Treatment of established status epilepticus in the elderly - a study protocol for a prospective multicenter double-blind comparative effectiveness trial (ToSEE)

BACKGROUND: Status epilepticus (SE) is a common neurological emergency condition that especially affects the elderly and old population. Older people with SE frequently have non-convulsive SE (NCSE) and are also at special risk of suffering a poor outcome. The application of benzodiazepines fails to control SE in about one third of the cases. For benzodiazepine refractory SE (BRSE) in elderly, there is little evidence that would justify the choice of one of the commonly used antiepileptic drugs. The present study aims to generate evidence for the treatment of BRSE in this age group. METHODS: We will conduct a prospective, randomized, double-blind comparative effectiveness study in more than twenty hospitals in Germany over a four-year period. Four hundred and seventy-seven elderly patients (≥ 65 years old) diagnosed with BRSE will be allocated by 1:1 randomization to receive either levetiracetam or valproate. All types of SE will be considered. For the diagnosis NCSE a verification by EEG is required. Levetiracetam or valproate will be administered in one single infusion. The primary endpoint is the stable cessation of ictal activity 15 min after the start of infusion persisting for the following 45 min of observation. EEG recording is maintained over the whole observation period, clinical examinations are conducted in predefined intervals. In case of treatment success patients and study staff remain blinded until 60 min after the start of the infusion. Adverse events will be recorded until the end of the study. EEG data will be reviewed by two external independent experts. To obtain data about the further treatment of SE, intrahospital complications and the functional outcome in the short term the study participants will be observed until the day of discharge or day 30 whichever is earliest. DISCUSSION: ToSEE is the first study which shall deliver evidence for the SE-therapy in the elderly and old population in a controlled prospective comparator study. By design it also shall collect information about therapy regimes and outcome aspects of this disease. TRIAL REGISTRATION: The trial has been registered at the German Clinical Trials Register on 3 July, 2020 (DRKS00022308, https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00022308).