title: CLOTBUST-Hands Free: pilot safety study of a novel operator-independent ultrasound device in patients with acute ischemic stroke.
abstract: OBJECTIVE
  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.
  
  
  BACKGROUND
  http://www.clinicaltrials.gov. Unique identifier: CLOTBUST-HF NCT01240356.
authors.affiliation: 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.).
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Barreto
authors.forename: Andrei V
authors.initials: AV
authors.lastname: Alexandrov
authors.forename: Loren
authors.initials: L
authors.lastname: Shen
authors.forename: April
authors.initials: A
authors.lastname: Sisson
authors.forename: Andrew W
authors.initials: AW
authors.lastname: Bursaw
authors.forename: Preeti
authors.initials: P
authors.lastname: Sahota
authors.forename: Hui
authors.initials: H
authors.lastname: Peng
authors.forename: Manouchehr
authors.initials: M
authors.lastname: Ardjomand-Hessabi
authors.forename: Renganayaki
authors.initials: R
authors.lastname: Pandurengan
authors.forename: Mohammad H
authors.initials: MH
authors.lastname: Rahbar
authors.forename: Kristian
authors.initials: K
authors.lastname: Barlinn
authors.forename: Hari
authors.initials: H
authors.lastname: Indupuru
authors.forename: Nicole R
authors.initials: NR
authors.lastname: Gonzales
authors.forename: Sean I
authors.initials: SI
authors.lastname: Savitz
authors.forename: James C
authors.initials: JC
authors.lastname: Grotta
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002545:Brain Ischemia / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000628:therapy*; D003131:Combined Modality Therapy; D005260:Female; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011446:Prospective Studies; D020521:Stroke / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000628:therapy*; D015912:Thrombolytic Therapy / Q000009:adverse effects / Q000295:instrumentation*; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use*; D016896:Treatment Outcome; D017585:Ultrasonography, Doppler, Transcranial / Q000009:adverse effects / Q000295:instrumentation
chemical_list: D005343:Fibrinolytic Agents; D010959:Tissue Plasminogen Activator
keywords: CLOTBUST; operator-independent device; reperfusion; sonothrombolysis; stroke; thrombolytic therapy; ultrasonography, doppler, transcranial