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Cardiovascular Drugs and Therapy

, Volume 29, Issue 2, pp 179–185 | Cite as

Rationale and Design of the Double-Blind, Randomized, Placebo-Controlled Multicenter Trial on Efficacy of Early Initiation of Eplerenone Treatment in Patients with Acute Heart Failure (EARLIER)

  • Masanori Asakura
  • Haruko Yamamoto
  • Kuniya Asai
  • Akihisa Hanatani
  • Ken-ichi Hirata
  • Atsushi Hirayakma
  • Kazuo Kimura
  • Youichi Kobayashi
  • Shin-ichi Momomura
  • Yoshihisa Nakagawa
  • Yutaro Nishi
  • Yoshihiko Saito
  • Yasuhiro Satoh
  • Takahisa Yamada
  • Akira Yamashina
  • Satoshi Yasuda
  • Tsutomu Yoshikawa
  • Akiko Kada
  • Hiroyuki Uesaka
  • Masafumi Kitakaze
  • on behalf of the EARLIER investigators and study coordinators
ORIGINAL ARTICLE

Abstract

Background and Aims

Aldosterone is one of the major factors to cause organ damage during an acute phase of heart failure (HF), and many reports have demonstrated that patients with acute decompensated HF (ADHF) have high blood aldosterone concentrations, and the high aldosterone concentrations predict poor prognosis in patients with HF. These findings suggest that eplerenone, an antagonist of aldosterone receptors may provide a new concept and strategy for the treatment of ADHF, protecting the heart and other organs during chronic phases, depending on the restoration of hemodynamic abnormalities.

Methods

EARLIER is an event-driven clinical trial with an estimated enrolment of 300 patients hospitalized with ADHF with reduced left ventricular ejection fraction. ADHF includes ischemic or non-ischemic HF, and patients can be enrolled within 72 h after the visit to the hospital. We randomize the patients taking standard therapies for ADHF to the eplerenone and placebo groups. Eplerenone, either 25 or 50 mg, is administered for 6 months in the eplerenone group, and the corresponding placebo is administered in the placebo group on top of the standard care. We set the primary endpoint as the incidence of the composite endpoint (cardiac death or first re-hospitalization due to cardiac disease) 6 months after the enrollment, and also check the quality of life, i.e., exercise capacity and safety features of eplerenone.

Conclusion and Perspectives

EARLIER is a clinical trial of eplerenone targeting ADHF and also the first multicenter investigator-initiated phase III trial in the cardiovascular field in Japan, funded by the Japanese government.

Keywords

Acute heart failure Acute myocardial infarction Eplerenone Aldosterone Cardiac death Re-hospitalization 

Notes

Acknowledgments

We acknowledge the great help from Ms Y.Miyawaki, M.Ono and C.Takayama, and Mr. T.Uraki for the secretarial works. Mr. M Yamamoto, Mr. S Fukunaga and Ms K Terasawa at the Center for Clinical Trial, the Japan Medical Association (JMACCT) advises us how to appropriately form the EARLIER study organization for study implementation.

Funding

This work was supported by a clinical trial promotion project of Japan Medical Association, which is funded by a Health Labour Sciences Research Grant from the Ministry of Health, Labour and Welfare.

Conflict of interest

MK, KA, KH, KK, YK, YS and AY received honorarium form Pfizer Japan. MK 、AH and YS received the research funding from Pfizer Japan. MK and TY is advisory board members of clinical trial on eplerenone in chronic heart failure (A6141114).

The drugs are generously provided by Pfizer USA based on the policy of J-GCP.

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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Masanori Asakura
    • 1
  • Haruko Yamamoto
    • 2
  • Kuniya Asai
    • 3
  • Akihisa Hanatani
    • 4
  • Ken-ichi Hirata
    • 5
  • Atsushi Hirayakma
    • 6
  • Kazuo Kimura
    • 7
  • Youichi Kobayashi
    • 8
  • Shin-ichi Momomura
    • 9
  • Yoshihisa Nakagawa
    • 10
  • Yutaro Nishi
    • 11
  • Yoshihiko Saito
    • 12
  • Yasuhiro Satoh
    • 13
  • Takahisa Yamada
    • 14
  • Akira Yamashina
    • 15
  • Satoshi Yasuda
    • 16
  • Tsutomu Yoshikawa
    • 17
  • Akiko Kada
    • 2
    • 18
  • Hiroyuki Uesaka
    • 1
  • Masafumi Kitakaze
    • 1
    • 19
  • on behalf of the EARLIER investigators and study coordinators
  1. 1.Department of Clinical Medicine and Development, National Cerebral and Cardiovascular CenterSuitaJapan
  2. 2.Department of Advanced Medical Technology Development, National Cerebral and Cardiovascular CenterSuitaJapan
  3. 3.Department of Cardiovascular MedicineNippon Medical SchoolTokyoJapan
  4. 4.Department of Cardiovascular MedicineOsaka City University Graduate School of MedicineOsakaJapan
  5. 5.Division of Cardiovascular MedicineKobe University Graduate School of MedicineKobeJapan
  6. 6.Division of Cardiology, Department of MedicineNihon University School of MedicineTokyoJapan
  7. 7.Yokohama City University Medical CenterYokohamaJapan
  8. 8.Division of Cardiology, Department of MedicineShowa University School of MedicineYokohamaJapan
  9. 9.Saitama Medical CenterJichi Medical UniversitySaitamaJapan
  10. 10.Tenri HospitalTenriJapan
  11. 11.St. Luke’s International HospitalTokyoJapan
  12. 12.First Department of Internal MedicineNara Medical UniversityKashiharaJapan
  13. 13.NHO Disaster Medical CenterTachikawaJapan
  14. 14.Osaka General Medical CenterOsakaJapan
  15. 15.Tokyo Medical University HospitalTokyoJapan
  16. 16.Department of Cardiovascular Medicine, National Cerebral and Cardiovascular CenterSuitaJapan
  17. 17.Sakakibara Heart InstituteFuchuJapan
  18. 18.NHO Nagoya Medical CenterNagoyaJapan
  19. 19.Departments of Clinical Medicine and DevelopmentNational Cerebral and CardiovascularSuitaJapan

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