Intraventricular Fibrinolysis Versus External Ventricular Drainage Alone in Aneurysmal Subarachnoid Hemorrhage: a Randomized Controlled Trial.
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 81
- 试验地点
- 1
- 主要终点
- Participants With Modified Rankin Scale (mRS) <=3 - Dichotomized Analysis.
研究概览
简要总结
Aneurysmal subarachnoid hemorrhage (SAH) is a devastating form of stroke, with delayed cerebral ischemia (DCI) as a major complication. There are several evidences, both in preclinical and in clinical studies that intraventricular fibrinolysis (IVF) controls the phenomenon that are leading to DCI. Here, the investigators propose to conduct a phase III trial to provide a clear evaluation of the impact of IVF after aneurysmal SAH.
详细描述
Introduction
Aneurysmal subarachnoid hemorrhage (SAH) is a devastating form of stroke, which often causes acute hydrocephalus requiring the insertion of an external ventricular drain (EVD). A major complication of aneurysmal SAH is delayed cerebral ischemia (DCI), which corresponds to the occurrence of an ischemic stroke up to 21 days after the aneurysm rupture. There are currently only few ways to prevent it. As DCI is linked to the presence of blood within the subarachnoid space, it has been hypothesized that removing this blood may decrease the risk of DCI. It could be obtained by injecting a fibrinolytic agent through the EVD, a therapeutic strategy named intraventricular fibrinolysis (IVF). There are several evidences, both in preclinical and in clinical studies that IVF controls the phenomenon that are leading to DCI. It has notably been shown in Phase I and Phase II trial that IVF in aneurysmal SAH is safe and may decrease the risk of DCI, with a trend to improve the rate of good functional outcome by about 10%. Here, the investigators propose to conduct a phase III trial to provide a clear evaluation of the impact of IVF after aneurysmal SAH.
Materials and methods
this study will include patients with aneurysmal SAH requiring external ventricular drainage. The investigators will perform a pragmatic randomized controlled trial: compare the standard of care, i.e. the EVD alone, to the experimental treatment, i.e. IVF, with an open design. After exclusion of the aneurysm, patients will be randomly allocated to receive either EVD alone or EVD+IVF (72 hours, 9 doses). The primary outcome will be the proportion of patients without severe disability 6 months after the aneurysm rupture, as evaluated by the modified Rankin Scale (mRS). The investigators plan to include 440 patients, to show an increase of the rate of good functional outcome of 10% in the EVD+IVF group compared to the EVD alone group (α=0.05 and β=0.8). To obtain such sample, a multicenter trial is mandatory, and to date 16 centers accepted to participate. Each center will include one patient per month, and the inclusion period is to last 48 months.
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
To minimize bias, the randomization and the treatment from V0 to the end of treatment will be performed by the local intensivist designed as investigator. The follow-up until day 4 (V1) to 6 months (V4), so the judgement criteria will be collected by the local neurosurgeon designed as investigator, who will be blinded to the treatment received.
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients (age 18-75) with SAH on initial CT-Scan examination.
- •SAH associated with hydrocephalus requiring external ventricular drainage.
- •Confirmation of an associated intracranial aneurysm by vascular imaging.
- •Time from onset to admission under 24 hours.
- •Exclusion of the aneurysm by surgical clipping or endovascular coiling before IVF.
- •Oral information on research and informed consent of the patient and/or his relatives.
排除标准
- •Patient with severe clinical presentation on admission: WFNS score =
- •Associated intracerebral hematoma of more than 2 cm in its larger width.
- •SAH diagnosed on lumbar puncture: original Fisher grade =
- •Impossibility to exclude the aneurysm within 72 hours following its rupture.
- •Patient previously treated with antiplatelet therapy or treated with antiplatelet therapy after the aneurysm exclusion.
- •Severe coagulopathy, including oral vitamin K antagonist.
- •Pregnant or lactating woman.
研究组 & 干预措施
EVD + IVF with Alteplase
Intraventricular fibrinolysis: Injection through the EVD of 1mg in 1 mL of Alteplase every eight hours during 3 days (9 doses).
干预措施: EVD + IVF with Alteplase (Drug)
结局指标
主要结局
Participants With Modified Rankin Scale (mRS) <=3 - Dichotomized Analysis.
时间窗: 6 months.
Proportion of patients without severe disability evaluated by the modified Rankin Scale (0-3). The modified Rankin Scale (mRS) is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. It is scored from 0 (perfect health without symptoms) to 6 (death).
次要结局
- Quality of life evaluated by the MOS SF-36 scale(6 months)
- DCI.(6 weeks)
- Rate of patients who returned to work.(6 months)
- Clinical deterioration caused by DCI.(1 month)
- Rebleeding.(4 days)
- Catheter related infection.(3 month)
- Death(6 months)
- Internal CSF shunt surgery.(3 months)
- EVD obstruction.(1 month)
- Asthenia.(6 months)