CLOTBUST-Hands Free：一种新型操作者独立超声设备在急性缺血性脑卒中患者中的 Pilot 安全性研究。

CLOTBUST-Hands Free: pilot safety study of a novel operator-independent ultrasound device in patients with acute ischemic stroke.

机构信息

From the Department of Neurology, Stroke Program (A.D.B., L.S., A.W.B., P.S., H.I., N.R.G., S.I.S., J.C.G.) and Center for Clinical and Translational Sciences (H.P., M.A.-H., R.P., M.H.R.), University of Texas Health Science Center at Houston, TX; Comprehensive Stroke Center, Department of Neurology, The University of Alabama at Birmingham (A.V.A., A.S.); and Department of Neurology, Dresden University Stroke Center, University of Technology Dresden, Dresden, Germany (K.B.).

出版信息

Stroke. 2013 Dec;44(12):3376-81. doi: 10.1161/STROKEAHA.113.002713. Epub 2013 Oct 24.

DOI:10.1161/STROKEAHA.113.002713

PMID:24159060

Abstract

BACKGROUND AND PURPOSE

The Combined Lysis of Thrombus in Brain Ischemia With Transcranial Ultrasound and Systemic T-PA-Hands-Free (CLOTBUST-HF) study is a first-in-human, National Institutes of Health-sponsored, multicenter, open-label, pilot safety trial of tissue-type plasminogen activator (tPA) plus a novel operator-independent ultrasound device in patients with ischemic stroke caused by proximal intracranial occlusion.

METHODS

All patients received standard-dose intravenous tPA, and shortly after tPA bolus, the CLOTBUST-HF device delivered 2-hour therapeutic exposure to 2-MHz pulsed-wave ultrasound. Primary outcome was occurrence of symptomatic intracerebral hemorrhage. All patients underwent pretreatment and post-treatment transcranial Doppler ultrasound or CT angiography. National Institutes of Health Stroke Scale scores were collected at 2 hours and modified Rankin scale at 90 days.

RESULTS

Summary characteristics of all 20 enrolled patients were 60% men, mean age of 63 (SD=14) years, and median National Institutes of Health Stroke Scale of 15. Sites of pretreatment occlusion were as follows: 14 of 20 (70%) middle cerebral artery, 3 of 20 (15%) terminal internal carotid artery, and 3 of 20 (15%) vertebral artery. The median (interquartile range) time to tPA at the beginning of sonothrombolysis was 22 (13.5-29.0) minutes. All patients tolerated the entire 2 hours of insonation, and none developed symptomatic intracerebral hemorrhage. No serious adverse events were related to the study device. Rates of 2-hour recanalization were as follows: 8 of 20 (40%; 95% confidence interval, 19%-64%) complete and 2 of 20 (10%; 95% confidence interval, 1%-32%) partial. Middle cerebral artery occlusions demonstrated the greatest complete recanalization rate: 8 of 14 (57%; 95% confidence interval, 29%-82%). At 90 days, 5 of 20 (25%, 95% confidence interval, 7%-49) patients had a modified Rankin scale of 0 to 1.

CONCLUSIONS

Sonothrombolysis using a novel, operator-independent device, in combination with systemic tPA, seems safe, and recanalization rates warrant evaluation in a phase III efficacy trial.

CLINICAL TRIAL REGISTRATION URL

http://www.clinicaltrials.gov. Unique identifier: CLOTBUST-HF NCT01240356.

摘要

背景与目的

经颅超声联合系统 tPA-免操作人员辅助（CLOTBUST-HF）溶栓治疗缺血性脑卒中的研究是一项由美国国立卫生研究院（NIH）资助的、首次在人体中进行的、多中心、开放性、初步安全性试验，旨在评估组织型纤溶酶原激活剂（tPA）联合新型免操作人员辅助超声设备治疗因近端颅内闭塞导致的缺血性脑卒中的安全性。

方法

所有患者均接受标准剂量的静脉内 tPA 治疗，tPA 推注后不久，CLOTBUST-HF 设备即给予 2 小时的 2MHz 脉冲波超声治疗。主要结局为症状性颅内出血的发生。所有患者均在治疗前和治疗后进行经颅多普勒超声或 CT 血管造影检查。在 2 小时和 90 天时采集 NIH 卒中量表评分，在 90 天时采集改良 Rankin 量表评分。

结果

所有 20 名入组患者的一般特征为：男性占 60%，平均年龄为 63（14）岁，NIH 卒中量表评分中位数为 15。治疗前的闭塞部位如下：20 例患者中有 14 例（70%）为大脑中动脉，3 例（15%）为颈内动脉终末段，3 例（15%）为椎动脉。开始超声溶栓时 tPA 的中位（四分位距）时间为 22（13.5-29.0）分钟。所有患者均耐受了整个 2 小时的超声治疗，无一例发生症状性颅内出血。无与研究设备相关的严重不良事件。2 小时再通率如下：20 例患者中有 8 例（40%；95%置信区间，19%-64%）完全再通，20 例患者中有 2 例（10%；95%置信区间，1%-32%）部分再通。大脑中动脉闭塞患者的完全再通率最高：14 例中有 8 例（57%；95%置信区间，29%-82%）。90 天时，20 例患者中有 5 例（25%；95%置信区间，7%-49%）的改良 Rankin 量表评分为 0-1 分。