Third international stroke trial (IST-3) of thrombolysis for acute ischaemic stroke.
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.


METHODS
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. With 3500 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).


BACKGROUND
ISRCTN25765518.
IST-3 Co-ordinating Centre, Neurosciences Trials Unit, Bramwell Dott Building, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, UK. Peter.Sandercock@ed.ac.uk
Peter
P
Sandercock
Richard
R
Lindley
Joanna
J
Wardlaw
Martin
M
Dennis
Steff
S
Lewis
Graham
G
Venables
Adam
A
Kobayashi
Anna
A
Czlonkowska
Eivind
E
Berge
Karsten Bruins
KB
Slot
Veronica
V
Murray
Andre
A
Peeters
Graeme
G
Hankey
Karl
K
Matz
Michael
M
Brainin
Stefano
S
Ricci
Maria Grazia
MG
Celani
Enrico
E
Righetti
Teresa
T
Cantisani
Gord
G
Gubitz
Steve
S
Phillips
Antonio
A
Arauz
Kameshwar
K
Prasad
Manuel
M
Correia
Phillippe
P
Lyrer