title: Design of a PROspective multi-national CLOTBUST collaboration on reperfusion therapies for stroke (CLOTBUST-PRO).
abstract: BACKGROUND
  The benefit of intravenous (i.v.) tissue plasminogen activator (tPA) in acute ischemic stroke (IS) is attributable to lysis of thrombus and restoration of perfusion to ischemic but not yet infarcted brain.
  
  
  OBJECTIVE
  Our multicentre collaborative group prospectively implemented a protocol for transcranial Doppler assessment of intracranial recanalization with tPA treatment based on the CLOTBUST clinical trial (CLOTBUST-PRO). We aim to determine whether early recanalization (within 1 h from tPA bolus) is independently associated with better 3-month outcome in patients with intracranial arterial occlusions and correlates to a shorter time interval elapsed from symptom onset to tPA bolus.
  
  
  METHODS
  Consecutive patients with acute IS due to intracranial arterial occlusions will be treated with standard i.v.-tPA and continuously monitored with 2 MHz Transcranial Doppler for arterial recanalization. Early recanalization will be determined with the previously validated Thrombolysis in Brain Ischemia flow-grading system within 60 min after tPA bolus. Power calculations are based on the assumption of alpha=0.05 (two-sided test) and probabilities of functional independence at 3 months of 0.50 and 0.35 in patients with early complete recanalization and persisting occlusion, respectively. Detection of a 15% difference with a power of 0.824 requires an estimated sample of 480 patients of whom 25% are expected to achieve early recanalization while 75% will have persisting occlusion at 1 h after tPA bolus. We also plan to test prespecified secondary hypotheses within the projected study sample.
  
  
  CONCLUSIONS
  CLOTBUST-PRO is designed to determine if the timing (within 1 h from tPA bolus) of tPA-induced arterial recanalization is an independent determinant of 3-month functional recovery. We also seek to demonstrate that the sooner the tPA is given to stroke patients, the earlier the recanalization occurs and the greater is the likelihood of functional independence at 3 months.
authors.affiliation: Department of Medicine (Neurology), University of Alberta, Alberta, Canada.
authors.forename: Maher
authors.initials: M
authors.lastname: Saqqur
authors.forename: Georgios
authors.initials: G
authors.lastname: Tsivgoulis
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Molina
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Demchuk
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Garami
authors.forename: Andrew
authors.initials: A
authors.lastname: Barreto
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Spengos
authors.forename: Alex
authors.initials: A
authors.lastname: Forteza
authors.forename: Robert
authors.initials: R
authors.lastname: Mikulik
authors.forename: Vijay K
authors.initials: VK
authors.lastname: Sharma
authors.forename: Alex
authors.initials: A
authors.lastname: Brunser
authors.forename: Patricia
authors.initials: P
authors.lastname: Martinez
authors.forename: Joan
authors.initials: J
authors.lastname: Montaner
authors.forename: Martin
authors.initials: M
authors.lastname: Kohrmann
authors.forename: Peter D
authors.initials: PD
authors.lastname: Schellinger
authors.forename: Andrei V
authors.initials: AV
authors.lastname: Alexandrov
mesh_terms: D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D006801:Humans; D007262:Infusions, Intravenous; D015337:Multicenter Studies as Topic; D011446:Prospective Studies; D015424:Reperfusion / Q000379:methods*; D012107:Research Design; D020521:Stroke / Q000628:therapy*; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D005343:Fibrinolytic Agents; D010959:Tissue Plasminogen Activator