NCT03785678已完成3 期
A Phase III, Prospective, Double-blind, Randomized, Placebo-controlled Trial of Thrombolysis in Imaging-eligible, Late-window Patients to Assess the Efficacy and Safety of Tenecteplase (TIMELESS)
适应症
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 458
- 试验地点
- 193
- 主要终点
- Ordinal Modified Rankin Scale (mRS) Score at Day 90
研究概览
简要总结
This study will evaluate the efficacy and safety of tenecteplase compared with placebo in participants with acute ischemic stroke (AIS).
All participants will receive standard-of-care therapy according to AmericanHeart Association/American Stroke Association clinical guidelines (2018). To determine eligibility for randomization, all participants will undergo multimodal CT or MRI at baseline. Only participants with a vessel occlusion (ICA or MCA M1/M2) and penumbral tissue will be randomized. The primary analysis is to compare the efficacy of tenecteplase versus placebo in all participants at Day 90.
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
- •Patient/legally authorized representative has signed the Informed Consent Form
- •Age >= 18 years
- •AIS symptom onset within 4.5 to 24 hours Signs and symptoms consistent with the diagnosis of an acute anterior circulation ischemic stroke involving occlusion of the ICA, M1, or M2 vessels
- •Functionally independent (mRS 0-2) prior to stroke onset
- •Baseline NIHSS >=5 and that remains >=5 immediately prior to randomization
- •Neuroimaging: ICA or M1, M2 occlusion (carotid occlusions can be cervical or intracranial, with or without tandem MCA lesions) by magnetic resonance angiography (MRA) or computed tomography angiography (CTA) AND target mismatch profile on CT perfusion or MR perfusion (ischemic core volume <70 mL, mismatch ratio is >=1.8 and mismatch volume is >= 15 mL)
- •The mismatch volume is determined by FDA-approved imaging software in real time based on the difference between the ischemic core lesion volume and the Tmax>6s lesion volume. If both a CT perfusion and a multimodal MRI scan are performed prior to enrollment, the later of the 2 scans is assessed to determine eligibility. Only an intracranial MRA is required for patients screened with MRA; cervical MRA is not required. Cervical and intracranial CTA are typically obtained simultaneously in patients screened with CTA, but only the intracranial CTA is required for enrollment.
- •Alternative neuroimaging:
- •If CTA (or MRA) is technically inadequate: Tmax>6s perfusion deficit consistent with an ICA or M1, M2 occlusion AND target mismatch profile (ischemic core volume <70 mL, mismatch ratio >= 1.8 and mismatch volume >= 15 mL as determined by RAPID software)
- •If magnetic resonance perfusion (MRP) is technically inadequate: ICA or M1, M2 occlusion (carotid occlusions can be cervical or intracranial; with or without tandem MCA lesions) by MRA (or CTA, if MRA is technically inadequate and a CTA was performed within 60 minutes prior to the MRI) AND diffusion-weighted imaging (DWI) lesion volume <=25 mL for an M1 or ICA occlusion and =<15 mL for an M2 occlusion
- •If CTP is technically inadequate: patient can be screened with MRI and randomized if neuroimaging criteria are met.
- •Ability to comply with the study protocol, in the investigator's judgment
排除标准
- •Current participation in another investigational drug or device study
- •Active internal bleeding
- •Known hypersensitivity or allergy to any ingredients of tenecteplase
- •Known bleeding diathesis
- •Known hereditary or acquired hemorrhagic diathesis, coagulation factor deficiency; recent oral anticoagulant therapy with INR >1.7
- •Use of one of the new oral anticoagulants within the last 48 hours (dabigatran, rivaroxaban, apixaban, edoxaban)
- •Intracranial neoplasm (except small meningioma), arteriovenous malformation, or aneurysm
- •Seizures at stroke onset if it precludes obtaining an accurate baseline NIHSS
- •Severe, uncontrolled hypertension (systolic blood pressure >180 mmHg or diastolic blood pressure > 110 mmHg)
- •For participants with suspected coagulopathy, platelet count must be checked prior to randomization and participant is excluded if baseline platelet count <100,000/microL
- •Baseline blood glucose >400 mg/dL (22.20 mmol/L)
- •Baseline blood glucose <50 mg/dL needs to be normalized prior to randomization
- •Clot retrieval attempted using a neurothrombectomy device prior to randomization
- •Intracranial or intraspinal surgery or trauma within 2 months
- •Treatment with a thrombolytic within the last 3 months prior to randomization
- •Other serious, advanced, or terminal illness (investigator judgment) with life expectancy less than 6 months
- •Pre-existing medical, neurological, or psychiatric disease that would confound the neurological or functional evaluations
- •History of cerebrovascular accident in the last 90 days
- •Presumed septic embolus; suspicion of bacterial endocarditis
- •Any other condition that, in the opinion of the investigator, precludes an endovascular procedure or poses a significant hazard to the patient if an endovascular procedure was to be performed
- •Unable to undergo a contrast brain perfusion scan with either MRI or CT
- •Extensive early ischemic change (hypodensity) on non-contrast CT estimated to be >1/3 MCA territory, or significant hypodensity outside the Tmax>6s perfusion lesion that invalidates mismatch criteria (if patient is enrolled based on CT perfusion criteria)
- •Significant mass effect
- •Acute symptomatic arterial occlusions in more than one vascular territory confirmed on CTA/MRA (e.g., bilateral MCA occlusions, or an MCA and a basilar artery occlusion)
- •Evidence of intracranial tumor (except small meningioma) acute intracranial hemorrhage, neoplasm, or arteriovenous malformation
结局指标
主要结局
Ordinal Modified Rankin Scale (mRS) Score at Day 90
时间窗: Day 90
The the modified Rankin score (mRS) is a 6-point scale commonly used to assess disability due to stroke, with higher values indicating worse outcomes. 0 = No symptoms 1. = No significant disability 2. = Slight disability 3. = Moderate disability 4. = Moderately severe disability 5. = Severe disability 6. = Death
次要结局
- Median NIHSS Score at Day 90(Day 90)
- Proportion of Patients With Good Recovery Based on the Glasgow Outcome Scale (GOS) at Day 90(Day 90)
- Mortality Rate up to Day 30 and Day 90(Day 30 and Day 90)
- Proportion of Patients With Reperfusion at 24 Hours Post-randomization(Day 2)
- Incidence of Symptomatic Intracranial Hemorrhage (sICH) Within 36 Hours(Within 36 hours (Day 2) of treatment)
- Proportion of Patients With Parenchymal Hematoma Type 2 (PH2) at the 72-96 Hour Visit(Day 3)
- Proportion of Patients With Functional Independence at Day 90(Day 90)
- Proportion of Patients With Recanalization at 24 Hours Post-randomization(Day 2)
- Proportion of Patients With Angiographic Reperfusion at Completion of Angiographic Procedure(Day 1)
- Proportion of Patients With a Barthel Index (BI) Score ≥ 95 at Day 90(Day 90)
研究者
研究点 (193)
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