ULTRASOUND ENHANCED THROMBOLYSIS FOR ISCHEMIC STROKE

超声增强溶栓治疗缺血性中风

• 批准号: 6629242
• 负责人: Andrei V Alexandrov
• 金额: $ 15.51万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-02-01 至 2005-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6629242
• 关键词: biomedical equipment development; brain circulation; cardiovascular disorder chemotherapy; cerebral hemorrhage; cerebral ischemia /hypoxia; clinical research; clinical trial phase II; combination therapy; dosage; fibrinolysis; human subject; human therapy evaluation; intravenous administration; outcomes research; patient monitoring device; patient oriented research; plasminogen activator; statistics /biometry; stroke therapy; ultrasonography; ultrasound; ultrasound biological effect; biomedical equipment development; brain circulation; cardiovascular disorder chemotherapy; cerebral hemorrhage; cerebral ischemia /hypoxia; clinical research; clinical trial phase II; combination therapy; dosage; fibrinolysis; human subject; human therapy evaluation; intravenous administration; outcomes research; patient monitoring device; patient oriented research; plasminogen activator; statistics /biometry; stroke therapy; ultrasonography; ultrasound; ultrasound biological effect

DESCRIPTION (Adapted From The Applicant's Abstract): Laboratory research has shown that various ultrasound frequencies can enhance clot lysis in the presence of tissue plasminogen activator (TPA). Dr Alexandrov has obtained pilot non-randomized data indicating recanalization and recovery rates higher than can be expected from the NINDS TPA Stroke Study when TPA infusion was monitored by 2 MHz transcranial Doppler JCD) in patients with acute ischemic stroke. The goal of this proposal is to develop a practical operator- independent ultrasound device and to demonstrate its effectiveness and safety in enhancing thrombolytic therapy for ischemic stroke. Enhancing performance of TPA with inexpensive external ultrasound can result in earlier recanalization, accelerated patient recovery and improved outcome. Major objectives of this proposal are: 1. to develop an operator- independent ultrasound device for diagnosis and monitoring of intracranial occlusions 2. to compare rates of recanalization and recovery between patients treated with standard TPA dose versus patients treated with TPA and also continuously monitored by the operator-independent ultrasound device in phase II-III randomized trials. Dr Alexandrov will learn biometry and clinical trial design methods under supervision of Dr James Grotta, UT-Houston, TX and develop the device under the supervision of Dr Merrill Spencer, Institute for Applied Physiology in Medicine, Seattle, WA. Also under Dr Grotta's supervision, Dr Alexandrov will then design and execute a randomized phase II trial. The primary specific aims for this pilot phase II study are: 1. To determine complete recanalization and early clinical recovery rates in patients treated with intravenous TPA and continuously monitored with an external ultrasound compared to those treated with standard TPA dose alone. 2. To determine if continuous monitoring of TPA infusion with external ultrasound is safe and will not result in higher rates of symptomatic intracerebral hemorrhage compared to controls. Data generated during this phase II trial will form the basis for a design of a properly powered multicenter phase III trial. Time table includes: Courses in biometry, statistical methods and research design (1st year, 2nd year) Device development, adjustments and pilot patient studies (1st year, 2nd year) Phase II randomized trial and preliminary data analysis (2nd year, 3rd year) Manuscript preparation, data presentation and follow-up grant writing (4th year)

描述（改编自申请人的摘要）：实验室研究已有 表明各种超声频率可以增强凝块溶解 组织纤溶酶原活化剂（TPA）的存在。 Alexandrov博士已获得 飞行员非随机数据，表明重新定性和恢复率更高 当TPA输注为时，Ninds TPA中风研究的预期 急性缺血患者的2 MHz经颅多普勒JCD监测 中风。该提案的目的是开发一个实用的操作员 - 独立的超声设备并证明其有效性和安全性 在增强缺血性中风的溶栓疗法方面。增强性能 具有廉价外部超声的TPA可能会导致更早的再收购， 加速患者康复并改善了预后。这个主要目标 提案是：1。开发一个操作员 - 独立的超声设备 诊断和监测颅内闭塞 2。比较接受治疗的患者之间的重新定性和恢复率 与标准TPA剂量相对于用TPA治疗的患者，也不断 在II-III期间由独立于操作员的超声设备监控 随机试验。 Alexandrov博士将学习生物特征和临床试验设计 在德克萨斯州乌特 - 霍斯顿的詹姆斯·格罗塔博士的监督下的方法 在适用研究所Merrill Spencer博士的监督下 华盛顿州西雅图的医学生理学。同样在格罗塔博士的监督下 然后，Alexandrov将设计并执行随机II期试验。这 该试点II期研究的主要特定目的是：1。确定 治疗的患者的完全回收和早期临床恢复率 静脉内TPA并连续使用外部超声监测 与仅用标准TPA剂量治疗的人相比。 2。确定是否 连续监测外部超声输注TPA是安全的，将会 与 控件。在此阶段II试验中生成的数据将构成 适当动力的多中心III期试验的设计。 时间表包括：生物标准，统计方法和研究的课程 设计（第一年，第二年）设备开发，调整和飞行员患者 研究（第一年，第二年）II期随机试验和初步数据 分析（第二年，第三年）手稿准备，数据显示和 后续赠款写作（第四年）