaction between treatment and week, baseline NYHA cohort (II, III/IV), baseline eGFR (30-<50 ml/min/1.73 m^2, >=50 ml/min/1.73 m^2) and baseline value.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Square Mean Difference
Estimated Value 0.08
Confidence Interval (2-Sided) 95%
-0.21 to 0.37
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.15
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Eplerenone, Placebo
Comments Change from baseline at Month 9 :Mixed effect model of repeated measurements with covariates of the treatment, Week, interaction between treatment and week, baseline NYHA cohort (II, III/IV), baseline eGFR (30-<50 ml/min/1.73 m^2, >=50 ml/min/1.73 m^2) and baseline value.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Square Mean Difference
Estimated Value -0.02
Confidence Interval (2-Sided) 95%
-0.34 to 0.30
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.16
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Eplerenone, Placebo
Comments Change from baseline at Month 13: Mixed effect model of repeated measurements with covariates of the treatment, Week, interaction between treatment and week, baseline NYHA cohort (II, III/IV), baseline eGFR (30-<50 ml/min/1.73 m^2, >=50 ml/min/1.73 m^2) and baseline value.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Square Mean Difference
Estimated Value 0.06
Confidence Interval (2-Sided) 95%
-0.27 to 0.39
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.17
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Eplerenone, Placebo
Comments Change from baseline at Month 17 : Mixed effect model of repeated measurements with covariates of the treatment, Week, interaction between treatment and week, baseline NYHA cohort (II, III/IV), baseline eGFR (30-<50 ml/min/1.73 m^2, >=50 ml/min/1.73 m^2) and baseline value.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Square Mean Difference
Estimated Value 0.02
Confidence Interval (2-Sided) 95%
-0.41 to 0.45
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.22
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Eplerenone, Placebo
Comments Change from baseline at Month 21 : Mixed effect model of repeated measurements with covariates of the treatment, Week, interaction between treatment and week, baseline NYHA cohort (II, III/IV), baseline eGFR (30-<50 ml/min/1.73 m^2, >=50 ml/min/1.73 m^2) and baseline value.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Square Mean Difference
Estimated Value -0.16
Confidence Interval (2-Sided) 95%
-0.56 to 0.24
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.20
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Eplerenone, Placebo
Comments Change from baseline at Month 25 : Mixed effect model of repeated measurements with covariates of the treatment, Week, interaction between treatment and week, baseline NYHA cohort (II, III/IV), baseline eGFR (30-<50 ml/min/1.73 m^2, >=50 ml/min/1.73 m^2) and baseline value.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Square Mean Difference
Estimated Value -0.15
Confidence Interval (2-Sided) 95%
-0.55 to 0.25
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.20
Estimation Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Eplerenone, Placebo
Comments Change from baseline at Month 29 : Mixed effect model of repeated measurements with covariates of the treatment, Week, interaction between treatment and week, baseline NYHA cohort (II, III/IV), baseline eGFR (30-<50 ml/min/1.73 m^2, >=50 ml/min/1.73 m^2) and baseline value.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Square Mean Difference
Estimated Value -0.09
Confidence Interval (2-Sided) 95%
-0.49 to 0.31
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.20
Estimation Comments [Not Specified]
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Eplerenone, Placebo
Comments Change from baseline at Month 33 : Mixed effect model of repeated measurements with covariates of the treatment, Week, interaction between treatment and week, baseline NYHA cohort (II, III/IV), baseline eGFR (30-<50 ml/min/1.73 m^2, >=50 ml/min/1.73 m^2) and baseline value.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Square Mean Difference
Estimated Value -0.07
Confidence Interval (2-Sided) 95%
-0.57 to 0.44
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.26
Estimation Comments [Not Specified]
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Eplerenone, Placebo
Comments Change from baseline at Month 37 :Mixed effect model of repeated measurements with covariates of the treatment, Week, interaction between treatment and week, baseline NYHA cohort (II, III/IV), baseline eGFR (30-<50 ml/min/1.73 m^2, >=50 ml/min/1.73 m^2) and baseline value.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Square Mean Difference
Estimated Value 0.02
Confidence Interval (2-Sided) 95%
-0.50 to 0.54
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.26
Estimation Comments [Not Specified]
Show Statistical Analysis 10 Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Eplerenone, Placebo
Comments Change from baseline at Month 42 :Mixed effect model of repeated measurements with covariates of the treatment, Week, interaction between treatment and week, baseline NYHA cohort (II, III/IV), baseline eGFR (30-<50 ml/min/1.73 m^2, >=50 ml/min/1.73 m^2) and baseline value.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Square Mean Difference
Estimated Value 0.20
Confidence Interval (2-Sided) 90%
-0.44 to 0.83
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.32
Estimation Comments [Not Specified]
Show Statistical Analysis 11 Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Eplerenone, Placebo
Comments Change from baseline at Month 48 : Mixed effect model of repeated measurements with covariates of the treatment, Week, interaction between treatment and week, baseline NYHA cohort (II, III/IV), baseline eGFR (30-<50 ml/min/1.73 m^2, >=50 ml/min/1.73 m^2) and baseline value.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Square Mean Difference
Estimated Value 0.13
Confidence Interval (2-Sided) 95%
-0.63 to 0.89
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.38
Estimation Comments [Not Specified]
Show Statistical Analysis 12 Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Eplerenone, Placebo
Comments Change from baseline at Week 4 : Mixed effect model of repeated measurements with covariates of the treatment, Week, interaction between treatment and week, baseline NYHA cohort (II, III/IV), baseline eGFR (30-<50 ml/min/1.73 m^2, >=50 ml/min/1.73 m^2) and baseline value.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Square Mean Difference
Estimated Value -0.13
Confidence Interval (2-Sided) 95%
-0.36 to 0.11
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.12
Estimation Comments [Not Specified]
Time Frame [Not Specified]
Adverse Event Reporting Description The same event may appear as both an adverse event and an serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non serious event during the study.
 
Arm/Group Title Eplerenone Placebo
Hide Arm/Group Description Participants with eGFR >=50 mL/min/1.73m^2 received eplerenone 25 mg tablet once daily up to Week 4 and participants with eGFR 30 to < 50 mL/min/1.73m^2 received eplerenone 25 mg tablet every other day up to Week 4. From Week 4 onward, the dose of eplerenone was limited to 50 mg once daily for participants with eGFR >=50 mL/min/1.73 m^2 and 25 mg once daily for participants with eGFR 30 to <50 mL/min/1.73 m^2 up to Month 48. Participants with eGFR >=50 mL/min/1.73m^2 received placebo matched with eplerenone tablet orally once daily from up to Week 4 and participants with eGFR 30 to <50 mL/min/1.73m^2 received placebo matched with eplerenone tablet every other day up to Week 4. From Week 4 onward, all participants received placebo matched with eplerenone tablet once daily up to Month 48.
All-Cause Mortality
Eplerenone Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Eplerenone Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   52/111 (46.85%)   65/110 (59.09%) 
Blood and lymphatic system disorders     
Anaemia * 1  1/111 (0.90%)  0/110 (0.00%) 
Bone marrow failure * 1  1/111 (0.90%)  0/110 (0.00%) 
Disseminated intravascular coagulation * 1  2/111 (1.80%)  0/110 (0.00%) 
Haemorrhagic diathesis * 1  1/111 (0.90%)  0/110 (0.00%) 
Cardiac disorders     
Angina pectoris * 1  2/111 (1.80%)  4/110 (3.64%) 
Angina unstable * 1  0/111 (0.00%)  1/110 (0.91%) 
Arrhythmia * 1  0/111 (0.00%)  1/110 (0.91%) 
Atrial fibrillation * 1  1/111 (0.90%)  2/110 (1.82%) 
Atrial flutter * 1  0/111 (0.00%)  1/110 (0.91%) 
Bradycardia * 1  0/111 (0.00%)  1/110 (0.91%) 
Cardiac failure * 1  27/111 (24.32%)  31/110 (28.18%) 
Cardiac failure acute * 1  1/111 (0.90%)  0/110 (0.00%) 
Cardiac failure chronic * 1  2/111 (1.80%)  1/110 (0.91%) 
Cardiac failure congestive * 1  2/111 (1.80%)  2/110 (1.82%) 
Cardiac sarcoidosis * 1  1/111 (0.90%)  0/110 (0.00%) 
Cardio-respiratory arrest * 1  1/111 (0.90%)  0/110 (0.00%) 
Congestive cardiomyopathy * 1  1/111 (0.90%)  0/110 (0.00%) 
Coronary artery stenosis * 1  2/111 (1.80%)  2/110 (1.82%) 
Intracardiac thrombus * 1  0/111 (0.00%)  1/110 (0.91%) 
Mitral valve incompetence * 1  0/111 (0.00%)  1/110 (0.91%) 
Myocardial infarction * 1  1/111 (0.90%)  0/110 (0.00%) 
Ventricular fibrillation * 1  1/111 (0.90%)  1/110 (0.91%) 
Ventricular tachycardia * 1  5/111 (4.50%)  3/110 (2.73%) 
Eye disorders     
Cataract * 1  2/111 (1.80%)  3/110 (2.73%) 
Retinal detachment * 1  1/111 (0.90%)  0/110 (0.00%) 
Gastrointestinal disorders     
Abdominal pain upper * 1  1/111 (0.90%)  0/110 (0.00%) 
Gastric ulcer * 1  1/111 (0.90%)  0/110 (0.00%) 
Gastric ulcer haemorrhage * 1  0/111 (0.00%)  1/110 (0.91%) 
Gastrointestinal haemorrhage * 1  1/111 (0.90%)  2/110 (1.82%) 
Inguinal hernia * 1  0/111 (0.00%)  1/110 (0.91%) 
Large intestine polyp * 1  1/111 (0.90%)  0/110 (0.00%) 
Pancreatitis acute * 1  1/111 (0.90%)  0/110 (0.00%) 
Protein-losing gastroenteropathy * 1  1/111 (0.90%)  0/110 (0.00%) 
General disorders     
Chest discomfort * 1  1/111 (0.90%)  1/110 (0.91%) 
Chest pain * 1  0/111 (0.00%)  1/110 (0.91%) 
Malaise * 1  0/111 (0.00%)  1/110 (0.91%) 
Multi-organ failure * 1  1/111 (0.90%)  0/110 (0.00%) 
Sudden cardiac death * 1  1/111 (0.90%)  2/110 (1.82%) 
Sudden death * 1  1/111 (0.90%)  0/110 (0.00%) 
Hepatobiliary disorders     
Cholecystitis * 1  0/111 (0.00%)  3/110 (2.73%) 
Infections and infestations     
Appendicitis * 1  0/111 (0.00%)  1/110 (0.91%) 
Bronchitis * 1  1/111 (0.90%)  0/110 (0.00%) 
Bronchopneumonia * 1  1/111 (0.90%)  0/110 (0.00%) 
Cellulitis * 1  0/111 (0.00%)  1/110 (0.91%) 
Device related infection * 1  0/111 (0.00%)  2/110 (1.82%) 
Disseminated tuberculosis * 1  0/111 (0.00%)  1/110 (0.91%) 
Endocarditis bacterial * 1  0/111 (0.00%)  1/110 (0.91%) 
Gastroenteritis * 1  2/111 (1.80%)  1/110 (0.91%) 
Influenza * 1  1/111 (0.90%)  0/110 (0.00%) 
Peritonitis * 1  1/111 (0.90%)  0/110 (0.00%) 
Pneumonia * 1  4/111 (3.60%)  5/110 (4.55%) 
Pneumonia bacterial * 1  0/111 (0.00%)  2/110 (1.82%) 
Pneumonia staphylococcal * 1  1/111 (0.90%)  0/110 (0.00%) 
Pyelonephritis * 1  0/111 (0.00%)  1/110 (0.91%) 
Sepsis * 1  3/111 (2.70%)  0/110 (0.00%) 
Injury, poisoning and procedural complications     
Brain contusion * 1  0/111 (0.00%)  1/110 (0.91%) 
Femur fracture * 1  0/111 (0.00%)  1/110 (0.91%) 
Muscle injury * 1  1/111 (0.90%)  0/110 (0.00%) 
Postoperative ileus * 1  1/111 (0.90%)  0/110 (0.00%) 
Road traffic accident * 1  0/111 (0.00%)  1/110 (0.91%) 
Spinal compression fracture * 1  2/111 (1.80%)  0/110 (0.00%) 
Spinal cord injury cervical * 1  0/111 (0.00%)  1/110 (0.91%) 
Investigations     
Blood pressure decreased * 1  0/111 (0.00%)  1/110 (0.91%) 
Metabolism and nutrition disorders     
Dehydration * 1  1/111 (0.90%)  0/110 (0.00%) 
Diabetes mellitus * 1  1/111 (0.90%)  2/110 (1.82%) 
Fluid retention * 1  1/111 (0.90%)  0/110 (0.00%) 
Metabolic acidosis * 1  0/111 (0.00%)  1/110 (0.91%) 
Musculoskeletal and connective tissue disorders     
Arthritis reactive * 1  1/111 (0.90%)  0/110 (0.00%) 
Lumbar spinal stenosis * 1  1/111 (0.90%)  0/110 (0.00%) 
Muscle haemorrhage * 1  0/111 (0.00%)  1/110 (0.91%) 
Rhabdomyolysis * 1  1/111 (0.90%)  0/110 (0.00%) 
Spinal column stenosis * 1  1/111 (0.90%)  0/110 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Bladder cancer * 1  1/111 (0.90%)  0/110 (0.00%) 
Colon adenoma * 1  0/111 (0.00%)  1/110 (0.91%) 
Colon cancer * 1  1/111 (0.90%)  0/110 (0.00%) 
Gastric cancer * 1  1/111 (0.90%)  0/110 (0.00%) 
Lung neoplasm malignant * 1  2/111 (1.80%)  2/110 (1.82%) 
Metastases to bone * 1  0/111 (0.00%)  1/110 (0.91%) 
Oesophageal carcinoma recurrent * 1  0/111 (0.00%)  1/110 (0.91%) 
Prostate cancer * 1  0/111 (0.00%)  1/110 (0.91%) 
Prostate cancer metastatic * 1  0/111 (0.00%)  1/110 (0.91%) 
Rectal cancer * 1  0/111 (0.00%)  1/110 (0.91%) 
Thyroid cancer metastatic * 1  1/111 (0.90%)  0/110 (0.00%) 
Nervous system disorders     
Cerebellar infarction * 1  0/111 (0.00%)  1/110 (0.91%) 
Cerebral haemorrhage * 1  0/111 (0.00%)  1/110 (0.91%) 
Cerebral infarction * 1  3/111 (2.70%)  2/110 (1.82%) 
Cerebrovascular accident * 1  1/111 (0.90%)  0/110 (0.00%) 
Cervical myelopathy * 1  1/111 (0.90%)  0/110 (0.00%) 
Loss of consciousness * 1  0/111 (0.00%)  1/110 (0.91%) 
Spondylitic myelopathy * 1  0/111 (0.00%)  1/110 (0.91%) 
Subarachnoid haemorrhage * 1  1/111 (0.90%)  0/110 (0.00%) 
Syncope * 1  0/111 (0.00%)  1/110 (0.91%) 
Transient ischaemic attack * 1  0/111 (0.00%)  1/110 (0.91%) 
Renal and urinary disorders     
Acute kidney injury * 1  0/111 (0.00%)  1/110 (0.91%) 
Chronic kidney disease * 1  1/111 (0.90%)  0/110 (0.00%) 
Renal failure * 1  2/111 (1.80%)  1/110 (0.91%) 
Renal impairment * 1  0/111 (0.00%)  3/110 (2.73%) 
Respiratory, thoracic and mediastinal disorders     
Chronic obstructive pulmonary disease * 1  1/111 (0.90%)  0/110 (0.00%) 
Organising pneumonia * 1  0/111 (0.00%)  1/110 (0.91%) 
Pleurisy * 1  1/111 (0.90%)  0/110 (0.00%) 
Pneumonia aspiration * 1  0/111 (0.00%)  1/110 (0.91%) 
Pneumothorax * 1  1/111 (0.90%)  0/110 (0.00%) 
Sleep apnoea syndrome * 1  0/111 (0.00%)  1/110 (0.91%) 
Upper respiratory tract inflammation * 1  0/111 (0.00%)  1/110 (0.91%) 
Vascular disorders     
Extremity necrosis * 1  1/111 (0.90%)  0/110 (0.00%) 
Haemorrhage * 1  1/111 (0.90%)  0/110 (0.00%) 
Hypotension * 1  0/111 (0.00%)  1/110 (0.91%) 
Peripheral arterial occlusive disease * 1  0/111 (0.00%)  2/110 (1.82%) 
Peripheral artery aneurysm * 1  1/111 (0.90%)  0/110 (0.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 18.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Eplerenone Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   89/111 (80.18%)   87/110 (79.09%) 
Blood and lymphatic system disorders     
Anaemia * 1  7/111 (6.31%)  6/110 (5.45%) 
Cardiac disorders     
Cardiac failure * 1  21/111 (18.92%)  32/110 (29.09%) 
Gastrointestinal disorders     
Chronic gastritis * 1  6/111 (5.41%)  3/110 (2.73%) 
Constipation * 1  8/111 (7.21%)  18/110 (16.36%) 
Diarrhoea * 1  7/111 (6.31%)  10/110 (9.09%) 
Haemorrhoids * 1  2/111 (1.80%)  6/110 (5.45%) 
Hepatobiliary disorders     
Hepatic function abnormal * 1  4/111 (3.60%)  7/110 (6.36%) 
Infections and infestations     
Bronchitis * 1  6/111 (5.41%)  8/110 (7.27%) 
Conjunctivitis * 1  7/111 (6.31%)  5/110 (4.55%) 
Nasopharyngitis * 1  37/111 (33.33%)  40/110 (36.36%) 
Upper respiratory tract infection * 1  5/111 (4.50%)  6/110 (5.45%) 
Injury, poisoning and procedural complications     
Contusion * 1  12/111 (10.81%)  5/110 (4.55%) 
Fall * 1  20/111 (18.02%)  20/110 (18.18%) 
Investigations     
Blood pressure decreased * 1  6/111 (5.41%)  4/110 (3.64%) 
Metabolism and nutrition disorders     
Dehydration * 1  10/111 (9.01%)  5/110 (4.55%) 
Diabetes mellitus * 1  7/111 (6.31%)  7/110 (6.36%) 
Hyperkalaemia * 1  8/111 (7.21%)  6/110 (5.45%) 
Hyperuricaemia * 1  11/111 (9.91%)  14/110 (12.73%) 
Hypokalaemia * 1  2/111 (1.80%)  11/110 (10.00%) 
Musculoskeletal and connective tissue disorders     
Back pain * 1  11/111 (9.91%)  9/110 (8.18%) 
Pain in extremity * 1  6/111 (5.41%)  3/110 (2.73%) 
Nervous system disorders     
Dizziness * 1  8/111 (7.21%)  5/110 (4.55%) 
Renal and urinary disorders     
Renal impairment * 1  5/111 (4.50%)  7/110 (6.36%) 
Reproductive system and breast disorders     
Atrophic vulvovaginitis * 1 [1]  0/26 (0.00%)  1/19 (5.26%) 
Respiratory, thoracic and mediastinal disorders     
Cough * 1  8/111 (7.21%)  9/110 (8.18%) 
Sleep apnoea syndrome * 1  0/111 (0.00%)  6/110 (5.45%) 
Upper respiratory tract inflammation * 1  1/111 (0.90%)  8/110 (7.27%) 
Skin and subcutaneous tissue disorders     
Eczema * 1  4/111 (3.60%)  6/110 (5.45%) 
Vascular disorders     
Hypertension * 1  9/111 (8.11%)  3/110 (2.73%) 
Hypotension * 1  4/111 (3.60%)  6/110 (5.45%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 18.0
[1]
As the event is gender specific, only female participants were evaluated.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Pfizer ClinicalTrials.gov Call Center
Organization: Pfizer, Inc.
Phone: 1-800-718-1021
EMail: ClinicalTrials.gov_Inquiries@pfizer.com
Layout table for additonal information
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT01115855     History of Changes
Other Study ID Numbers: A6141114
First Submitted: April 30, 2010
First Posted: May 4, 2010
Results First Submitted: September 5, 2016
Results First Posted: October 27, 2016
Last Update Posted: October 27, 2016