title: Update on the third international stroke trial (IST-3) of thrombolysis for acute ischaemic stroke and baseline features of the 3035 patients recruited.
abstract: BACKGROUND
  Intravenous recombinant tissue plasminogen activator (rtPA) is approved in Europe for use in patients with acute ischaemic stroke who meet strictly defined criteria. IST-3 sought to improve the external validity and precision of the estimates of the overall treatment effects (efficacy and safety) of rtPA in acute ischaemic stroke, and to determine whether a wider range of patients might benefit.
  
  
  METHODS
  International, multi-centre, prospective, randomized, open, blinded endpoint (PROBE) trial of intravenous rtPA in acute ischaemic stroke. Suitable patients had to be assessed and able to start treatment within 6 hours of developing symptoms, and brain imaging must have excluded intracranial haemorrhage and stroke mimics.
  
  
  RESULTS
  The initial pilot phase was double blind and then, on 01/08/2003, changed to an open design. Recruitment began on 05/05/2000 and closed on 31/07/2011, by which time 3035 patients had been included, only 61 (2%) of whom met the criteria for the 2003 European approval for thrombolysis. 1617 patients were aged over 80 years at trial entry. The analysis plan will be finalised, without reference to the unblinded data, and published before the trial data are unblinded in early 2012. The main trial results will be presented at the European Stroke Conference in Lisbon in May 2012 with the aim to publish simultaneously in a peer-reviewed journal. The trial result will be presented in the context of an updated Cochrane systematic review. We also intend to include the trial data in an individual patient data meta-analysis of all the relevant randomised trials.
  
  
  CONCLUSIONS
  The data from the trial will: improve the external validity and precision of the estimates of the overall treatment effects (efficacy and safety) of iv rtPA in acute ischaemic stroke; provide: new evidence on the balance of risk and benefit of intravenous rtPA among types of patients who do not clearly meet the terms of the current EU approval; and, provide the first large-scale randomised evidence on effects in patients over 80, an age group which had largely been excluded from previous acute stroke trials.
  
  
  BACKGROUND
  ISRCTN25765518.
authors: The IST-3 Co-ordinating Centre, Neurosciences Trial Unit, Bramwell Dott Building, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, UK. Peter.Sandercock@ed.ac.uk
authors: Peter
authors: P
authors: Sandercock
authors: Richard
authors: R
authors: Lindley
authors: Joanna
authors: J
authors: Wardlaw
authors: Martin
authors: M
authors: Dennis
authors: Karen
authors: K
authors: Innes
authors: Geoff
authors: G
authors: Cohen
authors: Will
authors: W
authors: Whiteley
authors: David
authors: D
authors: Perry
authors: Vera
authors: V
authors: Soosay
authors: David
authors: D
authors: Buchanan
authors: Graham
authors: G
authors: Venables
authors: Anna
authors: A
authors: Czlonkowska
authors: Adam
authors: A
authors: Kobayashi
authors: Eivind
authors: E
authors: Berge
authors: Karsten Bruins
authors: KB
authors: Slot
authors: Veronica
authors: V
authors: Murray
authors: Andre
authors: A
authors: Peeters
authors: Graeme J
authors: GJ
authors: Hankey
authors: Karl
authors: K
authors: Matz
authors: Michael
authors: M
authors: Brainin
authors: Stefano
authors: S
authors: Ricci
authors: Teresa A
authors: TA
authors: Cantisani
authors: Gordon
authors: G
authors: Gubitz
authors: Stephen J
authors: SJ
authors: Phillips
authors: Arauz
authors: A
authors: Antonio
authors: Manuel
authors: M
authors: Correia
authors: Phillippe
authors: P
authors: Lyrer
authors: Ingrid
authors: I
authors: Kane
authors: Erik
authors: E
authors: Lundstrom
mesh_terms: D000208:Acute Disease; D002545:Brain Ischemia / Q000188:drug therapy*; D004311:Double-Blind Method; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D006801:Humans; D011446:Prospective Studies; D018401:Sample Size; D020521:Stroke / Q000188:drug therapy*; D015912:Thrombolytic Therapy; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use*
chemical_list: D005343:Fibrinolytic Agents; D010959:Tissue Plasminogen Activator