A multicentre, randomized, double-blinded, placebo-controlled Phase III study to investigate EXtending the time for Thrombolysis in Emergency Neurological Deficits (EXTEND)

被引：154

作者：

Ma, Henry ^{[1
,2
]}

Parsons, Mark W. ^{[3
]}

Christensen, Soren ^{[4
]}

Campbell, Bruce C. V. ^{[4
]}

Churilov, Leonid ^{[1
]}

Connelly, Alan ^{[5
]}

Yan, Bernard ^{[4
]}

Bladin, Chris ^{[6
]}

Than Phan ^{[7
]}

Barber, Alan P. ^{[8
]}

Read, Stephen ^{[9
]}

Hankey, Graeme J. ^{[10
]}

Markus, Romesh ^{[11
]}

Wijeratne, Tissa ^{[12
]}

Grimley, R. ^{[13
]}

Mahant, N. ^{[14
]}

Kleinig, Tim ^{[15
]}

Sturm, John ^{[16
]}

Lee, A. ^{[17
]}

Blacker, D. ^{[18
]}

Gerraty, Richard ^{[19
]}

Krause, M. ^{[20
]}

Desmond, P. M. ^{[21
]}

McBride, S. J. ^{[24
,25
]}

Carey, Leanne ^{[1
]}

Howells, David W. ^{[1
]}

Hsu, C. Y. ^{[22
,23
]}

Davis, Stephen M.

Donnan, Geoffrey A. ^{[1
]}

机构：

[1] Univ Melbourne, Natl Stroke Res Inst, Florey Neurosci Inst, Heidelberg Hts, Vic, Australia

[2] Monash Univ, Monash Med Ctr, Dept Med, Clayton, Vic, Australia

[3] Univ Newcastle, John Hunter Hosp, Dept Neurol, Newcastle, NSW 2300, Australia

[4] Univ Melbourne, Royal Melbourne Hosp, Melbourne Brain Ctr, Dept Med, Heidelberg, Vic, Australia

[5] Florey Neurosci Inst, Brain Res Inst, Heidelberg Hts, Vic, Australia

[6] Box Hill Hosp, Dept Neurol, Melbourne, Australia

[7] Monash Univ, Dept Neurol, Monash Med Ctr, Clayton, Vic, Australia

[8] Auckland Hosp, Dept Neurol, Auckland, New Zealand

[9] Royal Brisbane & Womens Hosp, Dept Neurol, Brisbane, Qld, Australia

[10] Royal Perth Hosp, Dept Neurol, Perth, WA, Australia

[11] St Vincents Hosp, Dept Neurol, Sydney, NSW 2010, Australia

[12] Western Hosp, Dept Neurol, Melbourne, Vic, Australia

[13] Nambour Gen Hosp, Dept Neurol, Nambour, Qld, Australia

[14] Westmead Hosp, Dept Neurol, Sydney, NSW, Australia

[15] Royal Adelaide Hosp, Dept Neurol, Adelaide, SA 5000, Australia

[16] Univ Newcastle, Dept Neurol, Gosford Hosp, Newcastle, NSW 2300, Australia

[17] Flinders Med Ctr, Dept Neurol, Bedford Pk, SA, Australia

[18] Sir Charles Gairdner Hosp, Dept Neurol, Perth, WA, Australia

[19] Epworth Healthcare, Dept Neurol, Melbourne, Vic, Australia

[20] Royal N Shore Hosp, Dept Neurol, Sydney, NSW, Australia

[21] Royal Melbourne Hosp, Dept Neurol, Melbourne, Vic, Australia

[22] China Med Univ Hosp, Dept Neurol, Taichung, Taiwan

[23] China Med Univ, Grad Inst Clin Med Sci, Taichung, Taiwan

[24] CSIRO Preventat Hlth Flagship, Parkville, Vic, Australia

[25] CSIRO ICT Ctr, Australian E Hlth Res Ctr, Brisbane, Qld, Australia

来源：

INTERNATIONAL JOURNAL OF STROKE | 2012年 / 7卷 / 01期

关键词：

clinical trials; EXTEND; protocols; stroke; thrombolysis; time window; ACUTE ISCHEMIC-STROKE; WAKE-UP STROKE; CLINICAL-RESPONSE; DIFFUSION; ALTEPLASE; EPITHET; TOMOGRAPHY; DEFINITION; DEFUSE; TRIALS;

D O I：

10.1111/j.1747-4949.2011.00730.x

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

Background and hypothesis Thrombolytic therapy with tissue plasminogen activator is effective for acute ischaemic stroke within 4.5 h of onset. Patients who wake up with stroke are generally ineligible for stroke thrombolysis. We hypothesized that ischaemic stroke patients with significant penumbral mismatch on either magnetic resonance imaging or computer tomography at three- ( or 4.5 depending on local guidelines) to nine-hours from stroke onset, or patients with wake-up stroke within nine-hours from midpoint of sleep duration, would have improved clinical outcomes when given tissue plasminogen activator compared to placebo. Study design EXtending the time for Thrombolysis in Emergency Neurological Deficits is an investigator-driven, Phase III, randomized, multicentre, double-blind, placebo-controlled study. Ischaemic stroke patients presenting after the three- or 4.5-h treatment window for tissue plasminogen activator and within nine-hours of stroke onset or with wake-up stroke within nine-hours from the midpoint of sleep duration, who fulfil clinical (National Institutes of Health Stroke Score >= 4-26 and prestroke modified Rankin Scale <2) will undergo magnetic resonance imaging or computer tomography. Patients who also meet imaging criteria (infarct core volume <70 ml, perfusion lesion : infarct core mismatch ratio >1.2, and absolute mismatch >10 ml) will be randomized to either tissue plasminogen activator or placebo. Study outcome The primary outcome measure will be modified Rankin Scale 0-1 at day 90. Clinical secondary outcomes include categorical shift in modified Rankin Scale at 90 days, reduction in the National Institutes of Health Stroke Score by 8 or more points or reaching 0-1 at day 90, recurrent stroke, or death. Imaging secondary outcomes will include symptomatic intracranial haemorrhage, reperfusion and or recanalization at 24 h and infarct growth at day 90.

引用

页码：74 / 80

页数：7

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