Effects of Y-6 Sublingual Tablets for Patients With Acute Ischemic Stroke: A Phase Ⅱ, Randomized, Double-blind, Double-dummy, Placebo-controlled Parallel Trial
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 300
- 主要终点
- Proportion of mRS score recovered to 0~1 score
研究概览
简要总结
This study aims to evaluate the efficacy of Y-6 sublingual tablets in improving microcirculation dysfunction and reducing thrombo-inflammation in patients who had AIS caused by LVO and received reperfusion therapy. Moreover, we expect to evaluate the safety of using Y-6 sublingual tablet in such study population.
详细描述
This study rationale is based on the following scheme: in patients with acute ischemic stroke caused by LVO, receiving reperfusion therapy may cause futile recanalization and thus lead to microcirculation dysfunction and thrombo-inflammation as consequences. Cilostazol has antiplatelet effects and BBB protection and Dexborneol has anti-inflammatory effects; therefore, the multi-component tablet may exert neuroprotective effects in terms of improving microcirculation dysfunction and reducing thrombo-inflammation in patients with AIS after reperfusion therapy.
The primary purpose of this study is to investigate the proportion of modified-Rankin scale (mRS) score recovered to 0~1 score at 90±7 days after randomization.
The follow-up duration is 3 months, and the visit schedule is as follows: Subjects enrolled based on randomization procedures will receive visits at screening/baseline period, 24 ± 2 hours, 7 ± 2 days, 28 + 3 days and 90 ± 7 days after randomization, and in case of any events.
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
- 35 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •35 years old ≤ Age ≤ 80 years old;
- •Patients with acute ischemic stroke diagnosed within 24 hours of onset (time from onset to start of endovascular treatment);
- •Patients with first stroke or mRS score 0-1 prior to this onset ;
- •Patients with acute intracranial large vessel occlusion (LVO) confirmed by imaging examination, including occlusion of intracranial segments of internal carotid arteries, T-shaped bifurcation, MCA M1 and/or M2 segments and ACA A1 and/or A2 segments;
- •ASPECTS score ≥ 6 when screening;
- •6<NIHSS score ≤ 25 after this onset;
- •Patients who had the indications for mechanical thrombectomy and were scheduled for endovascular treatment;
- •Patients or his/her legal representatives were able to understand and sign the informed consent.
排除标准
- •Severe disorder of consciousness: NIHSS 1a consciousness level ≥2 points;
- •Patients with definite history of intracranial hemorrhage, including parenchymal hemorrhage, intraventricular hemorrhage, subarachnoid hemorrhage, subdural/external hematoma, etc. when screening;
- •Patients with previously diagnosed intracranial tumor, arteriovenous malformation, or aneurysm when screening;
- •Patients with bilateral LVO at anterior circulation or LVO at posterior circulation when screening;
- •Patients with LVO of unknown or rare etiology, e.g., due to dissection, vasculitis, etc. when screening;
- •Patients who have received treatment with tirofiban, warfarin, novel oral anticoagulants, argatroban, snake venom, defibrase, lumbrokinase or other defibrase therapy after onset, or platelet count <100×10^9/L;
- •Patients with severe hepatic insufficiency or renal insufficiency and received dialysis for various reasons when screening (severe hepatic insufficiency was defined as ALT > 3 × ULN or AST >3 × ULN; severe renal insufficiency was defined as serum creatinine >3.0 mg/dl (265.2 μmol/L) or creatinine clearance < 30 ml/min);
- •Patients with previously diagnosed hemorrhagic tendency (including but not limited to): with hereditary hemorrhagic disorders, such as hemophilia, when screening;
- •Patients with refractory hypertension that is difficult to be controlled by medication (systolic blood pressure > 180 mmHg or diastolic blood pressure > 110 mmHg);
- •Patients with history of major head trauma or stroke within 1 month prior to randomization;
- •Patients who have received intracranial or spinal surgery within 3 months prior to randomization;
- •Patients with history of major surgery or serious physical trauma within 1 month prior to randomization;
- •Patients with previously diagnosed hemorrhagic retinopathy;
- •Male subjects (or their mates) or female subjects who had planned to have a child during the whole study period and within 3 months after the end of the study period or were unwilling to use one or more non-drug contraceptive methods (e.g., complete abstinence, condoms, ligation, etc.) during the study period;
- •Patients with contraindications to known contrast agents or other contrast agents; patients who are allergic to Cilostazol or Dexborneol;
- •Patients who plan to receive other surgical or intervention therapy within 3 months, which might require discontinuation of the study drugs;
- •Patients with life expectancy of less than 3 months due to advanced stage of comorbidity;
- •Patients who have received treatment of investigational drugs or devices within previous 3 months;
- •Other investigator-evaluated conditions which may influence the compliance of patients or where it is not suitable for patients to participate in this trial.
研究组 & 干预措施
Low-dose Y-6 sublingual tablet group
One Y-6 sublingual tablet (each tablet contains 25 mg Cilostazol and 6 mg Dexborneol), one placebo of Y-6 sublingual tablet (each tablet contains 0 mg Cilostazol and 0.06 mg Dexborneol to simulate the cool taste of Y-6 sublingual tablets when taken), and two halves Cilostazol mimicry tablets (each tablet contains 0 mg Cilostazol).
干预措施: Low-dose Y-6 sublingual tablets (Drug)
High-dose Y-6 sublingual tablet group
Two Y-6 sublingual tablets (each tablet contains 25 mg Cilostazol and 6 mg Dexborneol), and two halves Cilostazol mimicry tablets (each tablet contains 0 mg Cilostazol).
干预措施: High-dose Y-6 sublingual tablets (Drug)
Low-dose Cilostazol group
Two tablets of placebo of Y-6 sublingual tablets (each tablet contains 0 mg Cilostazol and 0.06 mg Dexborneol to simulate the cool taste of Y-6 sublingual tablets when taken), one half Cilostazol tablet (each tablet contains 50 mg Cilostazol), and one half Cilostazol mimicry tablet(each tablet contains 0 mg Cilostazol).
干预措施: Low-dose Cilostazol (Drug)
High-dose Cilostazol group
Two tablets of placebo of Y-6 sublingual tablets (each tablet contains 0 mg Cilostazol and 0.06 mg Dexborneol to simulate the cool taste of Y-6 sublingual tablets when taken), and two halves Cilostazol tablet (each tablet contains 50 mg Cilostazol).
干预措施: High-dose Cilostazol (Drug)
Placebo group
Two tablets of placebo of Y-6 sublingual tablets (each tablet contains 0 mg Cilostazol and 0.06 mg Dexborneol to simulate the cool taste of Y-6 sublingual tablets when taken), and two halves Cilostazol mimicry tablets (each tablet contains 0 mg Cilostazol).
干预措施: Placebo (Drug)
结局指标
主要结局
Proportion of mRS score recovered to 0~1 score
时间窗: At 90±7 days after randomization
The modified Rankin Scale (mRS) decreasing to 0\~1 score. mRS Mainly measures patients' independent living ability, including physical function, activity ability and participation in daily life. A score of 0 on the mRS Scale indicates no symptoms and a score of 5 indicates severe disability.
次要结局
- Changes of NIHSS score between baseline and at 24 ± 2 hours, 7 ± 2 days and 28 + 3 days after randomization(At 24 ± 2 hours, 7 ± 2 days and 28 + 3 days after randomization)
- The mRS score at 90±7 days after randomization(At 90±7 days after randomization)
- Proportion of patients with combined vascular events at 90 ± 7 days after randomization(At 90 ± 7 days after randomization)
- Proportion of patients with early progression of stroke at 24 ± 2 hours after randomization(At 24 ± 2 hours after randomization)
研究者
yilong Wang
Vice President of Beijing Tiantan Hospital
Beijing Tiantan Hospital