title: Acute ischemic stroke: imaging-guided tenecteplase treatment in an extended time window.
abstract: BACKGROUND
  Tenecteplase is a modified tissue plasminogen activator with a longer half-life and higher fibrin specificity than alteplase.
  
  
  METHODS
  We conducted a prospective, nonrandomized, pilot study of 0.1 mg/kg IV tenecteplase given 3 to 6 hours after ischemic stroke onset. For a control group, we used patients contemporaneously treated with sub-3-hour 0.9 mg/kg IV alteplase following standard selection criteria. All patients underwent pretreatment and 24-hour perfusion/angiographic imaging with CT or MRI. Eligibility criteria for tenecteplase (but not alteplase) treatment included a perfusion lesion at least 20% greater than the infarct core, with an associated vessel occlusion. Primary outcomes, assessed blind to treatment group, were reperfusion (reduction in baseline-24-hour mean transit time lesion) and major vessel recanalization.
  
  
  RESULTS
  Fifteen patients received tenecteplase, and 35 patients received alteplase. The tenecteplase group had greater reperfusion (mean 74% vs 44% in the alteplase group, p = 0.01) and major vessel recanalization (10/15 tenecteplase vs 7/29 alteplase, p = 0.01). Despite later time to treatment, more tenecteplase patients (10/15 vs 7/35 alteplase, p = 0.001) had major neurologic improvement at 24 hours (NIH Stroke Scale reduction > or = 8). Four of the alteplase patients and none of the tenecteplase patients had parenchymal hematoma at 24 hours.
  
  
  CONCLUSIONS
  Tenecteplase 0.1 mg/kg, using advanced imaging guidance in an extended time window, may have significant biologic efficacy in acute ischemic stroke. The imaging selection differences between the tenecteplase and alteplase groups prevent a conclusive efficacy comparison. Nonetheless, these results lend support for randomized trials comparing tenecteplase with alteplase, preferably incorporating penumbral/angiographic imaging selection.
authors.affiliation: Department of Neurology, Radiology, and Centre for Clinical Epidemiology and Biostatistics, John Hunter Hospital/Hunter Medical Research Institute, University of Newcastle, Australia. mark.parsons@hnehealth.nsw.gov.au
authors.forename: M W
authors.initials: MW
authors.lastname: Parsons
authors.forename: F
authors.initials: F
authors.lastname: Miteff
authors.forename: G A
authors.initials: GA
authors.lastname: Bateman
authors.forename: N
authors.initials: N
authors.lastname: Spratt
authors.forename: A
authors.initials: A
authors.lastname: Loiselle
authors.forename: J
authors.initials: J
authors.lastname: Attia
authors.forename: C R
authors.initials: CR
authors.lastname: Levi
mesh_terms: D000368:Aged; D002545:Brain Ischemia / Q000150:complications*; D002533:Cerebral Angiography; D002560:Cerebrovascular Circulation; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D010960:Plasminogen Activators / Q000008:administration & dosage / Q000627:therapeutic use*; D011446:Prospective Studies; D012044:Regression Analysis; D020521:Stroke / Q000188:drug therapy* / Q000209:etiology*; D000077785:Tenecteplase; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage / Q000627:therapeutic use*; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome
chemical_list: D010960:Plasminogen Activators; D010959:Tissue Plasminogen Activator; D000077785:Tenecteplase