Update on the third international stroke trial (IST-3) of thrombolysis for acute ischaemic stroke and baseline features of the 3035 patients recruited

Peter Sandercock, Richard Lindley, Joanna Wardlaw, Martin Dennis, Karen Innes, Geoff Cohen, Will Whiteley, David Perry, Vera Soosay, David Buchanan, Graham Venables, Anna Czlonkowska, Adam Kobayashi, Eivind Berge, Karsten Bruins Slot, Veronica Murray, Andre Peeters, Graeme J Hankey, Karl Matz, Michael Brainin & 11 others Stefano Ricci, Teresa A Cantisani, Gordon Gubitz, Stephen J Phillips, Arauz Antonio, Manuel Correia, Phillippe Lyrer, Ingrid Kane, Erik Lundstrom, IST-3 Collaborative Group, Phyo Kyaw Myint

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Abstract

BACKGROUND: Intravenous recombinant tissue plasminogen activator (rtPA) is approved in Europe for use in patients with acute ischaemic stroke who meet strictly defined criteria. IST-3 sought to improve the external validity and precision of the estimates of the overall treatment effects (efficacy and safety) of rtPA in acute ischaemic stroke, and to determine whether a wider range of patients might benefit.

DESIGN: International, multi-centre, prospective, randomized, open, blinded endpoint (PROBE) trial of intravenous rtPA in acute ischaemic stroke. Suitable patients had to be assessed and able to start treatment within 6 hours of developing symptoms, and brain imaging must have excluded intracranial haemorrhage and stroke mimics.

RESULTS: The initial pilot phase was double blind and then, on 01/08/2003, changed to an open design. Recruitment began on 05/05/2000 and closed on 31/07/2011, by which time 3035 patients had been included, only 61 (2%) of whom met the criteria for the 2003 European approval for thrombolysis. 1617 patients were aged over 80 years at trial entry. The analysis plan will be finalised, without reference to the unblinded data, and published before the trial data are unblinded in early 2012. The main trial results will be presented at the European Stroke Conference in Lisbon in May 2012 with the aim to publish simultaneously in a peer-reviewed journal. The trial result will be presented in the context of an updated Cochrane systematic review. We also intend to include the trial data in an individual patient data meta-analysis of all the relevant randomised trials.

CONCLUSION: The data from the trial will: improve the external validity and precision of the estimates of the overall treatment effects (efficacy and safety) of iv rtPA in acute ischaemic stroke; provide: new evidence on the balance of risk and benefit of intravenous rtPA among types of patients who do not clearly meet the terms of the current EU approval; and, provide the first large-scale randomised evidence on effects in patients over 80, an age group which had largely been excluded from previous acute stroke trials.

TRIAL REGISTRATION: ISRCTN25765518.

Original languageEnglish
Article number252
Number of pages10
JournalTrials
Volume12
DOIs
Publication statusPublished - 30 Nov 2011

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Stroke
Tissue Plasminogen Activator
Safety
Intracranial Hemorrhages
Neuroimaging
Meta-Analysis
Age Groups

Keywords

  • acute disease
  • brain ischemia
  • double-blind method
  • fibrinolytic agents
  • humans
  • prospective studies
  • sample size
  • stroke
  • thrombolytic therapy
  • tissue plasminogen activator

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Update on the third international stroke trial (IST-3) of thrombolysis for acute ischaemic stroke and baseline features of the 3035 patients recruited. / Sandercock, Peter; Lindley, Richard; Wardlaw, Joanna; Dennis, Martin; Innes, Karen; Cohen, Geoff; Whiteley, Will; Perry, David; Soosay, Vera; Buchanan, David; Venables, Graham; Czlonkowska, Anna; Kobayashi, Adam; Berge, Eivind; Slot, Karsten Bruins; Murray, Veronica; Peeters, Andre; Hankey, Graeme J; Matz, Karl; Brainin, Michael; Ricci, Stefano; Cantisani, Teresa A; Gubitz, Gordon; Phillips, Stephen J; Antonio, Arauz; Correia, Manuel; Lyrer, Phillippe; Kane, Ingrid; Lundstrom, Erik; IST-3 Collaborative Group ; Myint, Phyo Kyaw.

In: Trials, Vol. 12, 252, 30.11.2011.

Research output: Contribution to journalArticle

Sandercock, P, Lindley, R, Wardlaw, J, Dennis, M, Innes, K, Cohen, G, Whiteley, W, Perry, D, Soosay, V, Buchanan, D, Venables, G, Czlonkowska, A, Kobayashi, A, Berge, E, Slot, KB, Murray, V, Peeters, A, Hankey, GJ, Matz, K, Brainin, M, Ricci, S, Cantisani, TA, Gubitz, G, Phillips, SJ, Antonio, A, Correia, M, Lyrer, P, Kane, I, Lundstrom, E, IST-3 Collaborative Group & Myint, PK 2011, 'Update on the third international stroke trial (IST-3) of thrombolysis for acute ischaemic stroke and baseline features of the 3035 patients recruited', Trials, vol. 12, 252. https://doi.org/10.1186/1745-6215-12-252
Sandercock, Peter ; Lindley, Richard ; Wardlaw, Joanna ; Dennis, Martin ; Innes, Karen ; Cohen, Geoff ; Whiteley, Will ; Perry, David ; Soosay, Vera ; Buchanan, David ; Venables, Graham ; Czlonkowska, Anna ; Kobayashi, Adam ; Berge, Eivind ; Slot, Karsten Bruins ; Murray, Veronica ; Peeters, Andre ; Hankey, Graeme J ; Matz, Karl ; Brainin, Michael ; Ricci, Stefano ; Cantisani, Teresa A ; Gubitz, Gordon ; Phillips, Stephen J ; Antonio, Arauz ; Correia, Manuel ; Lyrer, Phillippe ; Kane, Ingrid ; Lundstrom, Erik ; IST-3 Collaborative Group ; Myint, Phyo Kyaw. / Update on the third international stroke trial (IST-3) of thrombolysis for acute ischaemic stroke and baseline features of the 3035 patients recruited. In: Trials. 2011 ; Vol. 12.
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TY - JOUR

T1 - Update on the third international stroke trial (IST-3) of thrombolysis for acute ischaemic stroke and baseline features of the 3035 patients recruited

AU - Sandercock, Peter

AU - Lindley, Richard

AU - Wardlaw, Joanna

AU - Dennis, Martin

AU - Innes, Karen

AU - Cohen, Geoff

AU - Whiteley, Will

AU - Perry, David

AU - Soosay, Vera

AU - Buchanan, David

AU - Venables, Graham

AU - Czlonkowska, Anna

AU - Kobayashi, Adam

AU - Berge, Eivind

AU - Slot, Karsten Bruins

AU - Murray, Veronica

AU - Peeters, Andre

AU - Hankey, Graeme J

AU - Matz, Karl

AU - Brainin, Michael

AU - Ricci, Stefano

AU - Cantisani, Teresa A

AU - Gubitz, Gordon

AU - Phillips, Stephen J

AU - Antonio, Arauz

AU - Correia, Manuel

AU - Lyrer, Phillippe

AU - Kane, Ingrid

AU - Lundstrom, Erik

AU - IST-3 Collaborative Group

AU - Myint, Phyo Kyaw

PY - 2011/11/30

Y1 - 2011/11/30

N2 - BACKGROUND: Intravenous recombinant tissue plasminogen activator (rtPA) is approved in Europe for use in patients with acute ischaemic stroke who meet strictly defined criteria. IST-3 sought to improve the external validity and precision of the estimates of the overall treatment effects (efficacy and safety) of rtPA in acute ischaemic stroke, and to determine whether a wider range of patients might benefit.DESIGN: International, multi-centre, prospective, randomized, open, blinded endpoint (PROBE) trial of intravenous rtPA in acute ischaemic stroke. Suitable patients had to be assessed and able to start treatment within 6 hours of developing symptoms, and brain imaging must have excluded intracranial haemorrhage and stroke mimics.RESULTS: The initial pilot phase was double blind and then, on 01/08/2003, changed to an open design. Recruitment began on 05/05/2000 and closed on 31/07/2011, by which time 3035 patients had been included, only 61 (2%) of whom met the criteria for the 2003 European approval for thrombolysis. 1617 patients were aged over 80 years at trial entry. The analysis plan will be finalised, without reference to the unblinded data, and published before the trial data are unblinded in early 2012. The main trial results will be presented at the European Stroke Conference in Lisbon in May 2012 with the aim to publish simultaneously in a peer-reviewed journal. The trial result will be presented in the context of an updated Cochrane systematic review. We also intend to include the trial data in an individual patient data meta-analysis of all the relevant randomised trials.CONCLUSION: The data from the trial will: improve the external validity and precision of the estimates of the overall treatment effects (efficacy and safety) of iv rtPA in acute ischaemic stroke; provide: new evidence on the balance of risk and benefit of intravenous rtPA among types of patients who do not clearly meet the terms of the current EU approval; and, provide the first large-scale randomised evidence on effects in patients over 80, an age group which had largely been excluded from previous acute stroke trials.TRIAL REGISTRATION: ISRCTN25765518.

AB - BACKGROUND: Intravenous recombinant tissue plasminogen activator (rtPA) is approved in Europe for use in patients with acute ischaemic stroke who meet strictly defined criteria. IST-3 sought to improve the external validity and precision of the estimates of the overall treatment effects (efficacy and safety) of rtPA in acute ischaemic stroke, and to determine whether a wider range of patients might benefit.DESIGN: International, multi-centre, prospective, randomized, open, blinded endpoint (PROBE) trial of intravenous rtPA in acute ischaemic stroke. Suitable patients had to be assessed and able to start treatment within 6 hours of developing symptoms, and brain imaging must have excluded intracranial haemorrhage and stroke mimics.RESULTS: The initial pilot phase was double blind and then, on 01/08/2003, changed to an open design. Recruitment began on 05/05/2000 and closed on 31/07/2011, by which time 3035 patients had been included, only 61 (2%) of whom met the criteria for the 2003 European approval for thrombolysis. 1617 patients were aged over 80 years at trial entry. The analysis plan will be finalised, without reference to the unblinded data, and published before the trial data are unblinded in early 2012. The main trial results will be presented at the European Stroke Conference in Lisbon in May 2012 with the aim to publish simultaneously in a peer-reviewed journal. The trial result will be presented in the context of an updated Cochrane systematic review. We also intend to include the trial data in an individual patient data meta-analysis of all the relevant randomised trials.CONCLUSION: The data from the trial will: improve the external validity and precision of the estimates of the overall treatment effects (efficacy and safety) of iv rtPA in acute ischaemic stroke; provide: new evidence on the balance of risk and benefit of intravenous rtPA among types of patients who do not clearly meet the terms of the current EU approval; and, provide the first large-scale randomised evidence on effects in patients over 80, an age group which had largely been excluded from previous acute stroke trials.TRIAL REGISTRATION: ISRCTN25765518.

KW - acute disease

KW - brain ischemia

KW - double-blind method

KW - fibrinolytic agents

KW - humans

KW - prospective studies

KW - sample size

KW - stroke

KW - thrombolytic therapy

KW - tissue plasminogen activator

U2 - 10.1186/1745-6215-12-252

DO - 10.1186/1745-6215-12-252

M3 - Article

VL - 12

JO - Trials

JF - Trials

SN - 1745-6215

M1 - 252

ER -