Edaravone Dexborneol for Post-Stroke Epilepsy

Официальное название

A Randomized, Double-blind, Placebo-controlled, Multicenter Clinical Study of Edaravone Dexborneol Sublingual Tablets for the Prevention of Post-Stroke Epilepsy

Обзор

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.

Вмешательства

• Препарат Treatment of edaravone dexborneol sublingual tablets containin edaravone 30 mg plus borneol 6 mg, twice daily (with an interval of ≥6 hours between doses) for three months.
  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.
• Препарат Placebo
  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.

Первичные конечные точки

• Proportion of participants with composite seizure-related events [Срок оценки: Up to 24 months]

Вторичные конечные точки (12)

• Number of participants with late-onset clinical seizures [Срок оценки: Up to 24 months]
• Proportion of participants with new or worsening epileptiform EEG abnormalities [Срок оценки: Up to 24 months]
• Time to first late-onset clinical seizure [Срок оценки: Up to 24 months]
• Proportion of participants with electrographic seizures without clinical manifestations [Срок оценки: Up to 24 months]
• Proportion of participants with resolution of epileptiform EEG activity [Срок оценки: At 3, 6, 12, 18, and 24 months]
• Number of seizure episodes per participant [Срок оценки: Up to 24 months]
• Proportion of participants with severe seizure outcomes [Срок оценки: Up to 24 months]
• Change in Montreal Cognitive Assessment (MoCA) score from baseline [Срок оценки: Baseline, 3, 6, 12, 18, and 24 months]
• Change in Mini-Mental State Examination (MMSE) score from baseline [Срок оценки: Baseline, 3, 6, 12, 18, and 24 months]
• Change in modified Rankin Scale (mRS) score from baseline [Срок оценки: Baseline, 3, 6, 12, 18, and 24 months]
• Change in NIH Stroke Scale (NIHSS) score from baseline [Срок оценки: Baseline, 3, 6, 12, 18, and 24 months]
• Change in Stroke-Specific Quality of Life (SSQOL) score from baseline [Срок оценки: Baseline, 3, 6, 12, 18, and 24 months]

Критерии участия

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.

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

Четверное слепое

Основная цель

Профилактика

Центры проведения

Китай · 1 центр

• The First Affiliated Hospital of Wenzhou Medical University — Wenzhou

Публикации

• 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 PMID 38372981
• 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. PMID 40054180
• 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 stu PMID 29413315
• 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. PMID 19374657

Идентификаторы

NCT: NCT07604350 · KY2025-328-02 · KY2025-328-02

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗