Levetiracetam versus fosphenytoin as a second-line treatment after diazepam for status epilepticus: study protocol for a multicenter non-inferiority designed randomized control trial

Trials

Akio Kimura¹  Chikara Yonekawa²  Masahiro Asami³  Kensuke Nakamura⁴  Yuji Takahashi⁴  Yutaka Kondo⁵  Junya Kaneko⁶  Yoshiaki Inoue⁷  Aiki Marushima⁷  Eisei Hoshiyama⁸  Satoshi Egawa⁹  Takeshi Yamada^1,10  Kazushi Maruo^1,10 

[1] Department of Emergency Medicine and Critical Care, National Center for Global Health and Medicine, 1-21-1 Toyama Shinjuku, Tokyo, Japan;Department of Emergency Medicine, Jichi medical University Hospital, 3311-1 Yakushiji, 329-0498, Shimotsuke, Tochigi, Japan;Department of Emergency Medicine, Teikyo University Hospital, 2-11-1, Kaga Itabashi, 173-8606, Tokyo, Japan;Department of Emergency and Critical Care Medicine, Hitachi General Hospital, 2-1-1 Jonan-cho, 317-0077, Hitachi, Ibaraki, Japan;Department of Emergency and Critical Care Medicine, Juntendo University Urayasu Hospital, 2-1-1, Tomioka, 279-0021, Urayasu, Chiba, Japan;Department of Emergency and Critical Care Medicine, Nippon Medical School Tama Nagayama Hospital, 1―7―1 Nagayama, Tama, 206-8512, Tokyo, Japan;Department of Emergency and Critical Care Medicine, Tsukuba University Hospital, 1-1-1 Tennodai, 305-8577, Tsukuba, Ibaraki, Japan;Emergency and Critical Care Medical Center, Dokkyo Medical University, 880 Kitakobayashi Mibu, 321-0293, Shimotsuga, Tochigi, Japan;Neurointensive Care Unit, Neurosurgery, Stroke and Epilepsy Center, TMG Asaka Medical Center, 1340-1 Mizonuma, 351-0023, Asaka city, Saitama, Japan;Tsukuba Clinical Research & Development Organization, University of Tsukuba, 1-1-1 Tennodai, 305-8577, Tsukuba, Ibaraki, Japan;

关键词: Epilepsy;    Fosphenytoin;    Levetiracetam;    Phenytoin;    Seizure;   

DOI  :  10.1186/s13063-021-05269-7

来源: Springer

【 摘 要 】

BackgroundStatus epilepticus (SE) is an emergency condition for which rapid and secured cessation is important. Phenytoin and fosphenytoin, the prodrug of phenytoin with less severe adverse effects, have been recommended as second-line treatments. However, fosphenytoin causes severe adverse events, such as hypotension and arrhythmia. Levetiracetam reportedly has similar efficacy and higher safety for SE; however, evidence to support its use for adult SE is lacking. In the present study, a non-inferiority designed multicenter randomized controlled trial (RCT) is being conducted to compare levetiracetam with fosphenytoin after diazepam as a second-line treatment for SE.MethodsThis multicenter, prospective, and open-label RCT is conducted in emergency departments. Between December 23, 2019, and March 31, 2023, 176 patients with convulsive SE transported to an emergency room will be randomized into a fosphenytoin group and levetiracetam group at a ratio of 1:1. The definition of SE is “continuous seizures longer than 5 min or discrete seizures longer than 2 min with intervening consciousness disturbance.” In both groups, diazepam is initially administered at 1–20 mg, followed by intravenous fosphenytoin at 22.5 mg/kg or intravenous levetiracetam at 1000–3000 mg. The primary outcome is the seizure cessation rate within 30 min. Seizure recurrence within 24 h, severe adverse events, and intubation rate within 24 h are secondary outcomes.DiscussionThe present study was approved and conducted as an initiative study of the Japanese Association for Acute Medicine. If non-inferiority is identified, the society will pursue an application for the national health insurance coverage of levetiracetam for SE via a public knowledge-based application.Trial registrationJapan Registry of Clinical Trials jRCTs031190160. Registered on December 13, 2019

【 授权许可】

CC BY