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| ID | Type | Description | Link |
|---|---|---|---|
| 2023ZD0504900 | Other Grant/Funding Number | National Science and Technology Major Project |
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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.
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:
Following the 24-week treatment period, participants will enter a 28-week follow-up phase, making the total study duration 52 weeks per participant.
Primary and Secondary Endpoints
Primary endpoint (Week 24): A hierarchical composite endpoint including:
Secondary endpoints include (Week 24 & 52):
Cognitive and functional assessments (MoCA, MMSE, IADL, HAMD, TMT-A/B)
MRI markers of disease progression (e.g., white matter hyperintensities, infarct burden, microbleeds, brain atrophy)
Safety outcomes, including adverse events (AEs), treatment-related AEs (TRAEs), and serious AEs (SAEs).
4. Statistical Analysis The primary analysis will use the Win Ratio method to compare hierarchical composite endpoints between treatment groups. Secondary endpoints will be analyzed using Cochran-Mantel-Haenszel tests (for categorical outcomes) and Mixed-Effect Models for Repeated Measures (MMRM) (for continuous outcomes).
5. Significance This study aims to determine whether Edaravone Dexborneol Sublingual Tablets can improve functional outcomes, prevent cognitive decline, and reduce stroke recurrence in CSVD-related ischemic stroke. If successful, the findings may support a new treatment approach for this high-risk population.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Edaravone Dexborneol Sublingual Tablets | Experimental | One tablet of Edaravone Dexborneol Sublingual Tablet (containing 30mg Edaravone and 6mg Dexborneol) to be taken sublingually, twice daily. |
|
| Placebo | Placebo Comparator | One placebo tablet, to be taken sublingually, twice daily. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Edaravone Dexborneol Sublingual Tablets | Drug | One tablet of Edaravone Dexborneol Sublingual Tablet (containing 30mg Edaravone and 6mg Dexborneol) to be taken sublingually, twice daily. |
| Measure | Description | Time Frame |
|---|---|---|
| Hierarchical Composite Endpoint | This composite outcome consists of five hierarchical endpoints at 24 weeks, analyzed using the Win Ratio method:
| 24 weeks |
| All-Cause Mortality | 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. | 24weeks |
| Modified Rankin Scale (mRS) Score ≥2 | 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. | 24 weeks |
| Stroke Recurrence | 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 | 24 weeks |
| Change in Montreal Cognitive Assessment (MoCA) Score from Baseline |
| Measure | Description | Time Frame |
|---|---|---|
| All cause mortality | 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. | 24 weeks |
| Modified Rankin Scale (mRS) Score ≥2 |
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1. Inclusion Criteria:
2. Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| YiCheng Zhu, Doctor | Contact | (+86)01069156380 | zhuych910@163.com |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Peking Union Medical College Hospital | Recruiting | Beijing | China |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 38372981 | Result | 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. | |
| 31709115 |
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| ID | Term |
|---|---|
| D059345 | Cerebral Small Vessel Diseases |
| D000083242 | Ischemic Stroke |
| ID | Term |
|---|---|
| D002561 | Cerebrovascular Disorders |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
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| Placebo | Drug | One placebo tablet, to be taken sublingually, twice daily |
|
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.
| 24 weeks |
| Change in Vascular Dementia Assessment Scale-Cognitive Subscale (VaDAS-Cog) Score from Baseline | 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. | 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. |
| 24 weeks |
| Stroke recurrence | 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 | 24 weeks |
| Post-stroke cognitive impairment | Number of participants with post-stroke cognitive impairment, defined as a MOCA score < 22 | 24 weeks |
| Cognitive function (MMSE) | Changes in Mini-Mental State Examination (MMSE) score from baseline. MMSE includes the assessment of 11 cognitive functions, which encompass orientation, registration of information, attention/calculation abilities, recall, naming, repetition, comprehension (both verbal and written), writing, and visuospatial construction skills. The MMSE scale ranges from 0 to 30 points, with higher scores indicating a better outcome. | 24 weeks |
| Cognitive function (MoCA) | 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. | 24 weeks |
| Cognitive function (VaDAS-Cog) | Changes in Vascular Dementia Assessment Scale-Cognitive (VaDAS-Cog) score from baseline. 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. | 24 weeks |
| Depression (HAMD) | Changes in Hamilton Depression Rating Scale (HAMD) score from baseline. The HAMD is a widely used clinical tool for assessing the severity of depression. It consists of multiple items that evaluate various aspects of depressive symptoms, including mood, guilt, suicidal ideation, work and interest, among others. It is scored on a scale from 0 to 52, with higher scores indicating more severe symptoms. | 24 weeks |
| Activity of Daily Living | Changes in Instrumental Activities of Daily Living (IADL) score from baseline.IADL are activities that support daily life and are oriented toward interacting with your environment. Common IADLs include: Care of others; Care of pets; Child rearing; Communication management; Driving and community mobility; Financial management; Health management and maintenance; Home establishment and management; Meal preparation and clean up; Religious and spiritual activities and expressions; Safety procedure and emergency responses; Shopping. It is scored on a scale from 0 to 31, with higher scores indicating more severe symptoms. | 24 weeks |
| Adverse events | Adverse events, confirmed by the Clinical Event Committee. | 24 weeks |
| Serious adverse events | Serious adverse events, confirmed by the Clinical Event Committee. | 24 weeks |
| Liver function impairment | Number of participants with Alanine Aminotransferase level >2.0×upper limit of the normal | 24 weeks |
| Renal function impairment | Number of participants with serum creatinine >1.5×upper limit of the normal. | 24 weeks |
| Composite endpoint | Composite endpoint comprising all-cause mortality, mRS ≥2, and stroke recurrence. | 24 weeks |
| Change in White Matter Hyperintensity Fazekas Score from Baseline | The change in White Matter Hyperintensity (WMH) Fazekas Score from baseline to 52 weeks. The Fazekas scale is a validated measure of small vessel disease burden, ranging from 0 (no WMH) to 6 (severe WMH involvement). An increase in Fazekas score suggests disease progression, while a decrease or stabilization may indicate treatment efficacy. | 52 weeks |
| Number of New MRI-Confirmed Infarcts | The number of new infarcts confirmed by MRI at 52 weeks, compared to baseline. New infarcts are defined as newly developed ischemic lesions identified on diffusion-weighted imaging (DWI) or fluid-attenuated inversion recovery (FLAIR) sequences. A higher number of new infarcts indicates increased disease progression. | 52 weeks |
| Change in Number of Microbleeds from Baseline | The change in the number of microbleeds on MRI from baseline to 52 weeks, assessed using susceptibility-weighted imaging (SWI) or T2-weighted gradient-echo imaging*. Microbleeds are markers of cerebral small vessel disease and increased burden may indicate worsening vascular pathology. | 52 weeks |
| Change in White Matter Hyperintensity Volume from Baseline | The change in White Matter Hyperintensity (WMH) volume from baseline to 52 weeks, assessed using quantitative MRI analysis. This measure is to evaluate the impact of treatment on the progression of small vessel disease. A decrease in WMH volume suggests treatment efficacy. | 52 weeks |
| Change in Brain Atrophy Index from Baseline | The change in Brain Atrophy Index from baseline to 52 weeks, measured using MRI volumetric analysis. Brain atrophy is associated with cognitive decline and small vessel disease progression. A higher atrophy index suggests neurodegeneration, while stabilization or a slower rate of change may indicate treatment benefit | 52 weeks |
| All cause mortality | 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. | 52weeks |
| Modified Rankin Scale (mRS) Score ≥2 | 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. | 52weeks |
| Stroke recurrence | 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 | 52 weeks |
| Post-stroke cognitive impairment | Number of participants with post-stroke cognitive impairment, defined as a MOCA score < 22 | 52weeks |
| Cognitive function (MMSE) | Changes in Mini-Mental State Examination (MMSE) score from baseline. MMSE includes the assessment of 11 cognitive functions, which encompass orientation, registration of information, attention/calculation abilities, recall, naming, repetition, comprehension (both verbal and written), writing, and visuospatial construction skills. The MMSE scale ranges from 0 to 30 points, with higher scores indicating a better outcome. | 52weeks |
| Cognitive function (MoCA) | 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. | 52weeks |
| Cognitive function (VaDAS-Cog) | Changes in Vascular Dementia Assessment Scale-Cognitive (VaDAS-Cog) score from baseline. 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. | 52weeks |
| Depression (HAMD) | Changes in Hamilton Depression Rating Scale (HAMD) score from baseline. The HAMD is a widely used clinical tool for assessing the severity of depression. It consists of multiple items that evaluate various aspects of depressive symptoms, including mood, guilt, suicidal ideation, work and interest, among others. It is scored on a scale from 0 to 52, with higher scores indicating more severe symptoms. | 52weeks |
| Activity of Daily Living | Changes in Instrumental Activities of Daily Living (IADL) score from baseline.IADL are activities that support daily life and are oriented toward interacting with your environment. Common IADLs include: Care of others; Care of pets; Child rearing; Communication management; Driving and community mobility; Financial management; Health management and maintenance; Home establishment and management; Meal preparation and clean up; Religious and spiritual activities and expressions; Safety procedure and emergency responses; Shopping. It is scored on a scale from 0 to 31, with higher scores indicating more severe symptoms | 52weeks |
| Adverse events | Adverse events, confirmed by the Clinical Event Committee. | 52weeks |
| Serious adverse events | Serious adverse events, confirmed by the Clinical Event Committee. | 52weeks |
| Liver function impairment | Number of participants with Alanine Aminotransferase level >2.0×upper limit of the normal | 52weeks |
| Renal function impairment | Number of participants with serum creatinine >1.5×upper limit of the normal. | 52weeks |
| Composite endpoint | Composite endpoint comprising all-cause mortality, mRS ≥2, and stroke recurrence. | 52weeks |
| Result |
| Xu J, Wang Y, Wang A, Gao Z, Gao X, Chen H, Zhou J, Zhao X, Wang Y. Safety and efficacy of Edaravone Dexborneol versus edaravone for patients with acute ischaemic stroke: a phase II, multicentre, randomised, double-blind, multiple-dose, active-controlled clinical trial. Stroke Vasc Neurol. 2019 Apr 22;4(3):109-114. doi: 10.1136/svn-2018-000221. eCollection 2019 Sep. |
| 33588596 | Result | Xu J, Wang A, Meng X, Yalkun G, Xu A, Gao Z, Chen H, Ji Y, Xu J, Geng D, Zhu R, Liu B, Dong A, Mu H, Lu Z, Li S, Zheng H, Chen X, Wang Y, Zhao X, Wang Y; TASTE Trial Investigatorsdagger. Edaravone Dexborneol Versus Edaravone Alone for the Treatment of Acute Ischemic Stroke: A Phase III, Randomized, Double-Blind, Comparative Trial. Stroke. 2021 Mar;52(3):772-780. doi: 10.1161/STROKEAHA.120.031197. Epub 2021 Feb 16. |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D020521 | Stroke |