Efficacy and Safety of Edaravone Dexborneol Sublingual Tablet for Post-stroke Cognitive Impairment in Patients With Acute Ischemic Stroke: a Multicenter, Randomized, Double-blind, Placebo-controlled, Exploratory Phase II Clinical Trial.
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 226
- 试验地点
- 21
- 主要终点
- Adverse Events
研究概览
简要总结
This is a multicenter, randomized, double-blind, placebo-controlled, exploratory Phase II clinical trial.
The goal of this clinical trial is to assess the safety and efficacy of edaravone dexborneol sublingual tablets for post-stroke cognitive impairment in patients with acute ischemic stroke.
Participants will be required to receive 12 weeks treatment of edaravone dexborneol sublingual tablets or placebo during this study. The safety and efficacy endpoints will be compared in the patients with edaravone dexborneol sublingual tablets or placebo.
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
- 40 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥ 40 years and ≤ 80 years, male or female.
- •Diagnosed as ischemic stroke, no significant pre-stroke functional disability (mRS score ≤ 1prior to stroke onset).
- •The National Institutes of Stroke Scale score ≤ 20 points.
- •Time from onset to obtained informed consent form is within 7 days (including 7 days).
- •Presence of cognitive dysfunction at screening, i.e., MoCA scale score <
- •Patients with good cognitive function prior to stroke, without significant cognitive dysfunction and dementia.
- •Education level: primary school or above, and can complete the cognitive function test required per investigator's judgement.
- •female subjects of childbearing potential and male subjects whose female partners are of childbearing potential must be willing to and use contraception during the study treatment and within 30 days after the last dose of study drug and have no plans to donate sperm or eggs; female subjects of childbearing potential will have a negative pregnancy test;
- •obtain voluntary signed informed consent from the patient or his/her legal representative approved by the Ethics Committee.
排除标准
- •Presence of intracranial hemorrhagic disease confirmed by brain imaging.
- •Severe disturbance of consciousness: NIHSS 1a level of consciousness item score > 1 point.
- •Transient ischemic attack (TIA).
- •Systolic blood pressure ≥ 180 mmHg or diastolic blood pressure ≥ 120 mmHg after blood pressure control.
- •Poorly controlled diabetes (fasting blood glucose >10mmol/L and/or HbA1c>8%).
- •Patients with contraindications to MRI imaging.
- •For subjects who are scheduled to undergo EEG examination, Patients with contraindications for EEG examination.
- •Presence of cognitive dysfunction prior to stroke assessed by informants, that is, the average score of Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE, 16-item version) during the screening period was ≥ 3.19 and the total score was ≥
- •Patients who have been diagnosed with severe mental disorders prior to stroke.
- •Severe limb hemiplegia and aphasia and significantly affect cognitive function assessment.
- •Patients have received the cognitive enhancers and other anti-dementia drugs within 1 month before the screening period, including but not limited to cholinesterase inhibitors (donepezil, rivastigmine, galantamine) and non-competitive N-methyl-D-aspartate (NMDA) receptor antagonists (memantine) and other drugs (such as mannitol sodium capsules, Ginkgo Biloba Extract Injection, Compound Ginkgo Biloba Tablets, oxiracetam, aniracetam, piracetam，nicergoline, Lecanemab, Donanemab, Aducanumab, etc. ).
- •Have been diagnosed with severe active liver disease, such as acute hepatitis, chronic active hepatitis, cirrhosis, etc.; or ALT or AST > 2.0 × ULN.
- •Has been diagnosed with severe active kidney disease, renal insufficiency; or serum creatinine > 1.5 × ULN.
- •Thrombectomy or interventional therapy has been applied or planned after this episode.
- •History of malignancy; except for subjects with non-melanoma skin cancer (NMSC) that has been successfully treated and limited cervical cancer in situ. Subjects with a diagnosis of malignancy after enrollment may continue to participate in the study or not at the discretion of the investigator and at the discretion of the subject;
- •Suffering from a severe systemic disease with an expected survival period of <1 year;
- •hypersensitivity to dextran camphene, natural ice chips or edaravone or excipients (mannitol, copovidone, microcrystalline cellulose, cross-linked povidone, silicon dioxide, magnesium stearate);
- •pregnancy, lactation, and patients planning pregnancy;
- •history of major surgery within 4 weeks prior to enrollment;
- •participation in another clinical study within 30 days prior to randomization, or ongoing participation in another clinical study;
- •in the opinion of the investigator, not suitable for participation in this clinical study.
研究组 & 干预措施
Group of edaravone dexborneol sublingual tablet
Patients will receive edaravone dexborneol sublingual tablet twice daily of 24 weeks.
干预措施: Edaravone dexborneol sublingual tablet (Drug)
Placebo
Patients will receive placebo twice daily of 24 weeks.
干预措施: Placebo (Drug)
结局指标
主要结局
Adverse Events
时间窗: Until follow up 26 weeks or early termination
Adverse events (AE), treatment-related adverse events (TRAE), serious adverse events (SAE) in each group.
Number of discontinuation/withdrawal patients
时间窗: Until follow up 26 weeks or early termination
Discontinuation/withdrawal of patients in each group, including discontinuation due to adverse events.
The changes of the Vascular Dementia Assessment Scale-cognitive subscale (VaDAS-Cog) scores.
时间窗: Until follow up 24 weeks
The changes of the scores of the Vascular Dementia Assessment Scale-cognitive subscale (VaDAS-Cog) in each group after 24 weeks of treatment were compared with baseline. The minimum score is 0 and maximum score is 115 and the higher scores means the worse outcome.
次要结局
- The incidence of Post Stroke Cognitive Impairment（PSCI ）in each group(Week 12 and Week 24)
- The changes of Mini-Mental State Examination (MMSE) score(Week 12 and Week 24)
- The changes of Montreal Cognitive Assessment (MoCA) scale(Week 12 and Week 24)
- The changes of MoCA subscales(Week 12 and Week 24)
- Modified Rankin Scale (mRS) scores(Week 12 and Week 24)
- The changes of National Institutes of Health Stroke Scale(Week 4 , Week 12 and Week 24)
- The changes of the Vascular Dementia Assessment Scale-cognitive subscale (VaDAS-Cog) scores.(Week 12)