title: Perfusion-CT guided intravenous thrombolysis in patients with unknown-onset stroke: a randomized, double-blind, placebo-controlled, pilot feasibility trial.
abstract: BACKGROUND
  Patients with unknown stroke onset are generally excluded from acute recanalisation treatments. We designed a pilot study to assess feasibility of a trial of perfusion computed tomography (PCT)-guided thrombolysis in patients with ischemic tissue at risk of infarction and unknown stroke onset.
  
  
  METHODS
  Patients with a supratentorial stroke of unknown onset in the middle cerebral artery territory and significant volume of at-risk tissue on PCT were randomized to intravenous thrombolysis with alteplase (0.9 mg/kg) or placebo. Feasibility endpoints were randomization and blinded treatment of patients within 2 h after hospital arrival, and the correct application (estimation) of the perfusion imaging criteria.
  
  
  RESULTS
  At baseline, there was a trend towards older age [69.5 (57-78) vs. 49 (44-78) years] in the thrombolysis group (n = 6) compared to placebo (n = 6). Regarding feasibility, hospital arrival to treatment delay was above the allowed 2 h in three patients (25%). There were two protocol violations (17%) regarding PCT, both underestimating the predicted infarct in patients randomized in the placebo group. No symptomatic hemorrhage or death occurred during the first 7 days. Three of the four (75%) and one of the five (20%) patients were recanalized in the thrombolysis and placebo group respectively. The volume of non-infarcted at-risk tissue was 84 (44-206) cm(3) in the treatment arm and 29 (8-105) cm(3) in the placebo arm.
  
  
  CONCLUSIONS
  This pilot study shows that a randomized PCT-guided thrombolysis trial in patients with stroke of unknown onset may be feasible if issues such as treatment delays and reliable identification of tissue at risk of infarction tissue are resolved. Safety and efficiency of such an approach need to be established.
authors.affiliation: Department of Neurology Service, Center Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland. patrik.michel@chuv.ch
authors.forename: Patrik
authors.initials: P
authors.lastname: Michel
authors.forename: George
authors.initials: G
authors.lastname: Ntaios
authors.forename: Marc
authors.initials: M
authors.lastname: Reichhart
authors.forename: Christian
authors.initials: C
authors.lastname: Schindler
authors.forename: Julien
authors.initials: J
authors.lastname: Bogousslavsky
authors.forename: Philip
authors.initials: P
authors.lastname: Maeder
authors.forename: Reto
authors.initials: R
authors.lastname: Meuli
authors.forename: Max
authors.initials: M
authors.lastname: Wintermark
mesh_terms: D004311:Double-Blind Method; D005240:Feasibility Studies; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D055420:Perfusion Imaging / Q000379:methods*; D010865:Pilot Projects; D015990:Placebo Effect; D015641:Radiography, Interventional / Q000379:methods*; D020521:Stroke / Q000000981:diagnostic imaging* / Q000188:drug therapy*; D015912:Thrombolytic Therapy; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage*; D014057:Tomography, X-Ray Computed / Q000379:methods*; D016896:Treatment Outcome
chemical_list: D005343:Fibrinolytic Agents; D010959:Tissue Plasminogen Activator