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Heart FailurePhase 3J-EMPHASIS-HFNCT01115855

Clinical Study Of Eplerenone In Japanese Patients With Chronic Heart Failure

A Phase 3 study testing Eplerenone in people with Heart Failure, run by Pfizer's Upjohn has merged with Mylan to form Viatris Inc. at 54 sites in Japan.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

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

Who is it for?
Ages 55 years and older
Conditions the study is for
Heart Failure
What is being tested?
Eplerenone
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
221 participants
Where
54 sitesJapan
Study dates
Jul 2010to Sep 2015
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 55 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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)

Who cannot join

  • 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.

Trial locations and contacts

54 sites in 1 country.

54 sites in 1 country

Japan54 sites
  • Asahi General Hospital

    Asahi, Chiba, 289-2511

  • Juntendo University Hospital

    Bunkyo-ku, Tokyo, 113-8431

  • National Hospital Organization Chiba Medical Center

    Chiba, Chiba, 260-8606

  • Mitsui Memorial Hospital

    Chiyoda-Ku, Tokyo, 101-8643

  • University of Yamanashi Hospital

    Chūō, Yamanashi, 409-3898

  • Fujisawa City Hospital

    Fujisawa, Kanagawa, 251-8550

  • Kyushu University Hospital

    Fukuoka, Fukuoka, 812-8582

  • Hamanomachi Hospital

    Fukuoka, 810-8539

  • Fukushima Medical University Hospital

    Fukushima, 960-1295

  • Gifu Prefectural General Medical Center

    Gifu, 500-8727

  • Hakodate City Hospital

    Hakodate, Hokkaido, 041-8680

  • National Hospital Organization Hakodate National Hospital

    Hakodate-shi, Hokkai-do, 041-8512

  • Hamamatsu Rosai Hospital

    Hamamatsu, Shizuoka, 430-8525

  • Hyogo Brain and Heart Center

    Himeji, Hyōgo, 670-0981

  • Japanease Red Cross Society Himeji Hospital

    Himeji, Hyōgo, 670-8540

  • Aso Iizuka Hospital

    Iizuka-shi, Fukuoka, 820-8505

  • Nippon Medical School Chiba Hokusou Hospital

    Inzai, Chiba, 270-1694

  • Mitoyo General Hospital

    Kan’onjichō, Kagawa-ken, 769-1695

  • Nara Medical University Hospital

    Kashihara, Nara, 634-8522

  • Shuwa General Hospital

    Kasukabe-shi, Saitama, 344-0035

  • Kishiwada Tokushukai Hospital

    Kishiwada, Osaka, 596-0042

  • Tokushima Red Cross Hospital

    Komatsushimachō, Tokushima, 773-8502

  • Southern TOHOKU Research Institute for Neuroscience Southern TOHOKU Medical Clinic

    Kōriyama, Fukushima, 963-8052

  • Kumamoto University Hospital

    Kumamoto, 860-8556

  • Saiseikai Kumamoto Hospital

    Kumamoto, 861-4101

  • Kurume University Hospital

    Kurume-shi, Fukuoka, 830-0011

  • Kusatsu General Hospital

    Kusatsu-shi, Shiga, 525-8585

  • Ehime Prefectural Central Hospital

    Matuyama-shi, Ehime, 790-0024

  • Chubu Rosai Hospital

    Nagoya, Aichi-ken, 455-8530

  • The Hospital of Hyogo College of Medicine

    Nishinomiya, Hyōgo, 663-8501

  • Ogaki Municipal Hospital

    Ōgaki, Gifu, 503-8502

  • Japanese Red Cross Okayama Hospital

    Okayama, 700-8607

  • National Hospital Organization Osaka National Hospital

    Osaka, 540-0006

  • Osaka Police Hospital

    Osaka, 543-0035

  • Osaka General Medical Center

    Osaka, 558-8558

  • Kitasato University Hospital

    Sagamihara, Kanagawa, 252-0375

  • Saitama Medical Center Jichi Medical University

    Saitama-shi, Saitama, 330-0834

  • Sakai City Medical Center

    Sakai-shi, Osaka, 593-8304

  • Teine Keijinkai Clinic

    Sapporo, Hokkaido, 006-0811

  • Hokkaido University Hospital

    Sapporo, Hokkaido, 060-8648

  • National Hospital Organization Hokkaido Medical Center

    Sapporo, Hokkaido, 063-0005

  • National Hospital Organization Sendai Medical Center

    Sendai, Miyagi, 983-8520

  • Tosei General Hospital

    Seto, Aichi-ken, 489-8642

  • Jichi Medical University Hospital

    Shimotsuke-shi, Tochigi, 329-0498

  • Tokyo Women's Medical University Hospital

    Shinjuku-ku, Tokyo, 162-8666

  • National Cerebral and Cardiovascular Center Hospital

    Suita-shi, Osaka, 565-8565

  • National Hospital Organization Takasaki General Medical Center

    Takasaki-shi, 370-0829

  • Toride Kyodo General Hospital

    Toride-shi, Ibaraki, 302-0022

  • Toyama University Hospital

    Toyama, 930-0152

  • Mie University Hospital

    Tsu, Mie-ken, 514-8507

  • Ube-kohsan Central Hospital Corp.

    Ube, Yamaguchi, 755-0151

  • Yamaguchi University Hospital

    Ube, Yamaguchi, 755-8505

  • Gokeikai Osaka Kaisei Hospital

    Yodogawa-ku, Osaka, 532-0003

  • Tottori University Hospital

    Yonago-shi, Tottori, 683-8504

Other trials in Japan

About this study

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

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

Read the 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.

Conditions
Heart Failure
Being tested
Eplerenone, Placebo
Keywords
Double-blind, eplerenone, Japanese
Medical subject headings
Heart Failure

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • EplerenoneDrug

    Eplerenone 25 mg once every other day, 25mg once daily or 50 mg once daily

  • PlaceboDrug

    Placebo once daily or every once daily

Study groups in NCT01115855
Study groupRoleWhat they receive
Eplerenone armExperimentalAdd on standard heart failure therapy
Receives: Drug: Eplerenone
Placebo armPlacebo comparatorAdd on standard heart failure therapy
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Randomization up to the date when the last enrolled participant had been followed up for 1 year (up to 1744 days)

Secondary outcomes (21)
  1. 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.

    Measured: Randomization up to the date when the last enrolled participant had been followed up for 1 year (up to 1744 days)

  2. 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.

    Measured: Randomization up to the date when the last enrolled participant had been followed up for 1 year (up to 1744 days)

  3. 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.

    Measured: Randomization up to the date when the last enrolled participant had been followed up for 1 year (up to 1744 days)

  4. 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.

    Measured: Randomization up to the date when the last enrolled participant had been followed up for 1 year (up to 1744 days)

  5. 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.

    Measured: Randomization up to the date when the last enrolled participant had been followed up for 1 year (up to 1744 days)

  6. 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.

    Measured: Randomization up to the date when the last enrolled participant had been followed up for 1 year (up to 1744 days)

  7. 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.

    Measured: Randomization up to the date when the last enrolled participant had been followed up for 1 year (up to 1744 days)

  8. 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.

    Measured: Randomization up to the date when the last enrolled participant had been followed up for 1 year (up to 1744 days)

  9. 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.

    Measured: Randomization up to the date when the last enrolled participant had been followed up for 1 year (up to 1744 days)

  10. 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.

    Measured: Randomization up to the date when the last enrolled participant had been followed up for 1 year (up to 1744 days)

  11. 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.

    Measured: Randomization up to the date when the last enrolled participant had been followed up for 1 year (up to 1744 days)

  12. 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.

    Measured: Randomization up to the date when the last enrolled participant had been followed up for 1 year (up to 1744 days)

  13. 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.

    Measured: Randomization up to the date when the last enrolled participant had been followed up for 1 year (up to 1744 days)

  14. 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.

    Measured: Randomization up to the date when the last enrolled participant had been followed up for 1 year (up to 1744 days)

  15. 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.

    Measured: Randomization up to the date when the last enrolled participant had been followed up for 1 year (up to 1744 days)

  16. 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

    Measured: Baseline, Months 5,9,13,17,21,25,29,33,37,42,48, Final Visit (up to Month 48)

  17. 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

    Measured: Baseline, Months 5, 9, 13, 17, 21 ,25, 29, 33, 37, 42, 48 and Final Visit (up to Month 48)

  18. 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.

    Measured: Baseline, Months 5, 9, 13, 17, 21, 25, 29, 33, 37, 42, 48, Final Visit (up to Month 48)

  19. 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

    Measured: Baseline, Months 5, 9, 13, 17, 21, 25, 29, 33, 37, 42, 48, Final Visit (up to Month 48)

  20. 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).

    Measured: 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)

  21. 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.

    Measured: Baseline, Week 4, Months 5, 9, 13, 17, 21, 25, 29, 33, 37, 42, 48, Final Visit (up to Month 48)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted4 May 2010 (estimated)
  2. Study startJul 2010
  3. Primary completionSep 2015
  4. Study completionSep 2015

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Investigator, Outcomes assessor
Enrolment
221 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01115855
Sponsor's protocol ID
A6141114
Acronym
J-EMPHASIS-HF
Status last verified
Dec 2020
First submitted
30 Apr 2010
Last updated
22 Dec 2020
Data monitoring committee
Yes

Publications

  • Tsutsui H, Ito H, Kitakaze M, Komuro I, Murohara T, Izumi T, Sunagawa K, Yasumura Y, Yano M, Yamamoto K, Yoshikawa T, Tsutamoto T, Zhang J, Okayama A, Ichikawa Y, Kanmuri K, Matsuzaki M; J-EMPHASIS-HF Study Group. Double-Blind, Randomized, Placebo-Controlled Trial Evaluating the Efficacy and Safety of Eplerenone in Japanese Patients With Chronic Heart Failure (J-EMPHASIS-HF). Circ J. 2017 Dec 25;82(1):148-158. doi: 10.1253/circj.CJ-17-0323. Epub 2017 Aug 19.

    PubMed 28824029

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Eplerenone in people with Heart Failure, run by Pfizer's Upjohn has merged with Mylan to form Viatris Inc. at 54 sites in Japan.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 2 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 22 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 54 sites in Japan. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 27 Oct 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01115855, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Dec 2020.

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