Efficacy and Safety of Human Urinary Kallidinogenase for Acute Ischemic Stroke Patients Receiving Reperfusion Treatment

Summary

This study aims to explore the efficacy and safety of Human Urinary Kallidinogenase for acute ischemic stroke patients receiving intravenous thrombolysis and/or endovascular treatment.

Timeline

Start

2025-03

Primary completion

2026-12

Completion

2027-12

Publications

• Background Wang Y, Xu J, Zhao X, Wang D, Wang C, Liu L, Wang A, Meng X, Li H, Wang Y. Association of hypertension with stroke recurrence depends on ischemic stroke subtype. Stroke. 2013 May;44(5):1232-7. doi: 10.1161/STROKEAHA.111.000302. Epub 2013 Feb 26.
• Background Pan Y, Li Z, Li J, Jin A, Lin J, Jing J, Li H, Meng X, Wang Y, Wang Y. Residual Risk and Its Risk Factors for Ischemic Stroke with Adherence to Guideline-Based Secondary Stroke Prevention. J Stroke. 2021 Jan;23(1):51-60. doi: 10.5853/jos.2020.03391. Epub 2021 Jan 31.
• 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 Asadi H, Dowling R, Yan B, Wong S, Mitchell P. Advances in endovascular treatment of acute ischaemic stroke. Intern Med J. 2015 Aug;45(8):798-805. doi: 10.1111/imj.12652.
• Background 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.
• Background 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.
• Background 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.
• Background 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.
• Background Zi W, Qiu Z, Li F, Sang H, Wu D, Luo W, Liu S, Yuan J, Song J, Shi Z, Huang W, Zhang M, Liu W, Guo Z, Qiu T, Shi Q, Zhou P, Wang L, Fu X, Liu S, Yang S, Zhang S, Zhou Z, Huang X, Wang Y, Luo J, Bai Y, Zhang M, Wu Y, Zeng G, Wan Y, Wen C, Wen H, Ling W, Chen Z, Peng M, Ai Z, Guo F, Li H, Guo J, Guan H, Wang Z, Liu Y, Pu J, Wang Z, Liu H, Chen L, Huang J, Yang G, Gong Z, Shuai J, Nogueira RG, Yang Q; DEVT Trial Investigators. Effect of Endovascular Treatment Alone vs Intravenous Alteplase Plus Endovascular Treatment on Functional Independence in Patients With Acute Ischemic Stroke: The DEVT Randomized Clinical Trial. JAMA. 2021 Jan 19;325(3):234-243. doi: 10.1001/jama.2020.23523.
• Background Yang P, Zhang Y, Zhang L, Zhang Y, Treurniet KM, Chen W, Peng Y, Han H, Wang J, Wang S, Yin C, Liu S, Wang P, Fang Q, Shi H, Yang J, Wen C, Li C, Jiang C, Sun J, Yue X, Lou M, Zhang M, Shu H, Sun D, Liang H, Li T, Guo F, Ke K, Yuan H, Wang G, Yang W, Shi H, Li T, Li Z, Xing P, Zhang P, Zhou Y, Wang H, Xu Y, Huang Q, Wu T, Zhao R, Li Q, Fang Y, Wang L, Lu J, Li Y, Fu J, Zhong X, Wang Y, Wang L, Goyal M, Dippel DWJ, Hong B, Deng B, Roos YBWEM, Majoie CBLM, Liu J; DIRECT-MT Investigators. Endovascular Thrombectomy with or without Intravenous Alteplase in Acute Stroke. N Engl J Med. 2020 May 21;382(21):1981-1993. doi: 10.1056/NEJMoa2001123. Epub 2020 May 6.
• Background Wang H, Zi W, Hao Y, Yang D, Shi Z, Lin M, Wang S, Liu W, Wang Z, Liu X, Guo F, Liu Y, Xu G, Xiong Y, Liu X; ACTUAL Investigators. Direct endovascular treatment: an alternative for bridging therapy in anterior circulation large-vessel occlusion stroke. Eur J Neurol. 2017 Jul;24(7):935-943. doi: 10.1111/ene.13311. Epub 2017 May 11.
• Background Ye Q, Zhai F, Chao B, Cao L, Xu Y, Zhang P, Han H, Wang L, Xu B, Chen W, Wen C, Wang S, Wang R, Zhang L, Jiao L, Liu S, Zhu YC, Wang LD. Rates of intravenous thrombolysis and endovascular therapy for acute ischaemic stroke in China between 2019 and 2020. Lancet Reg Health West Pac. 2022 Feb 22;21:100406. doi: 10.1016/j.lanwpc.2022.100406. eCollection 2022 Apr.
• Background Shen H, Killingsworth MC, Bhaskar SMM. Comprehensive Meta-Analysis of Futile Recanalization in Acute Ischemic Stroke Patients Undergoing Endovascular Thrombectomy: Prevalence, Factors, and Clinical Outcomes. Life (Basel). 2023 Sep 26;13(10):1965. doi: 10.3390/life13101965.
• Background Wang A, Jia B, Zhang X, Huo X, Chen J, Gui L, Cai Y, Guo Z, Han Y, Peng Z, Jing P, Chen Y, Liu Y, Yang Y, Wang F, Sun Z, Li T, Sun H, Yuan H, Shao H, Gao L, Zhang P, Wang F, Cao X, Shi W, Li C, Yang J, Zhang H, Wang F, Deng J, Liu Y, Deng W, Song C, Chen H, He L, Zhao H, Li X, Yang H, Zhou Z, Wang Y, Miao Z; BAST Investigators. Efficacy and Safety of Butylphthalide in Patients With Acute Ischemic Stroke: A Randomized Clinical Trial. JAMA Neurol. 2023 Aug 1;80(8):851-859. doi: 10.1001/jamaneurol.2023.1871.
• Background Ling L, Hou Q, Xing S, Yu J, Pei Z, Zeng J. Exogenous kallikrein enhances neurogenesis and angiogenesis in the subventricular zone and the peri-infarction region and improves neurological function after focal cortical infarction in hypertensive rats. Brain Res. 2008 Apr 24;1206:89-97. doi: 10.1016/j.brainres.2008.01.099. Epub 2008 Mar 19.
• Background Xia CF, Yin H, Yao YY, Borlongan CV, Chao L, Chao J. Kallikrein protects against ischemic stroke by inhibiting apoptosis and inflammation and promoting angiogenesis and neurogenesis. Hum Gene Ther. 2006 Feb;17(2):206-19. doi: 10.1089/hum.2006.17.206.
• Background Miao J, Deng F, Zhang Y, Xie HY, Feng JC. Exogenous human urinary kallidinogenase increases cerebral blood flow in patients with acute ischemic stroke. Neurosciences (Riyadh). 2016 Apr;21(2):126-30. doi: 10.17712/nsj.2016.2.20150581.
• Background Li J, Chen Y, Zhang X, Zhang B, Zhang M, Xu Y. Human Urinary Kallidinogenase Improves Outcome of Stroke Patients by Shortening Mean Transit Time of Perfusion Magnetic Resonance Imaging. J Stroke Cerebrovasc Dis. 2015 Aug;24(8):1730-7. doi: 10.1016/j.jstrokecerebrovasdis.2015.03.032. Epub 2015 Jun 29.
• Background Zhang C, Tao W, Liu M, Wang D. Efficacy and safety of human urinary kallidinogenase injection for acute ischemic stroke: a systematic review. J Evid Based Med. 2012 Feb;5(1):31-9. doi: 10.1111/j.1756-5391.2012.01167.x.
• Background Huang Y, Wang B, Zhang Y, Wang P, Zhang X. Efficacy and safety of human urinary kallidinogenase for acute ischemic stroke: a meta-analysis. J Int Med Res. 2020 Sep;48(9):300060520943452. doi: 10.1177/0300060520943452.
• Background Wang YD, Lu RY, Huang XX, Yuan F, Hu T, Peng Y, Huang SQ. Human tissue kallikrein promoted activation of the ipsilesional sensorimotor cortex after acute cerebral infarction. Eur Neurol. 2011;65(4):208-14. doi: 10.1159/000325735. Epub 2011 Mar 22.
• Background Yan X, Chen H, Shang X. Human urinary kallidinogenase decreases the incidence of post-stroke cognitive impairment in acute ischemic stroke patients. J Integr Neurosci. 2022 Apr 8;21(3):80. doi: 10.31083/j.jin2103080.
• Background Han D, Chen X, Li D, Liu S, Lyu Y, Feng J. Human Urinary Kallidinogenase decreases recurrence risk and promotes good recovery. Brain Behav. 2018 Aug;8(8):e01033. doi: 10.1002/brb3.1033. Epub 2018 Jul 20.
• Background Wu J, Wu J, Wang L, Liu J. Urinary Kallidinogenase plus rt-PA Intravenous Thrombolysis for Acute Ischemic Stroke: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Comput Math Methods Med. 2022 May 17;2022:1500669. doi: 10.1155/2022/1500669. eCollection 2022.

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