Edaravone Dexborneol for Post-Stroke Epilepsy (EDEN-PSE)

Wenzhou Medical University

Status and phase: Not yet enrolling; Phase 3

Conditions: Post-stroke Seizure; Post-stroke Epilepsy

Treatments: 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

Funder types: Other

Identifiers

NCT07604350

KY2025-328-02 (Other Identifier)

Details and patient eligibility

About

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.

Enrollment: 160 estimated patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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.

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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160 participants in 2 patient groups, including a placebo group

Edaravone Dexborneol group

Experimental group

Description:

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.

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.

Control group

Placebo Comparator group

Description:

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.

Treatment:

Drug: Placebo