TrIal of Early Minimally Invasive Catheter Evacuation With Thrombolysis in IntraCerebral Hemorrhage (TIME-ICH): A Prospective, Multi-center, Open-label, Adaptive, Randomized Controlled Trial
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 750
- 试验地点
- 94
- 主要终点
- Functional Improvement - uw-mRS
研究概览
简要总结
TIME-ICH (TrIal of early Minimally Invasive catheter Evacuation with thrombolysis in IntraCerebral Hemorrhage) is a multicenter, randomized, adaptive clinical trial comparing best medical management to early minimally invasive surgery with thrombolysis (eMIST) in the treatment of acute spontaneous supratentorial intracerebral hemorrhage.
详细描述
Patients presenting to the emergency department with stroke due to supratentorial, spontaneous intracerebral hemorrhage ≥20mL volume will be assessed to determine their eligibility for randomization into the trial. If the patient gives informed consent they will be randomized 1:1 using central computerized allocation to early minimally invasive surgery with thrombolysis versus best medical management. The trial is prospective, randomized, open-label, blinded endpoint (PROBE) design. Adaptive sample size re-estimation will be performed when 250 patients have completed 180 days follow-up. Clinical efficacy will be determined by demonstrating an improvement in functional outcome, as determined by a blinded-assessment of the 180-day utility-weighted modified Rankin Scale (mRS).
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-randomization head CT demonstrating an acute, spontaneous, primary ICH;
- •ICH volume ≥ 20mL as calculated by the ABC/2 method;
- •The randomization can be completed within 8 hours after the onset of stroke symptoms (or the time last known to be well), and study intervention can reasonably be initiated within 4 hours after randomization.
- •Historical Modified Rankin Score 0 or 1;
- •Obtain informed consent from patient or legal representative.
排除标准
- •Infratentorial intraparenchymal hemorrhage including midbrain, pontine, or cerebellar;
- •Ruptured aneurysm, arteriovenous malformation (AVM), vascular anomaly, Moyamoya disease, venous sinus thrombosis, mass or tumor, hemorrhagic conversion of an ischemic infarct, tumor stroke, recurrence of a recent (<1 year) ICH, as diagnosed with radiographic imaging;
- •Presence of spot sign in CT angiography;
- •Blood pressure control before randomization is ineffective, systolic blood pressure > 220 mmHg;
- •Irreversible impaired brain stem function (bilateral fixed, dilated pupils and extensor motor posturing), GCS ≤ 4;
- •Hemorrhage with apparent midbrain extension with third nerve palsy or dilated and non-reactive pupils. Other (supranuclear) gaze abnormalities are not exclusions;
- •Intraventricular extension of the Hemorrhage is visually estimated to involve >50% of either of the lateral ventricles;
- •Any irreversible coagulopathy or known clotting disorder.
- •Platelet count < 750,000, INR > 1.4 after correction
- •Patients requiring long-term anti-coagulation that needs to be initiated < 30 days from index ICH;
- •Use of 2 or more antithrombotic drugs prior to symptom onset;
- •Patients with a mechanical heart valve;
- •Positive urine or serum pregnancy test in female subjects without documented history of surgical sterilization or is post-menopausal;
- •Urokinase allergy;
- •Any concurrent serious illness that would interfere with the outcome assessments including hepatic, renal, gastroenterologic, respiratory, cardiovascular, endocrinologic, immunologic, and hematologic disease;
- •Inability or unwillingness of patient or legal representative to give written informed consent;
- •Known life-expectancy of less than 6 months;
- •Participation in a concurrent interventional medical investigation or clinical trial.
研究组 & 干预措施
Best medical management (BMM)
Subjects will receive standard of care medical management for ICH.
Early Minimally Invasive Surgery with Thrombolysis (eMIST) plus best medical management (BMM)
Subjects will undergo minimally invasive catheter evacuation followed by up to 10 doses of 50000U of urokinase for intracerebral hemorrhage clot resolution.
干预措施: Early Minimally Invasive Surgery with Thrombolysis (eMIST) (Procedure)
结局指标
主要结局
Functional Improvement - uw-mRS
时间窗: 180 days
Functional Improvement as determined by utility-weighted modified Rankin Scale (uw-mRS) which is assigned to seven levels: 1.0, 0.91, 0.76, 0.65, 0.33, 0.0, and 0.0 (with higher scores indicating a better outcome, according to patients' assessment) at 180-days.
Functional Improvement - uw-mRS
时间窗: 180 days
Functional Improvement as determined by utility-weighted modified Rankin Scale (uw-mRS) which is assigned to seven levels: 1.0, 0.91, 0.76, 0.65, 0.33, 0.0, and 0.0 (with higher scores indicating a better outcome, according to patients' assessment) at 180-days.
次要结局
- Functional Improvement - uw-mRS(7 days, 14 days (discharge), 30 days and 90 days)
- Functional Improvement - good functional outcome(7 days, 14 days (discharge), 30 days, 90 days and 180 days)
- Clot Removal - Amount of Residual Blood(36 hours, 7 days and 14 days (discharge))
- Health-related quality of life - EQ-5D-5L(14 days (discharge), 30 days, 90 days and 180 days)
- Activities of Daily Living - Barthel Index(14 days (discharge), 30 days, 90 days and 180 days)
- Functional Improvement - uw-mRS(7 days, 14 days (discharge), 30 days and 90 days)
- Functional Improvement - good functional outcome(7 days, 14 days (discharge), 30 days, 90 days and 180 days)
- Mortality(180 days)
- Clot Removal - Amount of Residual Blood(36 hours, 7 days and 14 days (discharge))
- Health-related quality of life - EQ-5D-5L(14 days (discharge), 30 days, 90 days and 180 days)
- Activities of Daily Living - Barthel Index(14 days (discharge), 30 days, 90 days and 180 days)