INtra-arterial AltEplase folloWing successfuL reperfusIoN After mEchanical Thrombectomy
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 416
- 试验地点
- 21
- 主要终点
- Modified Rankin Scale at day 90
研究概览
简要总结
The NEWLINE trial is a multicenter, randomized, open-label, blinded endpoint (PROBE) trial evaluating whether adjunctive low-dose intra-arterial alteplase administered immediately after successful endovascular thrombectomy improves functional outcomes in adults with acute ischemic stroke due to anterior circulation large vessel occlusion. Eligible participants achieving successful reperfusion (eTICI 2b-3) within 24 hours of symptom onset will be randomized 1:1 to receive intra-arterial alteplase plus standard care or standard care alone. The primary outcome is excellent functional outcome (modified Rankin Scale score 0-1) at 90 days.
详细描述
Acute ischemic stroke caused by anterior circulation large vessel occlusion is commonly treated with endovascular thrombectomy (EVT), which achieves successful reperfusion in approximately 85-90% of treated patients. Despite successful reperfusion, many patients remain functionally disabled because of persistent microvascular obstruction, distal embolization, incomplete tissue reperfusion (the "no-reflow" phenomenon), and ischemia-reperfusion injury.
The NEWLINE trial is a prospective, multicenter, randomized, open-label, blinded endpoint (PROBE) trial designed to evaluate whether adjunctive low-dose intra-arterial alteplase administered immediately after successful EVT improves functional outcomes compared with standard medical care alone. Eligible adults with acute ischemic stroke due to anterior circulation large vessel occlusion who achieve successful reperfusion (expanded Thrombolysis in Cerebral Infarction [eTICI] grade 2b-3) within 24 hours of symptom onset will be randomly assigned in a 1:1 ratio to receive either adjunctive intra-arterial alteplase plus standard care or standard care alone.
The primary efficacy outcome is the proportion of participants achieving excellent functional outcome, defined as a modified Rankin Scale (mRS) score of 0-1, at 90 days after randomization. Key safety outcomes include symptomatic intracranial hemorrhage and all-cause mortality. The trial aims to determine whether adjunctive intra-arterial alteplase enhances neurological recovery after successful EVT without increasing the risk of major hemorrhagic complications or death.
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
The primary efficacy outcome (modified Rankin Scale [mRS] score 0-1 at 90 days) will be assessed by independent central outcome assessors who are blinded to treatment allocation, using a standardized structured interview conducted via video or telephone recording. Imaging outcomes will be evaluated by independent neuroradiologists at the Central Imaging Core Laboratory, who will remain blinded to treatment allocation and all clinical outcome data.
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.
- •No significant pre-stroke functional disability (pre-stroke mRS 0-1)
- •Clinical diagnosis of acute ischemic stroke with anterior LVO
- •Time from symptom onset to randomization within 24 hours, including wake-up stroke or unwitness stroke; the onset time refers to "Last Known Well" (LKW).
- •Baseline NIHSS of 6 - 25
- •Non-contrast CT (NCCT) or diffusion-weighted imaging (DWI)-MRI Alberta Stroke Program Early CT Score (ASPECTS) ≥
- •For patients with available perfusion imaging (CTP/MRP), additional criteria include: Ischemic core volume ≤ 70mL; Mismatch volume ≥ 15 ml; Mismatch ratio ≥ 1.8
- •Evidence of oclussion of the intracranial segment of the internal carotid artery (ICA), or M1 or M2 segment of the middle cerebral artery (MCA) on CT angiography (CTA) or MR angiography (MRA)
- •Treated with EVT resulting eTICI score of 2b-
- •Patients with an eTICI score of 2b-3 on the diagnostic cerebral angiography before MT are also eligible for the study.
- •Informed consent obtained from patient or acceptable patient surrogate.
排除标准
- •mRS score ≥ 2 before stroke onset
- •Anticipated advanced comorbid disease with life expectancy < 12 months
- •Acute head trauma
- •Severe hypertension with SBP > 185 mmHg or DBP > 110 mmHg and refractory to treatment.
- •Any active or recent major bleeding (gastrointestinal, urinary tract bleeding, etc.) in the last 30 days.
- •Contraindication to recombinant human tissue plasminogen activator (rt-PA) (except time to therapy).
- •Women who are pregnant at stroke onset.
- •Recent intracranial surgery in the past 30 days.
- •Known genetic or acquired bleeding disposition with anticoagulation factor deficiency.
- •Coagulation disorder with INR > 1.7 or use of new oral anticoagulants (within 48 hours of symptom onset).
- •Platelet count < 50 G/L.
- •Blood glucose < 2,8 mmol/L (50 mg/dl) or > 22,2 mmol/L (400 mg/dl)
- •Known severe renal insufficiency with glomerular filtration rate < 30 ml/min or blood creatinine > 220 µmol/L (2,5 mg/dl).
- •Requiring hemodialysis or peritoneal dialysis
- •Suspected vascular occlusion as a result of infective endocarditis
- •Suspected cerebral vasculitis based on medical history and/or angiographic evaluation.
- •Suspected aortic dissection
- •Severe allergy to contrast (non-mild rash allergy) or absolute contraindication to iodine contrast, heparin.
- •Acute ischemic stroke with significant mass effect or evidence of midline shift on baseline neuroimaging, or clinical signs of brain herniation
- •Suspected acute ischemic stroke involving multiple vascular territories or occlusion of two or more distinct vascular systems on neuroimaging
- •Evidence of intracranial hemorrhage (including hemorrhagic transformation) on neuroimaging
- •Brain tumor (with significant mass effect)
- •Stent placement and other situations during the EVT procedure that requires antiplatelet therapy or anti coagulation within the first 24 hours.
- •Extracranial segment occlusion of the ICA and post-procedural etiology suggests vascular dissection.
- •Intravenous heparin administration (however, heparinised saline flushes are allowed)
- •Procedure time > 90 min
- •Number of thrombectomy passes > 5
- •Complications occur during EVT: Vascular rupture, dissection, or contrast extravasation
- •Complete clinical recovery after rapid recanalization.
- •Participation in other interventional randomized clinical trials that may confound the outcome assessment of the study.
- •Any condition that, in the judgment of the investigator, makes the patient unsuitable for this study or where this study may impose a significant risk to the patient (e.g., inability to understand and/or comply with study procedures and/or follow-up due to psychiatric disorders, cognitive or emotional impairment).
- •Unlikely to be available for 90-day follow-up
研究组 & 干预措施
Standard medical treatment
Endovascular thrombectomy + Best Medical Management
干预措施: Endovascular thrombectomy (Device)
Adjunct intra-arterial thrombolysis following successful thrombectomy
Endovascular thrombectomy + Adjunct intra-arterial alteplase + Best Medical Management
干预措施: Endovascular thrombectomy (Device)
Adjunct intra-arterial thrombolysis following successful thrombectomy
Endovascular thrombectomy + Adjunct intra-arterial alteplase + Best Medical Management
干预措施: Alteplase (Drug)
结局指标
主要结局
Modified Rankin Scale at day 90
时间窗: 90 days post treatment
Proportion of participants achieving a Modified Rankin Scale (mRS) score of 0 or 1 at 90 days (±15 days). The Modified Rankin Scale ranges from 0 (no symptoms) to 6 (death). Lower scores indicate better functional outcomes; higher scores indicate worse disability.
SAFETY OUTCOME: symptomatic intracerebral hemorrahge (sICH ) rate at 24 hours.
时间窗: 24hours post EVT
Symptomatic intracranial hemorrhage (sICH) will be classified according to the Heidelberg Bleeding Classification.
次要结局
- The shift analysis of 90-day mRS(day 90 post treatment)
- SAFETY OUTCOME: Mortality at 90 days(Day 90 post endovascular treatment)
- Quality of life at 90 days(day 90 post treatment)
- NIHSS at 24h(24 ±12 hours post EVT)
- mRS 0-2 at 90 day(90 day post EVT)
- Any ICH(24 hour post EVT)
- Final eTICI reperfusion grade(Immediately after completion of intra-arterial alteplase administration.)
- To evaluate the incremental cost-effectiveness and cost-utility of adjunctive intra-arterial thrombolysis following successful angiographic reperfusion.(12 months ± 1 month)
研究者
Trung Nguyen
Stroke Neurologist
115 People's Hospital