Intravenous Thrombolysis With Recombinant Human TNK Tissue-type Plasminogen Activator (rhTNK-tPA) for Acute Non-large Vessel Occlusion in Extended Time Window--A Multicenter, Prospective, Randomized, Open-label, Blinded End-point Trial
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 570
- 试验地点
- 1
- 主要终点
- Excellent functional outcome
研究概览
简要总结
This study is designed to evaluate the efficacy of IV rhTNK-tPA between 4.5 to 24 hours from symptom onset in patients presenting with a non-large vessel occlusion ischemic stroke.
详细描述
OPTION is a multicenter, prospective, randomized, open-label, blinded end-point (PROBE) controlled trial of thrombolysis with rhTNK-tPA versus standard of care. A total of 568 patients will be enrolled at approximately 40 centers around China.
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)
盲法说明
An imaging core laboratory (ICL) is to provide an unbiased assessment of imaging measures. They are knowledgeable in the analysis of neuroradiological images and will be blinded, i.e. unaware of the patient's treatment allocation and trial outcome.
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
- •Clinical diagnosis of acute ischemic stroke
- •Age≥18 years
- •Pre-stroke mRS score≤1 points
- •Disabling stroke defined as follows:
- •Baseline NIHSS score 6-25 at the time of randomization,
- •Or NIHSS 4-5 with disabling deficit (e.g. hemianopia, aphasia, loss of hand function) as determined by the managing clinician
- •Onset (last-seen-well) time to treatment time between 4.5 and 24 hours
- •Written informed consent from patients or legally responsible representatives
- •The presence of a Target Mismatch on CT perfusion: ischemic core volume<50ml (defined as rCBF<30%), mismatch ratio≥1.2 (Tmax>6 sec lesion/core volume lesion), mismatch volume≥10ml
排除标准
- •Treatment with a thrombolytic within the last 72 hours or intention to receive intravenous thrombolysis
- •Contraindication to thrombolysis
- •Planned or anticipated treatment with endovascular therapy
- •Rapidly improving symptoms, particularly if in the judgment of the managing clinician that the improvement is likely to result in a NIHSS score<4 at randomization
- •Pregnancy or lactating; formal testing needed in women of childbearing potential
- •Brain tumor (with mass effect)
- •Hereditary or acquired hemorrhagic diathesis, coagulation factor deficiency
- •Impairment in coagulation due to comorbid disease or anticoagulant use. If on warfarin, international normalized ratio (INR) >1.7 or prothrombin time >15s; if use of any direct oral anticoagulant within the last 48 hours; if use of heparin/heparinoid within the last 24 hours
- •Use of glycoprotein Ⅱb-Ⅲa inhibitors within the last 72 hours
- •Baseline platelet count <100,000/μL
- •Undergoing hemodialysis or peritoneal dialysis; known severe renal insufficiency with glomerular filtration rate <30ml/min or serum creatinine >220mmol/L (2.5mg/dl)
- •Suspected aortic dissection
- •Major surgery or biopsy within the last 1 month
- •Any active bleeding within the previous 1 month (including gastrointestinal or urinary bleeding)
- •Known severe, life-threatening allergy (more severe than skin rash) to contrast agents
- •Severe, uncontrolled hypertension (systolic blood pressure >185mmHg or diastolic blood pressure >110mmHg)
- •Any terminal illness such that the patient would not be expected to survive more than half a year
- •Current participation in any investigational study that may confound outcome assessment of the study
- •Any condition that, in the judgement of the investigator, is inappropriate for participation in the trial or could impose hazards to the patient (e.g. inability to understand and/or follow the study procedures and/or follow-up due to mental disorders, cognitive or emotional disorders)
- •Specific Neuroimaging Exclusion Criteria:
- •Evidence of acute intracranial hemorrhage
- •Acute large vessel occlusion on magnetic resonance/ computed tomography angiography, including internal carotid artery (ICA), middle cerebral artery M1 segment (MCA-M1）, vertebral artery and basilar artery
研究组 & 干预措施
Intravenous rhTNK-tPA
rhTNK-tPA(0.25mg/kg) given as a single, intravenous bolus immediately upon randomization. Experimental treatment will be administered as a single intravenous bolus over 5-10 seconds as per the standard manufacturers' instructions for use.
干预措施: rhTNK-tPA (Drug)
Standard Medical Treatment
Antiplatelet therapy (aspirin or clopidogrel alone) at the discretion of local investigators according to Chinese Guidelines for Diagnosis and Treatment of Acute Ischemic Stroke 2023.
干预措施: Antiplatelet Agents (Drug)
结局指标
主要结局
Excellent functional outcome
时间窗: 90±7 days
Proportion of subjects with mRS 0-1 at 90±7 days
次要结局
- modified Rankin Scale (mRS) score(90±7 days)
- Good functional outcome(90±7 days)
- Rate of successful reperfusion(24 hours (-2/+12 hours))
- Infarct volume at 24 hours (-2/+12 hours)(24 hours (-2/+12 hours))
- Early clinical recovery(24 hours (-2/+12 hours))
- Change of National Institutes of Health Stroke Scale (NIHSS)(7±2 days)
- Functional health status and quality of life(90±7 days)