The third international stroke trial (IST-3) main results: primary and secondary outcomes among 3035 patients. The IST3 collaborative group - 156 hospitals in UK, Poland, Italy, Sweden, Norway, Australia, Portugal, Belgium, Austria, Switzerland, Canada, Mexico.
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The IST3 collaborative group - 156 hospitals in UK, Poland, Italy, Sweden, Norway, Australia, Portugal, Belgium, Austria, Switzerland, Canada, Mexico
Disclosures: Boehringer Ingelheim donated rt-PA and placebo for the first 300 patients but had no other part in the study.
23rd May 2012
Available online at www.thelancet.com
From 12.00 today
Randomised, open study i.v. rt-PA vs control
Target: 3100 acute ischaemic stroke < 6h
Randomised by phone or internet:
Key prognostic factors balanced
Imaging CT or MR
Oxford Handicap Scale (OHS) at 6 months
Primary outcome: % ‘alive and independent’ (OHS 0-2)
Secondary: ordinal ‘shift’ analysis of OHS1
1. Analysis plan. Int J Stroke. 2012;7:186-7
*Lancet May 23rd 2012
If patient fitted main eligibility/exclusion criteria clinician/patient/family discuss. If there is a:
Clear INDICATION FOR rt-PA →TREAT
(i.e. meets terms of current licence and patient agrees)
Clear CONTRAINDICATION TO rt-PA →DON’T TREAT
rt-PA ‘PROMISING BUT UNPROVEN’→RANDOMISE
1.Trials 2011, 12:252.
Fatal & non-fatal intracranial haemorrhage < 7 days primary and secondary outcomes among 3035 patients
P < 0.0001
applying the ‘Cochrane’ definition, of SICH, the 7% IST-3 frequency is comparable with the 7.3% (SITS) registry of 6483 patients treated within licence in routine clinical practice1
1. Wahlgren, Lancet 2007; 369: 275–82
= 14 more alive and independent
(95% CI -20 to 48) NS
Ordinal analysis 6 month OHS primary and secondary outcomes among 3035 patients
Favourable shift; adjusted common odds ratio 1·27 (95% CI 1·10- 1·47), p=0·001
or, the odds of surviving with less disability were 27% greater for patients treated with rt-PA
The treatment odds ratio in each subgroup has been adjusted for the linear effects of the other key variables
All ages 0-6 hrs
14more alive and independent (NS)
29 more ‘favourable outcome’ (p=0·018)
Favourable shift in OHS(p=0.001)
No difference in deaths
In patients > 80 years 0-6hrs
38 more alive and independent
In patients all ages < 3hrs
80 more alive and independent
Acknowledgements: primary and secondary outcomes among 3035 patients
The 3035 patients, the 156 hospitals in the IST-3 group, the Data Monitoring Committee, the MRC Steering Committee, Image Reading Panel, Event adjudication panel, International Advisory Board.
Funding: Medical Research Council (managed by NIHR on behalf of the MRC-NIHR partnership), Stroke Association, The Health Foundation,, The Research Council of Norway, AFA Insurances (Sweden), the Swedish Heart Lung Fund, The Foundation of Marianne and Marcus Wallenberg, Stockholm County Council and Karolinska Institute Joint ALF-project grants (Sweden), the Government of Poland, the Australian Heart Foundation, Australian NHMRC, the Swiss National Research Foundation, the Swiss Heart Foundation, the Foundation for health and cardio-/neurovascular research, Basel, Switzerland and the Assessorato alla Sanita, Regione dell'Umbria. Drug and placebo for the 300 patients in the double-blind component of the start-up phase were supplied by Boehringer-Ingelheim GMBh. IST-3 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 imaging work was undertaken at the Brain Imaging Research Centre, a member of the 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, the Dalhousie University Internal Medicine Research Fund.