Safety and Efficacy of Adjunct Tirofiban Treatment After Successful Mechanical Thrombectomy Recanalization in Acute Anterior Circulation Ischemic Stroke- A Multicenter, Prospective, Double-blind, Randomized Trial
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 1,380
- 试验地点
- 1
- 主要终点
- Proportion of patients functionally independent (mRS score 0 to 2) at 90 days
研究概览
简要总结
Acute ischemic stroke with large vessel occlusion is a frequently occurring life-threatening condition. Although endovascular treatment can effectively open occluded vessels, the successful reperfusion rate exceeds 80%, but the rate of good prognosis is less than 50%. The current clinical focus is on how to improve futile recanalization. Tirofiban is widely used in the treatment of stroke, as it can effectively prevent vascular reocclusion and improve microcirculation perfusion. It has the potential to improve futile recanalization, but there is a lack of high-level evidence-based medical support. This multicenter, prospective, double-blind, randomized controlled trial was conducted to assess the effectiveness and safety of sequential tirofiban therapy following successful mechanical thrombectomy within 24 hours of onset.
详细描述
Endovascular treatment is the primary approach for significantly improving the clinical prognosis of patients with acute large vessel occlusion, and it has been consistently recommended by both domestic and foreign guidelines. Successful vascular recanalization and restoration of ischemic tissue reperfusion are crucial for the favorable prognosis of patients with large vessel occlusion. However, the rate of successful reperfusion after endovascular treatment exceeds 80%, but the rate of favorable outcomes at 90 days follow-up is less than 50%. The reasons for ineffective recanalization include reperfusion injury, arterial reocclusion, hemorrhagic transformation, and microvascular reperfusion insufficiency. Although vascular recanalization can be visualized using DSA, not all microvascular beds can be effectively perfused, and persistent microocclusion of the capillary bed in ischemic tissue will also result in a poor prognosis. Currently, drug intervention is not commonly utilized to achieve successful recanalization after mechanical thrombectomy in clinical practice. Additionally, there is a lack of effective methods to improve ineffective recanalization.
Tirofiban is widely used in the treatment of stroke, as it can effectively prevent vascular reocclusion and improve microcirculation perfusion. It has the potential to improve futile recanalization, but there is a lack of high-level evidence-based medical support.
This is a prospective, randomized, multicenter, double-blind clinical trial. In 52 centers in China, 1360 patients with the following situations will be enrolled: achieved successful recanalization after mechanical thrombectomy (mTICI 2b/3) within 24h of stroke onset.
Patients will be randomly assigned into 2 groups according to the ratio of 1:1:
- experimental group received a bolus of tirofiban at a dosage of 5μg/kg (with a maximum dose not exceeding 0.5mg) through the catheter artery, followed by a continuous intravenous infusion at a rate of 0.1μg/(kg·min) for 24 hours.
- The control group was given a placebo in the same manner. Face to face interviews will be made on baseline, 24 hours after randomization, 48 hours after randomization, day 7 after randomization or discharge day. Day 90 after randomization will be interviewed by phone or face to face.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥18 years old;
- •NIHSS score: 6-30;
- •Symptom onset to random time of 24h, including wake-up stroke or unwitnessed stroke; The onset time of symptoms was defined as the last time of normal performance.
- •mRS 0-1 before the stroke;
- •Subject or legal representative can sign an informed consent form;
- •Clinical symptoms caused by acute occlusion of the following sites confirmed by CTA or MRA: intracranial segment of ICA, M1 segment of middle cerebral artery, M2 trunk of middle cerebral artery;
- •ASPECTS≥6 on NCCT or DWI;
- •After the end of mechanical thrombectomy, the mTICI was stable at 2b/3, and there was no secondary embolism in other non-offending vessels, or the diagnostic angiography before mechanical thrombectomy showed that the occluded vessels improved to mTICI 2b/3, and no mechanical thrombectomy was planned.
排除标准
- •Intra-arterial thrombolysis;
- •Tirofiban was used within 24 hours before endovascular treatment
- •Women who are known to be pregnant or lactating, or have a positive pregnancy test before randomization;
- •Allergy to tirofiban, radiocontrast agent or Nitinol materials;
- •Any active bleeding within 30 days before stroke or recent bleeding (gastrointestinal, urinary, etc.);
- •parenchymal organ surgery or biopsy within 14 days before stroke;
- •History of heparin-induced thrombocytopenia;
- •Platelet count < 100*10^9/L;
- •Being on hemodialysis or peritoneal dialysis; Known severe renal insufficiency (glomerular filtration rate < 30ml/min or serum creatinine > 220μmol/L).
- •Subjects requiring hemodialysis or peritoneal dialysis or who have contraindications to angiography for any reason;
- •The expected survival time is less than half a year (such as malignant tumors, serious heart and lung diseases, etc.);
- •Have participated in other interventional clinical studies that may have an impact on the outcome assessment;
- •Other circumstances that the investigator considers inappropriate for participation in the study or that may pose a significant risk to the patient (e.g., inability to understand and/or comply with study procedures and/or follow-up due to mental illness, cognitive or emotional disorder).
- •The midline shift of the brain or cerebral hernia, ventricular mass effect;
- •Acute intracranial hemorrhage on CT or MRI;
- •New bilateral acute stroke or intracranial multi-drainage large vessel occlusion;
- •Simple extracranial occlusion of the internal carotid artery.
研究组 & 干预措施
Tirofiban group
After the completion of endovascular treatment and successful recanalization (mTICI 2b/3), the patients were randomly assigned to the experimental group. Tirofiban 5μg/kg was administered intravenously through the catheter artery at a rate of 1ml/min, followed by an intravenous infusion of 0.1μg/(kg·min) for 24 hours. Standard medical treatment was administered after the surgery.
干预措施: Tirofiban (Drug)
placebo group
After the completion of endovascular treatment and successful recanalization (mTICI 2b/3), the patients were randomly assigned to the control group. Saline placebo was administered in the same manner as tirofiban group. Standard medical treatment was administered after the surgery.
干预措施: Saline placebo (Drug)
结局指标
主要结局
Proportion of patients functionally independent (mRS score 0 to 2) at 90 days
时间窗: 90 days after randomization
independent outcome at 90 days
Number of participants with symptomatic intracranial hemorrhage
时间窗: within 48 hours of randomization
According to Heidelberg Bleeding Classification
次要结局
- Modified ranking scale (mRS)(90 days after randomization)
- Proportion of patients non-disabled (mRS score 0 to 1) or return to pre-morbid mRS score at 90 days (for patients with mRS > 1)(90 days after randomization)
- Proportion of patients ambulatory or bodily needs-capable or better (mRS score 0 to 3)(90 days after randomization)
- Number of participants with improvement of neurological function(36 hours (24-48 hours) after randomization)
- Health-related quality of life, assessed with the European Quality Five Dimensions Five Level scale (EQ-5D-5L)(90 days after randomization)
- All-cause mortality(90 days after randomization)
- Proportion of intracranial hemorrhage of any type(within 48 hours of randomization)
研究者
Xiang Luo
Principal Investigator
Tongji Hospital