Efficacy and Safety of a Half-dose Bolus of r-SAK Prior to Primary PCI in ST-elevation Myocardial Infarction
NCT ID: NCT05410925
Last Updated: 2024-10-28
Study Results
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Basic Information
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RECRUITING
PHASE4
2260 participants
INTERVENTIONAL
2023-04-08
2027-12-31
Brief Summary
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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.
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Detailed Description
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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.
Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
QUADRUPLE
Study Groups
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r-SAK group
intravenous injection of single-bolus 5 mg r-SAK in 3 min
Recombinant staphylokinase
Intravenous injection of r-SAK is administered within 10 minutes after diagnosis of acute ST-segment elevation myocardial infarction
placebo group
intravenous injection of placebo in 3 min
Placebo
Intravenous injection of placebo is administered within 10 minutes after diagnosis of acute ST-segment elevation myocardial infarction
Interventions
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Recombinant staphylokinase
Intravenous injection of r-SAK is administered within 10 minutes after diagnosis of acute ST-segment elevation myocardial infarction
Placebo
Intravenous injection of placebo is administered within 10 minutes after diagnosis of acute ST-segment elevation myocardial infarction
Eligibility Criteria
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Inclusion Criteria
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
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
18 Years
75 Years
ALL
No
Sponsors
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The First Affiliated Hospital with Nanjing Medical University
OTHER
Responsible Party
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Chunjian Li
Director of Cardiology
Principal Investigators
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Chunjian Li, PHD
Role: PRINCIPAL_INVESTIGATOR
The First Affiliated Hospital with Nanjing Medical University
Locations
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The First Affiliated Hospital of Nanjing Medical University
Nanjing, Jiangsu, China
Changzhou Second People's Hospital
Changzhou, , China
Changzhou Wujin People's Hospital
Changzhou, , China
The First People's Hospital of Changzhou
Changzhou, , China
Chongqing Hospital of Jiangsu Province Hospital
Chongqing, , China
The second Affiliated Hospital of Dalian Medical University
Dalian, , China
Daqing Oilfield General Hospital
Daqing, , China
Dongguan People's Hospital
Dongguan, , China
Fengcheng People's Hospital
Fengcheng, , China
General Hospital of Southern Theatre Command
Guangzhou, , China
The Second Affiliated Hospital of Hainan Medical University
Hainan, , China
The Affiliated Hospital of Hangzhou Normal University
Hangzhou, , China
The Second Affiliated Hospital of Zhejiang University Medical College
Hangzhou, , China
The First Affiliated Hospital of Anhui Medical University
Hefei, , China
Huai'an First People's Hospital
Huai'an, , China
Huai'an Second People's Hospital
Huai'an, , China
Donghai Country People's Hospital
Lianyungang, , China
The First People's Hospital of Lianyungang
Lianyungang, , China
The Second People's Hospital of Lianyungang
Lianyungang, , China
Liyang Hospital of Jiangsu Province Hospital
Liyang, , China
The First Affiliated Hospital of Nanchang University
Nanchang, , China
Nanjing Tongren Hospital
Nanjing, , China
Sir Run Run Hospital Nanjing Medical University
Nanjing, , China
The Fourth Affiliated Hospital of Nanjing Medical University
Nanjing, , China
Nanjing Qixia District Hospital
Nanning, , China
Affiliated Hospital of Nantong University
Nantong, , China
Nantong First People's Hospital
Nantong, , China
The People's Hospital of Zhalaite
Neimeng, , China
Qingdao Municipal Hospital
Qingdao, , China
Qilu Hospital of Shandong University
Shandong, , China
Renji Hospital affiliated to Shanghai Jiaotong University
Shanghai, , China
Songjiang Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
Shanghai, , China
The People's Hospital of Liaoning Province
Shenyang, , China
Shenzhen People's Hospital
Shenzhen, , China
Suining County People's Hospital
Suining, , China
Nanjing Drum Tower Hospital Group Suqian Hospital
Suqian, , China
Suqian First Hospital
Suqian, , China
Suzhou Dushu Lake Hospital
Suzhou, , China
Suzhou Municipal Hospital of Anhui Province
Suzhou, , China
Suzhou Municipal Hospital
Suzhou, , China
The First Affiliated Hospital of Soochow University
Suzhou, , China
Wanbei Coal-Electricity Group General Hospital
Suzhou, , China
Taihe County Traditional Chinese Medicine Hospital
Taihe, , China
Taishan People's Hospital
Taishan, , China
Taizhou People's Hospital
Taizhou, , China
The First Affiliated Hospital of Wenzhou Medical University
Wenzhou, , China
The Second Affiliated Hospital of Wenzhou Medical University
Wenzhou, , China
Affiliated Hospital of Jiangnan University
Wuxi, , China
Wuxi People's Hospital
Wuxi, , China
Wuxi Second People's Hospital
Wuxi, , China
The Affiliated Hospital of Xuzhou Medical University
Xuzhou, , China
The People's Hospital of Jiawang District of Xuzhou City
Xuzhou, , China
Xuzhou Central Hospital
Xuzhou, , China
Yancheng No.1 People's Hospital
Yancheng, , China
Affiliated Hospital of Yangzhou University
Yangzhou, , China
Subei People's Hospital of Jiangsu province
Yangzhou, , China
Fuwai Central China Cardiovascular Hospital
Zhengzhou, , China
The 7th People's Hospital of Zhengzhou
Zhengzhou, , China
The First Affiliated Hospital of Zhengzhou University
Zhengzhou, , China
Affiliated Hospital of Jiangsu University
Zhenjiang, , China
Zhenjiang First People's Hospital
Zhenjiang, , China
Countries
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Central Contacts
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Facility Contacts
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Xin Chen, MD
Role: primary
Jianqiang Xiao, MD
Role: primary
Ling Yang, MD
Role: primary
Junhong Wang, MD
Role: primary
Hongyan Xing
Role: backup
Xin Zhao, MD
Role: primary
Zhiqi Sun, MD
Role: primary
Suxia Guo, MD
Role: primary
Wenbo Li, MD
Role: primary
Jinxia Zhang, MD
Role: primary
Yuewu Chen, MD
Role: primary
Peng Dong, MD
Role: primary
Jun Jiang, MD
Role: primary
Xianhe Lin, MD
Role: primary
Xiwen Zhang, MD
Role: primary
Naiquan Yang, MD
Role: primary
Jianling Zhou, MD
Role: primary
Bo Zhao, MD
Role: primary
Yilian Wang, MD
Role: primary
Junhong Wang, MD
Role: primary
Xiaoping Peng, MD
Role: primary
Jiakuan Wu, MD
Role: primary
Chunjian Li, MD
Role: primary
Pingxi Xiao, MD
Role: primary
Daxing Yang, MD
Role: primary
Hongzhuan Sheng, MD
Role: primary
Koulong Zheng, MD
Role: primary
Guofeng Chang, MD
Role: primary
Yibing Shao, MD
Role: primary
Yuguo Chen, MD
Role: primary
Jun Bu, MD
Role: primary
Lei Hou, MD
Role: primary
Bo Luan, MD
Role: primary
Da Yin, MD
Role: primary
Ruili Wang, MD
Role: primary
Hao Ding, MD
Role: primary
Zhiyong Zhang, MD
Role: primary
Yafeng Zhou, MD
Role: primary
Hailong Qiu, MD
Role: primary
Jun Zhang, MD
Role: primary
Tingbo Jiang, MD
Role: primary
Kun Zhu, MD
Role: primary
Daimei Ni, MD
Role: primary
Yan Chen, MD
Role: primary
Li Zhu, MD
Role: primary
Hao Zhou, MD
Role: primary
Xueqiang Guan, MD
Role: primary
Xiaoyan Wang, MD
Role: primary
Ruxing Wang, MD
Role: primary
Yan Jin, MD
Role: primary
Tongda Xu, MD
Role: primary
Yunjun Li, MD
Role: primary
Bing Han, MD
Role: primary
Yunfeng Ju, MD
Role: primary
Kaizheng Gong, MD
Role: primary
Yong Xie, MD
Role: primary
Xiaohui Zheng, MD
Role: primary
Yong Dong, MD
Role: primary
Zhanying Han, MD
Role: primary
Wei Yuan, MD
Role: primary
Tao Rui, MD
Role: primary
References
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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.
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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.
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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.
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Related Links
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Other Identifiers
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018
Identifier Type: -
Identifier Source: org_study_id
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