Intra-arterial Recombinant Human Tenecteplase Tissue-type Plasminogen Activator (rhTNK-tPA) Thrombolysis for Acute Medium Vessel Occlusion -- A Multicenter, Prospective, Randomized, Open-label, Blinded End-point Trial
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 382
- 主要终点
- Excellent outcome
研究概览
简要总结
Medium vessel occlusion (MeVO) accounts for 20-45% of acute ischemic stroke (AIS). Although patients with MeVO often present with relatively low NIHSS scores, up to one-third remain functionally dependent at follow-up despite receiving standard medical therapy, including intravenous thrombolysis. Recent randomized trials (DISTAL, ESCAPE-MeVO, DISCOUNT) have not demonstrated clinical benefit of endovascular treatment (EVT) for MeVO and have suggested higher risks of symptomatic intracranial hemorrhage and mortality, underscoring the need for safer and more targeted reperfusion strategies.
Intra-arterial thrombolysis (IAT) enables localized, high-concentration thrombolytic delivery with minimal mechanical manipulation, which may be advantageous for medium and distal vessels. Recombinant human TNK tissue-type plasminogen activator (rhTNK-tPA), a genetically engineered third-generation thrombolytic agent, has shown favorable pharmacologic properties and clinical safety in AIS, including in intra-arterial use following EVT. However, prospective evidence supporting its direct therapeutic role in MeVO-related AIS remains lacking.
This multicenter, prospective, open-label randomized controlled trial with blinded endpoint assessment is designed to evaluate the efficacy and safety of intra-arterial rhTNK-tPA thrombolysis in improving functional outcome in MeVO within 24 hours of symptom onset.
详细描述
This study is an investigator-initiated, multicenter, prospective, randomized, open-label, blinded-endpoint (PROBE) clinical trial designed to evaluate the efficacy and safety of intra-arterial rhTNK-tPA in improving 90-day functional outcomes in patients with MeVO stroke within 24 hours of symptom onset. The primary outcome is the proportion of patients achieving a modified Rankin Scale (mRS) score of 0-1 at 90 days. Eligible patients will be randomized in a 1:1 ratio to receive either intra-arterial rhTNK-tPA thrombolysis (0.125 mg/kg, Max 12.5mg) plus standard medical therapy or standard medical therapy alone. A total of 382 participants (191 per group) will be enrolled in this trial.
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
- 否
入选标准
- •Age ≥18 years
- •Pre-stroke mRS score 0-1
- •Baseline NIHSS ≥4 or symptoms deemed clearly disabling by treating physician (e.g., hemianopia, aphasia, or motor dysfunction)
- •Isolated medium distal vessel occlusion (i.e., an occlusion of the co-/non-dominant M2, the M3/M4 segment of the MCA, the A1/A2/A3 segment of the ACA or the P1/P2/P3 segment of the PCA) confirmed by CT angiography (CTA) or MR angiography (MRA)
- •Acute ischemic stroke within 24 hours of symptom onset, including wake-up stroke or unwitnessed stroke; The onset time of symptoms was defined as the last time of normal performance.
- •Acute ischemic stroke within 6-24 hours of onset, meeting at least one of the following imaging criteria:
- •Evidence of a hypoperfusion-ischemic core mismatch on CT or MRI perfusion, defined as an ischemic core volume <50mL, hypoperfused tissue volume to ischemic core volume ratio ≥1.2, and mismatch volume ≥10 mL
- •Evidence of a diffusion-hyperintensity mismatch, defined as absence of hyperintensity on fluidattenuated inversion recovery (FLAIR) imaging within ≥ 90% of the area of the diffusion weighted imaging (DWI) lesion)
- •The participant or legally authorized representative is capable of providing informed consent
排除标准
- •Evidence of intracranial hemorrhage
- •Any active bleeding (gastrointestinal, urinary, hemorrhagic retinopathy, etc.) or parenchymal organ surgery or biopsy within 30 days before stroke; Severe head trauma or stroke within the past 3 months
- •Persistent and uncontrolled hypertension, defined as systolic blood pressure >185 mmHg or diastolic blood pressure >110 mmHg
- •Inherited or acquired hemorrhagic tendancy; deficiency of anticoagulant factors; or on oral anticoagulant with an INR> 1.7
- •Blood glucose <2.8 mmol/L (50 mg/dl) or > 22.2mmol/L (400 mg/dl), platelets count <100*109/L, or hemoglobin <70g/L
- •Severe hepatic insufficiency, chronic hemodialysis and severe renal insufficiency (or recent blood tests suggesting a glomerular filtration rate <30 ml/min or blood creatinine> 200 mmol/L (2.5 mg/dl)
- •Women who are pregnant or breastfeeding
- •Allergy to rhTNK-tPA or radiocontrast agent
- •Participation in other clinical trials
- •Expected survival time less than 6 months (e.g., due to malignancy, severe cardiopulmonary disease, etc.)
- •Other conditions deemed by the investigator to make the patient unsuitable for participation or pose significant risks (e.g., inability to understand and/or comply with study procedures and/or follow-up due to mental illness, cognitive or emotional disorders)
研究组 & 干预措施
Intervention group
Patients of this group will receive intra-arterial rhTNK-tPA thrombolysis plus standard medical treatment
干预措施: Intra-arterial Thrombolysis (Procedure)
Intervention group
Patients of this group will receive intra-arterial rhTNK-tPA thrombolysis plus standard medical treatment
干预措施: Standard medical treatment (Drug)
Control group
Patients of this group will receive standard medical treatment alone
干预措施: Standard medical treatment (Drug)
结局指标
主要结局
Excellent outcome
时间窗: 90±7 days
Rate of modified Rankin scale (mRS) 0-1 at 90±7 days
次要结局
- Ordinal distribution of mRS(90±7 days)
- Quality of life (EQ-5D-5L)(90±7 days)
- Functional independence(90±7 days)
- Neurologic deficit (NIHSS score) changes(36±12 hours)
- Infarct core volume change from baseline(7±1 days or discharge if earlier)
研究者
Xiang Luo
Principal Investigator
Tongji Hospital