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.

Study Overview

• Status: Not yet recruiting
• Conditions: Post-stroke Seizure; Post-stroke Epilepsy
• Intervention / Treatment: Drug: 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.; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 160
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Xinshi Wang; Phone Number: +8613757897051; Email: wangxinshi@wmu.edu.cn

Study Locations

• China
  • Zhejiang
    • Wenzhou, Zhejiang, China, 325000
      • The First Affiliated Hospital of Wenzhou Medical University
      • Contact: Xinshi Wang; Phone Number: 8613757897051; Email: wangxinshi@wmu.edu.cn
      • Contact: Email: wangxinshi@wmu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: 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.
Placebo Comparator: 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.	Drug: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of participants with composite seizure-related events	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.	Up to 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with late-onset clinical seizures	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.	Up to 24 months
Proportion of participants with new or worsening epileptiform EEG abnormalities	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.	Up to 24 months
Time to first late-onset clinical seizure	Time from stroke onset to the first occurrence of a late-onset clinical seizure, measured in days.	Up to 24 months
Proportion of participants with electrographic seizures without clinical manifestations	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.	Up to 24 months
Proportion of participants with resolution of epileptiform EEG activity	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.	At 3, 6, 12, 18, and 24 months
Number of seizure episodes per participant	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.	Up to 24 months
Proportion of participants with severe seizure outcomes	Severe seizure outcomes include progression to status epilepticus or generalized tonic-clonic seizures. The distribution of seizure severity will be recorded.	Up to 24 months
Change in Montreal Cognitive Assessment (MoCA) score from baseline	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.	Baseline, 3, 6, 12, 18, and 24 months
Change in Mini-Mental State Examination (MMSE) score from baseline	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.	Baseline, 3, 6, 12, 18, and 24 months
Change in modified Rankin Scale (mRS) score from baseline	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.	Baseline, 3, 6, 12, 18, and 24 months
Change in NIH Stroke Scale (NIHSS) score from baseline	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.	Baseline, 3, 6, 12, 18, and 24 months
Change in Stroke-Specific Quality of Life (SSQOL) score from baseline	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.	Baseline, 3, 6, 12, 18, and 24 months
Change in Barthel Index from baseline	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.	Baseline, 3, 6, 12, 18, and 24 months
Number of participants with recurrent stroke events	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.	Up to 24 months
Number of participants with all-cause mortality	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.	Up to 24 months
Change in tumor necrosis factor-alpha (TNF-α) levels from baseline	Serum TNF-α levels will be measured to assess inflammatory response. Changes from baseline at each time point will be analyzed.	Baseline, 1 week, 1 month, 3 months, and 24 months
Change in interleukin-1 beta (IL-1β) levels from baseline	Serum IL-1β levels will be measured as a marker of inflammation. Changes from baseline will be analyzed.	Baseline, 1 week, 1 month, 3 months, and 24 months
Change in cyclooxygenase-2 (COX-2) levels from baseline	COX-2 expression levels will be measured as part of inflammatory pathway assessment. Changes from baseline will be analyzed.	Baseline, 1 week, 1 month, 3 months, and 24 months
Change in inducible nitric oxide synthase (iNOS) levels from baseline	iNOS levels will be measured to evaluate inflammatory and oxidative stress responses. Changes from baseline will be analyzed.	Baseline, 1 week, 1 month, 3 months, and 24 months
Number of participants with treatment-emergent adverse events	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.	Up to 24 months
Number of participants with serious adverse events	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.	Up to 24 months
Number of participants who discontinued treatment due to adverse events	Treatment discontinuation due to adverse events will be recorded as a measure of drug tolerability.	Up to 24 months

Collaborators and Investigators

• Sponsor: First Affiliated Hospital of Wenzhou Medical University
• Collaborators: Ningbo Medical Center Lihuili Hospital; The Central Hospital of Lishui City; Ningbo No.2 Hospital; The Third Affiliated Hospital of Wenzhou Medical University

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): June 1, 2030
• Study Completion (Estimated): December 1, 2030

Study Registration Dates

• First Submitted: September 14, 2025
• First Submitted That Met QC Criteria: May 20, 2026
• First Posted (Actual): May 22, 2026

Study Record Updates

• Last Update Posted (Actual): May 22, 2026
• Last Update Submitted That Met QC Criteria: May 20, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: edaravone dexborneol; post-stroke epilepsy
• Additional Relevant MeSH Terms: Amino Acids, Peptides, and Proteins; Proteins; Enzymes; Enzymes and Coenzymes; Oxidoreductases; Tumor Suppressor Proteins; Neoplasm Proteins; Short Chain Dehydrogenase-Reductases; NAD (+) and NADP (+) Dependent Alcohol Oxidoreductases; Alcohol Oxidoreductases; WW Domain-Containing Oxidoreductase; isoborneol
• Other Study ID Numbers: KY2025-328-02 (Other Identifier: Ethics Committee in Clinical Research (ECCR) of the First Affiliated Hospital of Wenzhou Medical University)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: De-identified individual participant data (IPD) will not be publicly shared due to privacy and ethical considerations. However, data may be made available to qualified researchers upon reasonable request, subject to institutional review and data sharing agreements.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No