Efficacy and Safety of Tirofiban Combined With Aspirin in Moderate Ischemic Stroke: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial
试验速览
- 阶段
- 4 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 1,168
- 试验地点
- 5
- 主要终点
- Proportion of patients with mRS 0-1 at 90 days (%)
研究概览
简要总结
Ischemic stroke accounts for the majority of stroke cases in China, and moderate ischemic stroke (NIHSS 4-10) carries a high risk of early neurologic deterioration (END) and long-term disability. Although intensified antiplatelet strategies reduce END, they have not consistently improved long-term functional outcome. Tirofiban, a selective glycoprotein IIb/IIIa receptor inhibitor, has shown a clinically meaningful trend toward better 90-day functional outcome (mRS 0-1) in prior tirofiban trials, but existing sample sizes were underpowered to detect this difference.
TAMIS is a multicenter, randomized, double-blind, placebo-controlled superiority trial in patients with acute moderate ischemic stroke (NIHSS 4-10) within 24 hours of last known well. Eligible patients are randomized 1:1 to tirofiban plus aspirin versus placebo plus aspirin, both on a background of guideline-based standard medical care. The primary efficacy endpoint is the proportion of patients with an excellent functional outcome (mRS 0-1) at 90 days. The primary safety endpoint is symptomatic intracranial hemorrhage within 48 (±12) hours by the Heidelberg criteria.
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
- •Age 18-80 years;
- •Acute ischemic stroke; time from last known well to randomization ≤ 24 hours;
- •Pre-randomization NIHSS score 4-10, with at least one of item 5 (upper limb) or item 6 (lower limb) ≥ 1;
- •Pre-stroke modified Rankin Scale (mRS) ≤ 1;
- •Written informed consent provided by the patient or a legally authorized representative.
排除标准
- •Intracranial hemorrhage confirmed by CT or MRI;
- •Has received or is planned to receive reperfusion therapy (thrombolysis or endovascular treatment);
- •Any definite cardioembolic source: chronic/paroxysmal atrial fibrillation, sick sinus syndrome, mitral stenosis, mechanical heart valve, endocarditis, intracardiac thrombus or vegetation, myocardial infarction within 3 months, dilated cardiomyopathy, left atrial spontaneous echo contrast, ejection fraction < 30%;
- •Definite indication for anticoagulation (atrial fibrillation, mechanical heart valve, deep vein thrombosis, pulmonary embolism);
- •Severe systemic disease (e.g., severe infection, severe hepatic or renal dysfunction);
- •Allergy to tirofiban and/or aspirin;
- •History of intracranial hemorrhage;
- •Planned use of NSAIDs affecting platelet function;
- •Gastrointestinal bleeding or major surgery within the past 3 months;
- •Planned or likely revascularization (any angioplasty or vascular surgery) within the next 3 months;
- •Planned surgery or intervention requiring discontinuation of antiplatelet therapy;
- •Stroke caused by angiography or surgery;
- •Prior non-atherosclerotic arterial disease, including moyamoya disease, arterial dissection, fibromuscular dysplasia;
- •Other structural brain disease (vascular malformation, tumor, abscess, multiple sclerosis, etc.) confirmed by CT/MRI;
- •Pregnancy or lactation;
- •Prior neurologic or psychiatric disease that would interfere with neurologic assessment;
- •Participation in another clinical trial;
- •Advanced disease with expected survival < 6 months;
- •Expected inability to complete follow-up.
研究组 & 干预措施
Placebo + Aspirin
Aspirin 100 mg once daily orally for 90 days, plus immediate intravenous tirofiban-matching placebo infusion (0.4 µg/kg/min × 30 min, then 0.1 µg/kg/min × 24 h) after randomization. Plus guideline-based standard care.
干预措施: Tirofiban-matching placebo (Drug)
Tirofiban + Aspirin
Aspirin 100 mg once daily orally for 90 days, plus immediate intravenous tirofiban after randomization: 0.4 µg/kg/min for the first 30 minutes, then 0.1 µg/kg/min for a total of 24 hours. Plus guideline-based standard care.
干预措施: Tirofiban (Drug)
结局指标
主要结局
Proportion of patients with mRS 0-1 at 90 days (%)
时间窗: At 90 days after randomization
Proportion of patients achieving an excellent functional outcome, defined as a modified Rankin Scale (mRS) score of 0 or 1 at 90 days after randomization.
Symptomatic intracranial hemorrhage within 48 (±12) hours (Heidelberg criteria) (%)
时间窗: 48 (±12) hours after randomization
Symptomatic intracranial hemorrhage within 48 (±12) hours (Heidelberg criteria) (%)
次要结局
- mRS score at 90 days (ordinal shift analysis)(At 90 days after randomization)
- Proportion with functional independence (mRS 0-2) at 90 days(At 90 days after randomization)
- Early neurologic deterioration (END) within 7 ± 1 days(Within 7 ± 1 days after randomization)
- Change in NIHSS from pre-randomization to discharge or discharge-day 6 (±1)(Discharge or discharge-day 6 (±1))
- EQ-5D-5L at 90 days(At 90 days after randomization)
- Any intracranial hemorrhage on imaging within 48 (±12) hours(Within 48 (±12) hours after randomization)
- 90-day all-cause mortality(At 90 days after randomization)
- Major extracranial bleeding within 48 (±12) hours (GUSTO moderate and severe)(Within 48 (±12) hours after randomization)
- Non-hemorrhagic serious adverse event rate(Within 90 days after randomization)
研究者
Zhongming Qiu
Professor
Xinqiao Hospital of Chongqing