Intra-arterial alteplase for acute ischaemic stroke after mechanical thrombectomy (PEARL): rationale and design of a multicentre, prospective, open-label, blinded-endpoint, randomised controlled trial

被引：9

作者：

Yang, Xinguang ^{[1
]}

He, Xiongjun ^{[2
]}

Pan, Dong ^{[3
]}

Xu, Yongteng ^{[1
]}

Peng, Huiyuan ^{[4
]}

Li, Kaifeng ^{[2
]}

Zhang, Min ^{[5
,6
]}

Zhu, Yingying ^{[7
]}

Chen, Yanting ^{[1
]}

He, Baixuan ^{[1
]}

Zhou, Hongxing ^{[2
]}

Li, Jie ^{[2
]}

Hou, Hongbiao ^{[1
]}

Sun, Haoyang ^{[1
]}

Liu, Yajie ^{[2
]}

Tang, Yamei ^{[1
]}

机构：

[1] Sun Yat Sen Univ, Sun Yat Sen Mem Hosp, Dept Neurol, Guangzhou, Peoples R China

[2] Southern Med Univ, Shenzhen Hosp, Dept Neurol, Shenzhen, Peoples R China

[3] Sun Yat Sen Univ, Affiliated Hosp 8, Dept Neurol, Shenzhen, Peoples R China

[4] Zhongshan Hosp Tradit Chinese Med, Zhongshan, Guangdong, Peoples R China

[5] Guangzhou Univ, Tradit Chinese Med Maoming Hosp, Affiliated Hosp 1, Maoming, Guangdong, Peoples R China

[6] Maoming Hosp Tradit Chinese Med, Maoming, Guangdong, Peoples R China

[7] Sun Yat Sen Univ, Sun Yat Sen Mem Hosp, Clin Res Design Div, Guangzhou, Peoples R China

来源：

BMJ OPEN | 2024年 / 14卷 / 11期

基金：

中国国家自然科学基金;

关键词：

Stroke; Clinical Trial; China; GLOBAL BURDEN; DISEASE;

D O I：

10.1136/bmjopen-2024-091059

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Introduction Successful reperfusion does not always lead to good neurological outcomes and impaired microcirculation can be one of the underlying causes. Intra-arterial alteplase after mechanical thrombectomy (MT) may improve microcirculation contributing to neurological recovery, but prospective randomised studies are still needed to validate its efficacy and safety. We aim to assess the efficacy and safety of intra-arterial alteplase after MT for acute ischaemic stroke (AIS) with large-vessel occlusion (LVO).Methods and analysis The Intra-arterial Alteplase for Acute Ischaemic Stroke After Mechanical Thrombectomy (PEARL) study is a multicentre, prospective, open-label, blinded-endpoint, randomised controlled trial. We consecutively screen AIS patients with anterior circulation LVO and National Institute of Health Stroke Scale of 6-25, who reach stable expanded Thrombolysis in Cerebral Infarction scores of 2b50-3 on angiography after MT. Eligible participants are 1:1 randomly assigned to the experimental group and the control group. Participants in the experimental group will receive intra-arterial alteplase (0.225 mg/kg and a maximum dose of 20 mg) after MT and standard medical treatment, while those in the control group will receive standard medical treatment alone after the procedure. The primary outcome is the proportion of patients with a 90-day modified Rankin scale of 0-1. A total of 324 participants are required to test the superiority hypothesis with 80% power at a two-tailed significance level of 0.05.Ethics and dissemination This study has been approved by the Ethics Committee of Sun Yat-sen Memorial Hospital, Sun Yat-sen University (SYSKY-2023-390-02) and will be conducted following the Declaration of Helsinki. Ethical approvals have been obtained separately for all centres participating in the study. Study results will be published in peer-reviewed academic journals.Trial registration number NCT05856851.

引用

页数：8

共 17 条

[1] Thrombectomy for Stroke at 6 to 16 Hours with Selection by Perfusion Imaging [J].

Albers, G. W. ;

Marks, M. P. ;

Kemp, S. ;

Christensen, S. ;

Tsai, J. P. ;

Ortega-Gutierrez, S. ;

McTaggart, R. A. ;

Torbey, M. T. ;

Kim-Tenser, M. ;

Leslie-Mazwi, T. ;

Sarraj, A. ;

Kasner, S. E. ;

Ansari, S. A. ;

Yeatts, S. D. ;

Hamilton, S. ;

Mlynash, M. ;

Heit, J. J. ;

Zaharchuk, G. ;

Kim, S. ;

Carrozzella, J. ;

Palesch, Y. Y. ;

Demchuk, A. M. ;

Bammer, R. ;

Lavori, P. W. ;

Broderick, J. P. ;

Lansberg, M. G. .

NEW ENGLAND JOURNAL OF MEDICINE, 2018, 378 (08) :708-718

[2] Tenecteplase versus Alteplase before Thrombectomy for Ischemic Stroke [J].

Campbell, B. C. V. ;

Mitchell, P. J. ;

Churilov, L. ;

Yassi, N. ;

Kleinig, T. J. ;

Dowling, R. J. ;

Yan, B. ;

Bush, S. J. ;

Dewey, H. M. ;

Thijs, V. ;

Scroop, R. ;

Simpson, M. ;

Brooks, M. ;

Asadi, H. ;

Wu, T. Y. ;

Shah, D. G. ;

Wijeratne, T. ;

Ang, T. ;

Miteff, F. ;

Levi, C. R. ;

Rodrigues, E. ;

Zhao, H. ;

Salvaris, P. ;

Garcia-Esperon, C. ;

Bailey, P. ;

Rice, H. ;

de Villiers, L. ;

Brown, H. ;

Redmond, K. ;

Leggett, D. ;

Fink, J. N. ;

Collecutt, W. ;

Wong, A. A. ;

Muller, C. ;

Coulthard, A. ;

Mitchell, K. ;

Clouston, J. ;

Mahady, K. ;

Field, D. ;

Ma, H. ;

Phan, T. G. ;

Chong, W. ;

Chandra, R. V. ;

Slater, L. -A. ;

Krause, M. ;

Harrington, T. J. ;

Faulder, K. C. ;

Steinfort, B. S. ;

Bladin, C. F. ;

Sharma, G. .

NEW ENGLAND JOURNAL OF MEDICINE, 2018, 378 (17) :1573-1582

[3] Global and regional burden of stroke during 1990-2010: findings from the Global Burden of Disease Study 2010 [J].

Feigin, Valery L. ;

Forouzanfar, Mohammad H. ;

Krishnamurthi, Rita ;

Mensah, George A. ;

Connor, Myles ;

Bennett, Derrick A. ;

Moran, Andrew E. ;

Sacco, Ralph L. ;

Anderson, Laurie ;

Truelsen, Thomas ;

O'Donnell, Martin ;

Venketasubramanian, Narayanaswamy ;

Barker-Collo, Suzanne ;

Lawes, Carlene M. M. ;

Wang, Wenzhi ;

Shinohara, Yukito ;

Witt, Emma ;

Ezzati, Majid ;

Naghavi, Mohsen ;

Murray, Christopher .

LANCET, 2014, 383 (9913) :245-255

[4] Endovascular thrombectomy after large-vessel ischaemic stroke: a meta-analysis of individual patient data from five randomised trials [J].

Goyal, Mayank ;

Menon, Bijoy K. ;

van Zwam, Wim H. ;

Dippel, Diederik W. J. ;

Mitchell, Peter J. ;

Demchuk, Andrew M. ;

Davalos, Antoni ;

Majoie, Charles B. L. M. ;

van der Lugt, Aad ;

de Miquel, Maria A. ;

Donnan, Geoff Rey A. ;

Roos, Yvo B. W. E. M. ;

Bonafe, Alain ;

Jahan, Reza ;

Diener, Hans-Christoph ;

van den Berg, Lucie A. ;

Levy, Elad I. ;

Berkhemer, Olvert A. ;

Pereira, Vitor M. ;

Rempel, Jeremy ;

Millan, Monica ;

Davis, Stephen M. ;

Roy, Daniel ;

Thornton, John ;

San Roman, Luis ;

Ribo, Marc ;

Beumer, Debbie ;

Stouch, Bruce ;

Brown, Scott ;

Campbell, Bruce C. V. ;

van Oostenbrugge, Robert J. ;

Saver, Jeff Rey L. ;

Hill, Michael D. ;

Jovin, Tudor G. .

LANCET, 2016, 387 (10029) :1723-1731

[5]

Kvistad CE., NOR-TEST, V2, P21, DOI [10.1016/S1474-4422(22)00124-7, DOI 10.1016/S1474-4422(22)00124-7]

[6] Time to treatment with intravenous alteplase and outcome in stroke: an updated pooled analysis of ECASS, ATLANTIS, NINDS, and EPITHET trials [J].

Lees, Kennedy R. ;

Bluhmki, Erich ;

von Kummer, Ruediger ;

Brott, Thomas G. ;

Toni, Danilo ;

Grotta, James C. ;

Albers, Gregory W. ;

Kaste, Markku ;

Marler, John R. ;

Hamilton, Scott A. ;

Tilley, Barbara C. ;

Davis, Stephen M. ;

Donnan, Geoffrey A. ;

Hacke, Werner ;

Ninds, Ecass Atlantis .

LANCET, 2010, 375 (9727) :1695-1703

[7]

Ma QF, 2021, LANCET PUBLIC HEALTH, V6, pE897, DOI 10.1016/S2468-2667(21)00228-0

[8] Intravenous tenecteplase compared with alteplase for acute ischaemic stroke in Canada (AcT): a pragmatic, multicentre, open-label, registry-linked, randomised, controlled, non-inferiority trial [J].

Menon, Bijoy K. ;

Buck, Brian H. ;

Singh, Nishita ;

Deschaintre, Yan ;

Almekhlafi, Mohammed A. ;

Coutts, Shelagh B. ;

Thirunavukkarasu, Sibi ;

Khosravani, Houman ;

Appireddy, Ramana ;

Moreau, Francois ;

Gubitz, Gord ;

Tkach, Aleksander ;

Catanese, Luciana ;

Dowlatshahi, Dar ;

Medvedev, George ;

Mandzia, Jennifer ;

Pikula, Aleksandra ;

Shankar, Jai ;

Williams, Heather ;

Field, Thalia S. ;

Manosalva, Alejandro ;

Siddiqui, Muzaffar ;

Zafar, Atif ;

Imoukhuede, Oje ;

Hunter, Gary ;

Demchuk, Andrew M. ;

Mishra, Sachin ;

Gioia, Laura C. ;

Jalini, Shirin ;

Cayer, Caroline ;

Phillips, Stephen ;

Elamin, Elsadig ;

Shoamanesh, Ashkan ;

Subramaniam, Suresh ;

Kate, Mahesh ;

Jacquin, Gregory ;

Camden, Marie-Christine ;

Benali, Faysal ;

Alhabli, Ibrahim ;

Bala, Fouzi ;

Horn, MacKenzie ;

Stotts, Grant ;

Hill, Michael D. ;

Gladstone, David J. ;

Poppe, Alexandre ;

Sehgal, Arshia ;

Zhang, Qiao ;

Lethebe, Brendan Cord ;

Doram, Craig ;

Ademola, Ayoola .

LANCET, 2022, 400 (10347) :161-169

[9] Thrombectomy 6 to 24 Hours after Stroke with a Mismatch between Deficit and Infarct [J].

Nogueira, R. G. ;

Jadhav, A. P. ;

Haussen, D. C. ;

Bonafe, A. ;

Budzik, R. F. ;

Bhuva, P. ;

Yavagal, D. R. ;

Ribo, M. ;

Cognard, C. ;

Hanel, R. A. ;

Sila, C. A. ;

Hassan, A. E. ;

Millan, M. ;

Levy, E. I. ;

Mitchell, P. ;

Chen, M. ;

English, J. D. ;

Shah, Q. A. ;

Silver, F. L. ;

Pereira, V. M. ;

Mehta, B. P. ;

Baxter, B. W. ;

Abraham, M. G. ;

Cardona, P. ;

Veznedaroglu, E. ;

Hellinger, F. R. ;

Feng, L. ;

Kirmani, J. F. ;

Lopes, D. K. ;

Jankowitz, B. T. ;

Frankel, M. R. ;

Costalat, V. ;

Vora, N. A. ;

Yoo, A. J. ;

Malik, A. M. ;

Furlan, A. J. ;

Rubiera, M. ;

Aghaebrahim, A. ;

Olivot, J. -M. ;

Tekle, W. G. ;

Shields, R. ;

Graves, T. ;

Lewis, R. J. ;

Smith, W. S. ;

Liebeskind, D. S. ;

Saver, J. L. ;

Jovin, T. G. .

NEW ENGLAND JOURNAL OF MEDICINE, 2018, 378 (01) :11-21

[10] Guidelines for the Early Management of Patients With Acute Ischemic Stroke: 2019 Update to the 2018 Guidelines for the Early Management of Acute Ischemic Stroke: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association [J].

Powers, William J. ;

Rabinstein, Alejandro A. ;

Ackerson, Teri ;

Adeoye, Opeolu M. ;

Bambakidis, Nicholas C. ;

Becker, Kyra ;

Biller, Jose ;

Brown, Michael ;

Demaerschalk, Bart M. ;

Hoh, Brian ;

Jauch, Edward C. ;

Kidwell, Chelsea S. ;

Leslie-Mazwi, Thabele M. ;

Ovbiagele, Bruce ;

Scott, Phillip A. ;

Sheth, Kevin N. ;

Southerland, Andrew M. ;

Summers, Deborah, V ;

Tirschwell, David L. .

STROKE, 2019, 50 (12) :E344-E418

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