1. Update on the third international stroke trial (IST-3) of thrombolysis for acute ischaemic stroke and baseline features of the 3035 patients recruited
- Author
-
Marta Bilik, Steve Vucic, Waldemar Brola, Monica Badve, Grzegorz Kozera, Joseph Kwan, David Werring, Erik Lundström, Anna Czlonkowska, Paul Bentley, Graeme Hankey, Alastair Buchan, David Doig, Christian Lueck, Maurizio BALESTRINO, Urszula Fiszer, Richard Lindley, Geoffrey Cloud, Francesco Corea, Karl Matz, Cathie Sudlow, Joana Damásio, Rui Felgueiras, Andrea Zini, William Whiteley, Stefan Engelter, Malcolm Robert Macleod, Luana Benedetti, Joanna Wardlaw, Peter Sandercock, Bartosz Karaszewski, Hedley Emsley, Jan Aaseth, Leo Bonati, Marta Leńska-Mieciek, Mark Wardle, Marc Randall, Antonio Arauz, UCL - SSS/IONS/NEUR - Clinical Neuroscience, and UCL - (SLuc) Service de neurologie
- Subjects
Neurology ,medicine.medical_treatment ,Medicine (miscellaneous) ,Research & Experimental Medicine ,Tissue plasminogen activator ,law.invention ,Brain Ischemia ,0302 clinical medicine ,Randomized controlled trial ,law ,Brain Ischemia drug therapy ,Data monitoring committee ,Pharmacology (medical) ,Thrombolytic Therapy ,030212 general & internal medicine ,Prospective Studies ,Prospective cohort study ,Stroke ,1102 Cardiorespiratory Medicine and Haematology ,lcsh:R5-920 ,Thrombolysis ,3. Good health ,Medicine, Research & Experimental ,Tissue Plasminogen Activator ,Acute Disease ,lcsh:Medicine (General) ,Life Sciences & Biomedicine ,medicine.drug ,medicine.medical_specialty ,Double-Blind Method, Fibrinolytic Agents ,Humans ,Sample Size ,Stroke drug therapy ,Update ,03 medical and health sciences ,ALTEPLASE ,Double-Blind Method ,Fibrinolytic Agents ,IST-3 collaborative group ,General & Internal Medicine ,medicine ,Science & Technology ,business.industry ,1103 Clinical Sciences ,medicine.disease ,Cardiovascular System & Hematology ,Emergency medicine ,Physical therapy ,business ,030217 neurology & neurosurgery ,Fibrinolytic agent - 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. 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
- Published
- 2011