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LevetIracetam vs. Fosphenytoine for status epilepticus: multi-center randomised non-blinded control trial (IENE ECT with LIFE)

Ibaraki ER Network Epilepsy Control Trial with LevetIracetam vs. FosphEnytoine (IENE ECT with LIFE)

176

In the fosphenytoin FPHT and levetiracetam LEV groups, mean ages were 65 and 67 years old, males accounted for 65.2 and 67.0%, mean heights were 163.0 and 161.5 cm, mean body weights were 60.3 and 57.9 kg, and median serum creatinine levels on admission were 0.87 and 0.86 mg/dL, respectively. Three patients in each group had a previous history of liver disease. The type of SE was mostly tonic clonic seizures; 71.3% in the FPHT group and 77.4% in the LEV group. The main cause of SE was a previous stroke, followed by idiopathic epilepsy, others, and brain neoplasms. Median seizure durations before treatment were 42 and 60 minutes in the FPHT and LEV groups, respectively. No significant differences were observed in any of the basic characteristics examined.

Among the 176 adult patients with SE enrolled during the study period, 82 were assigned to the FPHT group and 94 to the LEV group. The protocol was performed and completed on all patients. Three out of the 176 patients enrolled, 2 in the FPHT group and 1 in the LEV group, were diagnosed with pseudoseizures and removed from the analysis.

Serious adverse event within 1 hr of study drug administration developed in 3 patients (3.7%) in the FPHT group and none (0%) in the LEV group (p=0.061). One adverse event was cardiac arrest, which is clarified as Grade 4 in the Common Terminology Criteria for Adverse Events. This patient died and the death was not directly associated with the administration of FPHT. Respiratory arrest and hypotension were detected in one patient each in the FPHT group, which are clarified as Grade 3. No serious adverse event were reported in the LEV group. Serious adverse event within 24 hrs and 7 days were not reported in either group.

As the primary outcome, seizure cessation rates within 30 minutes from study drug administration were 83.8% (67/80) in the FPHT group and 89.2% (83/93) in the LEV group. The rate difference was 5.5% (95% confidence interval -4.7 to 15.7, p=0.29). The non-inferiority of LEV to FPHT was confirmed with p<0.001 by the Farrington-Manning test with a non-inferiority margin of 20%. Regarding the secondary outcome, seizure recurrence rates within 24 hrs were 15% in the FPHT group and 17.2% in LEV group (p=0.70), while intubation rates within 24 hrs were 15.0% in the FPHT group and 16.1% in the LEV group (p=0.84), without a significant difference. Regarding the Modified Rankin Scale 7 days after admission, 46.3% of patients in the FPHT group and 42.0% in the LEV group had a score of 0 (no symptoms) or 1 (no significant disability), and 3 patients in the FPHT group and 2 in the LEV group died. No significant differences were observed between the groups.

The efficacy of LEV was similar to that of FPHT for the treatment of adult SE following the administration of diazepam. Since it was associated with fewer serious adverse event, LEV is recommended as a second-line treatment for SE as an alternative to phenytoin/FPHT.

Dec. 31, 2023

No

no

https://jrct.niph.go.jp/latest-detail/jRCTs031190160

Inoue Yoshiaki

University of Tsukuba Hospital

2-1-1 Amakubo Tsukuba Ibaraki

yinoue@md.tsukuba.ac.jp

Nakamura Kensuke

Hitachi General Hospital

2-1-1 Jonancho Hitachi Ibaraki

+81-294-23-1111

knakamura-tky@umin.ac.jp

Complete

Dec. 16, 2019

Interventional

randomized controlled trial

open(masking not used)

active control

parallel assignment

treatment purpose

status epilepticus with convulsion, who were transfered by ambulance
The difinition of status epilepticus is as follows; over 5 minutes of continuous seizures, or over 2 minutes discrete seizures between which there is incomplete recovery of consciousness over JCS II-30
exclude non-convulsive seizure

under 20 years old
patients who entried this study in the past
patients in whom informed consent can not be obtained from proxies (If proxies can not be found, the study is performed and the consent is obtained after action.
already intubated patients before treatment
allergy to fosphenytoin or levetiracetam
pregnancy
pseudo-seizure
medical doctor considered inapropriate

Both

status epilepticus

At first, diazepam 1 - 20 mg is given in both groups.
Hosphenytoin group
After diazepam, hosphenytoin 22.5mg/kg+normal saline 100ml is given DIV by under 3mg/kg/min or 150mg/min
Levetiracetam group
After diazepam, levetiracetam 1000-3000mg is given DIV by 2-5mg/kg/min

status epilepticus

levetiracetam

status epilepticus

seizure stop within 30 min from start of study drugs administration

seizure reccurence within 24 h
severe adverse events
intubation rate

+81-29-853-3914

Sept. 20, 2019

none