Schellinger Peter D, Alexandrov Andrei V, Barreto Andrew D, Demchuk Andrew M, Tsivgoulis Georgios, Kohrmann Martin, Alleman John, Howard Virginia, Howard George, Alexandrov Anne W, Brandt Gordon, Molina Carlos A
Departments of Neurology and Geriatry, Johannes Wesling Medical Center, Minden, Germany.
Department of Neurology, University of Tennessee Health Science Center, Memphis, TN, USA.
Int J Stroke. 2015 Oct;10(7):1141-8. doi: 10.1111/ijs.12536. Epub 2015 Jun 29.
We designed a Phase 3 clinical trial to determine the safety and efficacy of adding transcranial ultrasound using an operator-independent headframe to recombinant tissue-plasminogen-activator for the treatment of acute ischemic stroke.
Combined lysis of thrombus with ultrasound and systemic tissue-plasminogen-activator for emergent revascularization in acute ischemic stroke is a randomized, double-blind, placebo-controlled clinical trial that will enroll subjects with the following main inclusion criteria: less than 4·5 hours from symptom onset (three-hours in US and Canada), age 18-80 years, baseline National Institutes of Health Stroke Scale score ≥ 10, and premorbid modified-Rankin-score of 0-1, eligibility for full dose recombinant tissue-plasminogen-activator. Subjects will receive two-hours of 2-MHz pulsed wave transcranial ultrasound (target group) or sham ultrasound (control group). The projected sample size is approximately 824 subjects.
The primary endpoint, based on intention-to-treat criteria of patients enrolled within three-hours of symptom onset is the comparison between target and control groups of modified-Rankin-score scores at day 90 poststroke assessed using the proportional odds method. The study will have two planned interim analyses after approximately one-third and two-thirds of subjects have reached the 90-day modified-Rankin-score evaluation. Safety outcomes are symptomatic intracranial hemorrhage within 24 h and an overall analysis of adverse events.
Since intravenous recombinant tissue-plasminogen-activator remains the only medical therapy to reverse ischemic stroke applicable in the emergency department, our trial will determine if the additional use of transcranial ultrasound improves functional outcomes in patients with severe acute ischemic stroke (NCT#01098981).
我们设计了一项3期临床试验，以确定在重组组织型纤溶酶原激活剂治疗急性缺血性卒中时，添加使用独立于操作者的头架进行经颅超声的安全性和有效性。
超声联合血栓溶解与全身组织型纤溶酶原激活剂用于急性缺血性卒中紧急血管再通是一项随机、双盲、安慰剂对照的临床试验，将纳入符合以下主要纳入标准的受试者：症状发作后少于4.5小时（美国和加拿大为3小时），年龄18 - 80岁，基线美国国立卫生研究院卒中量表评分≥10，病前改良Rankin评分0 - 1，符合全剂量重组组织型纤溶酶原激活剂使用条件。受试者将接受两小时的2兆赫脉冲波经颅超声（目标组）或假超声（对照组）。预计样本量约为824名受试者。
基于症状发作后三小时内入组患者的意向性治疗标准，主要终点是使用比例优势法评估卒中后90天时目标组与对照组改良Rankin评分的比较。在大约三分之一和三分之二的受试者达到90天改良Rankin评分评估后，该研究将进行两次计划中的中期分析。安全性结局为24小时内有症状性颅内出血以及不良事件的总体分析。
由于静脉注射重组组织型纤溶酶原激活剂仍然是急诊科可用于逆转缺血性卒中的唯一药物治疗方法，我们的试验将确定额外使用经颅超声是否能改善重度急性缺血性卒中患者的功能结局（NCT编号：01098981）。
