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