Tenecteplase versus standard of care for minor ischaemic stroke with proven occlusion (TEMPO-2): a randomised, open label, phase 3 superiority trial

被引：43

作者：

Coutts, Shelagh B. ^{[1
,2
,3
,5
]}

Ankolekar, Sandeep ^{[7
]}

Appireddy, Ramana ^{[8
]}

Arenillas, Juan F. ^{[9
,10
]}

Assis, Zarina ^{[11
,12
]}

Bailey, Peter ^{[1
,13
]}

Barber, Philip A. ^{[1
]}

Bazan, Rodrigo ^{[14
]}

Buck, Brian H. ^{[15
]}

Butcher, Ken S. ^{[16
]}

Camden, Marie -Christine ^{[17
]}

Campbell, Bruce C., V ^{[18
]}

Casaubon, Leanne K. ^{[19
]}

Catanese, Luciana ^{[21
]}

Chatterjee, Kausik ^{[22
]}

Choi, Philip M. C. ^{[23
,24
]}

Clarke, Brian ^{[25
]}

Dowlatshahi, Dar ^{[26
,27
]}

Ferrari, Julia ^{[28
]}

Field, Thalia S. ^{[29
]}

Ganesh, Aravind ^{[1
,3
,5
,6
]}

Ghia, Darshan ^{[31
,32
]}

Goyal, Mayank ^{[1
,2
,5
]}

Greisenegger, Stefan ^{[33
]}

Halse, Omid ^{[34
]}

Horn, Mackenzie ^{[1
]}

Hunter, Gary ^{[35
]}

Imoukhuede, Oje ^{[36
]}

Kelly, Peter J. ^{[37
]}

Kennedy, James ^{[38
]}

Kenney, Carol ^{[1
]}

Kleinig, Timothy J. ^{[39
,40
]}

Krishnan, Kailash ^{[41
]}

Lima, Fabricio ^{[42
]}

Mandzia, Jennifer L. ^{[43
]}

Marko, Martha ^{[33
]}

Martins, Sheila ^{[44
]}

Medvedev, George ^{[30
]}

Menon, Bijoy K. ^{[1
,2
,3
,5
]}

Mishra, Sachin M. ^{[15
]}

Molina, Carlos ^{[46
]}

Moussaddy, Aimen ^{[47
]}

Muir, Keith W. ^{[48
]}

Parsons, Mark W. ^{[49
]}

Penn, Andrew M. W. ^{[50
]}

Pille, Arthur ^{[45
]}

Pontes-Neto, Octavio M. ^{[51
]}

Roffe, Christine ^{[52
]}

Serena, Joaquin ^{[53
]}

Simister, Robert ^{[54
]}

机构：

[1] Univ Calgary, Dept Clin Neurosci, Cumming Sch Med, Calgary, AB T2N 2T9, Canada

[2] Univ Calgary, Dept Radiol, Cumming Sch Med, Calgary, AB, Canada

[3] Univ Calgary, Dept Community Hlth Sci, Cumming Sch Med, Calgary, AB, Canada

[4] Univ Calgary, Dept Med, Cumming Sch Med, Calgary, AB, Canada

[5] Univ Calgary, Hotchkiss Brain Inst, Cumming Sch Med, Calgary, AB, Canada

[6] Univ Calgary, Obrien Inst Publ Hlth, Cumming Sch Med, Calgary, AB, Canada

[7] Kings Coll Hosp London, Dept Neurol, London, England

[8] Queens Univ, Dept Med, Div Neurol, Kingston, ON, Canada

[9] Hosp Clin Univ, Dept Neurol, Stroke Program, Valladolid, Spain

[10] Univ Valladolid, Valladolid Hlth Res Inst, Dept Med, Valladolid, Spain

[11] Foothills Med Ctr, Dept Imaging, Calgary, AB, Canada

[12] Alberta Childrens Prov Gen Hosp, Calgary, AB, Canada

[13] Griffith Univ, Gold Coast, QLD, Australia

[14] Sao Paulo State Univ, Botucatu Med Sch, Sao Paulo, Brazil

[15] Univ Alberta, Dept Med, Div Neurol, Edmonton, AB, Canada

[16] Univ New South Wales, Sch Clin Med, Sydney, NSW, Australia

[17] CHU Quebec, Hop Enfant Jesus, Quebec City, PQ, Canada

[18] Univ Melbourne, Royal Melbourne Hosp, Melbourne Brain Ctr, Dept Med & Neurol, Parkville, VIC, Australia

[19] Univ Toronto, Univ Hlth Network, Toronto Western Hosp, Toronto, ON, Canada

[20] Univ Toronto, Sunnybrook Hlth Sci Ctr, Dept Med, Neurol, Toronto, ON, Canada

[21] McMaster Univ, Populat Hlth Res Inst, Hamilton, ON, Canada

[22] Countess Chester Hosp NHS Fdn Trust, Chester, England

[23] Eastern Hlth, Box Hill Hosp, Dept Neurosci, Melbourne, VIC, Australia

[24] Monash Univ, Eastern Hlth Clin Sch, Melbourne, VIC, Australia

[25] St Georges Univ Hosp, London, England

[26] Univ Ottawa, Dept Med, Ottawa, ON, Canada

[27] Ottawa Hosp, Ottawa Hosp Res Inst, Ottawa, ON, Canada

[28] St Johns God Hosp Vienna, Dept Neurol, Vienna, Austria

[29] Univ British Columbia, Vancouver Stroke Program, Div Neurol, Vancouver, BC, Canada

[30] Univ British Columbia, Royal Columbian Hosp, Vancouver, BC, Canada

[31] Fiona Stanley Hosp, Murdoch, WA, Australia

[32] Univ Western Australia, Perth, WA, Australia

[33] Med Univ Vienna, Dept Neurol, Vienna, Austria

[34] Imperial Coll Healthcare Trust, London, England

[35] Univ Saskatchewan, Saskatoon, SK, Canada

[36] Red Deer Reg Hosp Ctr, Red Deer, AB, Canada

[37] Univ Coll Dublin, Mater Univ Hosp Dublin, Sch Med, Dublin, Ireland

[38] Univ Oxford, John Radcliffe Hosp, Acute Multidisciplinary Imaging & Intervent Ctr, Radcliffe Dept Med, Oxford, England

[39] Royal Adelaide Hosp, Dept Neurol, Adelaide, SA, Australia

[40] Univ Adelaide, Dept Med, Adelaide, SA, Australia

[41] Nottingham Univ Hosp NHS Trust, Queens Med Ctr, Nottingham, England

[42] Hosp Geral Fortaleza, Fortaleza, Brazil

[43] Western Univ, Dept Clin Neurol Sci, London, ON, Canada

[44] Hosp Clin Porto Alegre, Porto Alegre, Brazil

[45] Hosp Moinhos de Vento, Neurol Dept, Porto Alegre, Brazil

[46] Hosp Valle De Hebron, Vall Dhebron Stroke Ctr, Barcelona, Spain

[47] McGill Univ, Montreal Neurol Inst, Hlth Ctr, Montreal, PQ, Canada

[48] Univ Glasgow, Sch Neurosci & Psychol, Glasgow, Scotland

[49] UNSW South West Sydney, Liverpool Hosp, Dept Neurol, Sydney, NSW, Australia

[50] Victoria Gen Hosp, Victoria, BC, Canada

来源：

LANCET | 2024年 / 403卷 / 10444期

基金：

加拿大健康研究院;

关键词：

ALTEPLASE; THERAPY; EVENTS; ATTACK; SCALE; MILD; MRI;

D O I：

10.1016/S0140-6736(24)00921-8

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Background Individuals with minor ischaemic stroke and intracranial occlusion are at increased risk of poor outcomes. Intravenous thrombolysis with tenecteplase might improve outcomes in this population. We aimed to test the superiority of intravenous tenecteplase over non-thrombolytic standard of care in patients with minor ischaemic stroke and intracranial occlusion or focal perfusion abnormality. Methods In this multicentre, prospective, parallel group, open label with blinded outcome assessment, randomised controlled trial, adult patients (aged >= 18 years) were included at 48 hospitals in Australia, Austria, Brazil, Canada, Finland, Ireland, New Zealand, Singapore, Spain, and the UK. Eligible patients with minor acute ischaemic stroke (National Institutes of Health Stroke Scale score 0-5) and intracranial occlusion or focal perfusion abnormality were enrolled within 12 h from stroke onset. Participants were randomly assigned (1:1), using a minimal sufficient balance algorithm to intravenous tenecteplase (0<middle dot>25 mg/kg) or non-thrombolytic standard of care (control). Primary outcome was a return to baseline functioning on pre-morbid modified Rankin Scale score in the intention-to-treat (ITT) population (all patients randomly assigned to a treatment group and who did not withdraw consent to participate) assessed at 90 days. Safety outcomes were reported in the ITT population and included symptomatic intracranial haemorrhage and death. This trial is registered with ClinicalTrials.gov, NCT02398656, and is closed to accrual. Findings The trial was stopped early for futility. Between April 27, 2015, and Jan 19, 2024, 886 patients were enrolled; 369 (42%) were female and 517 (58%) were male. 454 (51%) were assigned to control and 432 (49%) to intravenous tenecteplase. The primary outcome occurred in 338 (75%) of 452 patients in the control group and 309 (72%) of 432 in the tenecteplase group (risk ratio [RR] 0<middle dot>96, 95% CI 0<middle dot>88-1<middle dot>04, p=0<middle dot>29). More patients died in the tenecteplase group (20 deaths [5%]) than in the control group (five deaths [1%]; adjusted hazard ratio 3<middle dot>8; 95% CI 1<middle dot>4-10<middle dot>2, p=0<middle dot>0085). There were eight (2%) symptomatic intracranial haemorrhages in the tenecteplase group versus two (<1%) in the control group (RR 4<middle dot>2; 95% CI 0<middle dot>9-19<middle dot>7, p=0<middle dot>059). Interpretation There was no benefit and possible harm from treatment with intravenous tenecteplase. Patients with minor stroke and intracranial occlusion should not be routinely treated with intravenous thrombolysis.

引用

页码：2597 / 2605

页数：9

共 29 条

[1] European Stroke Organisation (ESO) expedited recommendation on tenecteplase for acute ischaemic stroke [J].

Alamowitch, Sonia ;

Turc, Guillaume ;

Palaiodimou, Lina ;

Bivard, Andrew ;

Cameron, Alan ;

De Marchis, Gian Marco ;

Fromm, Annette ;

Korv, Janika ;

Roaldsen, Melinda B. ;

Katsanos, Aristeidis H. ;

Tsivgoulis, Georgios .

EUROPEAN STROKE JOURNAL, 2023, 8 (01) :8-54

[2] Tenecteplase for Stroke at 4.5 to 24 Hours with Perfusion-Imaging Selection [J].

Albers, Gregory W. ;

Jumaa, Mouhammad ;

Purdon, Barbara ;

Zaidi, Syed F. ;

Streib, Christopher ;

Shuaib, Ashfaq ;

Sangha, Navdeep ;

Kim, Minjee ;

Froehler, Michael T. ;

Schwartz, Neil E. ;

Clark, Wayne M. ;

Kircher, Charles E. ;

Yang, Ming ;

Massaro, Lori ;

Lu, Xiao-Yu ;

Rippon, Gregory A. ;

Broderick, Joseph P. ;

Butcher, Ken ;

Lansberg, Maarten G. ;

Liebeskind, David S. ;

Nouh, Amre ;

Schwamm, Lee H. ;

Campbell, Bruce C. V. .

NEW ENGLAND JOURNAL OF MEDICINE, 2024, 390 (08) :701-711

[3] Why are stroke patients excluded from TPA therapy? An analysis of patient eligibility [J].

Barber, PA ;

Zhang, J ;

Demchuk, AM ;

Hill, MD ;

Buchan, AM .

NEUROLOGY, 2001, 56 (08) :1015-1020

[4] Validity and reliability of a quantitative computed tomography score in predicting outcome of hyperacute stroke before thrombolytic therapy [J].

Barber, PA ;

Demchuk, AM ;

Zhang, JJ ;

Buchan, AM .

LANCET, 2000, 355 (9216) :1670-1674

[5] Simplified Modified Rankin Scale Questionnaire Reproducibility Over the Telephone and Validation With Quality of Life [J].

Bruno, Askiel ;

Akinwuntan, Abiodun E. ;

Lin, Chen ;

Close, Brian ;

Davis, Kristin ;

Baute, Vanessa ;

Aryal, Tia ;

Brooks, Desiree ;

Hess, David C. ;

Switzer, Jeffrey A. ;

Nichols, Fenwick T. .

STROKE, 2011, 42 (08) :2276-2279

[6] Dual Antiplatelet Therapy vs Alteplase for Patients With Minor Nondisabling Acute Ischemic Stroke The ARAMIS Randomized Clinical Trial [J].

Chen, Hui-Sheng ;

Cui, Yu ;

Zhou, Zhong-He ;

Zhang, Hong ;

Wang, Li-Xia ;

Wang, Wei-Zhong ;

Shen, Li-Ying ;

Guo, Li-Yan ;

Wang, Er-Qiang ;

Wang, Rui-Xian ;

Han, Jing ;

Dong, Yu-Ling ;

Li, Jing ;

Lin, Yong-Zhong ;

Yang, Qing-Cheng ;

Zhang, Li ;

Li, Jing-Yu ;

Wang, Jin ;

Xia, Lei ;

Ma, Guang-Bin ;

Lu, Jiang ;

Jiang, Chang-Hao ;

Huang, Shu-Man ;

Wan, Li-Shu ;

Piao, Xiang-Yu ;

Li, Zhuo ;

Li, Yan-Song ;

Yang, Kui-Hua ;

Wang, Duo-Lao ;

Nguyen, Thanh N. .

JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2023, 329 (24) :2135-2144

[7] Tenecteplase-Tissue-Type Plasminogen Activator Evaluation for Minor Ischemic Stroke With Proven Occlusion [J].

Coutts, Shelagh B. ;

Dubuc, Veronique ;

Mandzia, Jennifer ;

Kenney, Carol ;

Demchuk, Andrew M. ;

Smith, Eric E. ;

Subramaniam, Suresh ;

Goyal, Mayank ;

Patil, Shivanand ;

Menon, Bijoy K. ;

Barber, Philip A. ;

Dowlatshahi, Dar ;

Field, Thalia ;

Asdaghi, Negar ;

Camden, Marie-Christine ;

Hill, Michael D. .

STROKE, 2015, 46 (03) :769-+

[8] What Causes Disability After Transient Ischemic Attack and Minor Stroke? Results From the CT And MRI in the Triage of TIA and minor Cerebrovascular Events to Identify High Risk Patients (CATCH) Study [J].

Coutts, Shelagh B. ;

Modi, Jayesh ;

Patel, Shiel K. ;

Aram, Heidi ;

Demchuk, Andrew M. ;

Goyal, Mayank ;

Hill, Michael D. .

STROKE, 2012, 43 (11) :3018-3022

[9] CT/CT Angiography and MRI Findings Predict Recurrent Stroke After Transient Ischemic Attack and Minor Stroke Results of the Prospective CATCH Study [J].

Coutts, Shelagh B. ;

Modi, Jayesh ;

Patel, Shiel K. ;

Demchuk, Andrew M. ;

Goyal, Mayank ;

Hill, Michael D. .

STROKE, 2012, 43 (04) :1013-1017

[10] Is the EuroQol a valid measure of health-related quality of life after stroke? [J].

Dorman, PJ ;

Waddell, F ;

Slattery, J ;

Dennis, M ;

Sandercock, P .

STROKE, 1997, 28 (10) :1876-1882

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