Fast Acute Sedation at Intensive Care vs. High-dose i.v. Anti-seizure Medication for Treatment of Non-convulsive Status Epilepticus (FAST-trial)

Non-Convulsive Status Epilepticus Clinical Trial

— FAST  

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05263674
• Other study ID #: 21/34684
• Secondary ID: 2021-003392-34
• Status: Recruiting
• Phase: Phase 3
• Start date: February 7, 2022
• Est. completion date: December 31, 2026

Study information

• Verified date: October 2023
• Source: University of Southern Denmark
• Contact: Christoph P. Beier, M.D.
• Phone: +4565411943
• Email: cbeier[@]health.sdu.dk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 140
• Est. completion date: December 31, 2026
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 120 Years

Eligibility

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

Related Conditions & MeSH terms

• Non-Convulsive Status Epilepticus
• Seizures
• Status Epilepticus

Intervention

Drug:
• Rapid sedation
High-dose Propofol (bolus 3-5 g / kg, maintenance dose 5-10 mg / kg / hour) to - 5 on the Richmond agitation sedation scale (RASS) for 20 hours, and a single anti-epileptic drug should be added as adjunctive therapy. Addition of low-dose Midazolam (max. 0.1 mg / kg / h) is permitted if deep sedation (defined clinically by RASS -5) is not possible with Propofol alone.

Locations

Country	Name	City	State
Denmark	Aarhus Universitetshospital	Aarhus
Denmark	Rigshospitalet	Copenhagen
Denmark	Odense University Hospital	Odense
Denmark	University Hospital of Zealand	Roskilde

Sponsors (4)

Lead Sponsor	Collaborator
University of Southern Denmark	Aarhus University Hospital, Copenhagen University Hospital, Denmark, University Hospital of Zealand

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Influence of cEEG on new neurological deficit	Patients receive either cEEG or spot EEG depending on the center. In this pre-specified analyses, the impact of cEEG vs. spot-EEG on the degree of new neurological deficits (outcome 3) will be compared	at discharge, on average after 7 days
Other	Duration of intensive care treatment	Definition: Time from intubation to discharge from ICU	at discharge, on average after 7 days
Other	Duration of hospitalization	Time from randomization to discharge from hospital in charge for acute treatment of NCSE	1-100 days, on average 7 days
Other	Proportion of patients with superrefractory status epilepticus	Proportion of patients that develop superrefractory status epilepticus after randomization but during current hospitalization	at discharge, on average after 7 days
Other	Survival after discharge	Determined at ambulatory control 3,6,12 and 24 months after randomization	3, 6, 12, and 24 months after randomization
Other	Quality of life after discharge	Determined using questionnaire/patient survey (Quality of Life in Epilepsy Inventory, Qolie-31 Danish translation), at ambulatory controls 3, 6, 12, and 24 months after randomization	3, 6, 12, and 24 months after randomization
Primary	Proportion of patients with continued NCSE on EEG after 24 h ("treatment failure")	NCSE diagnosed using EEG and defined by the "Salzburg criteria" for NCSE (e.g. Leitinger et al. Lancet Neurology, 2016)	24 hours after randomisation
Secondary	Number of treatment related complications	e.g. tracheostoma, infections	at discharge, on average after 7 days
Secondary	New neurological deficit	Neurological deficits are quantified using National Institute of Health Stroke Scale (NIHSS, maximum possible score is 42, the minimum score - indicating no deficits - is 0) at admission and discharge. New neurological deficit is defined as increase of NIHSS >5 at discharge	at discharge, on average after 7 days