Tenecteplase in Wake-up Ischaemic Stroke Trial (TWIST). A Randomised-controlled Trial of Thrombolytic Treatment With Tenecteplase for Acute Ischaemic Stroke Upon Awakening
试验速览
- 阶段
- 3 期
- 发起方
- 入组人数
- 600
- 试验地点
- 83
- 主要终点
- Functional outcome at 3 months.
研究概览
简要总结
Stroke is a leading causes of death and disability. At least 20% of strokes occur during sleep, so- called 'wake up stroke'. Thrombolysis with the clot-busting drug alteplase is effective for acute ischaemic stroke, provided that it is given within 4.5 hours of symptom onset. Patients with wake-up stroke are currently ineligible for clot-busting therapy. Previous studies indicate that many wake-up strokes occur just before awakening.
In this study, patients with wake-up stroke will be randomized to thrombolysis with tenecteplase and best standard treatment or to best standard treatment without thrombolysis. Tenecteplase has several potential advantages over alteplase, including very rapid action and that it can be given as a single injection. Prior to thrombolysis, a brain scan must be done to exclude bleeding or significant brain damage as a result from the stroke. We will use a CT scan to inform this decision. CT is used as a routine examination in all stroke patients. Other studies testing clot-busting treatment in wake-up stroke are using alteplase and more complex brain scans, which are not routinely available in the emergency situation in all hospitals.
详细描述
Background:
One in five strokes occur during sleep, but patients with "wake-up" stroke are not given thrombolytic therapy because time of stroke onset is unknown. On-going trials are testing alteplase, and use MRI techniques for selection of patients. Tenecteplase has many pharmacological advantages over alteplase: greater fibrin specificity, very rapid action, longer half-life, and single bolus administration. In addition, patient selection based on MRI findings risks excluding many patients that might otherwise benefit. TWIST will test tenecteplase and will not use MRI techniques for selection of patients. Plain CT and CT angiography (if possible) will be performed before randomisation, and CT perfusion will be performed at selected centres, as part of a sub-study.
Study design: TWIST is an international, multi-centre, randomised, open-label, blinded-endpoint trial of tenecteplase for acute ischaemic 'wake-up' stroke.
Study questions:
- Can tenecteplase given <4.5 hours of awakening improve functional outcome at 3 months?
- Can findings on cerebral plain CT and CT angiography (and CT perfusion, at selected centres) identify patients who benefit from such treatment, compared to other patients?
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
- 是
入选标准
- •Stroke symptoms on awakening that were not present before sleep
- •Clinical diagnosis of stroke with limb weakness with NIHSS score >=3, or dysphasia
- •Treatment with tenecteplase is possible within 4.5 hours of awakening
- •Written consent from the patient, non-written consent from the patient (witnessed by non-participating health care personnel), or written consent from the nearest family member
排除标准
- •Age <18 years
- •NIHSS score >25 or NIHSS consciousness score >2, or seizures during stroke onset
- •Findings on plain CT that indicate that the patient is unlikely to benefit from treatment:
- •Infarction comprising more than >1/3 of the middle cerebral artery territory on plain CT or CT perfusion
- •Intracranial haemorrhage, structural brain lesions which can mimic stroke (e.g cerebral tumour)
- •Active internal bleeding of high risk of bleeding, e.g.:
- •Major surgery, trauma or gastrointestinal or urinary tract haemorrhage within the previous 21 days, or arterial puncture at a non-compressible site within the previous 7 days
- •Any known defect in coagulation, e.g. current use of vitamin K antagonist with an INR >1.7 or prothrombin time >15 seconds, or use of direct thrombin inhibitors or direct factor Xa inhibitors during the last 24 hours (unless reversal of effect can be achieved by agents such as idarucizumab) or with elevated sensitive laboratory tests (such as activated partial thromboplastin time (aPTT), international normalized ratio (INR), platelet count, ecarin clotting time, thrombin time (TT), or appropriate factor Xa activity assays), or heparins during the last 24 hours or with an elevated aPTT greater than the upper limit of normal
- •Known defect of clotting or platelet function or platelet count below 100,000/mm3 (but patients on antiplatelet agents can be included)
- •Ischaemic stroke or myocardial infarction in previous 3 months, previous intracranial haemorrhage, severe traumatic brain injury or intracranial or intraspinal operation in previous 3 months, or known intracranial neoplasm, arteriovenous malformation or aneurysm
- •Contraindications to tenecteplase, e.g., acute bacterial endocarditis or pericarditis; acute pancreatitis; severe hepatic dysfunction, including hepatic failure, cirrhosis, portal hypertension; active hepatitis; systemic cancer with increased bleeding risk; haemostatic defect including secondary to severe hepatic, renal disease; organ biopsy; prolonged cardiopulmonary resuscitation > 2 min (within 2 weeks)
- •Persistent blood pressure elevation (systolic ≥185 mmHg or diastolic ≥110 mmHg), despite blood pressure lowering treatment
- •Blood glucose <2.7 or >20.0 mmol/L (use of finger-stick measurement devices is acceptable)
- •Pregnancy, positive pregnancy test, childbirth during last 10 days, or breastfeeding. In any woman of childbearing potential, a pregnancy test must be performed and the result assessed before trial entry
- •Other serious or life-threatening disease before the stroke: severe mental or physical disability (e.g. Mini Mental Status score <20, or mRS score ≥3), or life expectancy less than 12 months
- •Patient unavailability for follow-up (e.g. no fixed address)
研究组 & 干预措施
Tenecteplase
Tenecteplase + Best standard treatment
干预措施: Tenecteplase (Drug)
Control
No tenecteplase + Best standard treatment
干预措施: Control (Other)
结局指标
主要结局
Functional outcome at 3 months.
时间窗: 3 months
Functional outcome will be assessed by the modified Rankin Scale (mRS), values 0-6
次要结局
- Symptomatic intracranial haemorrhage during the first 7 days.(First 7 days)
- Asymptomatic intracranial haemorrhage during the first 7 days.(First 7 days)
- Recurrent ischaemic stroke during the first 7 days(First 7 days)
- Death from all cause(3 months)
- Barthel Index score(3 months)
- EuroQol Score (EQ-5D)(3 months)
- Mini Mental State Examination(3 months)
- Health-economic variables(3 months)
- Functional outcome at 3 months(3 months)