A Multicenter, Randomized, Double-Blind, Placebo-Controlled Phase II/III Clinical Trial of Y-6 Sublingual Tablets for the Treatment of Acute Perforator Artery Territory Infarction
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 944
- 试验地点
- 1
- 主要终点
- Proportion of participants achieving a modified Rankin Scale (mRS) score ≤1 after treatment
研究概览
简要总结
The goal of this clinical trial is to learn if Y-6 sublingual tablets work to improve functional outcomes in patients with acute perforating artery infarction. It will also learn about the safety of Y-6 sublingual tablets.
The main questions it aims to answer are:
Does Y-6 sublingual tablets increase the proportion of participants who achieve a modified Rankin Scale (mRS) score of 0-1 at Day 90 after treatment? What medical problems do participants have when taking Y-6 sublingual tablets?
Researchers will compare different doses of Y-6 sublingual tablets and placebo to evaluate the effectiveness and safety of Y-6 sublingual tablets in patients with acute perforating artery infarction.
Participants will:
Take Y-6 sublingual tablets or placebo according to the assigned treatment regimen.
Visit the clinic for assessments of neurological function, functional outcomes, and safety during the study period.
Complete clinical assessments, including neurological examinations, laboratory tests, and other safety evaluations.
Be followed for functional outcomes and safety events after treatment.
详细描述
This is a multicenter, randomized, double-blind, placebo-controlled, seamless adaptive Phase II/III clinical trial to evaluate the efficacy and safety of Y-6 sublingual tablets in patients with acute perforating artery infarction. The study consists of two stages. In Stage 1, participants will be randomly assigned to receive high-dose Y-6 sublingual tablets (2 tablets, containing a total of 12 mg of borneol and 50 mg of cilostazol), low-dose Y-6 sublingual tablets (1 tablet containing 6 mg of borneol and 25 mg of cilostazol plus 1 matching placebo tablet), or placebo (2 matching placebo tablets), in addition to standard antiplatelet therapy with aspirin (100mg). The purpose of Stage 1 is to evaluate the efficacy and safety of different doses of Y-6 sublingual tablets and select the recommended dose for Stage 2 based on interim analyses reviewed by an independent data monitoring committee (IDMC). In Stage 2, participants will be randomly assigned to receive the selected dose of Y-6 sublingual tablets or placebo, in addition to concomitant aspirin therapy, to confirm the efficacy and safety of Y-6 sublingual tablets. Participants will receive study treatment and be followed for efficacy and safety outcomes, including functional outcomes, adverse events, bleeding events, and other safety assessments
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
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female participants aged ≥18 and ≤80 years;
- •Onset of stroke within 72 hours before the first administration of study treatment;
- •Clinical symptoms and signs suggestive of an acute isolated perforating artery territory infarction (no cortical involvement, no multifocal involvement, NIHSS score between 4 and 15, and level of consciousness item 1a ≤1);
- •Pre-stroke modified Rankin Scale (mRS) score ≤1 before the current stroke onset;
- •Brain magnetic resonance imaging (MRI) diffusion-weighted imaging (DWI) showing an isolated infarction lesion in the perforating artery territory (including the basal ganglia, internal capsule, thalamus, pons, etc.) with a diameter <30 mm, and meeting at least one of the following criteria:
- •The infarct lesion involves at least 3 DWI axial slices;
- •The maximum diameter of the lesion on DWI is ≥15 mm;
- •The DWI lesion is connected to the ventral surface of the pons, located near the midline, unilateral, and does not cross the midline;
- •No severe stenosis of the parent artery supplying the infarct territory (severe stenosis defined as >70% stenosis on magnetic resonance angiography [MRA], or >50% stenosis on computed tomography angiography [CTA] or digital subtraction angiography [DSA]);
- •The participant or legally authorized representative voluntarily signs the informed consent form approved by the ethics committee.
排除标准
- •Known allergy to any component of the investigational product or its excipients;
- •Ischemic stroke caused by large artery atherosclerosis, cardioembolism, arterial dissection, or vasculitis identified at screening;
- •History of intracranial hemorrhagic diseases within 3 months prior to screening, including intracerebral hemorrhage, intraventricular hemorrhage, subarachnoid hemorrhage, subdural hematoma, or epidural hematoma;
- •History of other active or major neurological diseases, including recurrent seizures, intracranial tumors, vascular malformations (including arteriovenous malformations, arterial malformations, cavernous malformations), untreated aneurysms >3 mm in diameter, etc.;
- •History of congestive heart failure, or acute myocardial infarction within 3 months prior to screening, or severe cardiac dysfunction (NYHA class III-IV);
- •Significant head trauma, intracranial or spinal surgery, or severe physical trauma within 4 weeks prior to screening; major surgery within 3 months prior to screening; or planned endovascular treatment during the study period;
- •Severe hepatic or renal dysfunction at screening, or meeting any of the following criteria:
- •Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >3 × upper limit of normal (ULN);
- •Estimated glomerular filtration rate (eGFR) <45 mL/min/1.73 m² (calculated using the CKD-EPI equation based on serum creatinine; see Appendix 4);
- •Coagulation disorders, bleeding tendency, or active systemic bleeding at screening, including but not limited to:
- •Prothrombin time >1.5 × ULN;
- •Platelet count <100 × 10⁹/L;
- •Hemophilia, capillary fragility disorders, gastrointestinal bleeding, urinary tract bleeding, hemoptysis, vitreous hemorrhage, etc.;
- •Persistent systolic blood pressure ≥180 mmHg or diastolic blood pressure ≥110 mmHg despite antihypertensive treatment;
- •Known acute gastrointestinal ulcer;
- •History of asthma induced by salicylates or salicylate-containing substances (especially non-steroidal anti-inflammatory drugs [NSAIDs]);
- •Continuous use of dual antiplatelet therapy within 5 days prior to screening, or administration of loading doses of clopidogrel (300 mg) or ticagrelor (180 mg) after current stroke onset and before screening, or use of antiplatelet agents other than aspirin, cilostazol, clopidogrel, or ticagrelor after current stroke onset and before screening;
- •Received intravenous thrombolysis, thrombectomy, other endovascular treatment, or bridging therapy after current stroke onset; or received anticoagulants, batroxobin, defibrase, snake venom-derived preparations, or lumbrokinase therapy;
- •Presence of a clear indication for anticoagulation (suspected cardioembolic stroke, such as atrial fibrillation, known prosthetic heart valve, atrial myxoma, endocarditis, etc.) or a clear indication for dual antiplatelet therapy (such as recent coronary artery stenting or intracranial artery stenting);
- •Expected need for long-term use of NSAIDs other than the study medication;
- •Life expectancy ≤12 months;
- •Participation in any other interventional clinical trial within 3 months prior to screening or current participation in another clinical trial;
- •Male participants (or their partners) or female participants who plan to conceive during the study period, or participants unwilling to use one or more non-drug contraceptive methods (such as complete abstinence, condoms, sterilization, etc.) throughout the study period;
- •Pregnant or breastfeeding women;
- •Any other condition considered by the investigator to potentially affect compliance or make the participant unsuitable for participation in this study.
结局指标
主要结局
Proportion of participants achieving a modified Rankin Scale (mRS) score ≤1 after treatment
时间窗: Day 90(+7 days)
The scale ranges from 0 to 6, where a score of 0 indicates no symptoms and a score of 6 indicates death. Higher mRS scores represent greater disability.
次要结局
- Incidence of platelet count ≤100 × 10⁹/L after treatment(Day 30 (±3 days）、Day 90(+7 days）)
- Distribution of mRS scores after treatment(Day 90(+7 days))
- Proportion of participants with stroke-related disability after treatment(Day90 (+7 days))
- Change from baseline in NIHSS (National Institutes of Health Stroke Scale) scores at each assessment time point(Day90 (+7 days))
- Proportion of participants achieving a Barthel Index score ≥95 after treatment(Day 90 (+7 days))
- Proportion of participants with early neurological deterioration after treatment(72 hours (±12 hours) after treatment、Day 7 (±1 day))
- Proportion of participants with ischemic stroke after treatment(Day90 (+7 days))
- Incidence of moderate and severe bleeding events after treatment(Day 30 (±3 days)、Day 90 (+7 days))
- Incidence of intracranial hemorrhage after treatment(Day 30 (±3 days)、Day 90 (+7 days))
- Incidence of any bleeding events after treatment(Day 30 (±3 days)、Day 90 (+7 days))
- All-cause Mortality after treatment(Day 30 (±3 days)、Day 90 (+7 days))
- Incidence of new-onset moderate-to-severe headache after treatment(Day 30 (±3 days)、Day 90 (+7 days))
- Incidence and severity of adverse events after treatment(Day 90 (+7days))
- The Incidence of subject getting abnormal results of physical examinations after treatment(Day 90 (+7days))
- The Incidence of subject getting abnormal results of vital signs after treatment(Day 90 (+7days))
- The Incidence of subject getting abnormal results of laboratory tests after treatment(Day 90 (+7days))
- The Incidence of subject getting abnormal results of 12-lead electrocardiograms after treatment(Day 90 (+7 days))