Edaravone Dexborneol for Post-Stroke Epilepsy (EDEN-PSE)
A Randomized, Double-blind, Placebo-controlled, Multicenter Clinical Study of Edaravone Dexborneol Sublingual Tablets for the Prevention of Post-Stroke Epilepsy
This is a prospective, randomized, double-blind, placebo-controlled, multicenter clinical trial designed to evaluate the efficacy and safety of Edaravone Dexborneol sublingual tablets in preventing late-onset epilepsy in patients with acute ischemic stroke at high risk.
Eligible participants are adults aged 18-80 years with a confirmed diagnosis of acute ischemic stroke by clinical and imaging criteria (MRI or CT), enrolled within 48 hours of stroke onset. High risk for post-stroke epilepsy is defined as a SeLECT-EEG score ≥7. Patients must have no prior history of epilepsy or other central nervous system disorders associated with seizures. Key exclusion criteria include prior seizures before enrollment, recent stroke within the past 12 months, severe renal or hepatic dysfunction, significant cardiac insufficiency, drug hypersensitivity, pregnancy or lactation, and other conditions deemed unsuitable by investigators.
A total of approximately 160 participants will be randomized in a 1:1 ratio to receive either Edaravone Dexborneol sublingual tablets or matching placebo.
The primary endpoint is a composite outcome assessed within 2 years, defined as the occurrence of either: (1) definite clinical epileptic seizures, or (2) new-onset or worsening epileptiform EEG abnormalities (including IEDs, PDs, LRDAs) or electrographic seizures.
Secondary endpoints include: incidence of individual components of the primary outcome; time to first seizure; characteristics, severity, and frequency of seizures; longitudinal changes and resolution rate of epileptiform EEG activity; cognitive function assessed by MoCA and MMSE; neurological outcomes evaluated by mRS and NIHSS; quality of life and functional independence measured by SSQOL and Barthel Index; recurrence of stroke and all-cause mortality; changes in inflammatory biomarkers (TNF-α, IL-1β, COX-2, iNOS); and safety outcomes including treatment-emergent adverse events, serious adverse events, laboratory abnormalities, and treatment discontinuation due to adverse events.
All efficacy and safety outcomes will be independently reviewed by a blinded adjudication committee. Statistical analyses will include chi-square or Fisher's exact tests for categorical outcomes, Kaplan-Meier survival analysis with log-rank tests for time-to-event data, and Cox proportional hazards models to adjust for potential confounders.
The study period is planned from June 2026 to June 2030.
研究概览
地位
研究类型
注册 (估计的)
阶段
- 第三阶段
联系人和位置
学习联系方式
- 姓名：Xinshi Wang
- 电话号码：+8613757897051
- 邮箱：wangxinshi@wmu.edu.cn
学习地点
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Zhejiang
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Wenzhou、Zhejiang、中国、325000
- The First Affiliated Hospital of Wenzhou Medical University
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接触：
- Xinshi Wang
- 电话号码：8613757897051
- 邮箱：wangxinshi@wmu.edu.cn
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接触：
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参与标准
资格标准
适合学习的年龄
- 成人
- 年长者
接受健康志愿者
描述
Inclusion criteria: 1. Adults aged 18 to 80 years, of either sex.
2. Diagnosis of acute ischemic stroke confirmed by clinical presentation and neuroimaging (MRI or CT).
3. Time from stroke onset to screening/randomization ≤48 hours.
4. High risk of post-stroke epilepsy, defined as a SeLECT-EEG score ≥7, including: stroke severity (Se, 0-2 points), large-artery atherosclerosis etiology (L, 0-1 point), cortical involvement (C, 0-2 points), middle cerebral artery territory infarction (T, 0-1 point), and EEG findings (EEG, 0-2 points).
5. No prior history of epilepsy before the index stroke, and no history of other central nervous system disorders (e.g., traumatic brain injury, brain tumor) associated with seizures.
6. Conscious at enrollment or with recovered consciousness after treatment, and able to cooperate with sublingual medication administration and follow-up assessments.
7. Provision of written informed consent by the patient or a legally authorized representative.
Exclusion criteria: 1. History of epilepsy or occurrence of any seizure prior to screening.
2. History of ischemic or hemorrhagic stroke within 12 months prior to the index stroke.
3. Large cerebral infarction with severe intracranial hypertension on imaging after stroke, with limited life expectancy or inability to complete follow-up.
4. Severe renal impairment (significantly reduced eGFR according to contraindications of edaravone dexborneol) or a history of edaravone-related renal injury.
5. Severe hepatic dysfunction (ALT or AST >3 times the upper limit of normal) or severe heart failure (New York Heart Association class III-IV) that may preclude tolerance to the study drug.
6. Known hypersensitivity to edaravone or borneol, or a history of severe drug allergy.
7. Pregnant or breastfeeding women; women of childbearing potential unwilling to use effective contraception.
8. Presence of other serious diseases (e.g., advanced malignancy) that may affect survival or study compliance.
9. Any other condition that, in the investigator's judgment, makes the patient unsuitable for participation in the study.
学习计划
研究是如何设计的？
设计细节
- 主要用途：预防
- 分配：随机化
- 介入模型：并行分配
- 屏蔽：四人间
武器和干预
参与者组/臂 |
干预/治疗 |
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实验性的：Edaravone Dexborneol group
Participants in the experimental group will receive edaravone dexborneol sublingual tablets in addition to standard stroke therapy.
Each tablet contains edaravone 30 mg and borneol 6 mg.
The drug will be administered as one tablet sublingually twice daily, with an interval of at least 6 hours between doses.
Treatment will be initiated within 48 hours after stroke onset and continued for 3 months.
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In the experimental group, patients received edaravone dexborneol sublingual tablets in addition to standard stroke therapy.
Each tablet contained edaravone 30 mg plus borneol 6 mg, administered as one tablet sublingually twice daily (with an interval of ≥6 hours between doses).
Treatment was initiated as early as possible within 48 hours after stroke onset and continued for consecutive three months.
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安慰剂比较：Control group
Participants in the control group will receive matching placebo sublingual tablets with identical appearance, dosage form, and odor to the experimental drug.
The administration method, dosing frequency, and treatment duration will be the same as in the experimental group.
Both groups will receive standard stroke secondary prevention and rehabilitation therapy, without additional antiepileptic medications.
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In the control group, patients received placebo sublingual tablets identical in appearance, formulation, and odor to the investigational product (edaravone 0 mg plus borneol 60 μg, with trace borneol added to ensure odor matching).
Administration was initiated within 48 hours of stroke onset, at a regimen of one tablet sublingually twice daily (≥6-hour interval between doses), continued for consecutive three months.
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研究衡量的是什么？
主要结果指标
结果测量 |
措施说明 |
大体时间 |
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Proportion of participants with composite seizure-related events
大体时间：Up to 24 months
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Composite seizure-related events are defined as the occurrence of any of the following during follow-up: (1) clinical epileptic seizures occurring more than 7 days after stroke onset; (2) newly developed or worsening epileptiform activity on electroencephalography (EEG), including interictal epileptiform discharges (IEDs), periodic discharges (PDs), or lateralized rhythmic delta activity (LRDA); or (3) electrographic seizures.
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Up to 24 months
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
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Number of participants with late-onset clinical seizures
大体时间：Up to 24 months
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Late-onset seizures are defined as clinical epileptic seizures occurring more than 7 days after stroke onset.
The proportion of participants experiencing at least one seizure during follow-up will be recorded.
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Up to 24 months
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Proportion of participants with new or worsening epileptiform EEG abnormalities
大体时间：Up to 24 months
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Epileptiform EEG abnormalities include interictal epileptiform discharges (IEDs), periodic discharges (PDs), and lateralized rhythmic delta activity (LRDA).
New abnormalities are defined as findings not present on baseline EEG.
Worsening is defined as progression of pre-existing abnormalities compared with baseline, including increased frequency, transition to a continuous pattern, or expansion in spatial distribution.
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Up to 24 months
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Time to first late-onset clinical seizure
大体时间：Up to 24 months
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Time from stroke onset to the first occurrence of a late-onset clinical seizure, measured in days.
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Up to 24 months
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Proportion of participants with electrographic seizures without clinical manifestations
大体时间：Up to 24 months
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Electrographic seizures without clinical manifestations are defined as seizure activity detected on electroencephalography (EEG) without corresponding observable clinical symptoms.
Participants will be counted as having an event if one or more such events are detected during follow-up.
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Up to 24 months
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Proportion of participants with resolution of epileptiform EEG activity
大体时间：At 3, 6, 12, 18, and 24 months
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Among participants with epileptiform EEG activity at baseline, the proportion achieving resolution (conversion to normal EEG without epileptiform discharges) will be assessed at each follow-up visit.
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At 3, 6, 12, 18, and 24 months
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Number of seizure episodes per participant
大体时间：Up to 24 months
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Total number of seizure episodes per participant during the 24-month follow-up period will be recorded.
Median seizure frequency will be compared between groups.
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Up to 24 months
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Proportion of participants with severe seizure outcomes
大体时间：Up to 24 months
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Severe seizure outcomes include progression to status epilepticus or generalized tonic-clonic seizures.
The distribution of seizure severity will be recorded.
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Up to 24 months
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Change in Montreal Cognitive Assessment (MoCA) score from baseline
大体时间：Baseline, 3, 6, 12, 18, and 24 months
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Cognitive function will be assessed using the Montreal Cognitive Assessment (MoCA; total score range 0-30, higher scores indicate better cognitive function).
Changes in score from baseline will be evaluated at each follow-up visit.
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Baseline, 3, 6, 12, 18, and 24 months
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Change in Mini-Mental State Examination (MMSE) score from baseline
大体时间：Baseline, 3, 6, 12, 18, and 24 months
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Cognitive function will be assessed using the Mini-Mental State Examination (MMSE; total score range 0-30, higher scores indicate better cognitive function).
Changes in score from baseline will be evaluated at each follow-up visit.
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Baseline, 3, 6, 12, 18, and 24 months
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Change in modified Rankin Scale (mRS) score from baseline
大体时间：Baseline, 3, 6, 12, 18, and 24 months
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Functional neurological outcome will be assessed using the modified Rankin Scale (mRS; total score range 0-6, higher scores indicate greater disability).
Changes from baseline will be analyzed.
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Baseline, 3, 6, 12, 18, and 24 months
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Change in NIH Stroke Scale (NIHSS) score from baseline
大体时间：Baseline, 3, 6, 12, 18, and 24 months
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Neurological deficit severity will be assessed using the National Institutes of Health Stroke Scale (NIHSS; total score range 0-42, higher scores indicate greater neurological deficit).
Changes from baseline will be analyzed.
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Baseline, 3, 6, 12, 18, and 24 months
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Change in Stroke-Specific Quality of Life (SSQOL) score from baseline
大体时间：Baseline, 3, 6, 12, 18, and 24 months
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Quality of life will be assessed using the Stroke-Specific Quality of Life (SSQOL) scale (total score range 49-245, higher scores indicate better quality of life).
Changes in SSQOL total score from baseline will be evaluated at each follow-up time point.
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Baseline, 3, 6, 12, 18, and 24 months
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Change in Barthel Index from baseline
大体时间：Baseline, 3, 6, 12, 18, and 24 months
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Activities of daily living will be assessed using the Barthel Index (total score range 0-100, higher scores indicate greater independence).
Changes in Barthel Index score from baseline will be evaluated at each follow-up time point.
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Baseline, 3, 6, 12, 18, and 24 months
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Number of participants with recurrent stroke events
大体时间：Up to 24 months
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Recurrent stroke events include both ischemic and hemorrhagic stroke occurring after the index stroke.
The number of participants experiencing at least one recurrent stroke will be recorded.
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Up to 24 months
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Number of participants with all-cause mortality
大体时间：Up to 24 months
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All-cause mortality will be defined as death from any cause occurring during the study period.
The number of participants who die during follow-up will be recorded.
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Up to 24 months
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Change in tumor necrosis factor-alpha (TNF-α) levels from baseline
大体时间：Baseline, 1 week, 1 month, 3 months, and 24 months
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Serum TNF-α levels will be measured to assess inflammatory response.
Changes from baseline at each time point will be analyzed.
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Baseline, 1 week, 1 month, 3 months, and 24 months
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Change in interleukin-1 beta (IL-1β) levels from baseline
大体时间：Baseline, 1 week, 1 month, 3 months, and 24 months
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Serum IL-1β levels will be measured as a marker of inflammation.
Changes from baseline will be analyzed.
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Baseline, 1 week, 1 month, 3 months, and 24 months
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Change in cyclooxygenase-2 (COX-2) levels from baseline
大体时间：Baseline, 1 week, 1 month, 3 months, and 24 months
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COX-2 expression levels will be measured as part of inflammatory pathway assessment.
Changes from baseline will be analyzed.
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Baseline, 1 week, 1 month, 3 months, and 24 months
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Change in inducible nitric oxide synthase (iNOS) levels from baseline
大体时间：Baseline, 1 week, 1 month, 3 months, and 24 months
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iNOS levels will be measured to evaluate inflammatory and oxidative stress responses.
Changes from baseline will be analyzed.
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Baseline, 1 week, 1 month, 3 months, and 24 months
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Number of participants with treatment-emergent adverse events
大体时间：Up to 24 months
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Treatment-emergent adverse events (TEAEs) are defined as adverse events occurring after initiation of study treatment.
The number of participants experiencing at least one TEAE will be recorded.
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Up to 24 months
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Number of participants with serious adverse events
大体时间：Up to 24 months
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Serious adverse events (SAEs) include events that result in death, are life-threatening, require hospitalization, or result in significant disability.
The number of participants experiencing at least one SAE will be recorded.
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Up to 24 months
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Number of participants who discontinued treatment due to adverse events
大体时间：Up to 24 months
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Treatment discontinuation due to adverse events will be recorded as a measure of drug tolerability.
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Up to 24 months
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合作者和调查者
出版物和有用的链接
一般刊物
- Fu Y, Wang A, Tang R, Li S, Tian X, Xia X, Ren J, Yang S, Chen R, Zhu S, Feng X, Yao J, Wei Y, Dong X, Ling Y, Yi F, Deng Q, Guo C, Sui Y, Han S, Wen G, Li C, Dong A, Sun X, Wang Z, Shi X, Liu B, Fan D. Sublingual Edaravone Dexborneol for the Treatment of Acute Ischemic Stroke: The TASTE-SL Randomized Clinical Trial. JAMA Neurol. 2024 Feb 19;81(4):319-26. doi: 10.1001/jamaneurol.2023.5716. Online ahead of print. Erratum In: JAMA Neurol. 2024 Apr 1;81(4):425. doi: 10.1001/jamaneurol.2024.0883.
- Qiu W, Chen R, Pan L, Li Y, Xu Y, Li Y, Guo A, Huang W, Tan T, Li P, Xie C, Xu H, Lin L, Wang X. Edaravone dexborneol exerts anti-epileptic effects on rodent temporal lobe epilepsy by promoting NMDAR deactivation and inhibiting oxidative stress. Phytomedicine. 2025 May;140:156558. doi: 10.1016/j.phymed.2025.156558. Epub 2025 Mar 1.
- Galovic M, Dohler N, Erdelyi-Canavese B, Felbecker A, Siebel P, Conrad J, Evers S, Winklehner M, von Oertzen TJ, Haring HP, Serafini A, Gregoraci G, Valente M, Janes F, Gigli GL, Keezer MR, Duncan JS, Sander JW, Koepp MJ, Tettenborn B. Prediction of late seizures after ischaemic stroke with a novel prognostic model (the SeLECT score): a multivariable prediction model development and validation study. Lancet Neurol. 2018 Feb;17(2):143-152. doi: 10.1016/S1474-4422(17)30404-0.
- Hesdorffer DC, Benn EK, Cascino GD, Hauser WA. Is a first acute symptomatic seizure epilepsy? Mortality and risk for recurrent seizure. Epilepsia. 2009 May;50(5):1102-8. doi: 10.1111/j.1528-1167.2008.01945.x. Epub 2009 Jan 26.
研究记录日期
研究主要日期
学习开始 (估计的)
初级完成 (估计的)
研究完成 (估计的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (实际的)
研究记录更新
最后更新发布 (实际的)
上次提交的符合 QC 标准的更新
最后验证
更多信息
与本研究相关的术语
其他相关的 MeSH 术语
其他研究编号
- KY2025-328-02 (其他标识符：Ethics Committee in Clinical Research (ECCR) of the First Affiliated Hospital of Wenzhou Medical University)
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IPD 计划说明
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