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

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат 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.

Первичные конечные точки

• Proportion of patients with continued NCSE on EEG after 24 h ("treatment failure") [Срок оценки: 24 hours after randomisation]

Вторичные конечные точки (2)

• Number of treatment related complications [Срок оценки: at discharge, on average after 7 days]
• New neurological deficit [Срок оценки: at discharge, on average after 7 days]

Критерии участия

Критерии включения

• 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).

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Дания · 5 центров

• Aarhus Universitetshospital — Aarhus
• Rigshospitalet — Copenhagen
• Department of Neurology — Herlev
• Odense University Hospital — Odense
• University Hospital of Zealand — Roskilde

Публикации

• Cornwall CD, Piilgaard H, Engedal TS, Olsen HT, Moller K, Kroigard T, Uslu B, Christensen J, Sidaros A, Beier CP. Fast Acute Sedation at Intensive Care vs. High-Dose IV Anti-seizure Medication for Treatment of Non-convulsive Status Epilepticus: A Randomized, Multicenter Trial. Crit Care Explor. 2025 Sep 15;7(9):e1311. doi: 10.1097/CCE.0000000000001311. eCollection 2025 Sep 1. PMID 40953286

Идентификаторы

NCT: NCT05263674 · 21/34684 · 2021-003392-34

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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