ST Elevation Myocardial InfarctionPhase 4OPTIMA-6NCT05410925
Efficacy and Safety of a Half-dose Bolus of r-SAK Prior to Primary PCI in ST-elevation Myocardial Infarction
A Phase 4 study testing Recombinant staphylokinase in people with ST Elevation Myocardial Infarction, run by The First Affiliated Hospital with Nanjing Medical University at 61 sites in China.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- ST Elevation Myocardial Infarction
- What is being tested?
- Recombinant staphylokinase
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 2,260 participants
- Where
- 61 sitesChina
- Study dates
- 8 Apr 2023to 31 Dec 2027
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 18-75 years, weight ≥45 kg
- Diagnosed as STEMI (meeting the following two conditions simultaneously)
- Ischemic chest pain lasts ≥ 30 minutes
- 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
- Time from onset of persistent chest pain to randomization ≤12 hours
- Primary PCI expected to be performed ≥30 minutes, and ≤120 minutes
Who cannot join
- Cardiogenic shock
- 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 6 month)
- Ischemic stroke or TIA in the past 6 months
- History of hemorrhagic stroke
- Known intracranial aneurysm
- Severe trauma, surgery or head injury within 1 month
Show all 18Show fewer
- Suspected aortic dissection or infective endocarditis
- Puncture with difficult hemostasis by compression within 1 month (e.g., visceral biopsy, compartment puncture)
- Currently taking anticoagulants
- Known history of anemia with hemoglobin level <10 g/dL
- Known history of thrombocytopenia with platelet count <100×10⁹/L
- Poorly controlled hypertension ( ≥180/110 mmHg)
- 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)
- Known allergy to r-SAK
- Pregnancy, lactation, or planning for pregnancy
- History of chronic total occlusion, myocardial infarction or CABG
- Having taken antiplatelet drugs other than aspirin and ticagrelor, such as clopidogrel, prasugrel or cilostazol after the symptom onset
- Patients with other conditions that made them unsuitable to be recruited at the discretion of the investigators
Trial locations and contacts
61 sites in 1 country. Contact the study team or a site near you to ask about taking part.
61 sites in 1 country
China61 sites, 61 recruiting
- Recruiting
Changzhou Second People's Hospital
Changzhou
Xin Chen, MD
- Recruiting
Changzhou Wujin People's Hospital
Changzhou
Jianqiang Xiao, MD
- Recruiting
The First People's Hospital of Changzhou
Changzhou
Ling Yang, MD
- Recruiting
Chongqing Hospital of Jiangsu Province Hospital
Chongqing
Junhong Wang, MD
Hongyan Xing
- Recruiting
The second Affiliated Hospital of Dalian Medical University
Dalian
Xin Zhao, MD
- Recruiting
Daqing Oilfield General Hospital
Daqing
Zhiqi Sun, MD
- Recruiting
Dongguan People's Hospital
Dongguan
Suxia Guo, MD
- Recruiting
Fengcheng People's Hospital
Fengcheng
Wenbo Li, MD
- Recruiting
General Hospital of Southern Theatre Command
Guangzhou
Jinxia Zhang, MD
- Recruiting
The Second Affiliated Hospital of Hainan Medical University
Hainan
Yuewu Chen, MD
- Recruiting
The Affiliated Hospital of Hangzhou Normal University
Hangzhou
Peng Dong, MD, +86 13501352371
- Recruiting
The Second Affiliated Hospital of Zhejiang University Medical College
Hangzhou
Jun Jiang, MD
- Recruiting
The First Affiliated Hospital of Anhui Medical University
Hefei
Xianhe Lin, MD
- Recruiting
Huai'an First People's Hospital
Huai'an
Xiwen Zhang, MD
- Recruiting
Huai'an Second People's Hospital
Huai'an
Naiquan Yang, MD
- Recruiting
Donghai Country People's Hospital
Lianyungang
Jianling Zhou, MD
- Recruiting
The First People's Hospital of Lianyungang
Lianyungang
Bo Zhao, MD
- Recruiting
The Second People's Hospital of Lianyungang
Lianyungang
Yilian Wang, MD
- Recruiting
Liyang Hospital of Jiangsu Province Hospital
Liyang
Junhong Wang, MD
- Recruiting
The First Affiliated Hospital of Nanchang University
Nanchang
Xiaoping Peng, MD
- Recruiting
The First Affiliated Hospital of Nanjing Medical University
Nanjing, Jiangsu, 210029
Chunjian Li, PHD, +86 13701465229, lijay@njmu.edu.cn
Chen Li, MD, +86 13913886986, lcicewind@outlook.com
- Recruiting
Nanjing Tongren Hospital
Nanjing
Jiakuan Wu, MD
- Recruiting
Sir Run Run Hospital Nanjing Medical University
Nanjing
Chunjian Li, MD
- Recruiting
The Fourth Affiliated Hospital of Nanjing Medical University
Nanjing
Pingxi Xiao, MD
- Recruiting
Nanjing Qixia District Hospital
Nanning
Daxing Yang, MD
- Recruiting
Affiliated Hospital of Nantong University
Nantong
Hongzhuan Sheng, MD
- Recruiting
Nantong First People's Hospital
Nantong
Koulong Zheng, MD
- Recruiting
The People's Hospital of Zhalaite
Neimeng
Guofeng Chang, MD
- Recruiting
Qingdao Municipal Hospital
Qingdao
Yibing Shao, MD
- Recruiting
Qilu Hospital of Shandong University
Shandong
Yuguo Chen, MD
- Recruiting
Renji Hospital affiliated to Shanghai Jiaotong University
Shanghai
Jun Bu, MD
- Recruiting
Songjiang Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
Shanghai
Lei Hou, MD, +86 13564868096
- Recruiting
The People's Hospital of Liaoning Province
Shenyang
Bo Luan, MD
- Recruiting
Shenzhen People's Hospital
Shenzhen
Da Yin, MD
- Recruiting
Suining County People's Hospital
Suining
Ruili Wang, MD
- Recruiting
Nanjing Drum Tower Hospital Group Suqian Hospital
Suqian
Hao Ding, MD
- Recruiting
Suqian First Hospital
Suqian
Zhiyong Zhang, MD
- Recruiting
Suzhou Dushu Lake Hospital
Suzhou
Yafeng Zhou, MD
- Recruiting
Suzhou Municipal Hospital of Anhui Province
Suzhou
Hailong Qiu, MD
- Recruiting
Suzhou Municipal Hospital
Suzhou
Jun Zhang, MD, +86 18994427321
- Recruiting
The First Affiliated Hospital of Soochow University
Suzhou
Tingbo Jiang, MD
- Recruiting
Wanbei Coal-Electricity Group General Hospital
Suzhou
Kun Zhu, MD
- Recruiting
Taihe County Traditional Chinese Medicine Hospital
Taihe
Daimei Ni, MD
- Recruiting
Taishan People's Hospital
Taishan
Yan Chen, MD, +86 13580014030
- Recruiting
Taizhou People's Hospital
Taizhou
Li Zhu, MD
- Recruiting
The First Affiliated Hospital of Wenzhou Medical University
Wenzhou
Hao Zhou, MD
- Recruiting
The Second Affiliated Hospital of Wenzhou Medical University
Wenzhou
Xueqiang Guan, MD
- Recruiting
Affiliated Hospital of Jiangnan University
Wuxi
Xiaoyan Wang, MD
- Recruiting
Wuxi People's Hospital
Wuxi
Ruxing Wang, MD
- Recruiting
Wuxi Second People's Hospital
Wuxi
Yan Jin, MD
- Recruiting
The Affiliated Hospital of Xuzhou Medical University
Xuzhou
Tongda Xu, MD
- Recruiting
The People's Hospital of Jiawang District of Xuzhou City
Xuzhou
Yunjun Li, MD
- Recruiting
Xuzhou Central Hospital
Xuzhou
Bing Han, MD
- Recruiting
Yancheng No.1 People's Hospital
Yancheng
Yunfeng Ju, MD
- Recruiting
Affiliated Hospital of Yangzhou University
Yangzhou
Kaizheng Gong, MD
- Recruiting
Subei People's Hospital of Jiangsu province
Yangzhou
Yong Xie, MD
- Recruiting
Fuwai Central China Cardiovascular Hospital
Zhengzhou
Xiaohui Zheng, MD
- Recruiting
The 7th People's Hospital of Zhengzhou
Zhengzhou
Yong Dong, MD
- Recruiting
The First Affiliated Hospital of Zhengzhou University
Zhengzhou
Zhanying Han, MD
- Recruiting
Affiliated Hospital of Jiangsu University
Zhenjiang
Wei Yuan, MD
- Recruiting
Zhenjiang First People's Hospital
Zhenjiang
Tao Rui, MD
About this study
Official title: 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.
Read the 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.
- Conditions
- ST Elevation Myocardial Infarction
- Being tested
- Recombinant staphylokinase, Placebo
- Keywords
- ST Elevation Myocardial Infarction, Recombinant Staphylokinase, Thrombolysis
- Medical subject headings
- ST Elevation Myocardial Infarction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Recombinant staphylokinaseDrug
Intravenous injection of r-SAK is administered within 10 minutes after diagnosis of acute ST-segment elevation myocardial infarction
PlaceboDrug
Intravenous injection of placebo is administered within 10 minutes after diagnosis of acute ST-segment elevation myocardial infarction
| Study group | Role | What they receive |
|---|---|---|
| r-SAK group | Experimental | intravenous injection of single-bolus 5 mg r-SAK in 3 min Receives: Drug: Recombinant staphylokinase |
| placebo group | Placebo comparator | intravenous injection of placebo in 3 min Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
MACE
Defined as a composite of all-cause death, reinfarction, unplanned target vessel revascularization, heart failure or cardiogenic shock, major ventricular arrhythmia
Measured: Within 90 days
Secondary outcomes (12)
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
Measured: Within 90 days
NT-proBNP
The level of NT-proBNP
Measured: 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)
Measured: Day 5
LVEF assessed by echocardiogram
LVEF assessed by echocardiogram
Measured: 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
Measured: Immediately prior to PCI
The percentage of TIMI flow grade 3 prior to PCI
The percentage of TIMI flow grade 3 prior to PCI
Measured: 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
Measured: Immediately after PCI
The percentage of TIMI flow grade 3 after PCI
The percentage of TIMI flow grade 3 after PCI
Measured: Immediately after PCI
MACE
Defined as a composite of all-cause death, reinfarction, unplanned target vessel revascularization, heart failure or cardiogenic shock, major ventricular arrhythmia
Measured: Within 360 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
Measured: Within 360 days
NT-proBNP
The level of NT-proBNP
Measured: Day 360±7
LVEF assessed by echocardiogram
LVEF assessed by echocardiogram
Measured: Day 360±7
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jun 2022
- Study start8 Apr 2023
- Primary completion31 Dec 2026 (estimated)
- Study completion31 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (18)Papers the sponsor has linked to this study.
- Other trials for ST Elevation Myocardial InfarctionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 2,260 participants (estimated)
Sponsor and investigators
- Lead sponsor
- The First Affiliated Hospital with Nanjing Medical University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Chunjian Li, The First Affiliated Hospital with Nanjing Medical University
- Investigators
- Chunjian Li, PHD, Principal investigator, The First Affiliated Hospital with Nanjing Medical University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05410925
- Sponsor's protocol ID
- 018
- Acronym
- OPTIMA-6
- Status last verified
- Oct 2026
- First submitted
- 6 Jun 2022
- Last updated
- 30 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 31902409Bahit 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.
PubMed 29496021Heusch 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.
PubMed 24831770Juilliere 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.
PubMed 22357361Bradley 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.
PubMed 20082933Mangin 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.
PubMed 29096903Bai 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.
PubMed 32847319Schwartz 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.
PubMed 24296382Ren 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.
PubMed 34688099Vanderschueren S. [Staphylokinase for a better thrombolytic treatment of heart and platelet diseases]. Verh K Acad Geneeskd Belg. 2000;62(1):69-75. Dutch.
PubMed 10769618Ueshima S, Matsuo O. Development of new fibrinolytic agents. Curr Pharm Des. 2006;12(7):849-57. doi: 10.2174/138161206776056065.
PubMed 16515501Yamamoto 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.
PubMed 10709908Szemraj 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.
PubMed 17549308Vakili 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.
PubMed 29424308Li 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.
PubMed 17184583
Study at a glance
From the registry record, last updated by the sponsor on 30 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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)
- ClinicalTrials.gov ID
- NCT05410925
- Acronym / sponsor ID
- OPTIMA-6 / 018
- Conditions
- ST Elevation Myocardial Infarction
- Keywords
- ST Elevation Myocardial Infarction, Recombinant Staphylokinase, Thrombolysis
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 2,260 participants (estimated)
- Lead sponsor
- The First Affiliated Hospital with Nanjing Medical UniversityUniversity, hospital or other
- Study start
- 8 Apr 2023 (actual)
- Primary completion
- 31 Dec 2026 (estimated)
- Study completion
- 31 Dec 2027 (estimated)
- First posted
- 8 Jun 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| r-SAK group | Experimental | Drug: Recombinant staphylokinaseintravenous injection of single-bolus 5 mg r-SAK in 3 min |
| placebo group | Placebo comparator | Drug: Placebointravenous injection of placebo in 3 min |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Age 18-75 years, weight ≥45 kg
- Diagnosed as STEMI (meeting the following two conditions simultaneously)
- Time from onset of persistent chest pain to randomization ≤12 hours
- Primary PCI expected to be performed ≥30 minutes, and ≤120 minutes
Key exclusion criteria (18 listed)
- Cardiogenic shock
- 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 6 month)
- Ischemic stroke or TIA in the past 6 months
- History of hemorrhagic stroke
- Known intracranial aneurysm
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Recombinant staphylokinaseIntravenous injection of r-SAK is administered within 10 minutes after diagnosis of acute ST-segment elevation myocardial infarction | Drug | r-SAK group |
| PlaceboIntravenous injection of placebo is administered within 10 minutes after diagnosis of acute ST-segment elevation myocardial infarction | Drug | placebo group |
Primary outcome
MACE
Time frame: Within 90 days
Defined as a composite of all-cause death, reinfarction, unplanned target vessel revascularization, heart failure or cardiogenic shock, major ventricular arrhythmia
12 secondary outcomes
Each of the following cardiac and cerebrovascular events
Time frame: Within 90 days
NT-proBNP
Time frame: 1 day before discharge or day 7, day 90±3
CMR indexes
Time frame: Day 5
LVEF assessed by echocardiogram
Time frame: Day 90±3
The percentage of TIMI flow grade 2 and 3 prior to PCI
Time frame: Immediately prior to PCI
The percentage of TIMI flow grade 3 prior to PCI
Time frame: Immediately prior to PCI
The percentage of TIMI flow grade 2 and 3 after PCI
Time frame: Immediately after PCI
The percentage of TIMI flow grade 3 after PCI
Time frame: Immediately after PCI
MACE
Time frame: Within 360 days
Each of the following cardiac and cerebrovascular events
Time frame: Within 360 days
NT-proBNP
Time frame: Day 360±7
LVEF assessed by echocardiogram
Time frame: Day 360±7
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Oct 2026.
- Background: PubMed 31902409Gulati 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: PubMed 29496021Bahit 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: PubMed 24831770Heusch 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: PubMed 22357361Juilliere 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: PubMed 20082933Bradley 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: PubMed 29096903Mangin 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: PubMed 32847319Bai 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: PubMed 24296382Schwartz 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: PubMed 34688099Ren 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: PubMed 10769618Vanderschueren S. [Staphylokinase for a better thrombolytic treatment of heart and platelet diseases]. Verh K Acad Geneeskd Belg. 2000;62(1):69-75. Dutch.
- Background: PubMed 16515501Ueshima S, Matsuo O. Development of new fibrinolytic agents. Curr Pharm Des. 2006;12(7):849-57. doi: 10.2174/138161206776056065.
- Background: PubMed 10709908Yamamoto 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.
- Trial DesignLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Chunjian Li, PHD principal investigator
The First Affiliated Hospital with Nanjing Medical University
61 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Recombinant staphylokinase in people with ST Elevation Myocardial Infarction, run by The First Affiliated Hospital with Nanjing Medical University at 61 sites in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 30 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 61 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Chunjian Li, PHD (+86 13701465229, lijay@njmu.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
MACE (time frame: Within 90 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05410925, which also lists 18 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Oct 2026.