Transcript Baseline characteristics of the 3035 patients recruited in IST3 Peter Sandercock On behalf of the IST3 collaborative group UKSF Glasgow 30th November 2011 These results published.

Baseline characteristics of the
3035 patients recruited in IST3
Peter Sandercock
On behalf of the IST3 collaborative group
UKSF
Glasgow 30th November 2011
These results published today
www.trialsjournal.com
Main features of IST - 3
• Prospective, randomised, open, blinded endpoint
(PROBE) study of i.v. rt-PA vs control,
• Target 3100 patients
• < 6 h of acute ischaemic stroke
• Primary outcome: the proportion of patients alive and
independent at six months
• Randomisation by telephone or internet with
minimisation to balance on key prognostic factors
• Baseline & F/U Imaging: CT or MR,
• Blinded central expert panel review of scans
• Option to collect perfusion/angio data.
IST-3 trial: eligibility and
randomisation
If patient fits 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
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Number of patients
Recruitment 2000-2011
3500
3000
2500
2000
1500
1000
500
0
Pilot - Expansion - Main MRC phase
Year
Recruitment by country
No. of centres
No. of patients
%
UK
75
1447
48%
Poland
9
347
11%
Italy
21
326
11%
Sweden
18
297
10%
Norway
11
204
7%
Australia
10
179
6%
Portugal
4
82
3%
Belgium
1
73
2%
Austria
3
46
2%
Switzerland
2
23
1%
Canada
1
8
0.3%
Mexico
1
3
0.1%
Age: 1617 (53%) patients > 80
1400
1200
Number
1000
800
600
400
200
0
18-50
51-60
61-70
71-80
Age
81-90
91-100
Stroke severity: NIHSS
700
600
Number
500
400
300
200
100
0
0 to 5
6 to 10 11 to 15 16 to 20 21 to 35
NIHSS
Time to randomisation
1400
1200
Number
1000
39%
33%
28%
800
600
400
200
0
0-3
3-4.5
4.5-6
Time to randomisation (hrs)
Size of main subgroups
Delay (hours) from stroke to
randomisation
Age
0-3
3-4.5
4.5-6
<=80
177
558
683
>80
672
620
325
All
849
1178
1008
Summary
• IST3 will provide data on effects of rtPA in types of
patients currently outside the EU approval
• If positive, IST3 could justify the treatment of some
patients currently excluded from treatment in EU
(e.g. aged > 80)
• If negative or neutral, IST3 may limit ‘off-label’ use
by clarifying the ‘outer limits of benefit’ for some
patients
• The trial will provide randomised evidence on the
importance (or not) of
– ‘clinical contraindications’ (e.g. DM + prior stroke),1
– the use of advanced imaging
– other factors
1. Demaerschalk, 2. Mishra et al Neurology 2011
Acknowledgements:
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.
Funded by:
How many would have met the
EU approval for rtPA?
• Would meet the 2003 approval:1 61 (2%)
• Would meet the 2011 approval:2 350 (13%)
1.
2.
age <80, delay from onset to randomisation <3hours,
NIHSS 6 - 25, SBP <=185, DBP <= 110, 2.7 <=
glucose <=22 and no history of the combination of
prior stroke and diabetes mellitus
all the above + the time window was extended to 4.5
hours