caa a22 4500 606158847 CHVBK 20210128100621.0 cr unu---uuuuu 210128e20150401xx s 000 0 eng 10.1007/s10557-014-6565-2 doi (NATIONALLICENCE)springer-10.1007/s10557-014-6565-2 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) [Elektronische Daten] [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] 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 72h 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 50mg, is administered for 6months 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) 6months 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. Springer Science+Business Media New York, 2015 Acute heart failure nationallicence Acute myocardial infarction nationallicence Eplerenone nationallicence Aldosterone nationallicence Cardiac death nationallicence Re-hospitalization nationallicence Asakura Masanori Department of Clinical Medicine and Development, National Cerebral and Cardiovascular Center, Suita, Japan aut Yamamoto Haruko Department of Advanced Medical Technology Development, National Cerebral and Cardiovascular Center, Suita, Japan aut Asai Kuniya Department of Cardiovascular Medicine, Nippon Medical School, Tokyo, Japan aut Hanatani Akihisa Department of Cardiovascular Medicine, Osaka City University Graduate School of Medicine, Osaka, Japan aut Hirata Ken-ichi Division of Cardiovascular Medicine, Kobe University Graduate School of Medicine, Kobe, Japan aut Hirayakma Atsushi Division of Cardiology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan aut Kimura Kazuo Yokohama City University Medical Center, Yokohama, Japan aut Kobayashi Youichi Division of Cardiology, Department of Medicine, Showa University School of Medicine, Yokohama, Japan aut Momomura Shin-ichi Saitama Medical Center, Jichi Medical University, Saitama, Japan aut Nakagawa Yoshihisa Tenri Hospital, Tenri, Japan aut Nishi Yutaro St. Luke's International Hospital, Tokyo, Japan aut Saito Yoshihiko First Department of Internal Medicine, Nara Medical University, Kashihara, Japan aut Satoh Yasuhiro NHO Disaster Medical Center, Tachikawa, Japan aut Yamada Takahisa Osaka General Medical Center, Osaka, Japan aut Yamashina Akira Tokyo Medical University Hospital, Tokyo, Japan aut Yasuda Satoshi Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Japan aut Yoshikawa Tsutomu Sakakibara Heart Institute, Fuchu, Japan aut Kada Akiko Department of Advanced Medical Technology Development, National Cerebral and Cardiovascular Center, Suita, Japan aut Uesaka Hiroyuki Department of Clinical Medicine and Development, National Cerebral and Cardiovascular Center, Suita, Japan aut Kitakaze Masafumi Department of Clinical Medicine and Development, National Cerebral and Cardiovascular Center, Suita, Japan aut Cardiovascular Drugs and Therapy Springer US; http://www.springer-ny.com 29/2(2015-04-01), 179-185 0920-3206 29:2<179 2015 29 10557 https://doi.org/10.1007/s10557-014-6565-2 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s10557-014-6565-2 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Asakura Masanori Department of Clinical Medicine and Development, National Cerebral and Cardiovascular Center, Suita, Japan aut NATIONALLICENCE 700 1- Yamamoto Haruko Department of Advanced Medical Technology Development, National Cerebral and Cardiovascular Center, Suita, Japan aut NATIONALLICENCE 700 1- Asai Kuniya Department of Cardiovascular Medicine, Nippon Medical School, Tokyo, Japan aut NATIONALLICENCE 700 1- Hanatani Akihisa Department of Cardiovascular Medicine, Osaka City University Graduate School of Medicine, Osaka, Japan aut NATIONALLICENCE 700 1- Hirata Ken-ichi Division of Cardiovascular Medicine, Kobe University Graduate School of Medicine, Kobe, Japan aut NATIONALLICENCE 700 1- Hirayakma Atsushi Division of Cardiology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan aut NATIONALLICENCE 700 1- Kimura Kazuo Yokohama City University Medical Center, Yokohama, Japan aut NATIONALLICENCE 700 1- Kobayashi Youichi Division of Cardiology, Department of Medicine, Showa University School of Medicine, Yokohama, Japan aut NATIONALLICENCE 700 1- Momomura Shin-ichi Saitama Medical Center, Jichi Medical University, Saitama, Japan aut NATIONALLICENCE 700 1- Nakagawa Yoshihisa Tenri Hospital, Tenri, Japan aut NATIONALLICENCE 700 1- Nishi Yutaro St. Luke's International Hospital, Tokyo, Japan aut NATIONALLICENCE 700 1- Saito Yoshihiko First Department of Internal Medicine, Nara Medical University, Kashihara, Japan aut NATIONALLICENCE 700 1- Satoh Yasuhiro NHO Disaster Medical Center, Tachikawa, Japan aut NATIONALLICENCE 700 1- Yamada Takahisa Osaka General Medical Center, Osaka, Japan aut NATIONALLICENCE 700 1- Yamashina Akira Tokyo Medical University Hospital, Tokyo, Japan aut NATIONALLICENCE 700 1- Yasuda Satoshi Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Japan aut NATIONALLICENCE 700 1- Yoshikawa Tsutomu Sakakibara Heart Institute, Fuchu, Japan aut NATIONALLICENCE 700 1- Kada Akiko Department of Advanced Medical Technology Development, National Cerebral and Cardiovascular Center, Suita, Japan aut NATIONALLICENCE 700 1- Uesaka Hiroyuki Department of Clinical Medicine and Development, National Cerebral and Cardiovascular Center, Suita, Japan aut NATIONALLICENCE 700 1- Kitakaze Masafumi Department of Clinical Medicine and Development, National Cerebral and Cardiovascular Center, Suita, Japan aut NATIONALLICENCE 773 0- Cardiovascular Drugs and Therapy Springer US; http://www.springer-ny.com 29/2(2015-04-01), 179-185 0920-3206 29:2<179 2015 29 10557