A pragmatic approach to sonothrombolysis in acute ischaemic stroke: the Norwegian randomised controlled sonothrombolysis in acute stroke study (NOR-SASS)

作者：Nacu Aliona^*; Kvistad Christopher E; Logallo Nicola; Naess Halvor; Waje Andreassen Ulrike; Aamodt Anne Hege; Solhoff Ragnar; Lund Christian; Tobro Hakon; Ronning Ole Morten; Salvesen Rolf; Idicula Titto T; Thomassen Lars

来源：BMC Neurology, 2015, 15(1): 110.

DOI：10.1186/s12883-015-0359-4

• Randomised controlled trial
• Acute ischemic stroke
• Arterial occlusion
• Contrast
• Recanalisation
• Outcome
• Safety
• Sonolysis
• Sonothrombolysis
• Thrombolysis
• Transcranial ultrasound

Background: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 <= 41/2 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 r) is given as a continuous infusion for similar to 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.
Discussion: NOR-SASS is the first randomised controlled trial designed to test the superiority of contrast enhanced ultrasound treatment given <= 41/2 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.

• 出版日期2015-7-11