Specialized Program of Translational Research in Acute Stroke- Project 1

项目摘要（见说明）：尽管在中风预防及其急性治疗方面取得了重大进展，但中风仍然是全球第三大死亡原因和成人发病的主要原因。通过以最保守的方式定义“中风症状发作”，即患者最后一次就诊的时间，许多未被目击发病的患者自动不符合溶栓治疗的条件，即使他们的真实发病时间允许他们符合条件。如果存在一种技术可以替代人类证人，并证明中风实际上持续时间少于3.5小时，那么根据目前美国心脏协会（AHA）的指导方针，这些患者可以考虑接受阿替普酶治疗，如果符合纳入和排除标准，则可以接受治疗。许多中风患者在症状发现后3小时内被迅速送往医院，但FDA的适应症排除了静脉注射阿替普酶的考虑，如果自他们最后一次知道健康的时间超过3小时。我们建议使用先进的磁共振成像作为“证人”来证明那些没有人类证人的患者的卒中持续时间，在这些患者中进行开放标签的Ha期溶栓安全性研究。我们在ECASS3试验设计和当前AHA指南之后对其他资格标准进行了建模，以便将感兴趣的变量限制为使用MR作为中风发病时间的决定因素。我们将从研究中排除离上次就诊时间3小时内到达的患者，因为这些患者符合标签上的溶栓治疗条件。由于这项研究是开放标签的，研究者是非盲的，我们将使用更保守的ECASS-2对症状性脑出血的定义。其定义为任何伴有神经系统恶化的出血，如NIHSS评分高于基线值或前7天的最低值4分或更多，或任何出血导致死亡，并且不要求将脑出血归类为与神经系统恶化有因果关系。如果我们的研究是成功的，我们可以潜在地将歌词的使用扩展到中风患者人群中，他们目前几乎没有提供急性干预。

PROJECT SUMMARY (See instructions): Despite significant progress in stroke prevention and its acute treatment, stroke remains the third leading cause of death and a leading cause of adult morbidity worldwide. By defining "stroke symptom onset" in the most conservative manner, namely the time the patient was last seen well, many patients whose onset is unwitnessed are automatically ineligible for thrombolytic therapy even if their true time of onset would allow them to qualify. If a technique existed that could replace the human witness and testify that the stroke was in fact less than 3.5 hours duration, then these patients could be considered for alteplase treatment under current American Heart Association (AHA) guidelines, and be treated if eligible according to the inclusion and exclusion criteria. Many stroke patients are rapidly brought to the hospital within 3 hours of the time of symptom discovery, but FDA indications exclude them from consideration for intravenous alteplase if it has been greater than 3 hours since the time they were last known to be well. We propose to use advanced MR imaging as the "witness" to testify as to stroke duration in those patients who do not have a human witness in an open label Phase Ha safety study of thrombolysis in these patients. We have modeled the other eligibility criteria after the ECASS3 trial design and the current AHA guidelines in order to limit the variable of interest to the use of MR as the determinant of time of stroke onset. We will exclude patients from the study who arrive within 3 hours from last seen well since these patients are eligible for on-label treatment with thrombolysis. Because the study is open-label and investigators are unblinded, we will use the more conservative ECASS-2 definition of symptomatic ICH. This is defined as any hemorrhage with neurologic deterioration, as indicated by an NIHSS score that was higher by 4 points or more than the value at baseline or the lowest value in the first 7 days, or any hemorrhage leading to death, and does not require that the ICH be classified as causally linked to the neurologic deterioration. If our study is successful, we can potentially expand use of lyrics to a stroke patient population for whom little acute intervention is currently offered.