Levetiracetam versus fosphenytoin as a second-line treatment after diazepam for status epilepticus: study protocol for a multicenter non-inferiority designed randomized control trial
Abstract Background Status 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 advers...
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doaj-fc0337e786ca43afa70d51c2ce4f2bed2021-05-09T11:30:02ZengBMCTrials1745-62152021-05-0122111010.1186/s13063-021-05269-7Levetiracetam versus fosphenytoin as a second-line treatment after diazepam for status epilepticus: study protocol for a multicenter non-inferiority designed randomized control trialKensuke Nakamura0Aiki Marushima1Yuji Takahashi2Akio Kimura3Masahiro Asami4Satoshi Egawa5Junya Kaneko6Yutaka Kondo7Chikara Yonekawa8Eisei Hoshiyama9Takeshi Yamada10Kazushi Maruo11Yoshiaki Inoue12IENE ECT with the LIFE study groupDepartment of Emergency and Critical Care Medicine, Hitachi General HospitalDepartment of Emergency and Critical Care Medicine, Tsukuba University HospitalDepartment of Emergency and Critical Care Medicine, Hitachi General HospitalDepartment of Emergency Medicine and Critical Care, National Center for Global Health and MedicineDepartment of Emergency Medicine, Teikyo University HospitalNeurointensive Care Unit, Neurosurgery, Stroke and Epilepsy Center, TMG Asaka Medical CenterDepartment of Emergency and Critical Care Medicine, Nippon Medical School Tama Nagayama HospitalDepartment of Emergency and Critical Care Medicine, Juntendo University Urayasu HospitalDepartment of Emergency Medicine, Jichi medical University HospitalEmergency and Critical Care Medical Center, Dokkyo Medical UniversityTsukuba Clinical Research & Development Organization, University of TsukubaTsukuba Clinical Research & Development Organization, University of TsukubaDepartment of Emergency and Critical Care Medicine, Tsukuba University HospitalAbstract Background Status 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. Methods This 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. Discussion The 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 registration Japan Registry of Clinical Trials jRCTs031190160 . Registered on December 13, 2019https://doi.org/10.1186/s13063-021-05269-7EpilepsyFosphenytoinLevetiracetamPhenytoinSeizure |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Kensuke Nakamura Aiki Marushima Yuji Takahashi Akio Kimura Masahiro Asami Satoshi Egawa Junya Kaneko Yutaka Kondo Chikara Yonekawa Eisei Hoshiyama Takeshi Yamada Kazushi Maruo Yoshiaki Inoue IENE ECT with the LIFE study group |
spellingShingle |
Kensuke Nakamura Aiki Marushima Yuji Takahashi Akio Kimura Masahiro Asami Satoshi Egawa Junya Kaneko Yutaka Kondo Chikara Yonekawa Eisei Hoshiyama Takeshi Yamada Kazushi Maruo Yoshiaki Inoue IENE ECT with the LIFE study group 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 Epilepsy Fosphenytoin Levetiracetam Phenytoin Seizure |
author_facet |
Kensuke Nakamura Aiki Marushima Yuji Takahashi Akio Kimura Masahiro Asami Satoshi Egawa Junya Kaneko Yutaka Kondo Chikara Yonekawa Eisei Hoshiyama Takeshi Yamada Kazushi Maruo Yoshiaki Inoue IENE ECT with the LIFE study group |
author_sort |
Kensuke Nakamura |
title |
Levetiracetam versus fosphenytoin as a second-line treatment after diazepam for status epilepticus: study protocol for a multicenter non-inferiority designed randomized control trial |
title_short |
Levetiracetam versus fosphenytoin as a second-line treatment after diazepam for status epilepticus: study protocol for a multicenter non-inferiority designed randomized control trial |
title_full |
Levetiracetam versus fosphenytoin as a second-line treatment after diazepam for status epilepticus: study protocol for a multicenter non-inferiority designed randomized control trial |
title_fullStr |
Levetiracetam versus fosphenytoin as a second-line treatment after diazepam for status epilepticus: study protocol for a multicenter non-inferiority designed randomized control trial |
title_full_unstemmed |
Levetiracetam versus fosphenytoin as a second-line treatment after diazepam for status epilepticus: study protocol for a multicenter non-inferiority designed randomized control trial |
title_sort |
levetiracetam versus fosphenytoin as a second-line treatment after diazepam for status epilepticus: study protocol for a multicenter non-inferiority designed randomized control trial |
publisher |
BMC |
series |
Trials |
issn |
1745-6215 |
publishDate |
2021-05-01 |
description |
Abstract Background Status 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. Methods This 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. Discussion The 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 registration Japan Registry of Clinical Trials jRCTs031190160 . Registered on December 13, 2019 |
topic |
Epilepsy Fosphenytoin Levetiracetam Phenytoin Seizure |
url |
https://doi.org/10.1186/s13063-021-05269-7 |
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