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: 8147555
• 负责人: Karen L Furie
• 金额: $ 161.55万
• 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 2014-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8147555
• 关键词: 6-chloropenicillanic acid S-sulfoxide; Acute; Adult; Adverse event; Alteplase; American Heart Association; Cause of Death; Cessation of life; Clinical; Clinical Trials Design; Data; Data Set; Deterioration; Diffusion; Diffusion weighted imaging; Edema; Eligibility Determination; Enrollment; Ensure; Exclusion Criteria; FDA approved; Goals; Guidelines; Hemorrhage; Hospitals; Hour; Human; Image; Infarction; Intervention; Intracranial Hemorrhages; Intravenous; Ischemic Stroke; Label; Lesion; Life; Link; Lytic; Magnetic Resonance Imaging; Methods; Modeling; Monitor; Morbidity - disease rate; Neurologic; Patients; Pattern; Pharmaceutical Preparations; Phase; Probability; Publishing; Qualifying; Reperfusion Therapy; Reporting; Research Personnel; Safety; Serious Adverse Event; Specificity; Stroke; Stroke prevention; Symptoms; Techniques; Thrombolytic Therapy; Time; Tissues; Translational Research; acute stroke; arm; clinical efficacy; detector; early onset; follow-up; high risk; improved; inclusion criteria; interest; meetings; neuroimaging; novel; open label; patient population; programs; safety study; thrombolysis; time use

DESCRIPTION (provided by applicant): 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 within the first few hours of true stroke onset, 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 a multi-center, open-label, single-arm Phase 2a safety trial of thrombolysis in these patients. We have modeled the other eligibility criteria after the ECASS 3 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 intracranial hemorrhage (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 lytics to a stroke patient population for whom little acute intervention is currently offered. RELEVANCE: Stroke is a leading cause of death and morbidity in the US. Thrombolysis is approved by the FDA for treatment within 180 minutes from when a patient was last seen well. Approximately 25% of stroke patients have unwitnessed onset times. This study seeks to expand IV thrombolysis to these patients using neuroimaging as the "witness" to establish the stroke duration when a human witness is unavailable.

描述（由申请人提供）：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。如果有一种技术可以替代人类目击者，并证明卒中实际上发生在真正卒中发作的最初几个小时内，那么这些患者可以根据现行美国心脏协会（AHA）指南考虑接受阿替普酶治疗，如果符合入选和排除标准，则可以接受治疗。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”，以证明在这些患者中进行的多中心、开放标签、单臂2a期溶栓安全性试验中没有人类证人的患者的卒中持续时间。根据ECASS 3试验设计和现行AHA指南，我们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症状性颅内出血（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溶解剂的中风患者人群，目前很少提供急性干预。 相关性：卒中是美国死亡和发病的主要原因。FDA批准在患者最后一次就诊后180分钟内进行溶栓治疗。大约25%的中风患者的发病时间无人目睹。本研究旨在将静脉溶栓扩大到这些患者，使用神经影像学作为“证人”，以确定中风持续时间时，人类证人不可用。