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.
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
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
944
Y-6 sublingual tablets (in accordance with the optimal dose established in stage 1) taken sublingually twice daily for 90 consecutive days.
Placebo (in accordance with the optimal dose established in stage 1) taken sublingually twice daily for 90 consecutive days.
Beijing TianTan Hospital
Beijing, Beijing Municipality, China
Proportion of participants achieving a modified Rankin Scale (mRS) score ≤1 after treatment
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.
Time frame: Day 90(+7 days)
Distribution of mRS scores after treatment
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.
Time frame: Day 90(+7 days)
Proportion of participants with stroke-related disability after treatment
Stroke disability is defined as disability (modified Rankin Scale \[mRS\] score of 3-5), major adverse cardiovascular events (MACE), including myocardial infarction, stroke, and vascular death, and all-cause mortality.
Time frame: Day90 (+7 days)
Change from baseline in NIHSS (National Institutes of Health Stroke Scale) scores at each assessment time point
The NIHSS total score ranges from 0 to 42, with higher scores indicating worse neurological outcomes.
Time frame: Day90 (+7 days)
Proportion of participants achieving a Barthel Index score ≥95 after treatment
The Barthel Index (BI) is a measure of activities of daily living, with scores ranging from 0 to 100. Higher scores indicate greater independence, while lower scores indicate greater dependence on assistance for daily activities.
Time frame: Day 90 (+7 days)
Proportion of participants with early neurological deterioration after treatment
Early neurological deterioration means within 7 days after stroke attack, an increase in NIHSS of ≥2 points or an increase in hemiparesis of ≥1 point or an increase in impaired consciousness of ≥1 point from baseline and excluding progression of disease due to intracranial hemorrhage by examination of cranial CT or MRI and exacerbation of disease due to other non-stroke causes, such as cardiac insufficiency, hepatic insufficiency, renal insufficiency, etc.
Time frame: 72 hours (±12 hours) after treatment、Day 7 (±1 day)
Proportion of participants with ischemic stroke after treatment
Time frame: Day90 (+7 days)
Incidence of moderate and severe bleeding events after treatment
Bleeding events will be classified according to the GUSTO bleeding criteria. Severe or life-threatening bleeding is defined as intracerebral hemorrhage or bleeding resulting in substantial hemodynamic compromise requiring treatment. Moderate bleeding is defined as bleeding requiring blood transfusion. Minor bleeding is defined as other bleeding events not requiring transfusion or causing hemodynamic compromise.
Time frame: Day 30 (±3 days)、Day 90 (+7 days)
Incidence of intracranial hemorrhage after treatment
Time frame: Day 30 (±3 days)、Day 90 (+7 days)
Incidence of any bleeding events after treatment
Time frame: Day 30 (±3 days)、Day 90 (+7 days)
All-cause Mortality after treatment
Time frame: Day 30 (±3 days)、Day 90 (+7 days)
Incidence of platelet count ≤100 × 10⁹/L after treatment
Time frame: Day 30 (±3 days)、Day 90(+7 days)
Incidence of new-onset moderate-to-severe headache after treatment
Headache severity will be assessed using the 11-point Numerical Rating Scale (11-NRS). The scale ranging from 0 to 10, where 0 indicates no headache and 10 indicates the worst imaginable headache. Higher scores indicate greater headache severity.
Time frame: Day 30 (±3 days)、Day 90 (+7 days)
Incidence and severity of adverse events after treatment
Time frame: Day 90 (+7days)
The Incidence of subject getting abnormal results of physical examinations after treatment
Time frame: Day 90 (+7days)
The Incidence of subject getting abnormal results of vital signs after treatment
Time frame: Day 90 (+7days)
The Incidence of subject getting abnormal results of laboratory tests after treatment
Time frame: Day 90 (+7days)
The Incidence of subject getting abnormal results of 12-lead electrocardiograms after treatment
Time frame: Day 90 (+7 days)
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