Update
Update on the third international stroke trial (IST-3) of thrombolysis for acute ischaemic stroke and baseline features of the 3035 patients recruited
1 The IST-3 Co-ordinating Centre, Neurosciences Trial Unit, Bramwell Dott Building, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, UK
2 Discipline of Medicine, Sydney Medical School - Westmead and The George Institute for Global Health, University of Sydney, NSW 2006, Australia
3 Neurology Department, Sheffield Teaching Hospitals NHS Foundation Trust, Royal Hallamshire Hospital, Glossop Road, Sheffield S10 2JF. UK
4 2nd Department of Neurology, Institute of Psychiatry and Neurology, Sobieskiego Str. 9, 02- 957 Warsaw, and Department of Experimental and Clinical Pharmacology, Medical University of Warsaw. Krakowskie Przedmiescie Str. 26/28, 00-927 Warsaw, Poland
5 Department of Internal Medicine, Oslo University Hospital, Ullevål, Kirkeveien 166, NO-0407 Oslo, Norway
6 Department of Clinical Sciences, Karolinska Institutet, Danderyd Hospital, SE-182 88 Stockholm, Sweden
7 Service de neurologie, Cliniques universitaires Saint-Luc, Avenue Hippocrate 10, 1200 Bruxelles, Belgium
8 Department of Neurology, Royal Perth Hospital, Wellington Street, GPO Box X2213, Perth, Western Australia, 6001, Australia
9 Neurologische Abteilung, Landesklinikum Donauregion Tulln, Alter Ziegelweg 10, 3430 Tulln, Austria
10 UO Neurologia, ASL 1, Ospedale, Via Engels, 06012 Citta' di Castello PG, Italy
11 S C di Neurofisiopatologia, Azienda Ospedaliera di Perugia, Italy
12 Division of Neurology, Dalhousie University and Queen Elizabeth II Health Sciences Centre, Halifax Infirmary, 1796 Summer Street, Halifax, Nova Scotia B3H 3A7, Canada
13 Instituto Nacional de Neurologia, Insurgentes sur 3877, La Fama, 14269 Mexico DF, Mexico
14 Neurology Department, Hospital Geral de Santo Antonio, Largo Prof Abel Salazar, 4050 Porto, Portugal
15 Department of Neurology, University Hospital Basel, Petersgraben 4, CH-4031 Basel, Switzerland
16 Stroke Unit, Royal Sussex County Hospital, Eastern Road, Brighton, East Sussex, BN2 5BE, UK
17 Neurology, Institute of Neuroscience, Uppsala University Hospital, Ing 85, 2 tr, SE-751 85 Uppsala, Sweden
Trials 2011, 12:252 doi:10.1186/1745-6215-12-252
Published: 30 November 2011Abstract
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.
