Efficacy and Safety of a Half-dose Bolus of r-SAK Prior to Primary PCI in ST-elevation Myocardial Infarction

Summary

As an effective treatment for acute ST-segment elevation myocardial infarction (STEMI), early reperfusion may reduce the infarct size and improve the prognosis of patients. However, it remains uncertain whether adjunctive thrombolytic therapy administered immediately prior to primary percutaneous coronary intervention (PCI) improves outcomes in patients undergoing the procedure within 120 minutes. In this investigator-initiated, prospective, multi-center, randomized, double-blind, placebo-controlled trial, subjects meeting the inclusion/exclusion criteria should be randomly assigned 1:1 to the trial group (r-SAK) or the control group (placebo). The risk of major adverse cardiovascular events within 90 days will be observed.

Timeline

Start

2023-04-08

Primary completion

2026-12-31

Completion

2027-12-31

Publications

• Background Gulati R, Behfar A, Narula J, Kanwar A, Lerman A, Cooper L, Singh M. Acute Myocardial Infarction in Young Individuals. Mayo Clin Proc. 2020 Jan;95(1):136-156. doi: 10.1016/j.mayocp.2019.05.001.
• Background Bahit MC, Kochar A, Granger CB. Post-Myocardial Infarction Heart Failure. JACC Heart Fail. 2018 Mar;6(3):179-186. doi: 10.1016/j.jchf.2017.09.015.
• Background Heusch G, Libby P, Gersh B, Yellon D, Bohm M, Lopaschuk G, Opie L. Cardiovascular remodelling in coronary artery disease and heart failure. Lancet. 2014 May 31;383(9932):1933-43. doi: 10.1016/S0140-6736(14)60107-0. Epub 2014 May 13.
• Background Juilliere Y, Cambou JP, Bataille V, Mulak G, Galinier M, Gibelin P, Benamer H, Bouvaist H, Meneveau N, Tabone X, Simon T, Danchin N; FAST-MI Investigators. Heart failure in acute myocardial infarction: a comparison between patients with or without heart failure criteria from the FAST-MI registry. Rev Esp Cardiol (Engl Ed). 2012 Apr;65(4):326-33. doi: 10.1016/j.recesp.2011.10.027. Epub 2012 Feb 20.
• Background Bradley EH, Nallamothu BK, Herrin J, Ting HH, Stern AF, Nembhard IM, Yuan CT, Green JC, Kline-Rogers E, Wang Y, Curtis JP, Webster TR, Masoudi FA, Fonarow GC, Brush JE Jr, Krumholz HM. National efforts to improve door-to-balloon time results from the Door-to-Balloon Alliance. J Am Coll Cardiol. 2009 Dec 15;54(25):2423-9. doi: 10.1016/j.jacc.2009.11.003.
• Background Mangin L, Lotfi M, Puie P, Yayehd K, Ispas A, Belle L. [Management of high thrombus burden in primary PCI]. Ann Cardiol Angeiol (Paris). 2017 Dec;66(6):380-384. doi: 10.1016/j.ancard.2017.10.016. Epub 2017 Oct 31. French.
• Background Bai M, Pan CL, Zhao J, Zhao CR, Zhang B, Mu ZY, Meng XX, Zhou XH, Zhu YQ, Zhang Z. [Safety and efficacy of regional transport combined with PCI model in patients with STEMI after thrombolysis in northwest China]. Zhonghua Xin Xue Guan Bing Za Zhi. 2020 Aug 24;48(8):641-647. doi: 10.3760/cma.j.cn112148-20200228-00138. Chinese.
• Background Schwartz R, Weiss AT, Leibowitz D, Rot D, Pollak A, Lotan C, Alcalai R. Thrombolysis followed by coronary angiography versus primary percutaneous coronary intervention in non-anterior ST-elevation myocardial infarction. J Invasive Cardiol. 2013 Dec;25(12):632-6.
• Background Ren K, Gong H, Huang J, Liu Y, Dong Q, He K, Tian L, Zhang F, Yu A, Wu C. Thrombolytic and anticoagulant effects of a recombinant staphylokinase-hirudin fusion protein. Thromb Res. 2021 Dec;208:26-34. doi: 10.1016/j.thromres.2021.10.005. Epub 2021 Oct 14.
• Background Vanderschueren S. [Staphylokinase for a better thrombolytic treatment of heart and platelet diseases]. Verh K Acad Geneeskd Belg. 2000;62(1):69-75. Dutch.
• Background Ueshima S, Matsuo O. Development of new fibrinolytic agents. Curr Pharm Des. 2006;12(7):849-57. doi: 10.2174/138161206776056065.
• Background Yamamoto J, Kawano M, Hashimoto M, Sasaki Y, Yamashita T, Taka T, Watanabe S, Giddings JC. Adjuvant effect of antibodies against von Willebrand Factor, fibrinogen, and fibronectin on staphylokinase-induced thrombolysis as measured using mural thrombi formed in rat mesenteric venules. Thromb Res. 2000 Mar 1;97(5):327-33. doi: 10.1016/s0049-3848(99)00184-x.
• Background Szemraj J, Stankiewicz A, Rozmyslowicz-Szerminska W, Mogielnicki A, Gromotowicz A, Buczko W, Oszajca K, Bartkowiak J, Chabielska E. A new recombinant thrombolytic and antithrombotic agent with higher fibrin affinity - a staphylokinase variant. An in-vivo study. Thromb Haemost. 2007 Jun;97(6):1037-45. doi: 10.1160/th06-10-0562.
• Background Vakili B, Nezafat N, Negahdaripour M, Yari M, Zare B, Ghasemi Y. Staphylokinase Enzyme: An Overview of Structure, Function and Engineered Forms. Curr Pharm Biotechnol. 2017;18(13):1026-1037. doi: 10.2174/1389201019666180209121323.
• Background Li CJ, Huang J, Yang ZJ, Cao KJ. Thrombolytic efficacy of native recombinant staphylokinase on femoral artery thrombus of rabbits. Acta Pharmacol Sin. 2007 Jan;28(1):58-65. doi: 10.1111/j.1745-7254.2007.00455.x.
• Background Nedaeinia R, Faraji H, Javanmard SH, Ferns GA, Ghayour-Mobarhan M, Goli M, Mashkani B, Nedaeinia M, Haghighi MHH, Ranjbar M. Bacterial staphylokinase as a promising third-generation drug in the treatment for vascular occlusion. Mol Biol Rep. 2020 Jan;47(1):819-841. doi: 10.1007/s11033-019-05167-x. Epub 2019 Nov 1.
• Background Vanderschueren S, Barrios L, Kerdsinchai P, Van den Heuvel P, Hermans L, Vrolix M, De Man F, Benit E, Muyldermans L, Collen D, et al. A randomized trial of recombinant staphylokinase versus alteplase for coronary artery patency in acute myocardial infarction. The STAR Trial Group. Circulation. 1995 Oct 15;92(8):2044-9. doi: 10.1161/01.cir.92.8.2044.
• Background Armstrong PW, Burton J, Pakola S, Molhoek PG, Betriu A, Tendera M, Bode C, Adgey AA, Bar F, Vahanian A, Van de Werf F; CAPTORS II Investigators. Collaborative Angiographic Patency Trial Of Recombinant Staphylokinase (CAPTORS II). Am Heart J. 2003 Sep;146(3):484-8. doi: 10.1016/S0002-8703(03)00312-0.

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Indications