Cornwall Camilla Dyremose, Piilgaard Henning, Engedal Thorbjørn Søndergaard, Olsen Hanne Tanghus, Møller Kirsten, Krøigård Thomas, Uslu Bülent, Christensen Jakob, Sidaros Annette, Beier Christoph Patrick
Department of Neurology, Odense University Hospital, Odense, Denmark.
Department of Neurology, Zealand University Hospital, Roskilde, Denmark.
Crit Care Explor. 2025 Sep 15;7(9):e1311. doi: 10.1097/CCE.0000000000001311. eCollection 2025 Sep 1.
The management of refractory status epilepticus (SE) remains an area of low evidence with varying management strategies. Treatment in the ICU is often postponed due to potential complications from sedation, and it is unknown if its efficacy is superior to additional treatment attempts with IV anti-seizure medications (ASMs). The Fast Acute Sedation at Intensive Care vs. High-Dose IV Anti-Seizure Medication for Treatment of Non-Convulsive Status Epilepticus (FAST) trial aims to compare the efficacy of rapid sedation in the ICU vs. add-on high-dose IV ASM alone for the treatment of refractory SE.
METHODS/RESULTS: This prospective, randomized, multicenter trial will enroll adult patients with non-convulsive status epilepticus (NCSE) who either meet current EEG criteria or have unambiguous NCSE with minor motor phenomena ("subtle SE") but without ongoing tonic-clonic seizures that are refractory to benzodiazepines and treatment with at least one second-line ASM. Patients will be randomized to receive either rapid deep sedation for 20 hours with propofol and eventually low-dose midazolam or additional high-dose IV anticonvulsant therapy (levetiracetam, valproate, fosphenytoin, lacosamide, or topiramate) in the intermediate care unit. The primary endpoint is treatment failure, either defined as NCSE on EEG 24 hours after randomization or persistent NCSE after 3 hours despite therapy on continuous EEG or clinically. Secondary endpoints include assessment of new-onset neurologic deficits and modified Rankin Scale at discharge, economic analyses, length of hospital stay, in-hospital infections, and survival. Evaluations will be performed at baseline, discharge, and 3, 6, 12, and 24 months. The target sample size is 116 patients; we expect to have to randomize about 140 patients to reach the required number of patients.
The FAST trial is the first randomized clinical trial to investigate refractory NCSE. Regardless of the outcome, the results of this trial protocol will provide new class 1 evidence for the treatment of NCSE and establish the standard of care for this patient population in the future.
EU CT: 2024-515507-18-00/clinicaltrials.gov: NCT05263674.
难治性癫痫持续状态（SE）的管理仍然是一个证据不足且管理策略各异的领域。由于镇静可能带来潜在并发症，重症监护病房（ICU）的治疗往往会推迟，而且其疗效是否优于静脉注射抗癫痫药物（ASM）的额外治疗尝试尚不清楚。重症监护快速急性镇静与高剂量静脉注射抗癫痫药物治疗非惊厥性癫痫持续状态（FAST）试验旨在比较ICU中快速镇静与单独使用高剂量静脉注射ASM治疗难治性SE的疗效。
方法/结果：这项前瞻性、随机、多中心试验将纳入符合当前脑电图标准或患有明确的伴有轻微运动现象的非惊厥性癫痫持续状态（“轻微SE”）但无持续性强直阵挛性发作且对苯二氮䓬类药物难治且至少接受过一种二线ASM治疗的成年患者。患者将被随机分为两组，一组在中间护理单元接受丙泊酚快速深度镇静20小时并最终使用低剂量咪达唑仑，另一组接受额外的高剂量静脉注射抗惊厥治疗（左乙拉西坦、丙戊酸盐、磷苯妥英、拉科酰胺或托吡酯）。主要终点是治疗失败，定义为随机分组后24小时脑电图显示为非惊厥性癫痫持续状态或尽管在持续脑电图监测或临床上进行了治疗但3小时后仍持续存在非惊厥性癫痫持续状态。次要终点包括评估出院时新发神经功能缺损和改良Rankin量表、经济分析、住院时间、医院感染和生存率。评估将在基线、出院时以及3、6、12和24个月时进行。目标样本量为116名患者；我们预计需要随机分配约140名患者才能达到所需的患者数量。
FAST试验是首个研究难治性非惊厥性癫痫持续状态的随机临床试验。无论结果如何，本试验方案的结果将为非惊厥性癫痫持续状态的治疗提供新的1类证据，并在未来确立该患者群体的护理标准。
欧盟临床试验注册号：2024 - 515507 - 18 - 00/美国国立医学图书馆临床试验注册中心注册号：NCT05263674。
