Efficacy and Safety of a Half-dose Bolus of r-SAK Prior to Primary PCI in ST-elevation Myocardial Infarction (OPTIMA-6)

Efficacy and Safety of a Half-dose Bolus of r-SAK Prior to Primary PCI in ST-elevation Myocardial Infarction: a Multicenter Randomized Double-blind Placebo-controlled Trial (OPTIMA-6)

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.

Study Overview

• Status: Recruiting
• Conditions: ST Elevation Myocardial Infarction
• Intervention / Treatment: Drug: Recombinant staphylokinase; Drug: Placebo

Detailed Description

Acute myocardial infarction (AMI) is a serious and critical disease that causes acute coronary artery stenosis, spasm or occlusion due to the rupture or erosion of coronary artery plaque, resulting in myocardial ischemia and necrosis. Myocardial ischemia and necrosis can cause myocardial cell loss, ventricular remodeling and local inflammatory reaction, leading to decreased cardiac output or increased intracardiac pressure, and eventually progress to heart failure (HF), which seriously affects the prognosis of patients. The FAST-MI study found that 37.5% of AMI patients were complicated with HF, and the 1-year mortality of these patients was significantly increased. Early reperfusion treatment as an effective means of AMI treatment can promote myocardial reperfusion, save dying myocardium and reduce infarct area, which is of great significance to improve the clinical prognosis of patients.

At this stage, many primary hospitals do not have the conditions for emergency percutaneous coronary intervention (PCI). Transferring patients to PCI hospitals takes a lot of time, delaying the best time for early reperfusion treatment. In addition, the thrombus burden in the coronary artery increases with the prolongation of ischemia time. Stent implantation in the coronary artery with excessive thrombus burden is prone to slow blood flow or no reflow, resulting in the occurrence of major adverse cardiovascular events (MACE). In view of the above problems, guidelines suggest that if the estimated transit time is more than 120 minutes, thrombolytic therapy should be performed before transport; If the estimated transfer time is less than 120 minutes, it can be directly transferred to the PCI hospital.

However, it remains uncertain whether adjunctive thrombolytic therapy administered immediately prior to primary PCI improves outcomes in patients undergoing the procedure within 120 minutes ("facilitated PCI"). Multiple previous studies comparing facilitated PCI with primary PCI found facilitated PCI to be inferior in terms of clinical outcomes, while other studies based on reduced-dose thrombolysis confirmed the superiority of facilitated PCI in better patency of infarct-related artery (IRA). Recombinant staphylokinase (r-SAK), as the third-generation thrombolytic agent, may serve as the potential thrombolytic drug to contemporary facilitated PCI by virtue of its high fibrinolytic activity and fibrin selectivity.

Staphylokinase (SAK) is produced by Staphylococcus aureus and it is a protein containing 136 amino acid residues. Its ability for dissolving blood clots was first discovered in 1948. Studies have shown that SAK is not directly convert plasminogen (PLG) into plasminogen (PLi), but first combines with PLG in a 1:1 ratio to form a complex. The complex can lead to the exposure of PLG active site, from single chain to double chain PLi, resulting to form an active SAK-PLI complex, which subsequently activates PLG molecules. Then PLG transforms into PLi and further dissolve the thrombus.

R-SAK was developed in 1990 by Shanghai Institute of Plant and Biological Physiology. It is a gene recombinant drug prepared by molecular cloning of SAK gene in Escherichia coli. Its biological characteristics are very similar to natural SAK, and r-SAK is a highly fibrin-specific fibrinolysis agent. R-SAK is considered to be one of the most promising thrombolytic drugs due to its high thrombolysis activity (especially in platelet-rich arterial thrombosis), inactivation of system fibrinolysis, and few side effects. Clinical studies have shown that the efficacy of r-SAK in the treatment of AMI is better than urokinase, comparable to RT-PA, and it does not increase serious bleeding complications such as intracranial hemorrhage.

In terms of pharmacokinetics, r-SAK has a fast distribution and a long action time in human body. Half-lives of distribution term is 13.30±2.06min and elimination term is 67.94±21.39min when intravenous injection 10 mg r-SAK in 30min. A single bolus of r-SAK as early as possible during the first medical contact (such as prehospital care or primary hospitals or medical centers with conditional PCI) can maximize the time window for reperfusion therapy.

Achieving early reperfusion by means of facilitated PCI is consistent with the core of STEMI treatment, but the efficacy and safety of facilitated PCI are still controversial. OPTIMA-6, designed as shorter symptom onset to treatment time, a half-dose thrombolytic agent, and upstream use of the potent antiplatelet agent, will therefore evaluate the efficacy and safety of a half-dose bolus of r-SAK vs. placebo prior to primary PCI to inform clinical practice of contemporary facilitated PCI in patients with STEMI.

• Study Type: Interventional
• Enrollment (Estimated): 2260
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Chunjian Li, PHD; Phone Number: +86 13701465229; Email: lijay@njmu.edu.cn
• Study Contact Backup: Name: Chen Li, MD; Phone Number: +86 13913886986; Email: lcicewind@outlook.com

Study Locations

• China
  • Changzhou, China
    • Recruiting
    • The First People's Hospital of Changzhou
    • Contact: Ling Yang, MD
  • Changzhou, China
    • Recruiting
    • Changzhou Second People's Hospital
    • Contact: Xin Chen, MD
  • Changzhou, China
    • Recruiting
    • Changzhou Wujin People's Hospital
    • Contact: Jianqiang Xiao, MD
  • Chongqing, China
    • Recruiting
    • Chongqing Hospital of Jiangsu Province Hospital
    • Contact: Junhong Wang, MD
    • Contact: Hongyan Xing
  • Dalian, China
    • Recruiting
    • The Second Affiliated Hospital of Dalian Medical University
    • Contact: Xin Zhao, MD
  • Daqing, China
    • Recruiting
    • Daqing Oilfield General Hospital
    • Contact: Zhiqi Sun, MD
  • Dongguan, China
    • Recruiting
    • Dongguan People's Hospital
    • Contact: Suxia Guo, MD
  • Fengcheng, China
    • Recruiting
    • Fengcheng People's Hospital
    • Contact: Wenbo Li, MD
  • Guangzhou, China
    • Recruiting
    • General Hospital of Southern Theatre Command
    • Contact: Jinxia Zhang, MD
  • Hainan, China
    • Recruiting
    • The Second Affiliated Hospital of Hainan Medical University
    • Contact: Yuewu Chen, MD
  • Hangzhou, China
    • Recruiting
    • The Affiliated Hospital of Hangzhou Normal University
    • Contact: Peng Dong, MD; Phone Number: +86 13501352371
  • Hangzhou, China
    • Recruiting
    • The Second Affiliated Hospital of Zhejiang University Medical College
    • Contact: Jun Jiang, MD
  • Hefei, China
    • Recruiting
    • The First Affiliated Hospital of Anhui Medical University
    • Contact: Xianhe Lin, MD
  • Huai'an, China
    • Recruiting
    • Huai'an First People's Hospital
    • Contact: Xiwen Zhang, MD
  • Huai'an, China
    • Recruiting
    • Huai'an Second People's Hospital
    • Contact: Naiquan Yang, MD
  • Lianyungang, China
    • Recruiting
    • The First People's Hospital of Lianyungang
    • Contact: Bo Zhao, MD
  • Lianyungang, China
    • Recruiting
    • The Second People's Hospital of Lianyungang
    • Contact: Yilian Wang, MD
  • Lianyungang, China
    • Recruiting
    • Donghai Country People's Hospital
    • Contact: Jianling Zhou, MD
  • Liyang, China
    • Recruiting
    • Liyang Hospital of Jiangsu Province Hospital
    • Contact: Junhong Wang, MD
  • Nanchang, China
    • Recruiting
    • The First Affiliated Hospital of Nanchang University
    • Contact: Xiaoping Peng, MD
  • Nanjing, China
    • Recruiting
    • The Fourth Affiliated Hospital of Nanjing Medical University
    • Contact: Pingxi Xiao, MD
  • Nanjing, China
    • Recruiting
    • Sir Run Run Hospital Nanjing Medical University
    • Contact: Chunjian Li, MD
  • Nanjing, China
    • Recruiting
    • Nanjing Tongren Hospital
    • Contact: Jiakuan Wu, MD
  • Nanning, China
    • Recruiting
    • Nanjing Qixia District Hospital
    • Contact: Daxing Yang, MD
  • Nantong, China
    • Recruiting
    • Affiliated Hospital of Nantong University
    • Contact: Hongzhuan Sheng, MD
  • Nantong, China
    • Recruiting
    • Nantong First People's Hospital
    • Contact: Koulong Zheng, MD
  • Neimeng, China
    • Recruiting
    • The People's Hospital of Zhalaite
    • Contact: Guofeng Chang, MD
  • Qingdao, China
    • Recruiting
    • Qingdao Municipal Hospital
    • Contact: Yibing Shao, MD
  • Shandong, China
    • Recruiting
    • Qilu Hospital of Shandong University
    • Contact: Yuguo Chen, MD
  • Shanghai, China
    • Recruiting
    • Renji Hospital Affiliated to Shanghai Jiaotong University
    • Contact: Jun Bu, MD
  • Shanghai, China
    • Recruiting
    • Songjiang hospital Affiliated to Shanghai Jiao Tong University School of Medicine
    • Contact: Lei Hou, MD; Phone Number: +86 13564868096
  • Shenyang, China
    • Recruiting
    • The People's Hospital of Liaoning Province
    • Contact: Bo Luan, MD
  • Shenzhen, China
    • Recruiting
    • ShenZhen People's Hospital
    • Contact: Da Yin, MD
  • Suining, China
    • Recruiting
    • Suining County People's Hospital
    • Contact: Ruili Wang, MD
  • Suqian, China
    • Recruiting
    • Nanjing Drum Tower Hospital Group Suqian Hospital
    • Contact: Hao Ding, MD
  • Suqian, China
    • Recruiting
    • Suqian First Hospital
    • Contact: Zhiyong Zhang, MD
  • Suzhou, China
    • Recruiting
    • The First Affiliated Hospital of Soochow University
    • Contact: Tingbo Jiang, MD
  • Suzhou, China
    • Recruiting
    • Suzhou Municipal Hospital
    • Contact: Jun Zhang, MD; Phone Number: +86 18994427321
  • Suzhou, China
    • Recruiting
    • Suzhou Dushu Lake Hospital
    • Contact: Yafeng Zhou, MD
  • Suzhou, China
    • Recruiting
    • Suzhou Municipal Hospital of Anhui Province
    • Contact: Hailong Qiu, MD
  • Suzhou, China
    • Recruiting
    • Wanbei Coal-Electricity Group General Hospital
    • Contact: Kun Zhu, MD
  • Taihe, China
    • Recruiting
    • Taihe County Traditional Chinese Medicine Hospital
    • Contact: Daimei Ni, MD
  • Taishan, China
    • Recruiting
    • Taishan people's Hospital
    • Contact: Yan Chen, MD; Phone Number: +86 13580014030
  • Taizhou, China
    • Recruiting
    • Taizhou People's Hospital
    • Contact: Li Zhu, MD
  • Wenzhou, China
    • Recruiting
    • The First Affiliated Hospital of Wenzhou Medical University
    • Contact: Hao Zhou, MD
  • Wenzhou, China
    • Recruiting
    • The Second Affiliated Hospital of Wenzhou Medical University
    • Contact: Xueqiang Guan, MD
  • Wuxi, China
    • Recruiting
    • Wuxi People's Hospital
    • Contact: Ruxing Wang, MD
  • Wuxi, China
    • Recruiting
    • Affiliated Hospital of Jiangnan University
    • Contact: Xiaoyan Wang, MD
  • Wuxi, China
    • Recruiting
    • Wuxi Second People's Hospital
    • Contact: Yan Jin, MD
  • Xuzhou, China
    • Recruiting
    • The Affiliated Hospital of Xuzhou Medical University
    • Contact: Tongda Xu, MD
  • Xuzhou, China
    • Recruiting
    • Xuzhou Central Hospital
    • Contact: Bing Han, MD
  • Xuzhou, China
    • Recruiting
    • The People's Hospital of Jiawang District of Xuzhou City
    • Contact: Yunjun Li, MD
  • Yancheng, China
    • Recruiting
    • Yancheng No.1 People's Hospital
    • Contact: Yunfeng Ju, MD
  • Yangzhou, China
    • Recruiting
    • Subei People's Hospital of Jiangsu province
    • Contact: Yong Xie, MD
  • Yangzhou, China
    • Recruiting
    • Affiliated Hospital of Yangzhou University
    • Contact: Kaizheng Gong, MD
  • Zhengzhou, China
    • Recruiting
    • The First Affiliated Hospital of Zhengzhou University
    • Contact: Zhanying Han, MD
  • Zhengzhou, China
    • Recruiting
    • Fuwai Central China Cardiovascular Hospital
    • Contact: Xiaohui Zheng, MD
  • Zhengzhou, China
    • Recruiting
    • The 7th People's Hospital of Zhengzhou
    • Contact: Yong Dong, MD
  • Zhenjiang, China
    • Recruiting
    • Zhenjiang First People's Hospital
    • Contact: Tao Rui, MD
  • Zhenjiang, China
    • Recruiting
    • Affiliated Hospital of Jiangsu University
    • Contact: Wei Yuan, MD
  • Jiangsu
    • Nanjing, Jiangsu, China, 210029
      • Recruiting
      • The First Affiliated Hospital of Nanjing Medical University
      • Contact: Chunjian Li, PHD; Phone Number: +86 13701465229; Email: lijay@njmu.edu.cn
      • Contact: Chen Li, MD; Phone Number: +86 13913886986; Email: lcicewind@outlook.com
      • Principal Investigator: Chunjian Li, PHD
      • Sub-Investigator: Chen Li, MD
      • Sub-Investigator: Tian Wu, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age 18-75 years, weight ≥45 kg

2. Diagnosed as STEMI (meeting the following two conditions simultaneously)

   1. Ischemic chest pain lasts ≥ 30 minutes
   2. ECG indicates that ST-segment elevation of two or more contiguous precordial leads ≥ 0.1 mV, or ST-segment elevation of two or more contiguous precordial leads ≥ 0.2 mV
3. Time from onset of persistent chest pain to randomization ≤12 hours
4. Primary PCI expected to be performed ≥30 minutes, and ≤120 minutes

Exclusion Criteria:

1. Cardiogenic shock
2. Active bleeding or known at high risk of bleeding (including grade Ⅲ or Ⅳ retinopathy or retinal gastrointestinal or urinary tract hemorrhage within the past 1 month)
3. Ischemic stroke or TIA in the past 6 months
4. History of hemorrhagic stroke
5. Known intracranial aneurysm
6. Severe trauma, surgery or head injury within 1 month
7. Suspected aortic dissection or infective endocarditis
8. Puncture with difficult hemostasis by compression within 1 month (e.g., visceral biopsy, compartment puncture)
9. Currently taking anticoagulants
10. Poorly controlled hypertension ( ≥180/110 mmHg)
11. Severe hepatic or renal impairment indicated by the consultation or previous history (glutamic-pyruvic transaminase or glutamic oxalacetic transaminase >3 times upper limit of normal value; eGFR <15 ml/min/1.73m^2, calculated based on CKD-EPI)
12. Known allergy to r-SAK
13. Pregnancy, lactation, or planning for pregnancy
14. History of chronic total occlusion, myocardial infarction or CABG
15. Having taken antiplatelet drugs other than aspirin and ticagrelor, such as clopidogrel, prasugrel or cilostazol after the symptom onset
16. Patients with other conditions that made them unsuitable to be recruited at the discretion of the investigators

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: r-SAK group; intravenous injection of single-bolus 5 mg r-SAK in 3 min	Drug: Recombinant staphylokinase; Intravenous injection of r-SAK is administered within 10 minutes after diagnosis of acute ST-segment elevation myocardial infarction
Placebo Comparator: placebo group; intravenous injection of placebo in 3 min	Drug: Placebo; Intravenous injection of placebo is administered within 10 minutes after diagnosis of acute ST-segment elevation myocardial infarction

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MACE	Defined as a composite of all-cause death, reinfarction, unplanned target vessel revascularization, heart failure or cardiogenic shock, major ventricular arrhythmia	Within 90 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
NT-proBNP	The level of NT-proBNP	1 day before discharge or day 7, day 90±3
CMR indexes	Including infarct size, left ventricular ejection fraction (LVEF), microvascular obstruction (MVO) and intramuscular hemorrhage (IMH), assessed by cardiac magnetic resonance (CMR)	Day 5
LVEF assessed by echocardiogram	LVEF assessed by echocardiogram	Day 90±3
The percentage of TIMI flow grade 2 and 3 prior to PCI	The percentage of thrombolysis in myocardial infarction (TIMI) flow grade 2 and 3 prior to PCI	Immediately prior to PCI
The percentage of TIMI flow grade 3 prior to PCI	The percentage of TIMI flow grade 3 prior to PCI	Immediately prior to PCI
The percentage of TIMI flow grade 2 and 3 after PCI	The percentage of TIMI flow grade 2 and 3 after PCI	Immediately after PCI
The percentage of TIMI flow grade 3 after PCI	The percentage of TIMI flow grade 3 after PCI	Immediately after PCI
NT-proBNP	The level of NT-proBNP	Day 360±7
LVEF assessed by echocardiogram	LVEF assessed by echocardiogram	Day 360±7
MACE	Defined as a composite of all-cause death, reinfarction, unplanned target vessel revascularization, heart failure or cardiogenic shock, major ventricular arrhythmia	Within 360 days
Each of the following cardiac and cerebrovascular events	Including all-cause death, cardiovascular death, reinfarction, stroke, unplanned target vessel revascularization, heart failure or cardiogenic shock, major ventricular arrhythmia, cardiogenic rehospitalization, ventricular septal rupture, papillary muscle rupture, cardiac rupture, ventricular aneurysm	Within 90 days
Each of the following cardiac and cerebrovascular events	Including all-cause death, cardiovascular death, reinfarction, ischemic stroke, unplanned target vessel revascularization, heart failure or cardiogenic shock, major ventricular arrhythmia, cardiogenic rehospitalization, ventricular septal rupture, papillary muscle rupture, cardiac rupture, ventricular aneurysm	Within 360 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Major bleeding events during hospitalization or within 7 days (BARC 3, 5)	Major bleeding events during hospitalization or within 7 days (BARC 3, 5)	During hospitalization or within 7 days
Minor bleeding events during hospitalization or within 7 days (BARC 2)	Minor bleeding events during hospitalization or within 7 days (BARC 2)	During hospitalization or within 7 days
Major bleeding events within 90 days (BARC 3, 5)	Major bleeding events within 90 days (BARC 3, 5)	Within 90 days
Minor bleeding events within 90 days (BARC 2)	Minor bleeding events within 90 days (BARC 2)	Within 90 days

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital with Nanjing Medical University
• Investigators: Principal Investigator: Chunjian Li, PHD, The First Affiliated Hospital with Nanjing Medical University

Publications and helpful links

General Publications

• 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.
• Ueshima S, Matsuo O. Development of new fibrinolytic agents. Curr Pharm Des. 2006;12(7):849-57. doi: 10.2174/138161206776056065.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• Vanderschueren S. [Staphylokinase for a better thrombolytic treatment of heart and platelet diseases]. Verh K Acad Geneeskd Belg. 2000;62(1):69-75. Dutch.
• 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.
• 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.
• 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.

Helpful Links

• Trial Design

Study record dates

Study Major Dates

• Study Start (Actual): April 8, 2023
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: June 6, 2022
• First Submitted That Met QC Criteria: June 6, 2022
• First Posted (Actual): June 8, 2022

Study Record Updates

• Last Update Posted (Actual): October 28, 2024
• Last Update Submitted That Met QC Criteria: October 24, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: Thrombolysis; ST Elevation Myocardial Infarction; Recombinant Staphylokinase
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Heart Diseases; Necrosis; Myocardial Ischemia; Ischemia; ST Elevation Myocardial Infarction; Myocardial Infarction; Infarction
• Other Study ID Numbers: 018

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No