Naokata Sumitomo1, Hitoshi Horigome2, Masaru Miura3, Hiroshi Ono4, Hideaki Ueda5, Kiyohiro Takigiku6, Jun Yoshimoto7, Naoki Ohashi8, Tsugutoshi Suzuki9, Koichi Sagawa10, Hiroya Ushinohama10, Kazuhiro Takahashi11, Aya Miyazaki12, Heima Sakaguchi12, Mari Iwamoto13, Motoki Takamuro14, Chiho Tokunaga15, Tetsuji Nagano16. 1. Department of Pediatric Cardiology, Saitama Medical University International Medical Center, Saitama, Japan. Electronic address: sumitomo@saitama-med.ac.jp. 2. Department of Child Health, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan. 3. Division of Cardiology, Tokyo Metropolitan Children's Medical Center, Tokyo, Japan. 4. Division of Cardiology, National Center for Child Health and Development, Tokyo, Japan. 5. Department of Cardiology, Kanagawa Children's Medical Center, Yokohama, Japan. 6. Department of Pediatric Cardiology, Nagano Children's Hospital, Azumino, Japan. 7. Department of Pediatric Cardiology, Shizuoka Children's Hospital, Shizuoka, Japan. 8. Department of Pediatric Cardiology, Japan Community Health Care Organization Chukyo Hospital, Nagoya, Japan. 9. Department of Pediatric Electrophysiology, Osaka City General Hospital, Osaka, Japan. 10. Department of Pediatric Cardiology, Fukuoka Children's Hospital Medical Center, Fukuoka, Japan. 11. Department of Pediatric Cardiology, Okinawa Children's Medical Center, Okinawa, Japan. 12. Department of Pediatric Cardiology, National Cerebral and Cardiovascular Center, Osaka, Japan. 13. Department of Pediatrics, Saiseikai Yokohamashi Tobu Hospital, Yokohama, Japan. 14. Department of Pediatric Cardiology, Hokkaido Medical Center for Child Health and Rehabilitation, Sapporo, Japan. 15. Department of Cardiovascular Surgery, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan. 16. Ono Pharmaceutical Co. Ltd., Osaka, Japan.
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.
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 childtachyarrhythmia Using Landiolol in children with heart failure.