Clinical trial NCT04797013: Tenecteplase Reperfusion Therapy in Acute Ischemic Cerebrovascular Events-Ⅱ
Official title: A Phase 3, Multicentre,Open-label, Randomised Controlled, Non-inferiority Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Acute Ischemic Stroke
Keywords: rhTNK-tPA
acute
stroke
phaseⅢ
Acute Ischemic Stroke
rt-PA
Lead sponsor: Beijing Tiantan Hospital
Sponsor class: OTHER
Collaborators: name: Guangzhou Recomgen Biotech Co., Ltd.
First posted: 2021-03-15
Enrollment: 1430
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: multicenter, prospective, randomized, open label, blinded-endpoint (PROBE)，Parallel controls，Non-inferiority
Primary purpose: TREATMENT

Brief summary: A Phase Ⅲ, Multicenter, Prospective, Randomized, Open Label, Blinded-endpoint (PROBE) Controlled Trial of Recombinant Human TNK Tissue-type Plasminogen Activator (rhTNK-tPA) for Injection Versus Alteplase for Acute Ischemic Stroke Within 4.5 Hours

Detailed description: To test the hypothesis that rhTNK-tPA is non-inferior to alteplase in thrombolysis treatment when administered within 4.5 hours of ischemic stroke onset.

Eligibility criteria: Inclusion Criteria:

* Age ≥18 years old, no gender limitation;
* The time from onset to treatment was \< 4.5h;The time at which symptoms begin is defined as "the time at which they finally appear normal";
* The clinical diagnosis was ischemic stroke (the diagnosis followed the Chinese Guidelines for the Diagnosis and Treatment of Acute Ischemic Stroke 2018);
* MRS before onset was 0-1 points
* Baseline NIHSS 5-25(both included);
* Informed consent from the patient or surrogate.

Exclusion Criteria:

* Intended to proceed endovascular treatment;
* NIHSS consciousness score \>2;
* Allergy to tenecteplase or alteplase;
* Past history of intracranial hemorrhage ;
* A history of severe head trauma or stroke within 3 months;
* A history of intracranial or spinal surgery within 3 months;
* A history of gastrointestinal or urinary bleeding within 3 weeks;
* 2 weeks of major surgery;
* Arterial puncture was performed at the hemostasis site that was not easily compressed within 1 week;
* Intracranial tumors (except neuroectodermal tumors, such as meningiomas), large intracranial aneurysms;
* Intracranial hemorrhage (including parenchymal hemorrhage, intraventricular hemorrhage, subarachnoid hemorrhage, subdural/extradural hematoma, etc.);
* Active visceral bleeding;
* Aortic arch dissection was found;
* After active antihypertensive treatment, hypertension is still not under control: systolic blood pressure ≥180 mm Hg, or diastolic blood pressure ≥100 mm Hg;
* Propensity for acute bleeding, including platelet counts of less than 100×109/ L or otherwise;
* Blood glucose \<2.8 mmol/L or \>22.22 mmol/L;
* Oral warfarin anticoagulant with INR\>1.7 or PT\>15 s;
* Heparin treatment was received within 24 h;
* Thrombin inhibitors or factor Xa inhibitors were used within 48 h;
* Head CT or MRI showed a large infarction (infarcted area \> 1/3 of the middle cerebral artery);
* Subjects who are unable or unwilling to cooperate due to hemiplegia (Todd's palsy) after epileptic seizure or other neurological/psychiatric disorders;
* Pregnant women, lactating women, or subjects who do not agree to use effective contraception during the trial;
* Participation in other clinical trials within 3 months prior to screening;
* Unsuitability or participation in this study as judged by the Investigator may result in subjects being exposed to greater risk.

Primary outcomes:
measure: Excellent functional outcome
timeFrame: 90 days
Secondary outcomes:
measure: Good functional outcome
timeFrame: 90 days
measure: National Institutes of Health Stroke Scale (NIHSS)
timeFrame: 24 hours，day7
measure: EQ-5D
timeFrame: 90 days
measure: Barthel (BI)
timeFrame: 90 days
measure: Modified Rankin Scale(mRS)
timeFrame: 90 days
Other outcomes:
measure: Symptomatic intracranial hemorrhage(sICH)
timeFrame: 36 hours
measure: Asymptomatic intracranial hemorrhage
timeFrame: 90 days
measure: PH2 intracranial hemorrhage
timeFrame: 90 days
measure: Any intracranial hemorrhage
timeFrame: 90 days
measure: Systematic bleeding
timeFrame: 90 days
measure: Deaths
timeFrame: 90 days
measure: AEs/SAEs
timeFrame: 90 days
Locations:
city: Hefei
country: China
facility: The first affiliated hospital of ustc
state: Anhui
city: Xuancheng
country: China
facility: The people's hospltal of xuancheng city
state: Anhui
city: Beijing
country: China
facility: Beijing luhe hospital capital medical university
state: Beijing
city: Beijing
country: China
facility: Beijing Tiantan Hospital, Capital Medical University
state: Beijing
city: Chongqing
country: China
facility: Chongqing Three Gorges Central Hospital
state: Chongqing
city: Lanzhou
country: China
facility: The first hospital of lanzhou university
state: Gansu
city: Guangdong
country: China
facility: Guangdong Provincial Hospital of Traditional Chinese Medicine
state: Guangdong
city: Shaoguan
country: China
facility: Yue bei people's hospital
state: Guangdong
city: Guiyang
country: China
facility: Guizhou provincial people's hospital
state: Guizhou
city: Chengde
country: China
facility: Affiliated hospital of chengde medical university
state: Hebei
city: Shijiazhuang
country: China
facility: The first hospital of hebei medical university
state: Hebei
city: Shijiazhuang
country: China
facility: the Third Hospital of Hebei Medical University
state: Hebei
city: Tangshan
country: China
facility: Tangshan Workers ' Hospital
state: Hebei
city: Zhangjiakou
country: China
facility: The first affiliated hospital of hebei north university
state: Hebei
city: Daqing
country: China
facility: Daqing Oilfield General Hospital
state: Heilongjiang
city: Haerbin
country: China
facility: The 2ad affiliated hospital of harbin medical university
state: Heilongjiang
city: Jiaozuo
country: China
facility: Second People's Hospital of Jiaozuo City
state: Henan
city: Nanyang
country: China
facility: Nanyang central hospital
state: Henan
city: Nanyang
country: China
facility: Nanyang Nanshi Hospital
state: Henan
city: Nanyang
country: China
facility: Nayang second general hospital
state: Henan
city: Pingdingshan
country: China
facility: Pingmei Shenma Medical Group General Hospital
state: Henan
city: Xinxiang
country: China
facility: Xinxiang first people's hospital
state: Henan
city: Xinyang
country: China
facility: Xinyang central hospital
state: Henan
city: Zhengzhou
country: China
facility: The first affiliated hospital of zhengzhou university
state: Henan
city: Wuhan
country: China
facility: The central hospital of wuhan
state: Hunan
city: Baotou
country: China
facility: Inner Mongolia Baotou Hospita
state: Inner Mongolia
city: Chifeng
country: China
facility: Affiliated Hospital of Chifeng University
state: Inner Mongolia
city: Chifeng
country: China
facility: Kashkten Mongolian Medicine Hospital
state: Inner Mongolia
city: Hohhot
country: China
facility: Inner Mongolia People'S Hospital
state: Inner Mongolia
city: Huaian
country: China
facility: Huai an second people's hospital
state: Jiangsu
city: Taizhou
country: China
facility: Jiangsu taizhou people's hopital
state: Jiangsu
city: Xuzhou
country: China
facility: General Hospital of Xuzhou Mining Group
state: Jiangsu
city: Xuzhou
country: China
facility: Xuzhou central hospital
state: Jiangsu
city: Nanchang
country: China
facility: Third Affiliated Hospital of Nanchang University
state: Jiangxi
city: Changchun
country: China
facility: First Hospital of Jilin University
state: Jilin
city: Siping
country: China
facility: Jilin neuropsychiaric hospital
state: Jilin
city: Tonghua
country: China
facility: Tonghua Central Hospital
state: Jilin
city: Tonghua
country: China
facility: Meihekou Central Hospital
state: Jilin
city: Jinzhou
country: China
facility: The Firet Affiliated Hospital of Jinzhou Medical University
state: Liaoning
city: Shenyang
country: China
facility: Central hospital affiliated to shenyang medical college
state: Liaoning
city: Shenyang
country: China
facility: General Hospital of Northern War Zone, PLA
state: Liaoning
city: Shenyang
country: China
facility: The first hospital of china medical university
state: Liaoning
city: Shenyang
country: China
facility: The First People'S Hospital of Shenyang
state: Liaoning
city: Linyi
country: China
facility: Linyi City People Hospital
state: Shandong
city: Tengzhou
country: China
facility: Tengzhou Central People's Hospital
state: Shandong
city: Yantai
country: China
facility: Yantai Yuhuangding Hosopital
state: Shandong
city: Shanghai
country: China
facility: Huashan Hospital Affiliated to Fudan University
state: Shanghai
city: Changzhi
country: China
facility: Heping hospital affiliated to changzhi medical college
state: Shanxi
city: Datong
country: China
facility: General Hospital of Chinese Medicine and Coal
state: Shanxi
city: Datong
country: China
facility: The fifth people's s hospital of datong
state: Shanxi
city: Linfen
country: China
facility: Linfen central hospital
state: Shanxi
city: Linfen
country: China
facility: Linfen people's hospital
state: Shanxi
city: Taiyuan
country: China
facility: First Hospital of Shanxi Medical University
state: Shanxi
city: Taiyuan
country: China
facility: Shanxi Cardiovascular Hospital
state: Shanxi
city: Xianyang
country: China
facility: Xianyang Hospital of Yan ' an University
state: Shanxi
city: Mianyang
country: China
facility: Mianyang central hospital
state: Sichuan
city: Taiyuan
country: China
facility: Shanxi provincial prople's hospital
state: Taiyuan
city: Hangzhou
country: China
facility: The Second Affiliated Hospital Zhejiang University School of Medicine
state: Zhejiang
city: Lishui
country: China
facility: Lishui Central Hospital
state: Zhejiang
city: Taizhou
country: China
facility: Taizhou Enze Medical Center ( Group )
state: Zhejiang
city: Wenzhou
country: China
facility: Wenzhou Central Hospital
state: Zhejiang
Study officials:
affiliation: IRB of Beijing Tiantan Hospital,Capital Medical University
name: Wei Sun
role: STUDY_DIRECTOR
References:
citation: Campbell BCV, Mitchell PJ, Churilov L, Yassi N, Kleinig TJ, Dowling RJ, Yan B, Bush SJ, Thijs V, Scroop R, Simpson M, Brooks M, Asadi H, Wu TY, Shah DG, Wijeratne T, Zhao H, Alemseged F, Ng F, Bailey P, Rice H, de Villiers L, Dewey HM, Choi PMC, Brown H, Redmond K, Leggett D, Fink JN, Collecutt W, Kraemer T, Krause M, Cordato D, Field D, Ma H, O'Brien B, Clissold B, Miteff F, Clissold A, Cloud GC, Bolitho LE, Bonavia L, Bhattacharya A, Wright A, Mamun A, O'Rourke F, Worthington J, Wong AA, Levi CR, Bladin CF, Sharma G, Desmond PM, Parsons MW, Donnan GA, Davis SM; EXTEND-IA TNK Part 2 investigators. Effect of Intravenous Tenecteplase Dose on Cerebral Reperfusion Before Thrombectomy in Patients With Large Vessel Occlusion Ischemic Stroke: The EXTEND-IA TNK Part 2 Randomized Clinical Trial. JAMA. 2020 Apr 7;323(13):1257-1265. doi: 10.1001/jama.2020.1511.
citation: Burgos AM, Saver JL. Evidence that Tenecteplase Is Noninferior to Alteplase for Acute Ischemic Stroke: Meta-Analysis of 5 Randomized Trials. Stroke. 2019 Aug;50(8):2156-2162. doi: 10.1161/STROKEAHA.119.025080. Epub 2019 Jul 18.
citation: Hacke W, Kaste M, Bluhmki E, Brozman M, Davalos A, Guidetti D, Larrue V, Lees KR, Medeghri Z, Machnig T, Schneider D, von Kummer R, Wahlgren N, Toni D; ECASS Investigators. Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke. N Engl J Med. 2008 Sep 25;359(13):1317-29. doi: 10.1056/NEJMoa0804656.
citation: Campbell BCV, Ma H, Ringleb PA, Parsons MW, Churilov L, Bendszus M, Levi CR, Hsu C, Kleinig TJ, Fatar M, Leys D, Molina C, Wijeratne T, Curtze S, Dewey HM, Barber PA, Butcher KS, De Silva DA, Bladin CF, Yassi N, Pfaff JAR, Sharma G, Bivard A, Desmond PM, Schwab S, Schellinger PD, Yan B, Mitchell PJ, Serena J, Toni D, Thijs V, Hacke W, Davis SM, Donnan GA; EXTEND, ECASS-4, and EPITHET Investigators. Extending thrombolysis to 4.5-9 h and wake-up stroke using perfusion imaging: a systematic review and meta-analysis of individual patient data. Lancet. 2019 Jul 13;394(10193):139-147. doi: 10.1016/S0140-6736(19)31053-0. Epub 2019 May 22.
citation: 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.
citation: Kunz WG, Hunink MG, Almekhlafi MA, Menon BK, Saver JL, Dippel DWJ, Majoie CBLM, Jovin TG, Davalos A, Bracard S, Guillemin F, Campbell BCV, Mitchell PJ, White P, Muir KW, Brown S, Demchuk AM, Hill MD, Goyal M; HERMES Collaborators. Public health and cost consequences of time delays to thrombectomy for acute ischemic stroke. Neurology. 2020 Nov 3;95(18):e2465-e2475. doi: 10.1212/WNL.0000000000010867. Epub 2020 Sep 17.
citation: 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.
citation: 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.
citation: Kheiri B, Osman M, Abdalla A, Haykal T, Ahmed S, Hassan M, Bachuwa G, Al Qasmi M, Bhatt DL. Tenecteplase versus alteplase for management of acute ischemic stroke: a pairwise and network meta-analysis of randomized clinical trials. J Thromb Thrombolysis. 2018 Nov;46(4):440-450. doi: 10.1007/s11239-018-1721-3.
citation: Warner JJ, Harrington RA, Sacco RL, Elkind MSV. 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. Stroke. 2019 Dec;50(12):3331-3332. doi: 10.1161/STROKEAHA.119.027708. Epub 2019 Oct 30. No abstract available.
citation: Powers WJ, Rabinstein AA, Ackerson T, Adeoye OM, Bambakidis NC, Becker K, Biller J, Brown M, Demaerschalk BM, Hoh B, Jauch EC, Kidwell CS, Leslie-Mazwi TM, Ovbiagele B, Scott PA, Sheth KN, Southerland AM, Summers DV, Tirschwell DL; American Heart Association Stroke Council. 2018 Guidelines for the Early Management of Patients With Acute Ischemic Stroke: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke. 2018 Mar;49(3):e46-e110. doi: 10.1161/STR.0000000000000158. Epub 2018 Jan 24.
citation: Liu L, Chen W, Zhou H, Duan W, Li S, Huo X, Xu W, Huang L, Zheng H, Liu J, Liu H, Wei Y, Xu J, Wang Y; Chinese Stroke Association Stroke Council Guideline Writing Committee. Chinese Stroke Association guidelines for clinical management of cerebrovascular disorders: executive summary and 2019 update of clinical management of ischaemic cerebrovascular diseases. Stroke Vasc Neurol. 2020 Jun;5(2):159-176. doi: 10.1136/svn-2020-000378. Epub 2020 Jun 18.
citation: Ma H, Campbell BCV, Parsons MW, Churilov L, Levi CR, Hsu C, Kleinig TJ, Wijeratne T, Curtze S, Dewey HM, Miteff F, Tsai CH, Lee JT, Phan TG, Mahant N, Sun MC, Krause M, Sturm J, Grimley R, Chen CH, Hu CJ, Wong AA, Field D, Sun Y, Barber PA, Sabet A, Jannes J, Jeng JS, Clissold B, Markus R, Lin CH, Lien LM, Bladin CF, Christensen S, Yassi N, Sharma G, Bivard A, Desmond PM, Yan B, Mitchell PJ, Thijs V, Carey L, Meretoja A, Davis SM, Donnan GA; EXTEND Investigators. Thrombolysis Guided by Perfusion Imaging up to 9 Hours after Onset of Stroke. N Engl J Med. 2019 May 9;380(19):1795-1803. doi: 10.1056/NEJMoa1813046.
citation: Thomalla G, Simonsen CZ, Boutitie F, Andersen G, Berthezene Y, Cheng B, Cheripelli B, Cho TH, Fazekas F, Fiehler J, Ford I, Galinovic I, Gellissen S, Golsari A, Gregori J, Gunther M, Guibernau J, Hausler KG, Hennerici M, Kemmling A, Marstrand J, Modrau B, Neeb L, Perez de la Ossa N, Puig J, Ringleb P, Roy P, Scheel E, Schonewille W, Serena J, Sunaert S, Villringer K, Wouters A, Thijs V, Ebinger M, Endres M, Fiebach JB, Lemmens R, Muir KW, Nighoghossian N, Pedraza S, Gerloff C; WAKE-UP Investigators. MRI-Guided Thrombolysis for Stroke with Unknown Time of Onset. N Engl J Med. 2018 Aug 16;379(7):611-622. doi: 10.1056/NEJMoa1804355. Epub 2018 May 16.
citation: Seners P, Turc G, Maier B, Mas JL, Oppenheim C, Baron JC. Incidence and Predictors of Early Recanalization After Intravenous Thrombolysis: A Systematic Review and Meta-Analysis. Stroke. 2016 Sep;47(9):2409-12. doi: 10.1161/STROKEAHA.116.014181. Epub 2016 Jul 26.
citation: Goyal M, Demchuk AM, Menon BK, Eesa M, Rempel JL, Thornton J, Roy D, Jovin TG, Willinsky RA, Sapkota BL, Dowlatshahi D, Frei DF, Kamal NR, Montanera WJ, Poppe AY, Ryckborst KJ, Silver FL, Shuaib A, Tampieri D, Williams D, Bang OY, Baxter BW, Burns PA, Choe H, Heo JH, Holmstedt CA, Jankowitz B, Kelly M, Linares G, Mandzia JL, Shankar J, Sohn SI, Swartz RH, Barber PA, Coutts SB, Smith EE, Morrish WF, Weill A, Subramaniam S, Mitha AP, Wong JH, Lowerison MW, Sajobi TT, Hill MD; ESCAPE Trial Investigators. Randomized assessment of rapid endovascular treatment of ischemic stroke. N Engl J Med. 2015 Mar 12;372(11):1019-30. doi: 10.1056/NEJMoa1414905. Epub 2015 Feb 11.
citation: Jovin TG, Chamorro A, Cobo E, de Miquel MA, Molina CA, Rovira A, San Roman L, Serena J, Abilleira S, Ribo M, Millan M, Urra X, Cardona P, Lopez-Cancio E, Tomasello A, Castano C, Blasco J, Aja L, Dorado L, Quesada H, Rubiera M, Hernandez-Perez M, Goyal M, Demchuk AM, von Kummer R, Gallofre M, Davalos A; REVASCAT Trial Investigators. Thrombectomy within 8 hours after symptom onset in ischemic stroke. N Engl J Med. 2015 Jun 11;372(24):2296-306. doi: 10.1056/NEJMoa1503780. Epub 2015 Apr 17.
citation: Saver JL, Goyal M, Bonafe A, Diener HC, Levy EI, Pereira VM, Albers GW, Cognard C, Cohen DJ, Hacke W, Jansen O, Jovin TG, Mattle HP, Nogueira RG, Siddiqui AH, Yavagal DR, Baxter BW, Devlin TG, Lopes DK, Reddy VK, du Mesnil de Rochemont R, Singer OC, Jahan R; SWIFT PRIME Investigators. Stent-retriever thrombectomy after intravenous t-PA vs. t-PA alone in stroke. N Engl J Med. 2015 Jun 11;372(24):2285-95. doi: 10.1056/NEJMoa1415061. Epub 2015 Apr 17.
citation: Berkhemer OA, Fransen PS, Beumer D, van den Berg LA, Lingsma HF, Yoo AJ, Schonewille WJ, Vos JA, Nederkoorn PJ, Wermer MJ, van Walderveen MA, Staals J, Hofmeijer J, van Oostayen JA, Lycklama a Nijeholt GJ, Boiten J, Brouwer PA, Emmer BJ, de Bruijn SF, van Dijk LC, Kappelle LJ, Lo RH, van Dijk EJ, de Vries J, de Kort PL, van Rooij WJ, van den Berg JS, van Hasselt BA, Aerden LA, Dallinga RJ, Visser MC, Bot JC, Vroomen PC, Eshghi O, Schreuder TH, Heijboer RJ, Keizer K, Tielbeek AV, den Hertog HM, Gerrits DG, van den Berg-Vos RM, Karas GB, Steyerberg EW, Flach HZ, Marquering HA, Sprengers ME, Jenniskens SF, Beenen LF, van den Berg R, Koudstaal PJ, van Zwam WH, Roos YB, van der Lugt A, van Oostenbrugge RJ, Majoie CB, Dippel DW; MR CLEAN Investigators. A randomized trial of intraarterial treatment for acute ischemic stroke. N Engl J Med. 2015 Jan 1;372(1):11-20. doi: 10.1056/NEJMoa1411587. Epub 2014 Dec 17.
citation: Campbell BC, Mitchell PJ, Kleinig TJ, Dewey HM, Churilov L, Yassi N, Yan B, Dowling RJ, Parsons MW, Oxley TJ, Wu TY, Brooks M, Simpson MA, Miteff F, Levi CR, Krause M, Harrington TJ, Faulder KC, Steinfort BS, Priglinger M, Ang T, Scroop R, Barber PA, McGuinness B, Wijeratne T, Phan TG, Chong W, Chandra RV, Bladin CF, Badve M, Rice H, de Villiers L, Ma H, Desmond PM, Donnan GA, Davis SM; EXTEND-IA Investigators. Endovascular therapy for ischemic stroke with perfusion-imaging selection. N Engl J Med. 2015 Mar 12;372(11):1009-18. doi: 10.1056/NEJMoa1414792. Epub 2015 Feb 11.
citation: Goyal M, Menon BK, van Zwam WH, Dippel DW, Mitchell PJ, Demchuk AM, Davalos A, Majoie CB, van der Lugt A, de Miquel MA, Donnan GA, Roos YB, Bonafe A, Jahan R, Diener HC, van den Berg LA, Levy EI, Berkhemer OA, Pereira VM, Rempel J, Millan M, Davis SM, Roy D, Thornton J, Roman LS, Ribo M, Beumer D, Stouch B, Brown S, Campbell BC, van Oostenbrugge RJ, Saver JL, Hill MD, Jovin TG; HERMES collaborators. Endovascular thrombectomy after large-vessel ischaemic stroke: a meta-analysis of individual patient data from five randomised trials. Lancet. 2016 Apr 23;387(10029):1723-31. doi: 10.1016/S0140-6736(16)00163-X. Epub 2016 Feb 18.
citation: Fassbender K, Walter S, Grunwald IQ, Merzou F, Mathur S, Lesmeister M, Liu Y, Bertsch T, Grotta JC. Prehospital stroke management in the thrombectomy era. Lancet Neurol. 2020 Jul;19(7):601-610. doi: 10.1016/S1474-4422(20)30102-2.
citation: Bivard A, Lin L, Parsonsb MW. Review of stroke thrombolytics. J Stroke. 2013 May;15(2):90-8. doi: 10.5853/jos.2013.15.2.90. Epub 2013 May 31.
citation: 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.
citation: Coutts SB, Dubuc V, Mandzia J, Kenney C, Demchuk AM, Smith EE, Subramaniam S, Goyal M, Patil S, Menon BK, Barber PA, Dowlatshahi D, Field T, Asdaghi N, Camden MC, Hill MD; TEMPO-1 Investigators. Tenecteplase-tissue-type plasminogen activator evaluation for minor ischemic stroke with proven occlusion. Stroke. 2015 Mar;46(3):769-74. doi: 10.1161/STROKEAHA.114.008504. Epub 2015 Feb 12.
citation: 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.
citation: Li S, Campbell BCV, Schwamm LH, Fisher M, Parsons M, Li H, Pan Y, Wang Y; TRACE II investigators. Tenecteplase Reperfusion therapy in Acute ischaemic Cerebrovascular Events-II (TRACE II): rationale and design. Stroke Vasc Neurol. 2022 Feb;7(1):71-76. doi: 10.1136/svn-2021-001074. Epub 2021 Aug 26.