title: NOR-SASS (Norwegian Sonothrombolysis in Acute Stroke Study): Randomized Controlled Contrast-Enhanced Sonothrombolysis in an Unselected Acute Ischemic Stroke Population.
abstract: OBJECTIVE
  The NOR-SASS (Norwegian Sonothrombolysis in Acute Stroke Study) aimed to assess effect and safety of contrast-enhanced ultrasound treatment in an unselected acute ischemic stroke population.
  
  
  METHODS
  Patients treated with intravenous thrombolysis within 4.5 hours after symptom onset were randomized 1:1 to either contrast-enhanced sonothrombolysis (CEST) or sham CEST. A visible arterial occlusion on baseline computed tomography angiography was not a prerequisite for inclusion. Pulse-wave 2 MHz ultrasound was given for 1 hour and contrast (SonoVue) as an infusion for ≈30 minutes. Magnetic resonance imaging and angiography were performed after 24 to 36 hours. Primary study end points were neurological improvement at 24 hours defined as National Institutes of Health Stroke Scale score 0 or reduction of ≥4 National Institutes of Health Stroke Scale points compared with baseline National Institutes of Health Stroke Scale and favorable functional outcome at 90 days defined as modified Rankin scale score 0 to 1.
  
  
  RESULTS
  A total of 183 patients were randomly assigned to either CEST (93 patient) or sham CEST (90 patients). The rates of symptomatic intracerebral hemorrhage, asymptomatic intracerebral hemorrhage, or mortality were not increased in the CEST group. Neurological improvement at 24 hours and functional outcome at 90 days was similar in the 2 groups both in the intention-to-treat analysis and in the per-protocol analysis.
  
  
  CONCLUSIONS
  CEST is safe among unselected ischemic stroke patients with or without a visible occlusion on computed tomography angiography and with varying grades of clinical severity. There was, however, statistically no significant clinical effect of sonothrombolysis in this prematurely stopped trial.
  
  
  BACKGROUND
  URL: http://www.clinicaltrials.gov. Unique identifier: NCT01949961.
authors.affiliation: From the Department of Neurology (A.N., C.E.K., H.N., H.Ø., N.L., U.W.-A., L.T.) and Department of Radiology (G.N.), Haukeland University Hospital, Bergen, Norway; Department of Clinical Medicine (A.N., H.N., H.Ø., L.T.) and Department of Biostatistics (J.A.), University of Bergen, Norway; and Center for Age-Related Medicine (H.N.) and Department of Radiology (K.D.K.), Stavanger University Hospital, Norway. aliona.nacu@uib.no.
authors.forename: Aliona
authors.initials: A
authors.lastname: Nacu
authors.affiliation: From the Department of Neurology (A.N., C.E.K., H.N., H.Ø., N.L., U.W.-A., L.T.) and Department of Radiology (G.N.), Haukeland University Hospital, Bergen, Norway; Department of Clinical Medicine (A.N., H.N., H.Ø., L.T.) and Department of Biostatistics (J.A.), University of Bergen, Norway; and Center for Age-Related Medicine (H.N.) and Department of Radiology (K.D.K.), Stavanger University Hospital, Norway.
authors.forename: Christopher E
authors.initials: CE
authors.lastname: Kvistad
authors.affiliation: From the Department of Neurology (A.N., C.E.K., H.N., H.Ø., N.L., U.W.-A., L.T.) and Department of Radiology (G.N.), Haukeland University Hospital, Bergen, Norway; Department of Clinical Medicine (A.N., H.N., H.Ø., L.T.) and Department of Biostatistics (J.A.), University of Bergen, Norway; and Center for Age-Related Medicine (H.N.) and Department of Radiology (K.D.K.), Stavanger University Hospital, Norway.
authors.forename: Halvor
authors.initials: H
authors.lastname: Naess
authors.affiliation: From the Department of Neurology (A.N., C.E.K., H.N., H.Ø., N.L., U.W.-A., L.T.) and Department of Radiology (G.N.), Haukeland University Hospital, Bergen, Norway; Department of Clinical Medicine (A.N., H.N., H.Ø., L.T.) and Department of Biostatistics (J.A.), University of Bergen, Norway; and Center for Age-Related Medicine (H.N.) and Department of Radiology (K.D.K.), Stavanger University Hospital, Norway.
authors.forename: Halvor
authors.initials: H
authors.lastname: Øygarden
authors.affiliation: From the Department of Neurology (A.N., C.E.K., H.N., H.Ø., N.L., U.W.-A., L.T.) and Department of Radiology (G.N.), Haukeland University Hospital, Bergen, Norway; Department of Clinical Medicine (A.N., H.N., H.Ø., L.T.) and Department of Biostatistics (J.A.), University of Bergen, Norway; and Center for Age-Related Medicine (H.N.) and Department of Radiology (K.D.K.), Stavanger University Hospital, Norway.
authors.forename: Nicola
authors.initials: N
authors.lastname: Logallo
authors.affiliation: From the Department of Neurology (A.N., C.E.K., H.N., H.Ø., N.L., U.W.-A., L.T.) and Department of Radiology (G.N.), Haukeland University Hospital, Bergen, Norway; Department of Clinical Medicine (A.N., H.N., H.Ø., L.T.) and Department of Biostatistics (J.A.), University of Bergen, Norway; and Center for Age-Related Medicine (H.N.) and Department of Radiology (K.D.K.), Stavanger University Hospital, Norway.
authors.forename: Jörg
authors.initials: J
authors.lastname: Assmus
authors.affiliation: From the Department of Neurology (A.N., C.E.K., H.N., H.Ø., N.L., U.W.-A., L.T.) and Department of Radiology (G.N.), Haukeland University Hospital, Bergen, Norway; Department of Clinical Medicine (A.N., H.N., H.Ø., L.T.) and Department of Biostatistics (J.A.), University of Bergen, Norway; and Center for Age-Related Medicine (H.N.) and Department of Radiology (K.D.K.), Stavanger University Hospital, Norway.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Waje-Andreassen
authors.affiliation: From the Department of Neurology (A.N., C.E.K., H.N., H.Ø., N.L., U.W.-A., L.T.) and Department of Radiology (G.N.), Haukeland University Hospital, Bergen, Norway; Department of Clinical Medicine (A.N., H.N., H.Ø., L.T.) and Department of Biostatistics (J.A.), University of Bergen, Norway; and Center for Age-Related Medicine (H.N.) and Department of Radiology (K.D.K.), Stavanger University Hospital, Norway.
authors.forename: Kathinka D
authors.initials: KD
authors.lastname: Kurz
authors.affiliation: From the Department of Neurology (A.N., C.E.K., H.N., H.Ø., N.L., U.W.-A., L.T.) and Department of Radiology (G.N.), Haukeland University Hospital, Bergen, Norway; Department of Clinical Medicine (A.N., H.N., H.Ø., L.T.) and Department of Biostatistics (J.A.), University of Bergen, Norway; and Center for Age-Related Medicine (H.N.) and Department of Radiology (K.D.K.), Stavanger University Hospital, Norway.
authors.forename: Gesche
authors.initials: G
authors.lastname: Neckelmann
authors.affiliation: From the Department of Neurology (A.N., C.E.K., H.N., H.Ø., N.L., U.W.-A., L.T.) and Department of Radiology (G.N.), Haukeland University Hospital, Bergen, Norway; Department of Clinical Medicine (A.N., H.N., H.Ø., L.T.) and Department of Biostatistics (J.A.), University of Bergen, Norway; and Center for Age-Related Medicine (H.N.) and Department of Radiology (K.D.K.), Stavanger University Hospital, Norway.
authors.forename: Lars
authors.initials: L
authors.lastname: Thomassen
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002545:Brain Ischemia / Q000000981:diagnostic imaging* / Q000188:drug therapy / Q000453:epidemiology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009664:Norway / Q000453:epidemiology; D010743:Phospholipids / Q000008:administration & dosage*; D011159:Population Surveillance / Q000379:methods; D011446:Prospective Studies; D016037:Single-Blind Method; D020521:Stroke / Q000000981:diagnostic imaging* / Q000188:drug therapy / Q000453:epidemiology; D013459:Sulfur Hexafluoride / Q000008:administration & dosage*; D015912:Thrombolytic Therapy / Q000379:methods*; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage; D017585:Ultrasonography, Doppler, Transcranial / Q000379:methods*
chemical_list: D010743:Phospholipids; C420843:contrast agent BR1; D010959:Tissue Plasminogen Activator; D013459:Sulfur Hexafluoride
keywords: angiography; brain; randomized controlled trial; safety; stroke