Clinical trial NCT05263674: Fast Acute Sedation at Intensive Care vs. High-dose i.v. Anti-seizure Medication for Treatment of Non-convulsive Status Epilepticus (FAST-trial)
Official title: Fast Acute Sedation at Intensive Care vs. High-dose i.v. Anti-seizure Medication for Treatment of Non-convulsive Status Epilepticus (FAST-trial)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Non-Convulsive Status Epilepticus
Lead sponsor: University of Southern Denmark
Sponsor class: OTHER
Collaborators: name: Aarhus University Hospital
name: University Hospital of Zealand
name: Copenhagen University Hospital, Denmark
First posted: 2022-03-02
Enrollment: 140
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Comparison of two treatment strategies
Primary purpose: TREATMENT

Brief summary: This open-label, randomized multicenter trial aims at clarifying the standard of care of patients with non-convulsive status epilepticus not responding to treatment with benzodiazepines and at least one high-dose intra venous anti-seizure medication.

Detailed description: Persistent epileptic seizures, aka. status epilepticus (SE), are the second most common neurological cause of acute admissions. Around halv of the patients suffers from SE without prominent visible seizures ("convulsions"), which is referred to as non-convulsive status epilepticus (NCSE) and is afflicted with a long-term mortality of \>50% also in patients without concomittant acute brain disease. There are no evidence-based treatment guidelines for NCSE but patients usually receive treatment with benzodiazepines followed by i.v. anti-seizure medication. If seizures continues, further treatment is controversial. The participating centers have long-standing experience in treating NCSE but use different, internationally accepted treatment strategies. Some initiate aggressive treatment with fast sedation at intensive care aiming at immediate seizure control, other estimate that the side effects of sediation does not outweigh the potential benefit and try high-dose i.v. anti-seizure medication that only slightly impair conciousness - often with success.

This randomized, open label, multicenter trial (Eudract 2021-003392-34) aims at clarifying the treatment of patients with NSCE not responding to standard therapy. Patients with verified NCSE based on clinical parameter or using electroencephalography (EEG) are randomized into a fast acute sedation group and a group that receives at least one additional, high-dose anti-seizure mediciation.

Primary objective endpoint is treatment failure 24 h after randomization as determined by EEG. Secondary endpoints are e.g. seizure-induced neurological damage, treatment-related complications and neurological long-term outcome.

The statistical planing aims at showing superiority of aggressive treatment, 140 patients shall be included in a three years period at the University Hospitals in Aarhus, Odense, Roskilde and Copenhagen.

Eligibility criteria: Inclusion Criteria:

* Adult patients (older than 18 years) with EEG-verified NCSE, according to the Salzburg criteria, who have not responded to appropriate treatment with benzodiazepines and at least one 2nd line i.v. anti-seizure medication according to the current Danish national neurological treatment guidelines (Levetiracetam, Fosfenytoin or Valproate).

Exclusion Criteria:

* patients with epilepticus status due to acute neuroinfection (e.g. bacterial meningitis or viral encephalitis)
* acute traumatic or spontaneous intracranial hemorrhage
* suspicion of cerebral anoxia / hypoxia / hypoglycemia / epileptic encephalopathy
* contraindications to anti-seizure medication defined in the protocol
* contraindications to anesthesia treatment in intensive care
* focal motor status epilepticus without relevant conscious influence (Glasgow Coma Scale\> 13)
* known epileptic encephalopathy
* Clinical need for acute intubation

Primary outcomes:
measure: Proportion of patients with continued NCSE on EEG after 24 h ("treatment failure")
timeFrame: 24 hours after randomisation
Secondary outcomes:
measure: Number of treatment related complications
timeFrame: at discharge, on average after 7 days
measure: New neurological deficit
timeFrame: at discharge, on average after 7 days
Other outcomes:
measure: Influence of cEEG on new neurological deficit
timeFrame: at discharge, on average after 7 days
measure: Duration of intensive care treatment
timeFrame: at discharge, on average after 7 days
measure: Duration of hospitalization
timeFrame: 1-100 days, on average 7 days
measure: Proportion of patients with superrefractory status epilepticus
timeFrame: at discharge, on average after 7 days
measure: Survival after discharge
timeFrame: 3, 6, 12, and 24 months after randomization
measure: Quality of life after discharge
timeFrame: 3, 6, 12, and 24 months after randomization
Locations:
city: Aarhus
country: Denmark
facility: Aarhus Universitetshospital
city: Copenhagen
country: Denmark
facility: Rigshospitalet
city: Odense
country: Denmark
facility: Odense University Hospital
city: Roskilde
country: Denmark
facility: University Hospital of Zealand
Study officials:
References: