A Multicenter, Three-Arm, Open-Label, Endpoint-Blinded Randomized Controlled Trial to Evaluate the Optimal Infusion Duration of Early Tirofiban Treatment After Intravenous Thrombolysis in Patients With Acute Ischemic Stroke (INSTANT-2)
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 1,482
- 试验地点
- 10
- 主要终点
- Proportion of patients with mRS 0-1 at 90 days
研究概览
简要总结
Acute ischemic stroke is a leading cause of disability and mortality among dults in China. Although intravenous thrombolysis serves as first-line reperfusion therapy, nearly half of patients fail to achieve vascular recanalization. The reocclusion rate ranges from 14% to 34%, and many patients are left with residual neurological deficits. Early antiplatelet therapy initiated after thrombolysis may sustain persistent reperfusion and improve prognosis. However, current guidelines generally recommend delaying antiplatelet treatment until 24 hours post-thrombolysis due to bleeding risks, and direct evidence for the optimal initiation timing remains lacking. Tirofiban is a rapidly acting, short-half-life, reversible glycoprotein IIb/IIIa receptor antagonist. Previous studies indicate its potential benefits and acceptable safety when administered after intravenous thrombolysis.
This is a multicenter, three-arm, open-label, endpoint-blinded randomized controlled trial. A total of 1482 non-cardioembolic patients without large or medium vessel occlusion and with residual neurological deficits (NIHSS ≥4) after thrombolysis will be enrolled. Participants will be randomly allocated to the tirofiban 24-hour group, tirofiban 48-hour group, or blank control group. The primary outcome is the proportion of patients with excellent functional outcome defined as modified Rankin Scale (mRS) score 0-1 at 90 days. Symptomatic intracranial hemorrhage and neurological outcomes will also be evaluated. The study aims to determine the optimal duration of tirofiban treatment after thrombolysis and provide high-level evidence for precise interventions in the acute phase of stroke.
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
- Double (Care Provider, Outcomes Assessor)
盲法说明
Participants and treating investigators are unblinded (open-label). Outcome assessors for primary endpoint are blinded to treatment assignment.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥ 18 years.
- •Diagnosis of acute ischemic stroke meeting the diagnostic criteria from Chinese Guidelines for the Diagnosis and Treatment of Acute Ischemic Stroke 2023, and the patient has received intravenous thrombolysis with tenecteplase, alteplase or reteplase.
- •Disabling stroke remains at 2-24 hours after completion of intravenous thrombolysis. Disabling stroke is defined as NIHSS score ≥ 4, or single limb motor subscore ≥
- •Written informed consent is obtained from the patient or legal representative.
排除标准
- •Intracranial hemorrhage confirmed by CT or MRI after intravenous thrombolysis and prior to randomization.
- •CTA/MRA/DSA demonstrates occlusion of the internal carotid artery, M1 or M2 segment of the middle cerebral artery, anterior cerebral artery, or vertebrobasilar artery.
- •History of atrial fibrillation or suspected cardioembolic stroke. Platelet count <100×10⁹/L on routine blood test.
- •Renal insufficiency with estimated glomerular filtration rate (eGFR) <30 mL/min.
- •Pregnant or breastfeeding women.
- •Pre-existing neurological or psychiatric disorders that interfere with neurological function assessment.
- •History of bleeding disorders, severe cardiac, hepatic or renal disease, or sepsis.
- •Brain tumor with mass effect on imaging (excluding small meningioma). Intracranial aneurysm or arteriovenous malformation (AVM).
- •Advanced illness with life expectancy less than 6 months.
- •Current participation in another clinical trial.
- •Other conditions deemed unsuitable for enrollment by the investigator.
研究组 & 干预措施
Arm C: Standard care control group
No tirofiban is administered after intravenous thrombolysis.
干预措施: No Interventions (Other)
Arm A: Tirofiban 24-hour group
Arm A: Patients receive tirofiban for 24 hours after intravenous thrombolysis.
干预措施: Tirofiban Injection (Drug)
Arm B: Tirofiban 48-hour group
Arm B: Patients receive tirofiban for 48 hours after intravenous thrombolysis.
干预措施: Tirofiban Injection (Drug)
结局指标
主要结局
Proportion of patients with mRS 0-1 at 90 days
时间窗: 90 days after randomization
Percentage of participants achieving modified Rankin Scale (mRS) score 0 or 1 at 90 days after randomization.
次要结局
- mRS score at 90 days(90 days after randomization)
- EQ-5D-5L score at 90 days(90 days after randomization)
- Proportion of patients with mRS 0-2 at 90 days(90 days after randomization)
- Proportion of patients with mRS 0-3 at 90 days(90 days after randomization)
- Proportion of early neurological improvement(48 hours after randomization)
研究者
Zhongming Qiu
Professor
Xinqiao Hospital of Chongqing