title: 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).
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Clinical Medicine and Development, National Cerebral and Cardiovascular Center, Suita, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Asakura
authors.forename: Haruko
authors.initials: H
authors.lastname: Yamamoto
authors.forename: Kuniya
authors.initials: K
authors.lastname: Asai
authors.forename: Akihisa
authors.initials: A
authors.lastname: Hanatani
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Hirata
authors.forename: Atsushi
authors.initials: A
authors.lastname: Hirayakma
authors.forename: Kazuo
authors.initials: K
authors.lastname: Kimura
authors.forename: Youichi
authors.initials: Y
authors.lastname: Kobayashi
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Momomura
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Nakagawa
authors.forename: Yutaro
authors.initials: Y
authors.lastname: Nishi
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Saito
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Satoh
authors.forename: Takahisa
authors.initials: T
authors.lastname: Yamada
authors.forename: Akira
authors.initials: A
authors.lastname: Yamashina
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yasuda
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Yoshikawa
authors.forename: Akiko
authors.initials: A
authors.lastname: Kada
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Uesaka
authors.forename: Masafumi
authors.initials: M
authors.lastname: Kitakaze
mesh_terms: D000208:Acute Disease; D000328:Adult; D002985:Clinical Protocols; D004311:Double-Blind Method; D061345:Early Medical Intervention / Q000379:methods*; D000077545:Eplerenone; D005260:Female; D006333:Heart Failure / Q000188:drug therapy*; D006801:Humans; D008297:Male; D000451:Mineralocorticoid Receptor Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D013148:Spironolactone / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D000451:Mineralocorticoid Receptor Antagonists; D013148:Spironolactone; D000077545:Eplerenone