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 and Phillippe Lyrer¹⁷ for the IST-3 collaborative group

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

²The University of Sydney, Discipline of Medicine, Westmead Hospital (C24), The University of Sydney NSW 2006, Australia

³Neurology Department, Sheffield Teaching Hospitals NHS Foundation Trust, Royal Hallamshire Hospital, Glossop Road, Sheffield S10 2JF, UK

⁴2nd Department of Neurology, Institute of Psychiatry and Neurology, Sobieskiego Str 9, 02-957 Warsaw, Poland

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

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

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

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

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

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

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

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

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

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

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

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

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

author email corresponding author email

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


Published:	17 June 2008

Abstract

Background

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.

Design

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

ISRCTN25765518