Tenecteplase Thrombolysis for Acute Ischemic Stroke in the 4.5-9-Hour Window Guided by DWI-FLAIR Mismatch: A Multicenter, Prospective, Randomized, Double-Blind, Placebo-Controlled Trial
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 564
- 试验地点
- 1
- 主要终点
- Modified Rankin Scale (mRS)
研究概览
简要总结
The goal of this clinical trial is to evaluate the efficacy and safety of tenecteplase administered 4.5-9 hours after stroke onset (defined as the time the patient was first found with symptoms, including wake-up stroke and unwitnessed stroke) in patients with acute ischemic stroke (AIS) guided by DWI-FLAIR mismatch on MRI. The main questions it aims to answer are:
- Does tenecteplase improve functional outcomes at 90 days compared with standard treatments in AIS patients administered 4.5-9 hours after stroke onset guided by DWI-FLAIR mismatch?
- The safety of tenecteplase thrombolysis for AIS patients in the 4.5-9 hours guided by DWI-FLAIR mismatch.
Researchers will compare tenecteplase to placebo to see if it is effective and safe for these patients.
Participants will be randomly assigned (1:1) immediately after randomization:
- Tenecteplase group: received tenecteplase, intravenously as a bolus administered over a period of 5 to 10 seconds at a dose of 0.25 mg per kilogram (maximum dose, 25 mg), plus aspirin placebo (300 mg).
- Control group: aspirin (300 mg) plus tenecteplase placebo. From day 2 to day 90, all patients will be conformed to the 2023 Chinese Guidelines for Diagnosis and Treatment of Acute Ischemic Stroke.
详细描述
Current clinical guidelines recommend intravenous thrombolysis (IVT) for eligible AIS patients within 4.5 hours of symptom onset. However, approximately 67 to 75% of patients present after 4.5 hours after stroke onset or with an unknown time of onset. CT perfusion (CTP) and perfusion-diffusion magnetic resonance imaging (MRI) have demonstrated that potentially viable brain tissue may persist beyond 4.5 hours after stroke onset. Recent trials, such as EXTEND, TRACE III, and the HOPE study, suggest that IVT can improve functional outcomes in AIS patients with salvageable brain tissue identified beyond 4.5 hours and up to 24 hours, using advanced perfusion imaging. Nonetheless, due to the high cost of perfusion software in developing countries, extended-window thrombolysis has not been widely implemented in many stroke centers. Therefore, it is crucial to develop alternative strategies to guide IVT in patients beyond 4.5 hours.
In recent years, the mismatch between a visible acute ischemic lesion on diffusion-weighted imaging (DWI) and the absence of a corresponding hyperintensity on fluid-attenuated inversion recovery (FLAIR) has been recognized as a predictor of symptom onset within 4.5 hours before imaging. The WAKE-UP trial demonstrated that among AIS patients with unknown time of onset (last known well >4.5 hours) and DWI-FLAIR mismatch, IVT administered within 4.5 hours after symptom recognition significantly improved functional outcomes. However, approximately 30% of AIS patients exhibit DWI-FLAIR mismatch between 4.5 and 9 hours after onset. Whether these patients can benefit from thrombolysis remains uncertain.
TRUST-MISMATCH is a multicenter, prospective, randomized, double-blind, placebo-controlled clinical. We want to evaluate the efficacy and safety of tenecteplase administered 4.5-9 hours after stroke onset (defined as the time the patient was first found with symptoms, including wake-up stroke and unwitnessed stroke) in AIS patients guided by DWI-FLAIR mismatch on MRI.
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
- •Age ≥ 18 years;
- •AIS with symptom onset 4.5-9 hours before enrollment, including wake-up stroke and unwitnessed stroke (onset time defined as when symptoms were first noticed);
- •Imaging criteria:
- •DWI-FLAIR mismatch: visible lesion on DWI with no marked visible lesion on FLAIR;
- •DWI infarct core not exceeding one-third of the middle cerebral artery territory, one-half of the anterior cerebral artery territory, or one-half of the posterior cerebral artery territory;
- •NIHSS score 4-25;
- •First-ever stroke or previous stroke without significant disability (pre-stroke mRS ≤ 1);
- •Signed informed consent from the patient or legally authorized representative.
排除标准
- •Planned endovascular treatment;
- •Contradictory to MRI examination;
- •MRI image not qualified for evaluation;
- •Serious neurological deficits before onset (mRS≥2);
- •Obvious head injuries or strokes within 3 months;
- •Subarachnoid or intracranial hemorrhage;
- •History of intracranial hemorrhage;
- •Intracranial tumor, arteriovenous malformation or aneurysm;
- •Intracranial or spinal cord surgery within 3 months;
- •Active internal hemorrhage;
- •platelet count of <100000/mm3;
- •Aortic arch dissection;
- •Heparin therapy within 24 hours;
- •Oral warfarin is being taken and INR>1.6 or APTT abnormal;
- •Oral anticoagulation therapy;
- •Systolic pressure≥185 mmHg or diastolic pressure≥110 mmHg;
- •Blood glucose < 50 mg/dl (2.7mmol/L);
- •Neurological deficit after epileptic seizures;
- •Major surgery within 1 month;
- •Gastrointestinal or urinary tract hemorrhage within the previous 30 days;
- •Myocardial infarction within 3 months;
- •Allergy to study drugs;
- •Unlikely to adhere to the trial protocol or follow-up;
- •Any condition that, in the judgment of the investigator could impose hazards to the patient if study therapy is initiated or affect the participation of the patient in the study;
- •Participation in other interventional clinical trials within the previous 3 months.
研究组 & 干预措施
Tenecteplase group:
Patients will receive tenecteplase, intravenously as a bolus administered over a period of 5 to 10 seconds at a dose of 0.25 mg per kilogram (maximum dose, 25 mg), plus aspirin placebo (300 mg) immediately after randomization.From day 2 to day 90, all patients will be conformed to the 2023 Chinese Guidelines for Diagnosis and Treatment of Acute Ischemic Stroke.
干预措施: Placebo (Drug)
Control group
Patients will receive asprin(300mg) plus intravenous TNK(placebo, 0.25mg/kg, a maximum of 25 mg) immediately after randomization. From day 2 to day 90, patients will be conformed to the 2023 Chinese Guidelines for Diagnosis and Treatment of Acute Ischemic Stroke.
干预措施: Placebo (Drug)
Tenecteplase group:
Patients will receive tenecteplase, intravenously as a bolus administered over a period of 5 to 10 seconds at a dose of 0.25 mg per kilogram (maximum dose, 25 mg), plus aspirin placebo (300 mg) immediately after randomization.From day 2 to day 90, all patients will be conformed to the 2023 Chinese Guidelines for Diagnosis and Treatment of Acute Ischemic Stroke.
干预措施: TNK-tPA (Drug)
Control group
Patients will receive asprin(300mg) plus intravenous TNK(placebo, 0.25mg/kg, a maximum of 25 mg) immediately after randomization. From day 2 to day 90, patients will be conformed to the 2023 Chinese Guidelines for Diagnosis and Treatment of Acute Ischemic Stroke.
干预措施: Aspirin (Drug)
结局指标
主要结局
Modified Rankin Scale (mRS)
时间窗: 90 ± 7 days
Proportion of subjects of excellent outcome defined as mRS (0-1) at 90 ± 7 days.
次要结局
- Modified Rankin Scale (mRS)(90 ± 7 days)
- National Institutes of Health Stroke Scale (NIHSS)(24 hours and 7 days)
- Barthel (BI)(90 ± 7 days)
- EuroQol 5-Dimension (EQ-5D)(90 ± 7 days)
研究者
Bo Song
Chief Physician、Professor
The First Affiliated Hospital of Zhengzhou University