Thrombolysis Treated With TNK-tPA in Acute Ischemic Stroke Patients （3T Stroke-Ⅲ）

Summary

The trial is prospective, randomized, open-label, blinded endpoint (PROBE) design. Patients with acute ischemic stroke, who are eligible for standard intravenous thrombolysis within 4.5 hours of stroke onset will be randomized 1:1 to 0.25mg/kg or 0.9 mg/kg alteplase before all participants undergo endovascular thrombectomy.

Timeline

Start

2022-10-26

Primary completion

2023-11-04

Completion

2024-03-29

Publications

• Background Guidelines Editing Group of Chinese Stroke Society, Guidelines for the Diagnosis and Treatment of High-risk Non-Disabling Ischemic Cerebrovascular Events, Chinese Journal of Stroke, June 2016, 11 (6), p481-491.
• Background Chinese Journal of Circulation, China Cardiovascular Disease Report 2015.
• Background CAST: randomised placebo-controlled trial of early aspirin use in 20,000 patients with acute ischaemic stroke. CAST (Chinese Acute Stroke Trial) Collaborative Group. Lancet. 1997 Jun 7;349(9066):1641-9.
• Background Hao Zilong, Liu Ming, Li Wei, et al. Stroke registration method and basic characteristics and functional outcomes of 3123 patients in Chengdu [J]. Chinese Journal of Neurology, 2011,12 (44) : 826-831.
• Background Wang Z, Li J, Wang C, Yao X, Zhao X, Wang Y, Li H, Liu G, Wang A, Wang Y. Gender differences in 1-year clinical characteristics and outcomes after stroke: results from the China National Stroke Registry. PLoS One. 2013;8(2):e56459. doi: 10.1371/journal.pone.0056459. Epub 2013 Feb 13.
• Background Wei JW, Heeley EL, Wang JG, Huang Y, Wong LK, Li Z, Heritier S, Arima H, Anderson CS; ChinaQUEST Investigators. Comparison of recovery patterns and prognostic indicators for ischemic and hemorrhagic stroke in China: the ChinaQUEST (QUality Evaluation of Stroke Care and Treatment) Registry study. Stroke. 2010 Sep;41(9):1877-83. doi: 10.1161/STROKEAHA.110.586909. Epub 2010 Jul 22.
• Background Bandera E, Botteri M, Minelli C, Sutton A, Abrams KR, Latronico N. Cerebral blood flow threshold of ischemic penumbra and infarct core in acute ischemic stroke: a systematic review. Stroke. 2006 May;37(5):1334-9. doi: 10.1161/01.STR.0000217418.29609.22. Epub 2006 Mar 30.
• Background Donnan GA, Baron JC, Ma H, Davis SM. Penumbral selection of patients for trials of acute stroke therapy. Lancet Neurol. 2009 Mar;8(3):261-9. doi: 10.1016/S1474-4422(09)70041-9.
• Background Haley EC Jr, Thompson JL, Grotta JC, Lyden PD, Hemmen TG, Brown DL, Fanale C, Libman R, Kwiatkowski TG, Llinas RH, Levine SR, Johnston KC, Buchsbaum R, Levy G, Levin B; Tenecteplase in Stroke Investigators. Phase IIB/III trial of tenecteplase in acute ischemic stroke: results of a prematurely terminated randomized clinical trial. Stroke. 2010 Apr;41(4):707-11. doi: 10.1161/STROKEAHA.109.572040. Epub 2010 Feb 25.
• Background Parsons M, Spratt N, Bivard A, Campbell B, Chung K, Miteff F, O'Brien B, Bladin C, McElduff P, Allen C, Bateman G, Donnan G, Davis S, Levi C. A randomized trial of tenecteplase versus alteplase for acute ischemic stroke. N Engl J Med. 2012 Mar 22;366(12):1099-107. doi: 10.1056/NEJMoa1109842.
• Background Huang X, Cheripelli BK, Lloyd SM, Kalladka D, Moreton FC, Siddiqui A, Ford I, Muir KW. Alteplase versus tenecteplase for thrombolysis after ischaemic stroke (ATTEST): a phase 2, randomised, open-label, blinded endpoint study. Lancet Neurol. 2015 Apr;14(4):368-76. doi: 10.1016/S1474-4422(15)70017-7. Epub 2015 Feb 26.
• Background Logallo N, Novotny V, Assmus J, Kvistad CE, Alteheld L, Ronning OM, Thommessen B, Amthor KF, Ihle-Hansen H, Kurz M, Tobro H, Kaur K, Stankiewicz M, Carlsson M, Morsund A, Idicula T, Aamodt AH, Lund C, Naess H, Waje-Andreassen U, Thomassen L. Tenecteplase versus alteplase for management of acute ischaemic stroke (NOR-TEST): a phase 3, randomised, open-label, blinded endpoint trial. Lancet Neurol. 2017 Oct;16(10):781-788. doi: 10.1016/S1474-4422(17)30253-3. Epub 2017 Aug 2.
• Background Campbell BCV, Mitchell PJ, Churilov L, Yassi N, Kleinig TJ, Dowling RJ, Yan B, Bush SJ, Dewey HM, Thijs V, Scroop R, Simpson M, Brooks M, Asadi H, Wu TY, Shah DG, Wijeratne T, Ang T, Miteff F, Levi CR, Rodrigues E, Zhao H, Salvaris P, Garcia-Esperon C, Bailey P, Rice H, de Villiers L, Brown H, Redmond K, Leggett D, Fink JN, Collecutt W, Wong AA, Muller C, Coulthard A, Mitchell K, Clouston J, Mahady K, Field D, Ma H, Phan TG, Chong W, Chandra RV, Slater LA, Krause M, Harrington TJ, Faulder KC, Steinfort BS, Bladin CF, Sharma G, Desmond PM, Parsons MW, Donnan GA, Davis SM; EXTEND-IA TNK Investigators. Tenecteplase versus Alteplase before Thrombectomy for Ischemic Stroke. N Engl J Med. 2018 Apr 26;378(17):1573-1582. doi: 10.1056/NEJMoa1716405.
• Background Emberson J, Lees KR, Lyden P, Blackwell L, Albers G, Bluhmki E, Brott T, Cohen G, Davis S, Donnan G, Grotta J, Howard G, Kaste M, Koga M, von Kummer R, Lansberg M, Lindley RI, Murray G, Olivot JM, Parsons M, Tilley B, Toni D, Toyoda K, Wahlgren N, Wardlaw J, Whiteley W, del Zoppo GJ, Baigent C, Sandercock P, Hacke W; Stroke Thrombolysis Trialists' Collaborative Group. Effect of treatment delay, age, and stroke severity on the effects of intravenous thrombolysis with alteplase for acute ischaemic stroke: a meta-analysis of individual patient data from randomised trials. Lancet. 2014 Nov 29;384(9958):1929-35. doi: 10.1016/S0140-6736(14)60584-5. Epub 2014 Aug 5.
• Background National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. Tissue plasminogen activator for acute ischemic stroke. N Engl J Med. 1995 Dec 14;333(24):1581-7. doi: 10.1056/NEJM199512143332401.
• Background Hacke W, Kaste M, Fieschi C, von Kummer R, Davalos A, Meier D, Larrue V, Bluhmki E, Davis S, Donnan G, Schneider D, Diez-Tejedor E, Trouillas P. Randomised double-blind placebo-controlled trial of thrombolytic therapy with intravenous alteplase in acute ischaemic stroke (ECASS II). Second European-Australasian Acute Stroke Study Investigators. Lancet. 1998 Oct 17;352(9136):1245-51. doi: 10.1016/s0140-6736(98)08020-9.
• Background Clark WM, Wissman S, Albers GW, Jhamandas JH, Madden KP, Hamilton S. Recombinant tissue-type plasminogen activator (Alteplase) for ischemic stroke 3 to 5 hours after symptom onset. The ATLANTIS Study: a randomized controlled trial. Alteplase Thrombolysis for Acute Noninterventional Therapy in Ischemic Stroke. JAMA. 1999 Dec 1;282(21):2019-26. doi: 10.1001/jama.282.21.2019.
• Background Zheng H, Yang Y, Chen H, Li C, Chen Y, Shi FD, Yang L, Cui X, Lu Z, Liang Y, Cui S, Xu A, Wu Y, Sun Y, Wang Y. Thrombolysis with alteplase 3-4.5 hours after acute ischaemic stroke: the first multicentre, phase III trial in China. Stroke Vasc Neurol. 2020 Sep;5(3):285-290. doi: 10.1136/svn-2020-000337. Epub 2020 May 28.
• Background Standards and procedures for rapid reporting of safety data during drug clinical trials

Drugs

Indications