Treatment of Acute Ischemic Stroke With Edaravone Dexborneol Sublingual Tablets in Small Vessel Disease: A Randomized, Double-Blind, Placebo-Controlled Study
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 600
- 试验地点
- 1
- 主要终点
- Hierarchical Composite Endpoint
研究概览
简要总结
This study is a multicenter, randomized, double-blind, placebo-controlled trial designed to evaluate the efficacy and safety of Edaravone Dexborneol Sublingual Tablets in patients with acute ischemic stroke due to small vessel disease (TASTE-SVD).
The study will enroll approximately 600 participants aged 30 to 80 years who have experienced a recent small subcortical infarct (RSSI) confirmed by MRI. Participants will be randomized in a 1:1 ratio into either the Edaravone Dexborneol Sublingual Tablets group or the placebo group, with a 24-week treatment period followed by a 28-week follow-up.
The primary endpoint is a hierarchical composite endpoint at week 24, including all-cause mortality, modified Rankin Scale (mRS) score ≥2, recurrent stroke, changes in MoCA score, and changes in VaDAS-Cog score.
Secondary endpoints include additional functional and cognitive assessments at 24 and 52 weeks, as well as MRI markers of white matter hyperintensities, new infarctions, microbleeds, and brain atrophy. Safety assessments will include adverse events (AEs), treatment-related adverse events (TRAEs), and serious adverse events (SAEs).
The study aims to determine whether Edaravone Dexborneol Sublingual Tablets improve functional outcomes and cognitive performance in patients with small vessel disease-related stroke.
详细描述
This study is a multicenter, randomized, double-blind, placebo-controlled clinical trial evaluating the efficacy and safety of Edaravone Dexborneol Sublingual Tablets in patients with acute ischemic stroke due to small vessel disease (TASTE-SVD).
- Background and Rationale Cerebral small vessel disease (CSVD) is a major contributor to stroke, cognitive decline, and disability. Currently, there are no approved targeted therapies specifically addressing the pathophysiology of CSVD-related ischemic stroke. Edaravone Dexborneol, a novel free radical scavenger and anti-inflammatory agent, has shown neuroprotective effects in preclinical models and clinical trials for ischemic stroke. The TASTE-SL trial demonstrated that Edaravone Dexborneol improved functional outcomes at 90 days in acute ischemic stroke patients.
- Study Design and Methods A total of 600 participants will be recruited across 50 clinical sites in China. Participants must be 30-80 years old and have an MRI-confirmed recent small subcortical infarct (RSSI).
Eligible participants will be randomized 1:1 into:
- Treatment group: Edaravone Dexborneol Sublingual Tablets (Edaravone 30 mg + Dexborneol 6 mg), twice daily for 24 weeks.
- Control group: Placebo, twice daily for 24 weeks.
Following the 24-week treatment period, participants will enter a 28-week follow-up phase, making the total study duration 52 weeks per participant. 3. Primary and Secondary Endpoints
Primary endpoint (Week 24): A hierarchical composite endpoint including:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 30 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age: Between 30 and 80 years .
- •MRI-confirmed recent small subcortical infarct (RSSI): A lesion in the small penetrating artery territory, detected as DWI hyperintensity and ADC hypointensity, with a maximum axial diameter ≤20 mm.
- •White Matter Hyperintensity (WMH) Burden: Fazekas score ≥2 (total score range: 0-6).
- •Time from Stroke Onset: ≤3 weeks from symptom onset to randomization.
- •Pre-stroke Functional Status: Modified Rankin Scale (mRS) ≤1 before the index stroke.
- •Cognitive Function: No prior diagnosis of cognitive impairment or dementia.
- •Education Level: At least primary school education and capable of completing cognitive assessments as judged by the investigator.
- •Contraception Requirements:Women of childbearing potential and male participants with female partners of childbearing potential must agree to use effective contraception during the study and 30 days after the last dose of the investigational drug.Female participants must have a negative pregnancy test before enrollment.
- •Informed Consent: Participants or their legal representatives must voluntarily sign an informed consent form (ICF).
排除标准
- •Intracranial Hemorrhagic Diseases: Evidence of hemorrhagic stroke, epidural hematoma, subarachnoid hemorrhage, or other bleeding disorders detected by head imaging (MRI/CT).However, hemorrhagic transformation may be assessed by the investigator for potential inclusion.
- •Severe Consciousness Disturbance: NIHSS item 1a score >1 (indicative of significant impairment in consciousness).
- •Cortical Infarcts or Other Brain Abnormalities:Co-existing cortical infarcts, hydrocephalus, or other non-vascular white matter diseases (e.g., multiple sclerosis, carbon monoxide poisoning-related leukoencephalopathy).
- •Severe Carotid Artery Stenosis: Requiring surgical intervention (>50% stenosis).
- •Systemic Conditions Affecting Cognition:Endocrine disorders, vitamin deficiencies, systemic autoimmune diseases that can cause cognitive impairment.
- •Neurological Disorders Associated with Cognitive Decline:CNS infections, Creutzfeldt-Jakob disease, primary Parkinson's disease, epilepsy, brain tumors, or severe traumatic brain injury.
- •Pre-existing Severe Psychiatric Disorders:Diagnosed with major depressive disorder, vascular cognitive impairment, Alzheimer's disease, Parkinson's disease dementia, Lewy body dementia, frontotemporal dementia, or any cognitive dysfunction unrelated to stroke.
- •Severe Physical Disability or Language Impairment:Severe hemiplegia or aphasia that significantly affects cognitive assessment.
- •Use of Cognitive-Enhancing Medications:Within 4 weeks prior to screening, including but not limited to:Cholinesterase inhibitors (donepezil, rivastigmine, galantamine), NMDA receptor antagonists (memantine),Other neuroprotective agents (sodium oligomannate, lecanemab)
- •Severe Liver or Kidney Dysfunction:Active liver disease (acute hepatitis, chronic active hepatitis, cirrhosis) or ALT/AST >2× ULN.
- •Severe renal impairment (serum creatinine >1.5× ULN).
- •Life Expectancy <1 year due to severe systemic diseases.
- •Contraindications to MRI:Participants with MRI-incompatible implants, severe claustrophobia, or inability to undergo MRI.
- •Known Allergies:History of hypersensitivity to Dexborneol, natural borneol, edaravone, or any excipients (e.g., mannitol, copovidone, microcrystalline cellulose, silica, magnesium stearate).
- •Pregnancy and Lactation:Pregnant or lactating women, or those planning pregnancy during the study period.
- •Participation in Other Clinical Trials:Enrolled in another clinical trial within the last 30 days.
- •Other Investigator-Determined Factors:Any other medical, psychological, or social condition that, in the investigator's judgment, makes the patient unsuitable for participation.
研究组 & 干预措施
Edaravone Dexborneol Sublingual Tablets
One tablet of Edaravone Dexborneol Sublingual Tablet (containing 30mg Edaravone and 6mg Dexborneol) to be taken sublingually, twice daily.
干预措施: Edaravone Dexborneol Sublingual Tablets (Drug)
Placebo
One placebo tablet, to be taken sublingually, twice daily.
干预措施: Placebo (Drug)
结局指标
主要结局
Hierarchical Composite Endpoint
时间窗: 24 weeks
This composite outcome consists of five hierarchical endpoints at 24 weeks, analyzed using the Win Ratio method: 1. All-Cause Mortality 2. Modified Rankin Scale (mRS) Score ≥2 3. Stroke Recurrence 4. Change in Montreal Cognitive Assessment (MoCA) Score from Baseline 5. Change in Vascular Dementia Assessment Scale-Cognitive Subscale (VaDAS-Cog) Score from Baseline The Win Ratio approach will be used to analyze these outcomes in order of priority.
All-Cause Mortality
时间窗: 24weeks
The number of participants who experience all-cause mortality at 24 weeks. All-cause mortality includes death from any reason, such as cardiovascular, neurological, or other systemic causes. This measure is used to assess the overall survival impact of the intervention.
Modified Rankin Scale (mRS) Score ≥2
时间窗: 24 weeks
The proportion of participants with a modified Rankin Scale (mRS) score ≥2 at 24 weeks. The mRS is a widely used functional outcome measure that assesses the degree of disability or dependence in daily activities following a stroke. The scale ranges from 0 (no symptoms) to 6 (death), with scores of 2 or higher indicating functional dependence. A higher proportion of participants with mRS ≥2 suggests a worse functional outcome.
Stroke Recurrence
时间窗: 24 weeks
The number of participants who experience a recurrent stroke within 24 weeks of treatment. Recurrent stroke is defined as a new ischemic or hemorrhagic stroke occurring after the initial qualifying event, confirmed by neurological symptoms lasting ≥24 hours and neuroimaging evidence (MRI or CT). This measure assesses the effectiveness of the intervention in preventing subsequent strokes
Change in Montreal Cognitive Assessment (MoCA) Score from Baseline
时间窗: 24 weeks
The change in Montreal Cognitive Assessment (MoCA) scores from baseline to 24 weeks of treatment. The MoCA is a cognitive screening tool that assesses multiple domains, including attention, concentration, executive function, memory, language, visuospatial skills, abstract thinking, calculation, and orientation. Scores range from 0 to 30, with higher scores indicating better cognitive function. A greater positive change from baseline represents an improvement in cognitive function.
Change in Vascular Dementia Assessment Scale-Cognitive Subscale (VaDAS-Cog) Score from Baseline
时间窗: 24 weeks
The change in Vascular Dementia Assessment Scale-Cognitive Subscale (VaDAS-Cog) score from baseline to 24 weeks of treatment. The VaDAS-Cog is a neuropsychological assessment tool specifically designed to evaluate cognitive impairments associated with vascular dementia. VaDAS-Cog was created by adding five subtests to the ADAS-Cog that reflect attention and executive functions. The total score ranges from 0 to 70, with lower scores indicating lesser severity.
次要结局
- Activity of Daily Living(52weeks)
- Adverse events(52weeks)
- Serious adverse events(52weeks)
- Liver function impairment(52weeks)
- Renal function impairment(52weeks)
- Composite endpoint(52weeks)
- Change in White Matter Hyperintensity Fazekas Score from Baseline(52 weeks)
- Number of New MRI-Confirmed Infarcts(52 weeks)
- Change in Number of Microbleeds from Baseline(52 weeks)
- Change in White Matter Hyperintensity Volume from Baseline(52 weeks)
- Change in Brain Atrophy Index from Baseline(52 weeks)
- All cause mortality(52weeks)
- Modified Rankin Scale (mRS) Score ≥2(52weeks)
- Stroke recurrence(52 weeks)
- Post-stroke cognitive impairment(52weeks)
- Cognitive function (MMSE)(52weeks)
- Cognitive function (MoCA)(52weeks)
- Cognitive function (VaDAS-Cog)(52weeks)
- Depression (HAMD)(52weeks)