Third international stroke trial (IST-3)
IST-3 was a randomised controlled trial to assess the benefits and harms of intravenous thrombolysis with the clot-busting drug alteplase within 6 h of acute ischaemic stroke. The trial involved 3035 patients from 12 countries. The trial demonstrated that alteplase treatment reduced long-term disability, significantly increased the likelihood of independence, and improved quality of life in stroke survivors of all ages for up to 18 months after treatment.
The IST-3 Collaborative Group
Co-Principal Investigators: Professor Peter Sandercock (University of Edinburgh) and Professor Richard Lindley (Sydney Medical School – Westmead Hospital, and the George Institute for Global Health, University of Sydney)
- The benefits and harms of intravenous thrombolysis with recombinant tissue plasminogen activator within 6 h of acute ischaemic stroke (the third international stroke trial [IST-3]): a randomised controlled trial. Lancet, 2012. DOI: 10.1016/S0140-6736(12)60768-5 (open access)
- Recombinant tissue plasminogen activator for acute ischaemic stroke: an updated systematic review and meta-analysis. Lancet, 2012. DOI: 10.1016/S0140-6736(12)60738-7 (open access)
- Effect of thrombolysis with alteplase within 6 h of acute ischaemic stroke on long-term outcomes (the third International Stroke Trial [IST-3]): 18-month follow-up of a randomised controlled trial. Lancet Neurology, 2013. DOI: 10.1016/S1474-4422(13)70130-3 (open access)
Plain English summaries
Professor Peter Sandercock - Unravelling the mystery of stroke disease: the clue's in the numbers (November 2014)
IST-3 presentations at ESC London 2013
IST-3 presentations at ESC Lisbon 2012
Protocol and statistical analysis plan
The data is accessible via Edinburgh Datashare at DOI: 10.1016/S0140-6736(16)30414-7. Metadata is freely available. If you wish to access the raw data, please apply for access by clicking on one of the 'padlocked' links.
The University of Edinburgh and NHS Lothian were joint sponsors.
The start-up phase was supported by a grant from the Stroke Association, UK. The expansion phase was funded by the Health Foundation UK.
The main phase of the trial was funded by: UK Medical Research Council (MRC) (grant numbers G0400069 and EME 09-800-15) and managed by the National Institutes of Health Research (NIHR) on behalf of the MRC-NIHR partnership; the Research Council of Norway; Arbetsmarknadens Partners Forsakringsbolag (AFA) Insurances Sweden; the Swedish Heart Lung Fund; The Foundation of Marianne and Marcus Wallenberg, Stockholm County Council; Karolinska Institute Joint ALF-project grants Sweden, the Polish Ministry of Science and Education (grant number 2PO5B10928); the Australian Heart Foundation; Australian National Health and Medical Research Council (NHMRC); the Swiss National Research Foundation; the Swiss Heart Foundation; the Foundation for Health and Cardio-/Neurovascular Research, Basel, Switzerland; the Assessorato alla Sanita, Regione dell'Umbria, Italy; and, Danube University, Krems, Austria.
Boehringer-Ingelheim GmbH donated drug and placebo for the 300 patients in the double-blind phase, but thereafter had no role whatsoever in the trial. The UK Stroke Research Network (SRN study ID 2135) adopted the trial in 01/05/2006, supported the initiation of new UK sites, and in some centres, and, after that date, data collection was undertaken by staff funded by the network or working for associated NHS organisations.
IST-3 gratefully acknowledges the extensive support of the NIHR Stroke Research Network, NHS Research Scotland (NRS), through the Scottish Stroke Research Network, and the National Institute for Social Care and Health Research Clinical Research Centre (NISCHR CRC). The central imaging work was undertaken at the Brain Imaging Research Centre, a member of the Scottish Imaging Network A Platform for Scientific Excellence (SINAPSE) collaboration, at the Division of Clinical Neurosciences, University of Edinburgh. SINAPSE is funded by the Scottish Funding Council (SFC) and the Chief Scientist Office of the Scottish Executive (CSO). Additional support was received from Chest Heart and Stroke Scotland, DesAcc, University of Edinburgh, Danderyd Hospital R&D Department, Karolinska Institutet, Oslo University Hospital, and the Dalhousie University Internal Medicine Research Fund.
Follow Prof Peter Sandercock on Twitter at @IST_3 for tweets about randomised controlled trials, evidenced-based medicine and global stroke.