title: A randomized trial of tenecteplase versus alteplase for acute ischemic stroke.
abstract: BACKGROUND
  Intravenous alteplase is the only approved treatment for acute ischemic stroke. Tenecteplase, a genetically engineered mutant tissue plasminogen activator, is an alternative thrombolytic agent.
  
  
  METHODS
  In this phase 2B trial, we randomly assigned 75 patients to receive alteplase (0.9 mg per kilogram of body weight) or tenecteplase (0.1 mg per kilogram or 0.25 mg per kilogram) less than 6 hours after the onset of ischemic stroke. To favor the selection of patients most likely to benefit from thrombolytic therapy, the eligibility criteria were a perfusion lesion at least 20% greater than the infarct core on computed tomographic (CT) perfusion imaging at baseline and an associated vessel occlusion on CT angiography. The coprimary end points were the proportion of the perfusion lesion that was reperfused at 24 hours on perfusion-weighted magnetic resonance imaging and the extent of clinical improvement at 24 hours as assessed on the National Institutes of Health Stroke Scale (NIHSS, a 42-point scale on which higher scores indicate more severe neurologic deficits).
  
  
  RESULTS
  The three treatment groups each comprised 25 patients. The mean (±SD) NIHSS score at baseline for all patients was 14.4±2.6, and the time to treatment was 2.9±0.8 hours. Together, the two tenecteplase groups had greater reperfusion (P=0.004) and clinical improvement (P<0.001) at 24 hours than the alteplase group. There were no significant between-group differences in intracranial bleeding or other serious adverse events. The higher dose of tenecteplase (0.25 mg per kilogram) was superior to the lower dose and to alteplase for all efficacy outcomes, including absence of serious disability at 90 days (in 72% of patients, vs. 40% with alteplase; P=0.02).
  
  
  CONCLUSIONS
  Tenecteplase was associated with significantly better reperfusion and clinical outcomes than alteplase in patients with stroke who were selected on the basis of CT perfusion imaging. (Funded by the Australian National Health and Medical Research Council; Australia New Zealand Clinical Trials Registry number, ACTRN12608000466347.).
authors.affiliation: Department of Neurology, John Hunter Hospital-Hunter Medical Research Institute, University of Newcastle, Newcastle, NSW, Australia. mark.parsons@hnehealth.nsw.gov.au
authors.forename: Mark
authors.initials: M
authors.lastname: Parsons
authors.forename: Neil
authors.initials: N
authors.lastname: Spratt
authors.forename: Andrew
authors.initials: A
authors.lastname: Bivard
authors.forename: Bruce
authors.initials: B
authors.lastname: Campbell
authors.forename: Kong
authors.initials: K
authors.lastname: Chung
authors.forename: Ferdinand
authors.initials: F
authors.lastname: Miteff
authors.forename: Bill
authors.initials: B
authors.lastname: O'Brien
authors.forename: Christopher
authors.initials: C
authors.lastname: Bladin
authors.forename: Patrick
authors.initials: P
authors.lastname: McElduff
authors.forename: Chris
authors.initials: C
authors.lastname: Allen
authors.forename: Grant
authors.initials: G
authors.lastname: Bateman
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Donnan
authors.forename: Stephen
authors.initials: S
authors.lastname: Davis
authors.forename: Christopher
authors.initials: C
authors.lastname: Levi
mesh_terms: D000368:Aged; D002545:Brain Ischemia / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016037:Single-Blind Method; D020521:Stroke / Q000188:drug therapy*; D000077785:Tenecteplase; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D005343:Fibrinolytic Agents; D010959:Tissue Plasminogen Activator; D000077785:Tenecteplase