Post-stroke Epilepsy, Post-stroke Seizure
Conditions
Keywords
post-stroke epilepsy, edaravone dexborneol
Brief summary
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.
Interventions
DRUGTreatment 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.
DRUGPlacebo
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.
Sponsors
First Affiliated Hospital of Wenzhou Medical University
The Third Affiliated Hospital of Wenzhou Medical University
Ningbo Medical Center Lihuili Hospital
The Central Hospital of Lishui City
Ningbo No.2 Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of participants with composite seizure-related events | Up to 24 months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with late-onset clinical seizures | Up to 24 months | 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. |
| Proportion of participants with new or worsening epileptiform EEG abnormalities | Up to 24 months | 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. |
| Time to first late-onset clinical seizure | Up to 24 months | Time from stroke onset to the first occurrence of a late-onset clinical seizure, measured in days. |
| Proportion of participants with electrographic seizures without clinical manifestations | Up to 24 months | 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. |
| Proportion of participants with resolution of epileptiform EEG activity | At 3, 6, 12, 18, and 24 months | 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. |
| Number of seizure episodes per participant | Up to 24 months | 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. |
| Proportion of participants with severe seizure outcomes | Up to 24 months | Severe seizure outcomes include progression to status epilepticus or generalized tonic-clonic seizures. The distribution of seizure severity will be recorded. |
| Change in Montreal Cognitive Assessment (MoCA) score from baseline | Baseline, 3, 6, 12, 18, and 24 months | 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. |
| Change in Mini-Mental State Examination (MMSE) score from baseline | Baseline, 3, 6, 12, 18, and 24 months | 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. |
| Change in modified Rankin Scale (mRS) score from baseline | Baseline, 3, 6, 12, 18, and 24 months | 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. |
| Change in NIH Stroke Scale (NIHSS) score from baseline | Baseline, 3, 6, 12, 18, and 24 months | 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. |
| Change in Stroke-Specific Quality of Life (SSQOL) score from baseline | Baseline, 3, 6, 12, 18, and 24 months | 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. |
| Change in Barthel Index from baseline | Baseline, 3, 6, 12, 18, and 24 months | 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. |
| Number of participants with recurrent stroke events | Up to 24 months | 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. |
| Number of participants with all-cause mortality | Up to 24 months | 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. |
| Change in tumor necrosis factor-alpha (TNF-α) levels from baseline | Baseline, 1 week, 1 month, 3 months, and 24 months | Serum TNF-α levels will be measured to assess inflammatory response. Changes from baseline at each time point will be analyzed. |
| Change in interleukin-1 beta (IL-1β) levels from baseline | Baseline, 1 week, 1 month, 3 months, and 24 months | Serum IL-1β levels will be measured as a marker of inflammation. Changes from baseline will be analyzed. |
| Change in cyclooxygenase-2 (COX-2) levels from baseline | Baseline, 1 week, 1 month, 3 months, and 24 months | COX-2 expression levels will be measured as part of inflammatory pathway assessment. Changes from baseline will be analyzed. |
| Change in inducible nitric oxide synthase (iNOS) levels from baseline | Baseline, 1 week, 1 month, 3 months, and 24 months | iNOS levels will be measured to evaluate inflammatory and oxidative stress responses. Changes from baseline will be analyzed. |
| Number of participants with treatment-emergent adverse events | Up to 24 months | 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. |
| Number of participants with serious adverse events | Up to 24 months | 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. |
| Number of participants who discontinued treatment due to adverse events | Up to 24 months | Treatment discontinuation due to adverse events will be recorded as a measure of drug tolerability. |
Countries
China
Contacts
CONTACTXinshi Wang
Outcome results
None listed