Clinical Study Of Eplerenone In Japanese Patients With Chronic Heart Failure
- Registration Number
- NCT01115855
- Lead Sponsor
- Pfizer's Upjohn has merged with Mylan to form Viatris Inc.
- Brief Summary
A study to compare the efficacy and safety of eplerenone in Japanese chronic heart failure patients with placebo.
- Detailed 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 & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 221
- 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)
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo arm Placebo Add on standard heart failure therapy Eplerenone arm Eplerenone Add on standard heart failure therapy
- Primary Outcome Measures
Name Time Method Number of Participants With First Occurrence of Cardiovascular (CV) Mortality or Hospitalization Due to Heart Failure (HF) Randomization up to the date when the last enrolled participant had been followed up for 1 year (up to 1744 days) 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.
- Secondary Outcome Measures
Name Time Method Number of Participants With First Occurrence of Cardiovascular (CV) Mortality, Hospitalization Due to Heart Failure (HF), or Addition/Increase of Heart Failure (HF) Medication Randomization up to the date when the last enrolled participant had been followed up for 1 year (up to 1744 days) 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.
Number of Participants With With First Occurrence of All-Cause Mortality Randomization up to the date when the last enrolled participant had been followed up for 1 year (up to 1744 days) 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.
Number of Participants With With First Occurrence of Cardiovascular Mortality Randomization up to the date when the last enrolled participant had been followed up for 1 year (up to 1744 days) 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.
Number of Participants With First Occurrence of All-cause Hospitalization Randomization up to the date when the last enrolled participant had been followed up for 1 year (up to 1744 days) 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.
Number of Participants With First Occurrence of Hospitalization Due to Heart Failure (HF) Randomization up to the date when the last enrolled participant had been followed up for 1 year (up to 1744 days) 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.
Number of Participants With First Occurrence of All-cause Mortality or All-cause Hospitalization Randomization up to the date when the last enrolled participant had been followed up for 1 year (up to 1744 days) 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.
Number of Participants With First Occurrence of Heart Failure (HF) Mortality or Heart Failure (HF) Hospitalization Randomization up to the date when the last enrolled participant had been followed up for 1 year (up to 1744 days) 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.
Number of Participants With First Occurrence of Cardiovascular (CV) Hospitalization Randomization up to the date when the last enrolled participant had been followed up for 1 year (up to 1744 days) 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.
Number of Participants With First Occurrence of Addition/Increase of Heart Failure (HF) Medication Due to Heart Failure (HF) Worsening Randomization up to the date when the last enrolled participant had been followed up for 1 year (up to 1744 days) 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.
Number of Participants With First Occurrence of Fatal/Non-Fatal Stroke Randomization up to the date when the last enrolled participant had been followed up for 1 year (up to 1744 days) Hazard ratio of Eplerenone versus placebo for first occurrence of the event was obtained from a Cox proportional hazards model.
Number of Participants With First Occurrence of Fatal/Non-Fatal Myocardial Infarction (MI) Randomization up to the date when the last enrolled participant had been followed up for 1 year (up to 1744 days) Hazard ratio of Eplerenone versus placebo for first occurrence of the event was obtained from a Cox proportional hazards model.
Number of Participants With First Occurrence of New Onset Atrial Fibrillation/Flutter Randomization up to the date when the last enrolled participant had been followed up for 1 year (up to 1744 days) 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.
Number of Participants With First Occurrence of Hospitalisation Due to Worsening Renal Function Randomization up to the date when the last enrolled participant had been followed up for 1 year (up to 1744 days) 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.
Number of Participants With First Occurrence of Hospitalization for Hyperkalemia Randomization up to the date when the last enrolled participant had been followed up for 1 year (up to 1744 days) 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.
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) 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) 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 Baseline, Months 5, 9, 13, 17, 21, 25, 29, 33, 37, 42, 48, Final Visit (up to Month 48) LVEF was calculated based on end-diastolic volume measured by two-dimensional echocardiography.
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) 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 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) 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).
Number of Participants With First Occurrence of New Onset Diabetes Mellitus Randomization up to the date when the last enrolled participant had been followed up for 1 year (up to 1744 days) 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.
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 Baseline, Week 4, Months 5, 9, 13, 17, 21, 25, 29, 33, 37, 42, 48, Final Visit (up to Month 48) 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.
Trial Locations
- Locations (54)
Hakodate City Hospital
🇯🇵Hakodate, Hokkaido, Japan
Hokkaido University Hospital
🇯🇵Sapporo, Hokkaido, Japan
Hyogo Brain and Heart Center
🇯🇵Himeji, Hyogo, Japan
Asahi General Hospital
🇯🇵Asahi, Chiba, Japan
Ehime Prefectural Central Hospital
🇯🇵Matuyama-shi, Ehime, Japan
Kyushu University Hospital
🇯🇵Fukuoka-shi, Fukuoka-ken, Japan
Aso Iizuka Hospital
🇯🇵Iizuka-shi, Fukuoka-ken, Japan
Ogaki Municipal Hospital
🇯🇵Ogaki, Gifu, Japan
The Hospital of Hyogo College of Medicine
🇯🇵Nishinomiya, Hyogo, Japan
Nara Medical University Hospital
🇯🇵Kashihara, Nara, Japan
Sakai City Medical Center
🇯🇵Sakai-shi, Osaka, Japan
Gokeikai Osaka Kaisei Hospital
🇯🇵Yodogawa-ku, Osaka, Japan
Shuwa General Hospital
🇯🇵Kasukabe-shi, Saitama, Japan
Jichi Medical University Hospital
🇯🇵Shimotsuke-shi, Tochigi, Japan
Juntendo University Hospital
🇯🇵Bunkyo-ku, Tokyo, Japan
Tokyo Women's Medical University Hospital
🇯🇵Shinjuku-ku, Tokyo, Japan
Tottori University Hospital
🇯🇵Yonago-shi, Tottori, Japan
Southern TOHOKU Research Institute for Neuroscience Southern TOHOKU Medical Clinic
🇯🇵Koriyama, Fukushima, Japan
Kurume University Hospital
🇯🇵Kurume-shi, Fukuoka-ken, Japan
Fujisawa City Hospital
🇯🇵Fujisawa, Kanagawa, Japan
Japanease Red Cross Society Himeji Hospital
🇯🇵Himeji, Hyogo, Japan
National Hospital Organization Sendai Medical Center
🇯🇵Sendai-shi, Miyagi-ken, Japan
Mie University Hospital
🇯🇵Tsu, MIE, Japan
Saitama Medical Center Jichi Medical University
🇯🇵Saitama-shi, Saitama, Japan
Kusatsu General Hospital
🇯🇵Kusatsu-shi, Shiga-ken, Japan
Ube-kohsan Central Hospital Corp.
🇯🇵Ube-city, Yamaguchi, Japan
University of Yamanashi Hospital
🇯🇵Chuo, Yamanashi, Japan
Yamaguchi University Hospital
🇯🇵Ube, Yamaguchi, Japan
Hamanomachi Hospital
🇯🇵Fukuoka, Japan
Osaka General Medical Center
🇯🇵Osaka, Japan
National Hospital Organization Takasaki General Medical Center
🇯🇵Takasaki-shi, Japan
National Hospital Organization Osaka National Hospital
🇯🇵Osaka, Japan
Osaka Police Hospital
🇯🇵Osaka, Japan
National Hospital Organization Hakodate National Hospital
🇯🇵Hakodate-shi, Hokkai-do, Japan
Nippon Medical School Chiba Hokusou Hospital
🇯🇵Inzai, Chiba, Japan
Chubu Rosai Hospital
🇯🇵Nagoya, Aichi, Japan
Tosei General Hospital
🇯🇵Seto, Aichi, Japan
National Hospital Organization Chiba Medical Center
🇯🇵Chiba-shi, Chiba-ken, Japan
Teine Keijinkai Clinic
🇯🇵Sapporo, Hokkaido, Japan
Kitasato University Hospital
🇯🇵Sagamihara, Kanagawa, Japan
National Hospital Organization Hokkaido Medical Center
🇯🇵Sapporo, Hokkaido, Japan
Mitoyo General Hospital
🇯🇵Kannonji, Kagawa, Japan
Hamamatsu Rosai Hospital
🇯🇵Hamamatsu-shi, Shizuoka, Japan
Tokushima Red Cross Hospital
🇯🇵Komatsushima, Tokushima, Japan
Mitsui Memorial Hospital
🇯🇵Chiyoda-Ku, Tokyo, Japan
Toride Kyodo General Hospital
🇯🇵Toride-shi, Ibaraki, Japan
National Cerebral and Cardiovascular Center Hospital
🇯🇵Suita-shi, Osaka-fu, Japan
Kishiwada Tokushukai Hospital
🇯🇵Kishiwada, Osaka, Japan
Japanese Red Cross Okayama Hospital
🇯🇵Okayama, Japan
Fukushima Medical University Hospital
🇯🇵Fukushima, Japan
Gifu Prefectural General Medical Center
🇯🇵Gifu, Japan
Kumamoto University Hospital
🇯🇵Kumamoto, Japan
Saiseikai Kumamoto Hospital
🇯🇵Kumamoto, Japan
Toyama University Hospital
🇯🇵Toyama, Japan