Specialized Program of Translational Research in Acute Stroke- Project 1

急性中风转化研究专门计划 - 项目 1

• 批准号: 8480203
• 负责人: Lee H Schwamm
• 金额: $ 161.11万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-20 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8480203
• 关键词: Acute; Adult; Adverse event; Alteplase; American Heart Association; Cause of Death; Cerebral hemisphere hemorrhage; Cessation of life; Clinical; Clinical Trials Design; Code; Data; Data Set; Deterioration; Diffusion; Diffusion weighted imaging; Edema; Eligibility Determination; Enrollment; Exclusion Criteria; FDA approved; Goals; Growth; Guidelines; Hemorrhage; Hospitals; Hour; Human; Image; Infarction; Instruction; Intervention; Intravenous; Ischemic Stroke; Label; Lesion; Life; Link; Magnetic Resonance Imaging; Methods; Modeling; Monitor; Morbidity - disease rate; Multimodal Imaging; Names; Neurologic; Patients; Pattern; Phase; Probability; Publishing; Qualifying; Relative (related person); Reperfusion Therapy; Reporting; Research Personnel; Safety; Sensitivity and Specificity; Serious Adverse Event; Specificity; Statistical Models; Stroke; Stroke prevention; Symptoms; Techniques; Thrombolytic Therapy; Time; Tissues; Translational Research; acute stroke; arm; clinical efficacy; detector; follow-up; high risk; improved; inclusion criteria; interest; meetings; neuroimaging; novel; open label; patient population; patient safety; programs; safety study; thrombolysis; time use

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.

项目总结（见说明）：尽管在卒中预防及其急性治疗方面取得了重大进展，但卒中仍然是全球第三大死亡原因和成人发病率的主要原因。通过以最保守的方式定义“卒中症状发作”，即患者最后一次被观察到良好的时间，许多发作未被观察到的患者自动不符合溶栓治疗的条件，即使他们的真实发作时间允许他们符合条件。如果存在一种技术，可以取代人类证人，并证明中风实际上是小于3.5小时的持续时间，那么这些患者可以考虑根据现行的美国心脏协会（AHA）指南进行阿替普酶治疗，如果符合入选和排除标准，则进行治疗。许多卒中患者在发现症状后3小时内被迅速送往医院，但FDA的适应症将其排除在静脉注射阿替普酶的考虑范围之外，如果自最后一次知道他们身体状况良好后超过3小时。我们建议使用先进的MR成像作为“证人”，在这些患者的开放标签IIa期溶栓安全性研究中证明没有人类证人的患者的卒中持续时间。我们根据ECASS 3试验设计和现行AHA指南对其他合格性标准进行了建模，以将关注变量限制为使用MR作为卒中发作时间的决定因素。我们将从研究中排除在最后一次观察良好后3小时内到达的患者，因为这些患者有资格接受标签内溶栓治疗。由于本研究是开放标签的，研究者是非盲的，我们将使用更保守的ECASS-2症状性ICH定义。这被定义为任何伴有神经功能恶化的出血，如NIHSS评分比基线值或前7天的最低值高4分或以上，或任何导致死亡的出血，并且不需要将ICH归类为与神经功能恶化有因果关系。如果我们的研究是成功的，我们可以潜在地扩大使用歌词中风患者人群，目前很少提供急性干预。