Ultra-early Tranexamic Acid After Subarachnoid Hemorrhage. A Prospective, Randomized, Multicenter Study.
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 955
- 试验地点
- 1
- 主要终点
- Modified Rankin Scale (mRS)
研究概览
简要总结
This is a multicenter, prospective, randomized, open-label trial with blinded endpoint (PROBE) assessment. Adult patients with the diagnosis of non-traumatic SAH, as proven by computed tomography (CT) within 24 hours after the onset of headache, will be randomly assigned to the treatment group or the control group. Patients in the treatment group will receive standard treatment with the addition of a bolus of TXA (1 g intravenously) immediately after randomization, followed by continuous infusion of 1 g per 8 hours until the start of aneurysm treatment, or a maximum of 24 hours after the start of medication. Patients in the control group will receive standard treatment without TXA. The primary outcome measure is favorable functional outcome, defined as a score of 0 to 3 on the modified Rankin Scale (mRS), at 6 months after SAH. Primary outcome will be determined by a trial nurse blinded for treatment allocation.
详细描述
Approximately 50% of all patients with a subarachnoid hemorrhage (SAH) die due to the hemorrhage or subsequent complications. There are several major causes for this course, such as in-hospital rebleed in 21.5% which most frequently occurs within the first 6 hours after the primary hemorrhage ("ultra-early rebleed"). A major part of the patients with a rebleed die during hospital admission and when they survive, they develop more severe cognitive dysfunctions. Reducing the rebleeds by ultra-early administration of tranexamic acid (TXA) could be a major factor in improving the functional outcome after SAH.
To evaluate whether SAH patients treated by state-of-the-art SAH management with additional ultra-early and short term TXA administration have a significantly higher percentage of favourable outcome after six months (score 0-3 on the Modified Rankin Scale) compared to the group treated by up-to-date SAH management without additional TXA.
To evaluate whether: 1) TXA reduces in-hospital rebleeds and case fatalities; 2) TXA causes more ischemic stroke 3) TXA causes more complications (such as thromboembolic events, hydrocephalus, extracranial thrombosis or hemorrhagic complications) during treatment, admission and follow-up; 4) there is a difference in causes of poor outcome between groups; 5) there is a difference in discharge locations between groups; 6) there is an association between the time between hemorrhage and TXA administration and outcome; 7) TXA increases (micro)infarctions after endovascular treatment; 8) TXA reduces health-care costs between discharge and six months after hemorrhage; 9) TXA improves quality of life at six months after hemorrhage; 10) there are differences in rebleed rates and outcome between genders or groups with different WFNS scores at admission.
Multicenter, prospective, randomized, open label treatment with blind endpoint assessment.
Adult patients (18 years and older) included within 24 hours after SAH. Group one: standard treatment with additional administration of 1 g TXA intravenously in ten minutes, immediately after the diagnosis SAH, succeeded by continuous infusion of 1 g per 8 hours until a maximum of 24 hours. Group two: standard treatment with no TXA administration. Both groups undergo a standardized and validated interview at discharge and six months after hemorrhage to assess the modified Rankin Scale score, and both groups receive a questionnaire to evaluate health-care costs and quality of life.
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
PROBE Design
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
- •Admission to one of the study centers or their referring hospitals
- •CT-confirmed SAH with most recent ictus less than 24 hours ago Definition: subarachnoid hemorrhage is a bleeding pattern on computed tomography with hyperdensity in the basal cisterns and/or Sylvian or interhemipheric fissures or a intraparenchymal hyperdensity consistent with a hematoma from an anterior, a pericallosal, a posterior or a middle cerebral artery aneurysm.
排除标准
- •No proficiency of the Dutch or English language
- •No loss of consciousness after the hemorrhage with WFNS grade 1 or 2 on admission in combination with a perimesencephalic hemorrhage Definition: on CT examination presence of hyperdensities exclusively in the basal cisterns maximal extending to the proximal part of the Sylvian fissure or posterior part of the interhemispheric fissure, without evidence for intracerebral or intraventricular haemorrhage (except slight sedimentation)
- •Bleeding pattern on CT compatible with a traumatic SAH
- •Treatment for deep vein thrombosis or pulmonary embolism
- •History of a blood coagulation disorder (a hypercoagulability disorder)
- •Pregnancy checked with a pregnancy test in women in their childbearing period
- •History of severe renal (serum creatinin >150 mmol/L)
- •History of severe liver failure (AST > 150 U/l or ALT > 150 U/l or AF > 150 U/l or γ-GT > 150 U/l)
- •Imminent death within 24 hours
研究组 & 干预措施
Tranexamic Acid
Eligible subjects are randomly assigned to immediate administration of TXA (1 g i.v.) after a diagnosis of SAH, as confirmed by CT-scan of the brain, continued by continuous infusion of 1 g per 8 hours to a maximum of 24 hours after start of medication. A maximum of 4 g TXA (1 g bolus + 3x 1 g continuous infusion) can be administered to one patient.
干预措施: Tranexamic Acid (Drug)
结局指标
主要结局
Modified Rankin Scale (mRS)
时间窗: six months
Good (mRS 0-3) and Poor (mRS 4-6)
次要结局
- Discharge location(six months)
- Ischemic stroke (Dealyed cerebral ischemia)(14-20 days)
- Hemorrhagic complications (intra- and extracranial)(six months)
- Hydrocephalus and treatment modality(six months)
- Infarctions on MR imaging at six months after endovascular treatment(six months)
- Date and cause of death(Maximum six month)
- Cause of poor outcome(six months)
- Rebleed and time interval after first hemorrhage(six months)
- Thromboembolic events during endovascular treatment(up to 48 hours)
- Extracranial thrombosis(six months)
- Time interval from last hemorrhage to first TXA administration(24 hours)
- Quality of life at six months after hemorrhage(six months)
- Health-care costs between discharge and six months after hemorrhage(three and six months)
研究者
R. Post
Drs.
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)