Clinical Study Of Eplerenone In Japanese Patients With Chronic Heart Failure

Heart Failure Clinical Trial

— J-EMPHASIS-HF  

Official title:

The Effect Of Eplerenone Versus Placebo On Cardiovascular Mortality And Heart Failure Hospitalization In Japanese Subjects With Chronic Heart Failure

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01115855
• Other study ID #: A6141114
• Status: Completed
• Phase: Phase 3
• Start date: July 2010
• Est. completion date: September 2015

Study information

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

Clinical Trial Summary

A study to compare the efficacy and safety of eplerenone in Japanese chronic heart failure patients with placebo.

Description:

The aim of this study was to show consistency with the EMPHASIS-HF trial (NCT00232180), which was defined as a HR of the primary endpoint of below 1.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 221
• Est. completion date: September 2015
• Est. primary completion date: September 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 55 Years and older

Eligibility

Inclusion Criteria:

• Japanese chronic systolic heart failure patients with LVEF =<30% by echocardiography and NYHA II or more

• Patients who receive standard therapy (Angiotensin converting enzyme inhibitors, angiotensin receptor blockers, beta-blocker or diuretic)

Exclusion Criteria:

• Patients with a myocardial infarction, stroke, cardiac surgery or percutaneous coronary intervention within 30 days prior to randomization.

• Patients with serum potassium >5.0 mmol/L or eGFR <30 ml/min/1.73 m2.

Related Conditions & MeSH terms

• Heart Failure

Intervention

Drug:
• Eplerenone
Eplerenone 25 mg once every other day, 25mg once daily or 50 mg once daily
• Placebo
Placebo once daily or every once daily

Locations

Country	Name	City	State
Japan	Asahi General Hospital	Asahi	Chiba
Japan	Juntendo University Hospital	Bunkyo-ku	Tokyo
Japan	National Hospital Organization Chiba Medical Center	Chiba-shi	Chiba-ken
Japan	Mitsui Memorial Hospital	Chiyoda-Ku	Tokyo
Japan	University of Yamanashi Hospital	Chuo	Yamanashi
Japan	Fujisawa City Hospital	Fujisawa	Kanagawa
Japan	Hamanomachi Hospital	Fukuoka
Japan	Kyushu University Hospital	Fukuoka-shi	Fukuoka-ken
Japan	Fukushima Medical University Hospital	Fukushima
Japan	Gifu Prefectural General Medical Center	Gifu
Japan	Hakodate City Hospital	Hakodate	Hokkaido
Japan	National Hospital Organization Hakodate National Hospital	Hakodate-shi	Hokkai-do
Japan	Hamamatsu Rosai Hospital	Hamamatsu-shi	Shizuoka
Japan	Hyogo Brain and Heart Center	Himeji	Hyogo
Japan	Japanease Red Cross Society Himeji Hospital	Himeji	Hyogo
Japan	Aso Iizuka Hospital	Iizuka-shi	Fukuoka-ken
Japan	Nippon Medical School Chiba Hokusou Hospital	Inzai	Chiba
Japan	Mitoyo General Hospital	Kannonji	Kagawa
Japan	Nara Medical University Hospital	Kashihara	Nara
Japan	Shuwa General Hospital	Kasukabe-shi	Saitama
Japan	Kishiwada Tokushukai Hospital	Kishiwada	Osaka
Japan	Tokushima Red Cross Hospital	Komatsushima	Tokushima
Japan	Southern TOHOKU Research Institute for Neuroscience Southern TOHOKU Medical Clinic	Koriyama	Fukushima
Japan	Kumamoto University Hospital	Kumamoto
Japan	Saiseikai Kumamoto Hospital	Kumamoto
Japan	Kurume University Hospital	Kurume-shi	Fukuoka-ken
Japan	Kusatsu General Hospital	Kusatsu-shi	Shiga-ken
Japan	Ehime Prefectural Central Hospital	Matuyama-shi	Ehime
Japan	Chubu Rosai Hospital	Nagoya	Aichi
Japan	The Hospital of Hyogo College of Medicine	Nishinomiya	Hyogo
Japan	Ogaki Municipal Hospital	Ogaki	Gifu
Japan	Japanese Red Cross Okayama Hospital	Okayama
Japan	National Hospital Organization Osaka National Hospital	Osaka
Japan	Osaka General Medical Center	Osaka
Japan	Osaka Police Hospital	Osaka
Japan	Kitasato University Hospital	Sagamihara	Kanagawa
Japan	Saitama Medical Center Jichi Medical University	Saitama-shi	Saitama
Japan	Sakai City Medical Center	Sakai-shi	Osaka
Japan	Hokkaido University Hospital	Sapporo	Hokkaido
Japan	National Hospital Organization Hokkaido Medical Center	Sapporo	Hokkaido
Japan	Teine Keijinkai Clinic	Sapporo	Hokkaido
Japan	National Hospital Organization Sendai Medical Center	Sendai-shi	Miyagi-ken
Japan	Tosei General Hospital	Seto	Aichi
Japan	Jichi Medical University Hospital	Shimotsuke-shi	Tochigi
Japan	Tokyo Women's Medical University Hospital	Shinjuku-ku	Tokyo
Japan	National Cerebral and Cardiovascular Center Hospital	Suita-shi	Osaka-fu
Japan	National Hospital Organization Takasaki General Medical Center	Takasaki-shi
Japan	Toride Kyodo General Hospital	Toride-shi	Ibaraki
Japan	Toyama University Hospital	Toyama
Japan	Mie University Hospital	Tsu	MIE
Japan	Yamaguchi University Hospital	Ube	Yamaguchi
Japan	Ube-kohsan Central Hospital Corp.	Ube-city	Yamaguchi
Japan	Gokeikai Osaka Kaisei Hospital	Yodogawa-ku	Osaka
Japan	Tottori University Hospital	Yonago-shi	Tottori

Sponsors (1)

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

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With First Occurrence of Cardiovascular (CV) Mortality or Hospitalization Due to Heart Failure (HF)	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.	Randomization up to the date when the last enrolled participant had been followed up for 1 year (up to 1744 days)
Secondary	Number of Participants With First Occurrence of Cardiovascular (CV) Mortality, Hospitalization Due to Heart Failure (HF), or Addition/Increase of Heart Failure (HF) Medication	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.	Randomization up to the date when the last enrolled participant had been followed up for 1 year (up to 1744 days)
Secondary	Number of Participants With With First Occurrence of All-Cause Mortality	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.	Randomization up to the date when the last enrolled participant had been followed up for 1 year (up to 1744 days)
Secondary	Number of Participants With With First Occurrence of Cardiovascular Mortality	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.	Randomization up to the date when the last enrolled participant had been followed up for 1 year (up to 1744 days)
Secondary	Number of Participants With First Occurrence of All-cause Hospitalization	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.	Randomization up to the date when the last enrolled participant had been followed up for 1 year (up to 1744 days)
Secondary	Number of Participants With First Occurrence of Hospitalization Due to Heart Failure (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.	Randomization up to the date when the last enrolled participant had been followed up for 1 year (up to 1744 days)
Secondary	Number of Participants With First Occurrence of All-cause Mortality or All-cause Hospitalization	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.	Randomization up to the date when the last enrolled participant had been followed up for 1 year (up to 1744 days)
Secondary	Number of Participants With First Occurrence of Heart Failure (HF) Mortality or Heart Failure (HF) Hospitalization	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.	Randomization up to the date when the last enrolled participant had been followed up for 1 year (up to 1744 days)
Secondary	Number of Participants With First Occurrence of Cardiovascular (CV) Hospitalization	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.	Randomization up to the date when the last enrolled participant had been followed up for 1 year (up to 1744 days)
Secondary	Number of Participants With First Occurrence of Addition/Increase of Heart Failure (HF) Medication Due to Heart Failure (HF) Worsening	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.	Randomization up to the date when the last enrolled participant had been followed up for 1 year (up to 1744 days)
Secondary	Number of Participants With First Occurrence of Fatal/Non-Fatal Stroke	Hazard ratio of Eplerenone versus placebo for first occurrence of the event was obtained from a Cox proportional hazards model.	Randomization up to the date when the last enrolled participant had been followed up for 1 year (up to 1744 days)
Secondary	Number of Participants With First Occurrence of Fatal/Non-Fatal Myocardial Infarction (MI)	Hazard ratio of Eplerenone versus placebo for first occurrence of the event was obtained from a Cox proportional hazards model.	Randomization up to the date when the last enrolled participant had been followed up for 1 year (up to 1744 days)
Secondary	Number of Participants With First Occurrence of New Onset Atrial Fibrillation/Flutter	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.	Randomization up to the date when the last enrolled participant had been followed up for 1 year (up to 1744 days)
Secondary	Number of Participants With First Occurrence of New Onset Diabetes Mellitus	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.	Randomization up to the date when the last enrolled participant had been followed up for 1 year (up to 1744 days)
Secondary	Number of Participants With First Occurrence of Hospitalisation Due to Worsening Renal Function	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.	Randomization up to the date when the last enrolled participant had been followed up for 1 year (up to 1744 days)
Secondary	Number of Participants With First Occurrence of Hospitalization for Hyperkalemia	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.	Randomization up to the date when the last enrolled participant had been followed up for 1 year (up to 1744 days)
Secondary	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		Baseline, Months 5,9,13,17,21,25,29,33,37,42,48, Final Visit (up to Month 48)
Secondary	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		Baseline, Months 5, 9, 13, 17, 21 ,25, 29, 33, 37, 42, 48 and Final Visit (up to Month 48)
Secondary	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	LVEF was calculated based on end-diastolic volume measured by two-dimensional echocardiography.	Baseline, Months 5, 9, 13, 17, 21, 25, 29, 33, 37, 42, 48, Final Visit (up to Month 48)
Secondary	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		Baseline, Months 5, 9, 13, 17, 21, 25, 29, 33, 37, 42, 48, Final Visit (up to Month 48)
Secondary	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	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).	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)
Secondary	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	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.	Baseline, Week 4, Months 5, 9, 13, 17, 21, 25, 29, 33, 37, 42, 48, Final Visit (up to Month 48)

External Links

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