Nacu Aliona, Kvistad Christopher E, Logallo Nicola, Naess Halvor, Waje-Andreassen Ulrike, Aamodt Anne Hege, Solhoff Ragnar, Lund Christian, Tobro Håkon, Rønning Ole Morten, Salvesen Rolf, Idicula Titto T, Thomassen Lars
Department of Neurology, Haukeland University Hospital, N-5021, Bergen, Norway.
Department of Clinical Medicine, University of Bergen, Bergen, Norway.
BMC Neurol. 2015 Jul 11;15:110. doi: 10.1186/s12883-015-0359-4.
Ultrasound accelerates thrombolysis with tPA (sonothrombolysis). Ultrasound in the absence of tPA also accelerates clot break-up (sonolysis). Adding intravenous gaseous microbubbles may potentiate the effect of ultrasound in both sonothrombolysis and sonolysis. The Norwegian Sonothrombolysis in Acute Stroke Study aims in a pragmatic approach to assess the effect and safety of contrast enhanced ultrasound treatment in unselected acute ischaemic stroke patients.
METHODS/DESIGN: Acute ischaemic stroke patients ≥ 18 years, with or without visible arterial occlusion on computed tomography angiography (CTA) and treatable ≤ 4(½) hours after symptom onset, are included in NOR-SASS. NOR-SASS is superimposed on a separate trial randomising patients with acute ischemic stroke to either tenecteplase or alteplase (The Norwegian Tenecteplase Stroke Trial NOR-TEST). The NOR-SASS trial has two arms: 1) the thrombolysis-arms (NOR-SASS A and B) includes patients given intravenous thrombolysis (tenecteplase or alteplase), and 2) the no-thrombolysis-arm (NOR-SASS C) includes patients with contraindications to thrombolysis. First step randomisation of NOR-SASS A is embedded in NOR-TEST as a 1:1 randomisation to either tenecteplase or alteplase. Second step NOR-SASS randomisation is 1:1 to either contrast enhanced sonothrombolysis (CEST) or sham CEST. Randomisation in NOR-SASS B (routine alteplase group) is 1:1 to either CEST or sham CEST. Randomisation of NOR-SASS C is 1:1 to either contrast enhanced sonolysis (CES) or sham CES. Ultrasound is given for one hour using a 2-MHz pulsed-wave diagnostic ultrasound probe. Microbubble contrast (SonoVue®) is given as a continuous infusion for ~30 min. Recanalisation is assessed at 60 min after start of CEST/CES. Magnetic resonance imaging and angiography is performed after 24 h of stroke onset. Primary study endpoints are 1) major neurological improvement measured with NIHSS score at 24 h and 2) favourable functional outcome defined as mRS 0-1 at 90 days.
NOR-SASS is the first randomised controlled trial designed to test the superiority of contrast enhanced ultrasound treatment given ≤ 4(½) hours after stroke onset in an unselected acute ischaemic stroke population eligible or not eligible for intravenous thrombolysis, with or without a defined arterial occlusion on CTA. If a positive effect and safety can be proven, contrast enhanced ultrasound treatment will be an option for all acute ischaemic stroke patients. EudraCT No 201200032341; www.clinicaltrials.gov NCT01949961.
超声可加速组织型纤溶酶原激活剂（tPA）介导的溶栓作用（超声溶栓）。在无tPA的情况下，超声也可加速血栓溶解（超声溶解）。添加静脉注射气态微泡可能会增强超声在超声溶栓和超声溶解中的作用。挪威急性卒中超声溶栓研究旨在以务实的方法评估在未经选择的急性缺血性卒中患者中进行对比增强超声治疗的效果和安全性。
方法/设计：年龄≥18岁、在计算机断层血管造影（CTA）上有或无可见动脉闭塞且在症状发作后≤4（½）小时内可治疗的急性缺血性卒中患者被纳入挪威急性卒中超声溶栓研究（NOR-SASS）。NOR-SASS叠加在一项将急性缺血性卒中患者随机分为接受替奈普酶或阿替普酶治疗的单独试验上（挪威替奈普酶卒中试验NOR-TEST）。NOR-SASS试验有两个组：1）溶栓组（NOR-SASS A和B）包括接受静脉溶栓治疗（替奈普酶或阿替普酶）的患者，2）非溶栓组（NOR-SASS C）包括有溶栓禁忌证的患者。NOR-SASS A的第一步随机分组作为1:1随机分组嵌入NOR-TEST中，随机分为接受替奈普酶或阿替普酶治疗。NOR-SASS的第二步随机分组为1:1，随机分为接受对比增强超声溶栓（CEST）或假CEST。NOR-SASS B（常规阿替普酶组）的随机分组为1:1，随机分为接受CEST或假CEST。NOR-SASS C的随机分组为1:1，随机分为接受对比增强超声溶解（CES）或假CES。使用2MHz脉冲波诊断超声探头进行1小时的超声治疗。微泡造影剂（声诺维®）持续输注约30分钟。在开始CEST/CES后60分钟评估再通情况。在卒中发作24小时后进行磁共振成像和血管造影。主要研究终点为：1）在24小时时用美国国立卫生研究院卒中量表（NIHSS）评分衡量的主要神经功能改善，2）在90天时定义为改良Rankin量表（mRS）0 - 1分的良好功能结局。
NOR-SASS是第一项随机对照试验，旨在测试在卒中发作后≤4（½）小时对未经选择的急性缺血性卒中人群（无论是否符合静脉溶栓条件、CTA上有无明确动脉闭塞）进行对比增强超声治疗的优越性。如果能证明其有效性和安全性，对比增强超声治疗将成为所有急性缺血性卒中患者的一种选择。欧盟临床试验注册号201200032341；www.clinicaltrials.gov NCT01949961。
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