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The third international stroke trial (IST-3) of thrombolysis for acute ischaemic stroke

Peter Sandercock1*, Richard Lindley2, Joanna Wardlaw1, Martin Dennis1, Steff Lewis1, Graham Venables3, Adam Kobayashi4, Anna Czlonkowska5, Eivind Berge6, Karsten Bruins Slot6, Veronica Murray7, Andre Peeters8, Graeme Hankey9, Karl Matz10, Michael Brainin10, Stefano Ricci11, Maria Grazia Celani11, Enrico Righetti11, Teresa Cantisani12, Gord Gubitz13, Steve Phillips13, Antonio Arauz14, Kameshwar Prasad15, Manuel Correia16, Phillippe Lyrer17 and the IST-3 collaborative group

Author Affiliations

1 The IST-3 Co-ordinating Centre, Neurosciences Trials Unit, Bramwell Dott Building, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, UK

2 The University of Sydney, Discipline of Medicine, Westmead Hospital (C24), The 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, Poland

5 Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, ul.Krakowskie Przedmiescie 26/28, 00-927 Warsaw, Poland

6 Department of Internal Medicine, Ullevaal University Hospital, NO-0407 Oslo, Norway

7 Karolinska Institutet, Department of Clinical Sciences, Danderyd Hospital, SE-182 88 Stockholm, Sweden

8 Service de neurologie, Cliniques universitaires Saint-Luc, Avenue Hippocrate 10, 1200 Bruxelles, Belgium

9 Royal Perth Hospital, Wellington Street, GPO Box X2213, Perth, Western Australia, 6001, Australia

10 Landesklinikum Donauregion Tulln, Neurologische Abteilung, Alter Ziegelweg 10, 3430 Tulln, Austria

11 Ospedale Beato Giacoma Villa, Citta della Pieve, 06062-Perugia, Italy

12 S C di Neurofisiopatologia, Azienda Ospedaliera di Perugia, Italy

13 Division of Neurology, Dalhousie University and Queen Elizabeth II Health Sciences Centre, Halifax Infirmary, 1796 Summer Street, Halifax, Nova Scotia B3H 3A7, Canada

14 Instituto Nacional de Neurologia, Insurgentes sur 3877, La Fama, 14269 Mexico DF, Mexico

15 Department of Neurology, Neurosciences Centre, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110029, India

16 Neurology Department, Hospital Geral de Santo Antonio, Largo Prof Abel Salazar, 4050 Porto, Portugal

17 Department of Neurology, University Hospital Basel, Petersgraben 4, CH-4031 Basel, Switzerland

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Trials 2008, 9:37  doi:10.1186/1745-6215-9-37

Published: 17 June 2008



Intravenous recombinant tissue plasminogen activator (rt-PA) is approved for use in selected patients with ischaemic stroke within 3 hours of symptom onset. IST-3 seeks to determine whether a wider range of patients may benefit.


International, multi-centre, prospective, randomized, open, blinded endpoint (PROBE) trial of intravenous rt-PA in acute ischaemic stroke. Suitable patients must be assessed and able to start treatment within 6 hours of developing symptoms, and brain imaging must have excluded intracerebral haemorrhage. With 1000 patients, the trial can detect a 7% absolute difference in the primary outcome. With3500 patients, it can detect a 4.0% absolute benefit & with 6000, (mostly treated between 3 & 6 hours), it can detect a 3% benefit.

Trial procedures

Patients are entered into the trial by telephoning a fast, secure computerised central randomisation system or via a secure web interface. Repeat brain imaging must be performed at 24–48 hours. The scans are reviewed 'blind' by expert readers. The primary measure of outcome is the proportion of patients alive and independent (Modified Rankin 0–2) at six months (assessed via a postal questionnaire mailed directly to the patient). Secondary outcomes include: events within 7 days (death, recurrent stroke, symptomatic intracranial haemorrhage), outcome at six months (death, functional status, EuroQol).

Trial registration