TY - JOUR
T1 - Update on the third international stroke trial (IST-3) of thrombolysis for acute ischaemic stroke and baseline features of the 3035 patients recruited
AU - IST-3 collaborative group
AU - Sandercock, Peter
AU - Lindley, Richard
AU - Wardlaw, Joanna
AU - Dennis, Martin
AU - Innes, Karen
AU - Cohen, Geoff
AU - Whiteley, Will
AU - Perry, David
AU - Soosay, Vera
AU - Buchanan, David
AU - Venables, Graham
AU - Czlonkowska, Anna
AU - Kobayashi, Adam
AU - Berge, Eivind
AU - Slot, Karsten Bruins
AU - Murray, Veronica
AU - Peeters, Andre
AU - Hankey, Graeme J
AU - Matz, Karl
AU - Brainin, Michael
AU - Ricci, Stefano
AU - Cantisani, Teresa A
AU - Gubitz, Gordon
AU - Phillips, Stephen J
AU - Antonio, Arauz
AU - Correia, Manuel
AU - Lyrer, Phillippe
AU - Kane, Ingrid
AU - Lundstrom, Erik
PY - 2011/11/30
Y1 - 2011/11/30
N2 - 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.DESIGN: 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.CONCLUSION: 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.TRIAL REGISTRATION: ISRCTN25765518.
AB - 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.DESIGN: 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.CONCLUSION: 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.TRIAL REGISTRATION: ISRCTN25765518.
KW - Acute Disease
KW - Brain Ischemia/drug therapy
KW - Double-Blind Method
KW - Fibrinolytic Agents/therapeutic use
KW - Humans
KW - Prospective Studies
KW - Sample Size
KW - Stroke/drug therapy
KW - Thrombolytic Therapy
KW - Tissue Plasminogen Activator/therapeutic use
U2 - 10.1186/1745-6215-12-252
DO - 10.1186/1745-6215-12-252
M3 - Article
C2 - 22129158
SN - 1745-6215
VL - 12
SP - 252
JO - Trials
JF - Trials
ER -