Thrombolysis Treated With TNK-tPA in Acute Ischemic Stroke Patients: a Multi-center, Block Randomized, Positive Drug Parallel Controlled Phase II Trial
试验速览
- 阶段
- 2 期
- 发起方
- 入组人数
- 225
- 试验地点
- 28
- 主要终点
- Modified Rankin Scale(mRS)
研究概览
简要总结
The trial is prospective, block randomized, open-label, blinded endpoint (PROBE) design. Patients with acute ischemic stroke, who are eligible for standard intravenous thrombolysis within 4.5 hours of stroke onset will be randomized 1:1:1 to 0.25mg/kg or 0.40mg/kg intravenous tenecteplase or 0.9 mg/kg alteplase before all participants undergo endovascular thrombectomy.
详细描述
The study will be a multi-center, prospective, randomized, open- label, blinded endpoint (PROBE), controlled phase 2 trial (3 arm with 1:1:1 randomization) in ischemic stroke patients. Imagine is performed with CT or MRI acutely with imaging follow-up at 24-30 hours. The sample size is 225.
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
- Single (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;
- •The clinical diagnosis was Acute ischemic stroke The time from onset to treatment was < 4.5h; The time at which symptoms begin is defined as "the time at which they finally appear normal";
- •mRS before onset was ≤1 points;
- •Baseline NIHSS (at the time of randomization) should be > 5 and ≤25 points;
- •Informed consent from the patient or surrogate.
排除标准
- •Intracranial hemorrhage identified by CT or MRI (CMBs detected by SWI is not counted);
- •Massive anterior cerebral infarction identified by CT or MRI (ASPECT < 6 or lesions larger than one third of the territory of the middle cerebral artery or with a volume larger than 70mL)
- •A history of severe CNS damage (such as aneurysm or arteriovenous malformation, craniocerebral trauma, intracranial or spinal cord surgery)
- •Onset with seizures, and the paralysis was suspected to be related to Todd paralysis.
- •Administration of heparin within 48 hours preceding the onset of stroke with a baseline APTT exceeding the upper limit of the normal range.
- •Oral anticoagulant (such as warfarin) treatment with baseline INR>1.7 or PT>15 s;
- •Administration of thrombin inhibitors or factor Xa inhibitors within 48 hours preceding the onset of stroke with abnormal coagulation parameters or platelet count;
- •BP couldn't be controlled with aggressive treatment. Uncontrolled hypertension was defined as systolic blood pressure >185 mmHg or diastolic blood pressure >110 mmHg, measured for three times every 10 minutes.
- •Platelet count of less than 100×109/ L;
- •Blood glucose <50 mg/dl (<2.8 mmol/L) or >400 mg/dl (22.22 mmol/L);
- •History of intracranial hemorrhage or active hemorrhagic disease. (Such as gastrointestinal, urinary tract or retinal bleeding)
- •Tumors with an increased risk of bleeding.
- •Prolonged or traumatic cardiopulmonary resuscitation (>2 min), delivery within the last 10 days or recent puncture of non-compression vessels such as subclavian vein or jugular vein
- •Acute pancreatitis or severe liver disease, including liver failure, cirrhosis, portal hypertension, esophageal varicose veins, and active hepatitis;
- •Aortic arch dissection;
- •Major surgery or severe trauma in the past 2 weeks;
- •Subjects had serious, fatal, or disabling disease with an expected survival of less than 3 months;
- •Unable to complete neurological assessment and follow-up visits because of dementia or mental illness;
- •Pregnant women, lactating women, or have positive pregnancy test;
- •Allergy to tenecteplase or alteplase or their components;
- •Participation in other clinical trials within 3 months prior to screening;
- •Unsuitable to involve in this study or would result in increased risk, as judged by the investigators.
研究组 & 干预措施
Alteplase
Patients will receive intravenous Alteplase at the standard licensed dose of 0.9 mg/kg up to a maximum of 90mg, 10% as bolus and the remainder over 1 hour.
干预措施: Alteplase (Drug)
Tenecteplase 0.25mg/kg
Patients will receive intravenous Tenecteplase, 0.25mg/kg, maximum 25mg, administered as a bolus over 5~10 seconds
干预措施: Tenecteplase (Drug)
Tenecteplase 0.4mg/kg
Patients will receive intravenous Tenecteplase, 0.4mg/kg, maximum 40mg, administered as a bolus over 5~10 seconds
干预措施: Tenecteplase (Drug)
结局指标
主要结局
Modified Rankin Scale(mRS)
时间窗: 90±7 days
Proportion of subjects with mRS scores of (0-1) at 90±7 days.(Comments:The minimum and maximum values are from 0 to 6,and higher scores mean a worse outcome.)
次要结局
- Modified Rankin Scale(mRS)(90±7 days)
- National Institutes of Health Stroke Scale (NIHSS)(7±2days or discharge)
- The new vascular events(90±7 days)
- Deaths(90±7 days)
- EQ-5D(90±7 days)
研究者
Yongjun Wang
President of Beijing Tiantan Hospital, Capital Medical University, Director of Neurology Center
Beijing Tiantan Hospital