CLOTBUST-HF Combined Lysis of Thrombus in Brain Ischemia with Transcranial Ultras

CLOTBUST-HF 联合经颅超声溶解脑缺血血栓

• 批准号: 7657026
• 负责人: JAMES C GROTTA
• 金额: $ 13.4万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7657026
• 关键词: Acute; Adverse event; Brain; Brain Ischemia; Brain hemorrhage; Brain imaging; Cerebral hemisphere hemorrhage; Clinical; Clinical Trials; Cytolysis; Data; Development; Device Safety; Devices; Diagnosis; Diagnostic; Diagnostic Equipment; Disruption; Doppler Ultrasound; Effectiveness; Enrollment; Equipment Safety; Favorable Clinical Outcome; Frequencies; Funding; Grant; Hand; Hour; Human Resources; Image; Incidence; Intravenous; Ischemic Stroke; Lytic; Magnetic Resonance Imaging; Measures; Methods; Microbubbles; Modality; Monitor; Neurologic; Outcome; Output; Participant; Patients; Permeability; Phase; Phase II Clinical Trials; Problem Solving; Rate; Recovery; Risk; Safety; Standards of Weights and Measures; Stroke; System; Technology; Texas; Therapeutic; Thrombus; Training; Ultrasonic Therapy; Ultrasonography; United States Food and Drug Administration; Universities; artery occlusion; disabling disease; efficacy trial; healthy volunteer; improved; novel; thrombolysis

Diagnostic 2-MHz frequency TCD ultrasound is a safe, bedside, repeatable and fast method that can diagnose arterial occlusion, continuously monitor recanalization and may be therapeutic in the setting of thrombolysis. A phase II study carried out within our previous SPOTRIAS grant demonstrated that stroke patients who received 2 hours of continuous TCD ultrasound in addition to rt-PA were significantly more likely to achieve complete recanalization compared to rt-PA alone with no increased risk of brain hemorrhage. Although TCD ultrasound improves recanalization, a definitive efficacy trial aimed at demonstrating improved patient outcomes would require more than 500 patients. To date, only operator-dependent hand-held devices have been shown to be safe and possibly effective. Unfortunately, the lack of widespread availability of trained personnel has limited its application. Development of an operator-independent TCD system would solve this problem and improve enrollment into ultrasound-enhanced stroke clinical trials. Through previous SPOTRIAS funding, such a device was developed at the University of Texas-Houston. The primary specific aim for this pilot phase l/ll study is to determine the safety of a novel, external Hands-Free transcranial Doppler ultrasound system. Importantly, since the Hands-Free TCD ultrasound system will not exceed current energy output standards of FDA approved diagnostic equipment, safety concerns are not anticipated yet will be carefully monitored and evaluated in three distinct groups. Safety and tolerability of the new Hands-Free TCD system, which also uses 2-MHz frequency ultrasound energy, will first be established in healthy volunteers. Safety in these healthy participants will be determined by detailed neurological exams and pre- and post-ultrasound brain MRIs. Next, safety of the device will be evaluated in two different sets of acute ischemic stroke patients: 0-3 hour patients treated with standard IV rt-PA and 3-6 hour non-lytic, image-selected patients treated with sonolysis (ultrasound + microbubbles). Safety in these stroke patients will be measured by incidence of symptomatic intracerebral hemorrhage and adverse events. Our primary hypothesis is that replacing conventional TCD ultrasound hand-held technology with a Hands-Free system will be safe in healthy volunteers as well as acute ischemic stroke patients. Our secondary hypothesis is that Hands-Free TCD will display similar recanalization and early clinical recovery rates compared to available historical diagnostic TCD ultrasound controls exposed to conventional, FDA-approved TCD technology. Data generated during this study will evaluate the safety of replacing an operator-dependent TCD device with an operator-independent system. Our long-term objective is to provide the widespread availability of ultrasoundenhanced thrombolysis which would significantly improve enrollment into ultrasound-stroke trials in order to establish effectiveness of this new treatment. If superior efficacy is established by combining rt-PA and Hands- Free TCD ultrasound, thousands more stroke patients could benefit and recover from their disabling disease.

诊断 2 MHz 频率 TCD 超声是一种安全、床边、可重复且快速的方法，可以诊断 动脉闭塞，持续监测再通，并且可能在溶栓治疗中具有治疗作用。一个 我们之前的 SPOTRIAS 资助中进行的 II 期研究表明，接受 2 除了 rt-PA 之外，持续数小时的 TCD 超声更有可能实现完全治疗 与单独使用 rt-PA 相比，血管再通并没有增加脑出血的风险。 尽管 TCD 超声可改善再通，但一项明确的疗效试验旨​​在证明改善 患者的结果需要超过 500 名患者。迄今为止，只有依赖于操作员的手持设备才具有 已被证明是安全的并且可能有效。不幸的是，缺乏广泛的受过训练的人员 人员限制了其应用。开发独立于操作员的 TCD 系统将解决这个问题 问题并提高超声增强中风临床试验的入组率。通过之前的 SPOTRIAS 德克萨斯大学休斯顿分校开发了这种设备。 该试验阶段 l/ll 研究的主要具体目标是确定新型外部免提装置的安全性 经颅多普勒超声系统。重要的是，由于免提 TCD 超声系统不会超过 FDA 批准的诊断设备的当前能量输出标准，尚未预计安全问题 将在三个不同的组中进行仔细监测和评估。新型免提装置的安全性和耐受性 TCD 系统也使用 2 MHz 频率超声能量，将首先在健康志愿者中建立。 这些健康参与者的安全性将通过详细的神经学检查以及超声检查前后确定 脑部核磁共振成像。接下来，将在两组不同的急性缺血性中风患者中评估该装置的安全性：0-3 接受标准 IV rt-PA 治疗 1 小时的患者，以及接受超声波溶解治疗 3-6 小时非溶解、图像选择的患者 （超声波+微泡）。这些中风患者的安全性将通过症状的发生率来衡量 脑出血和不良事件。 我们的主要假设是用免提技术取代传统的 TCD 超声手持式技术 该系统对于健康志愿者以及急性缺血性中风患者都是安全的。我们的次要假设是 与现有的 TCD 相比，免提 TCD 将显示出相似的再通率和早期临床恢复率 历史诊断 TCD 超声控制暴露于 FDA 批准的传统 TCD 技术。 本研究期间生成的数据将评估用以下设备替换依赖于操作员的 TCD 设备的安全性： 独立于操作员的系统。我们的长期目标是广泛提供超声增强技术 溶栓治疗将显着提高超声卒中试验的入组率，以便 确定这种新疗法的有效性。如果通过结合 rt-PA 和 Hands- 建立了卓越的疗效 免费 TCD 超声检查使更多的中风患者能够受益并从致残性疾病中康复。