Evaluating the Efficacy, Safety, and Tolerability of Serelaxin When Added to Standard Therapy in Asian Patients With Acute Heart Failure: Design and Rationale of RELAX-AHF-ASIA Trial.
BACKGROUND
Acute heart failure (AHF), a common and growing health concern worldwide, is associated with high risk of post-discharge rehospitalization and mortality. Existing evidence indicates potential therapeutic benefits of serelaxin in Caucasian AHF patients, but corresponding data in Asians remain scarce. RELAX-AHF-ASIA, a multinational, randomized, double-blind, placebo-controlled, phase III trial, will evaluate the effects of serelaxin on symptom relief and clinical outcomes in Asian AHF patients, with the use of novel assessments.


RESULTS
Patients with AHF, systolic blood pressure ≥125 mm Hg, and mild to moderate renal dysfunction will be randomized within 16 hours of presentation to receive 48-hour intravenous infusion of 30 µg ⋅ kg-1⋅ d-1serelaxin or placebo in addition to standard therapy. The composite primary end point includes: (1) treatment success (moderate/marked improvement in patient-reported dyspnea and physician-assessed signs of congestion on day 2); (2) treatment failure (in-hospital worsening of signs and/or symptoms of heart failure [HF] requiring intensification of intravenous HF therapy or mechanical ventilation, renal/circulatory support, rehospitalization due to HF/renal-failure, or death through day 5); and (3) unchanged status. Secondary end points include time to in-hospital worsening HF through day 5 and all-cause and cardiovascular deaths through day 180.


CONCLUSIONS
RELAX-AHF-ASIA, the largest randomized clinical trial in Asian AHF patients to date, has a novel composite primary end point and the potential to become a hallmark of AHF trials.
Cardiology and Intensive Care Unit, Nippon Medical School, Musashi-Kosugi Hospital, Kawasaki, Japan. Electronic address: nms-ns@nms.ac.jp.
Naoki
N
Sato
National Heart Centre Singapore and Duke-NUS, Singapore.
Carolyn S P
CS
Lam
University of California, San Francisco, and San Francisco Veterans Affairs Medical Center, Los Angeles, California.
John R
JR
Teerlink
Division of Cardiology, University of California, San Diego, La Jolla, California.
Barry H
BH
Greenberg
Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University, Fukuoka, Japan.
Hiroyuki
H
Tsutsui
Department of Internal Medicine, Seoul National University, College of Medicine, Seoul, South Korea.
Byung-Hee
BH
Oh
Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China.
Jian
J
Zhang
Novartis Pharmaceuticals Corporation, East Hanover, New Jersey.
Martin
M
Lefkowitz
Novartis Pharmaceuticals Corporation, East Hanover, New Jersey.
Tsushung A
TA
Hua
Novartis Pharma, Basel, Switzerland.
Thomas
T
Holbro
Novartis Pharmaceuticals Corporation, East Hanover, New Jersey.
Miriam
M
Marshood
Novartis Pharmaceuticals Corporation, East Hanover, New Jersey.
Xing Li
XL
Wang
Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai, China.
Junbo
J
Ge
D000208:Acute Disease; D000368:Aged; D001208:Asia / Q000453:epidemiology; D002317:Cardiovascular Agents / Q000627:therapeutic use*; D002423:Cause of Death / Q000639:trends; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004361:Drug Tolerance; D005260:Female; D006333:Heart Failure / Q000188:drug therapy* / Q000453:epidemiology; D006801:Humans; D015994:Incidence; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000008:administration & dosage; D012065:Relaxin / Q000008:administration & dosage*; D015996:Survival Rate / Q000639:trends; D016896:Treatment Outcome
D002317:Cardiovascular Agents; D011994:Recombinant Proteins; C577649:serelaxin protein, human; D012065:Relaxin
Asian; Serelaxin; acute heart failur; efficacy