THrombolysis for Acute Wake-up and Unclear-onset Strokes With Alteplase at 0.6 mg/kg Trial (THAWS)
试验速览
- 阶段
- 3 期
- 发起方
- 入组人数
- 300
- 试验地点
- 1
- 主要终点
- Modified Rankin Scale 0-1
研究概览
简要总结
The purpose of this study is to clarify efficacy and safety of MRI-based intravenous thrombolysis with alteplase for patients with acute wake-up ischemic stroke and those having acute ischemic stroke with unknown time of symptom onset.
详细描述
THAWS is an investigator initiated Japanese multicenter randomized controlled clinical trial of MRI based thrombolysis in patients with acute wake-up ischemic stroke and those having acute ischemic stroke with unknown time of symptom onset. Intravenous thrombolysis with alteplase of 0.6mg/kg, different from 0.9mg/kg used in other countries, is available as effective and safe treatment of acute stroke within 4.5 hours of symptom onset in Japan. However, time of symptom onset is unknown in about 25% of acute stroke patients. These patients are currently excluded from intravenous thrombolysis with alteplase. The objective of the THAWS project is to provide effective treatment options for acute stroke patients with unknown time of symptom onset. The purpose of this study is to clarify efficacy and safety of MRI-based intravenous thrombolysis with alteplase of 0.6mg/kg for patients with acute wake-up ischemic stroke and those having acute ischemic stroke with unknown time of symptom onset. Eligible patients will be selected based on MRI findings indicative of acute ischemic stroke less than 4.5 hours of age.
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
- 20 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Clinical diagnosis of acute ischemic stroke with unknown symptom onset (e.g. acute wake-up ischemic stroke, acute ischemic stroke with unknown time of symptom onset)
- •Last known well without neurological symptoms >4.5 hours of treatment initiation
- •Treatment can be started within 4.5 hours of symptom recognition (e.g. awaking)
- •Acute stroke MRI including diffusion weighted imaging (DWI) and fluid attenuated inversion recovery (FLAIR) completed
- •Alberta Stroke Program Early CT score (ASPECTS) on initial DWI is 5 or more
- •No marked parenchymal hyperintensity visible on FLAIR
- •Initial NIHSS ≥2
- •Written informed consent by patient or next of kin
排除标准
- •Pre-stroke Modified Rankin Scale (mRS) >1 (patients who have inability to carry out all daily activities and require some help or supervision)
- •Contraindications in the Japanese guideline for the intravenous application of recombinant tissue-type plasminogen activator (alteplase)
- •History of nontraumatic intracranial hemorrhage
- •History of stroke within the last 1 month (excluding transient ischemic attack)
- •History of significant head/spinal injury or surgery within the last 3 months
- •History of gastrointestinal or urinary tract bleeding within the last 21 days
- •History of major surgery or significant trauma other than head injury within the last 14 days
- •Hypersensitivity to alteplase
- •Suspected subarachnoid hemorrhage
- •Concurrent acute aortic dissection
- •Concurrent hemorrhage (e.g., intracranial, gastrointestinal, urinary tract, or retroperitoneal, hemoptysis)
- •Systolic blood pressure ≥185 mmHg despite antihypertensive therapy
- •Diastolic blood pressure ≥110 mmhg despite antihypertensive therapy
- •Significant hepatic disorder
- •Acute pancreatitis
- •Blood glucose <50mg/dL or >400 mg/dL
- •Platelet count ≤100,000/mm3
- •International normalized ratio of prothrombin time (PT-INR) >1.7 or Prolonged activated partial thromboplastin time (aPTT: >1.5 times the baseline value [>approximately 40 seconds only as a guide]) for patients on anticoagulation therapy or those with abnormal coagulation
- •Any contraindication to MRI (e.g. cardiac pacemaker)
- •Extensive early ischemic change in brain stem or cerebellum (e.g., more than half of brain stem or more than one hemisphere of cerebellum)
- •Planned or anticipated treatment with surgery or endovascular reperfusion strategies (e.g., intra-arterial thrombolysis, mechanical recanalization techniques)
- •Pregnant, lactating, or potentially pregnant
- •Life expectancy 6 months or less by judgment of the investigator
- •Inappropriate for study enrollment by judgment of the investigator
研究组 & 干预措施
Alteplase
Intravenous tissue-type plasminogen activator (alteplase)
干预措施: Tissue-type plasminogen activator (alteplase) (Drug)
Standard Care
Standard treatment for acute stroke
干预措施: Standard care (Other)
结局指标
主要结局
Modified Rankin Scale 0-1
时间窗: 90 days after stroke onset
次要结局
- Major bleeding(Up to 90 days after stroke onset)
- Categorical shift in NIHSS score at 7 days(7 days after the initiation of treatment)
- Modified Rankin Scale 0-2(90 days after stroke onset)
- Categorical shift in modified Rankin Scale score(90 days after stroke onset)
- Parenchymal hemorrhage type-2 (PH-2)(24 hours after the initiation of treatment)
- Symptomatic intracranial hemorrhage (sICH) in SITS-MOST(24 hours after the initiation of treatment)
- Modified Rankin Scale 6(90 days after stroke onset)
- Categorical shift in National Institutes of Health (NIHSS) score at 24 h(24 hours after the initiation of treatment)
- sICH as defined in European Cooperative Acute Stroke Study (ECASS) II(24 hours after the initiation of treatment)
- sICH as defined in National Institute of Neurological Disorders and Stroke (NINDS)(24 hours after the initiation of treatment)
- Infarct volume(7 days after stroke onset)
- Infarct volume growth(7 days after stroke onset)
研究者
Kazunori Toyoda
Director and Chair, Department of Cerebrovascular Medicine
National Cerebral and Cardiovascular Center, Japan