title: Study design for control of HEART rate in inFant and child tachyarrhythmia with heart failure Using Landiolol (HEARTFUL): A prospective, multicenter, uncontrolled clinical trial.
abstract: BACKGROUND
  Persistent tachycardia in pediatric patients after congenital heart surgery further deteriorates their hemodynamic condition, and may become fatal. Therefore, immediate control of the tachycardia is mandatory in these patients. For this purpose, quick-acting, short-acting, titratable intravenous agents are required. However, there are no agents with such characteristics among the drugs approved for control of pediatric arrhythmias in Japan, and thus novel and effective medications for these patients are awaited. Landiolol, an ultrashort-acting β-blocker, was approved in 2013 for tachyarrhythmias in adult patients with heart failure. However, its efficacy and safety in pediatric patients remain unclear. The aim of this prospective, multicenter, open-label phase IIb/III study is to investigate the efficacy and safety of landiolol in pediatric patients with tachyarrhythmias as well as heart failure.
  
  
  METHODS
  Eligible patients are aged ≥ 3 months and <15 years, and have tachyarrhythmia (atrial fibrillation, atrial flutter, supraventricular tachycardia) as well as heart failure. The primary endpoint of the study is ≥20% reduction from baseline heart rate or return to normal sinus rhythm within 2h after starting intravenous administration of landiolol. Patients will receive intravenous infusion of landiolol, starting at 1μg/kg/min. The dose will be increased by 1μg/kg/min every 15-20min until the tachycardia rate has decreased by >20% or tachycardia has terminated, and the dose will then be maintained or further increased depending on the patient's condition. The study was started in April 2015 and will end within a few years.
  
  
  CONCLUSIONS
  The study was designed and designated the "HEARTFUL study" in the hope of establishing a basis for control of HEART rate in inFant and child tachyarrhythmia Using Landiolol in children with heart failure.
authors.affiliation: Department of Pediatric Cardiology, Saitama Medical University International Medical Center, Saitama, Japan. Electronic address: sumitomo@saitama-med.ac.jp.
authors.forename: Naokata
authors.initials: N
authors.lastname: Sumitomo
authors.affiliation: Department of Child Health, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Horigome
authors.affiliation: Division of Cardiology, Tokyo Metropolitan Children's Medical Center, Tokyo, Japan.
authors.forename: Masaru
authors.initials: M
authors.lastname: Miura
authors.affiliation: Division of Cardiology, National Center for Child Health and Development, Tokyo, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ono
authors.affiliation: Department of Cardiology, Kanagawa Children's Medical Center, Yokohama, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Ueda
authors.affiliation: Department of Pediatric Cardiology, Nagano Children's Hospital, Azumino, Japan.
authors.forename: Kiyohiro
authors.initials: K
authors.lastname: Takigiku
authors.affiliation: Department of Pediatric Cardiology, Shizuoka Children's Hospital, Shizuoka, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Yoshimoto
authors.affiliation: Department of Pediatric Cardiology, Japan Community Health Care Organization Chukyo Hospital, Nagoya, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Ohashi
authors.affiliation: Department of Pediatric Electrophysiology, Osaka City General Hospital, Osaka, Japan.
authors.forename: Tsugutoshi
authors.initials: T
authors.lastname: Suzuki
authors.affiliation: Department of Pediatric Cardiology, Fukuoka Children's Hospital Medical Center, Fukuoka, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Sagawa
authors.affiliation: Department of Pediatric Cardiology, Fukuoka Children's Hospital Medical Center, Fukuoka, Japan.
authors.forename: Hiroya
authors.initials: H
authors.lastname: Ushinohama
authors.affiliation: Department of Pediatric Cardiology, Okinawa Children's Medical Center, Okinawa, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Takahashi
authors.affiliation: Department of Pediatric Cardiology, National Cerebral and Cardiovascular Center, Osaka, Japan.
authors.forename: Aya
authors.initials: A
authors.lastname: Miyazaki
authors.affiliation: Department of Pediatric Cardiology, National Cerebral and Cardiovascular Center, Osaka, Japan.
authors.forename: Heima
authors.initials: H
authors.lastname: Sakaguchi
authors.affiliation: Department of Pediatrics, Saiseikai Yokohamashi Tobu Hospital, Yokohama, Japan.
authors.forename: Mari
authors.initials: M
authors.lastname: Iwamoto
authors.affiliation: Department of Pediatric Cardiology, Hokkaido Medical Center for Child Health and Rehabilitation, Sapporo, Japan.
authors.forename: Motoki
authors.initials: M
authors.lastname: Takamuro
authors.affiliation: Department of Cardiovascular Surgery, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.
authors.forename: Chiho
authors.initials: C
authors.lastname: Tokunaga
authors.affiliation: Ono Pharmaceutical Co. Ltd., Osaka, Japan.
authors.forename: Tetsuji
authors.initials: T
authors.lastname: Nagano
mesh_terms: D000293:Adolescent; D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D001281:Atrial Fibrillation / Q000188:drug therapy* / Q000503:physiopathology; D001282:Atrial Flutter / Q000188:drug therapy* / Q000503:physiopathology; D002648:Child; D002675:Child, Preschool; D005260:Female; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007223:Infant; D007262:Infusions, Intravenous; D008297:Male; D009025:Morpholines / Q000627:therapeutic use*; D012107:Research Design; D013610:Tachycardia / Q000188:drug therapy* / Q000503:physiopathology; D014508:Urea / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D000319:Adrenergic beta-Antagonists; D009025:Morpholines; C077049:landiolol; D014508:Urea
keywords: Heart failure; Landiolol; Pediatric tachyarrhythmia; β-Blocker