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.
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.
Authors: Werner Hacke; Markku Kaste; Erich Bluhmki; Miroslav Brozman; Antoni Dávalos; Donata Guidetti; Vincent Larrue; Kennedy R Lees; Zakaria Medeghri; Thomas Machnig; Dietmar Schneider; Rüdiger von Kummer; Nils Wahlgren; Danilo Toni Journal: N Engl J Med Date: 2008-09-25 Impact factor: 91.245
Authors: Inke R König; Andreas Ziegler; Erich Bluhmki; Werner Hacke; Philip M W Bath; Ralph L Sacco; Hans C Diener; Christian Weimar Journal: Stroke Date: 2008-04-10 Impact factor: 7.914
Authors: William N Whiteley; Douglas Thompson; Gordon Murray; Geoff Cohen; Richard I Lindley; Joanna Wardlaw; Peter Sandercock Journal: Stroke Date: 2014-03-06 Impact factor: 7.914
Authors: William N Whiteley; Douglas Thompson; Gordon Murray; Geoff Cohen; Richard I Lindley; Joanna Wardlaw; Peter Sandercock Journal: Stroke Date: 2014-11-04 Impact factor: 7.914
Authors: Peter Sandercock; Joanna M Wardlaw; Richard I Lindley; Martin Dennis; Geoff Cohen; Gordon Murray; Karen Innes; Graham Venables; Anna Czlonkowska; Adam Kobayashi; Stefano Ricci; Veronica Murray; Eivind Berge; Karsten Bruins Slot; Graeme J Hankey; Manuel Correia; Andre Peeters; Karl Matz; Phillippe Lyrer; Gord Gubitz; Stephen J Phillips; Antonio Arauz Journal: Lancet Date: 2012-05-23 Impact factor: 79.321