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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT01115855
First received: April 30, 2010
Last updated: September 5, 2016
Last verified: September 2016
  Purpose
A study to compare the efficacy and safety of eplerenone in Japanese chronic heart failure patients with placebo.

Condition Intervention Phase
Heart Failure
Drug: Eplerenone
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: The Effect Of Eplerenone Versus Placebo On Cardiovascular Mortality And Heart Failure Hospitalization In Japanese Subjects With Chronic Heart Failure

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • Number of Participants With First Occurrence of Cardiovascular (CV) Mortality or Hospitalization Due to Heart Failure (HF) [ Time Frame: Randomization up to the date when the last enrolled participant had been followed up for 1 year (up to 1744 days) ] [ Designated as safety issue: Yes ]
    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:
  • Number of Participants With First Occurrence of Cardiovascular (CV) Mortality, Hospitalization Due to Heart Failure (HF), or Addition/Increase of Heart Failure (HF) Medication [ Time Frame: Randomization up to the date when the last enrolled participant had been followed up for 1 year (up to 1744 days) ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Randomization up to the date when the last enrolled participant had been followed up for 1 year (up to 1744 days) ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Randomization up to the date when the last enrolled participant had been followed up for 1 year (up to 1744 days) ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Randomization up to the date when the last enrolled participant had been followed up for 1 year (up to 1744 days) ] [ Designated as safety issue: Yes ]
    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) [ Time Frame: Randomization up to the date when the last enrolled participant had been followed up for 1 year (up to 1744 days) ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Randomization up to the date when the last enrolled participant had been followed up for 1 year (up to 1744 days) ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Randomization up to the date when the last enrolled participant had been followed up for 1 year (up to 1744 days) ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Randomization up to the date when the last enrolled participant had been followed up for 1 year (up to 1744 days) ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Randomization up to the date when the last enrolled participant had been followed up for 1 year (up to 1744 days) ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Randomization up to the date when the last enrolled participant had been followed up for 1 year (up to 1744 days) ] [ Designated as safety issue: Yes ]
    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) [ Time Frame: Randomization up to the date when the last enrolled participant had been followed up for 1 year (up to 1744 days) ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Randomization up to the date when the last enrolled participant had been followed up for 1 year (up to 1744 days) ] [ Designated as safety issue: Yes ]
    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 New Onset Diabetes Mellitus [ Time Frame: Randomization up to the date when the last enrolled participant had been followed up for 1 year (up to 1744 days) ] [ Designated as safety issue: Yes ]
    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.

  • Number of Participants With First Occurrence of Hospitalisation Due to Worsening Renal Function [ Time Frame: Randomization up to the date when the last enrolled participant had been followed up for 1 year (up to 1744 days) ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Randomization up to the date when the last enrolled participant had been followed up for 1 year (up to 1744 days) ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Baseline, Months 5,9,13,17,21,25,29,33,37,42,48, Final Visit (up to Month 48) ] [ Designated as safety issue: No ]
  • 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 [ Time Frame: Baseline, Months 5, 9, 13, 17, 21 ,25, 29, 33, 37, 42, 48 and Final Visit (up to Month 48) ] [ Designated as safety issue: No ]
  • 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 [ Time Frame: Baseline, Months 5, 9, 13, 17, 21, 25, 29, 33, 37, 42, 48, Final Visit (up to Month 48) ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline, Months 5, 9, 13, 17, 21, 25, 29, 33, 37, 42, 48, Final Visit (up to Month 48) ] [ Designated as safety issue: No ]
  • 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 [ 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) ] [ Designated as safety issue: No ]
    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).

  • 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 [ Time Frame: Baseline, Week 4, Months 5, 9, 13, 17, 21, 25, 29, 33, 37, 42, 48, Final Visit (up to Month 48) ] [ Designated as safety issue: No ]
    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.


Enrollment: 221
Study Start Date: July 2010
Study Completion Date: September 2015
Primary Completion Date: September 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Eplerenone arm
Add on standard heart failure therapy
Drug: Eplerenone
Eplerenone 25 mg once every other day, 25mg once daily or 50 mg once daily
Placebo Comparator: Placebo arm
Add on standard heart failure therapy
Drug: Placebo
Placebo once daily or every once daily

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.
  Eligibility

Ages Eligible for Study:   55 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01115855

  Hide Study Locations
Locations
Japan
Chubu Rosai Hospital
Nagoya, Aichi, Japan, 455-8530
Tosei General Hospital
Seto, Aichi, Japan, 489-8642
National Hospital Organization Chiba Medical Center
Chiba-shi, Chiba-ken, Japan, 260-8606
Asahi General Hospital
Asahi, Chiba, Japan, 289-2511
Nippon Medical School Chiba Hokusou Hospital
Inzai, Chiba, Japan, 270-1694
Ehime Prefectural Central Hospital
Matuyama-shi, Ehime, Japan, 790-0024
Kyushu University Hospital
Fukuoka-shi, Fukuoka-ken, Japan, 812-8582
Aso Iizuka Hospital
Iizuka-shi, Fukuoka-ken, Japan, 820-8505
Kurume University Hospital
Kurume-shi, Fukuoka-ken, Japan, 830-0011
Southern TOHOKU Research Institute for Neuroscience Southern TOHOKU Medical Clinic
Koriyama, Fukushima, Japan, 963-8052
Ogaki Municipal Hospital
Ogaki, Gifu, Japan, 503-8502
National Hospital Organization Hakodate National Hospital
Hakodate-shi, Hokkai-do, Japan, 041-8512
Hakodate City Hospital
Hakodate, Hokkaido, Japan, 041-8680
Teine Keijinkai Clinic
Sapporo, Hokkaido, Japan, 006-0811
Hokkaido University Hospital
Sapporo, Hokkaido, Japan, 060-8648
National Hospital Organization Hokkaido Medical Center
Sapporo, Hokkaido, Japan, 063-0005
Hyogo Brain and Heart Center
Himeji, Hyogo, Japan, 670-0981
Japanease Red Cross Society Himeji Hospital
Himeji, Hyogo, Japan, 670-8540
The Hospital of Hyogo College of Medicine
Nishinomiya, Hyogo, Japan, 663-8501
Toride Kyodo General Hospital
Toride-shi, Ibaraki, Japan, 302-0022
Mitoyo General Hospital
Kannonji, Kagawa, Japan, 769-1695
Fujisawa City Hospital
Fujisawa, Kanagawa, Japan, 251-8550
Kitasato University Hospital
Sagamihara, Kanagawa, Japan, 252-0375
Mie University Hospital
Tsu, MIE, Japan, 514-8507
National Hospital Organization Sendai Medical Center
Sendai-shi, Miyagi-ken, Japan, 983-8520
Nara Medical University Hospital
Kashihara, Nara, Japan, 634-8522
National Cerebral and Cardiovascular Center Hospital
Suita-shi, Osaka-fu, Japan, 565-8565
Kishiwada Tokushukai Hospital
Kishiwada, Osaka, Japan, 596-0042
Sakai City Medical Center
Sakai-shi, Osaka, Japan, 593-8304
Gokeikai Osaka Kaisei Hospital
Yodogawa-ku, Osaka, Japan, 532-0003
Shuwa General Hospital
Kasukabe-shi, Saitama, Japan, 344-0035
Saitama Medical Center Jichi Medical University
Saitama-shi, Saitama, Japan, 330-0834
Kusatsu General Hospital
Kusatsu-shi, Shiga-ken, Japan, 525-8585
Hamamatsu Rosai Hospital
Hamamatsu-shi, Shizuoka, Japan, 430-8525
Jichi Medical University Hospital
Shimotsuke-shi, Tochigi, Japan, 329-0498
Tokushima Red Cross Hospital
Komatsushima, Tokushima, Japan, 773-8502
Juntendo University Hospital
Bunkyo-ku, Tokyo, Japan, 113-8431
Mitsui Memorial Hospital
Chiyoda-Ku, Tokyo, Japan, 101-8643
Tokyo Women's Medical University Hospital
Shinjuku-ku, Tokyo, Japan, 162-8666
Tottori University Hospital
Yonago-shi, Tottori, Japan, 683-8504
Ube-kohsan Central Hospital Corp.
Ube-city, Yamaguchi, Japan, 755-0151
Yamaguchi University Hospital
Ube, Yamaguchi, Japan, 755-8505
University of Yamanashi Hospital
Chuo, Yamanashi, Japan, 409-3898
Hamanomachi Hospital
Fukuoka, Japan, 810-8539
Fukushima Medical University Hospital
Fukushima, Japan, 960-1295
Gifu Prefectural General Medical Center
Gifu, Japan, 500-8727
Kumamoto University Hospital
Kumamoto, Japan, 860-8556
Saiseikai Kumamoto Hospital
Kumamoto, Japan, 861-4101
Japanese Red Cross Okayama Hospital
Okayama, Japan, 700-8607
National Hospital Organization Osaka National Hospital
Osaka, Japan, 540-0006
Osaka Police Hospital
Osaka, Japan, 543-0035
Osaka General Medical Center
Osaka, Japan, 558-8558
National Hospital Organization Takasaki General Medical Center
Takasaki-shi, Japan, 370-0829
Toyama University Hospital
Toyama, Japan, 930-0152
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT01115855     History of Changes
Other Study ID Numbers: A6141114 
Study First Received: April 30, 2010
Results First Received: September 5, 2016
Last Updated: September 5, 2016
Health Authority: Japan: Ministry of Health, Labor and Welfare

Keywords provided by Pfizer:
Double-blind
eplerenone
Japanese

Additional relevant MeSH terms:
Heart Failure
Heart Diseases
Cardiovascular Diseases
Eplerenone
Spironolactone
Mineralocorticoid Receptor Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Diuretics, Potassium Sparing
Diuretics
Natriuretic Agents

ClinicalTrials.gov processed this record on December 02, 2016