Acute Myocardial InfarctionPhase 4NCT05023681
The OPTIMA-5 Trail
A Phase 4 study testing Recombinant Staphylokinase and normal saline in people with Acute Myocardial Infarction, run by The First Affiliated Hospital with Nanjing Medical University at 9 sites in China.
Trial summary
This study was a prospective, multicenter, randomized, controlled, excellence clinical trial. Subjects meeting the inclusion/exclusion criteria were randomly assigned 1:1 to r-SAK group or the control group (normal saline). Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Acute Myocardial Infarction
- What is being tested?
- Recombinant Staphylokinase and normal saline
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 200 participants
- Where
- 9 sitesChina
- Study dates
- 29 Oct 2021to 14 Sep 2022
- Phase
- Phase 4
- Are there results?
- None posted in the registry
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 old, weight ≥45kg, gender is not limited.
- Diagnosis of acute ST-segment elevation myocardial infarction (both of the following) (A) Ischemic chest pain lasting more than 30 minutes; (B) Ecg indicates ST-segment elevation ≥ 0.1mV in 2 or more limb leads, or ST-segment elevation ≥ 0.2mV in 2 or more adjacent chest leads;
- Time from onset of persistent ischemic chest pain to randomization ≤12 hours;
- Coronary angiography and/or PCI are expected to be performed within 2 hours of r-SAK thrombolysis.
Who cannot join
- Non-ST-segment elevation myocardial infarction;
- STEMI with cardiogenic shock;
- active bleeding or bleeding tendency, including Ⅲ, Ⅳ period history of retinopathy, retinal hemorrhage, gastrointestinal tract and urinary tract hemorrhage (1 month), ischemic stroke happened over the past 6 months, transient ischemic attack (TIA) happened over the past 6 weeks, hemorrhagic stroke in the past, unexplained platelet count < 100 x 109 / L or Hemoglobin <100g/L;
- Having a history of central nervous system trauma or known intracranial aneurysm;
- Recent (within 1 month) severe trauma, surgery or head injury;
- Suspected aortic dissection, infective endocarditis;
Show all 16Show fewer
- Recent history of puncture which difficult hemostasis by compression (visceral biopsy, compartment puncture);
- Long-term use and/or current use of anticoagulant drugs;
- Hypertension not well controlled ≥180/110mmHg;
- Having severe hepatic and renal impairment (ALT, AST, γ-GT > 2.5 times the upper limit of normal value; Cr > 1.5 times upper normal);
- Known allergies to r-SAK;
- Pregnant, breastfeeding or planned pregnancy women and male patients with family planning;
- Patients who have participated in other clinical trials in the past 3 months;
- Having a history of myocardial infarction or CABG;
- Having taken antiplatelet drugs after pain onset, such as clopidogrel, prasugrel, cilostazol etc;
- Other reasons that patients considered unsuitable for inclusion by researchers.
Trial locations and contacts
9 sites in 1 country.
9 sites in 1 country
China9 sites
Changzhou Second People's Hospital
Changzhou
The second Affiliated Hospital of Dalian Medical University
Dalian
The Second Affiliated Hospital of Zhejiang University Medical College
Hangzhou
Huai 'an Second People's Hospital affiliated to Nanjing Medical University
Huai'an
Lianyungang First People's Hospital
Lianyungang
The First Affiliated Hospital of Nanjing Medical University
Nanjing, Jiangsu, 210029
Renji Hospital affiliated to Shanghai Jiaotong University
Shanghai
Taizhou People's Hospital
Taizhou
Affiliated Hospital of Jiangnan University
Wuxi
About this study
Official title: Efficacy and Safety of an Early Phase Single Bolus r-SAK for Acute Myocardial Infarction: a Multi-center Randomized Clinical Trial (OPTIMA-5)
This study was a prospective, multicenter, randomized, controlled, excellence clinical trial. Subjects meeting the inclusion/exclusion criteria were randomly assigned 1:1 to r-SAK group or the control group (normal saline). Emergency coronary angiography was performed and cardiac magnetic resonance imaging was performed 5 days after surgery, followed up to 30 days.
At present, there is still a lack of clinical evidence on whether thrombolytic therapy is performed for acute ST-segment elevation myocardial infarction <2 hours after the first medical contact and prime PCI. Compared to prime PCI, early thrombolytic therapy can undoubtedly shorten the implementation time of reperfusion strategy to the maximum. For highly effective thrombolytic drugs, it should also shorten the reperfusion time, reduce thrombotic load, possibly reduce the area of myocardial infarction and improve the prognosis of patients. In this study, normal saline was used as the control. To observe the efficacy of thrombolytic therapy with single intravenous infusion of recombinant glucokinase (r-SAK) at the first time in acute ST-segment elevation myocardial infarction. And the effect of r-SAK on improving myocardial tissue level perfusion, reducing myocardial infarction size, improving cardiac function and clinical prognosis in STEMI patients.
Read the detailed description
Acute myocardial infarction (AMI) is one of the leading causes of death all over the world. Even if patients with AMI survive the acute period without death, some ones would inevitably develop into chronic heart failure due to myocardial ischemia caused by segmental ventricular wall dyskinesia, myocardial remodeling, etc., which would seriously affect the prognosis of these patients. Early intensive treatment is the decisive factor to reduce the death of patients with AMI. However, the primary hospitals where patients firstly visit do not have the ability of Primary Percutaneous Transluminal Coronary Intervention (PCI) the guidelines recommend. They have to transport patients to a center that has the conditions for emergency interventional treatment. But this transportation will delay a lot of time, resulting in the extension of MI area. More importantly, the thrombus load in coronary arteries would increase with time, and the implantation of stents in vessels with a large thrombus load will often lead to slow flow or no flow, which is a relative contraindication for interventional therapy.
At present, the guidelines recommend loading dose antiplatelet therapy and transport to the superior hospital for prime PCI within 2 hours if the first hospital for acute myocardial infarction does not have the conditions for emergency interventional therapy. Current guidelines recommend that thrombolytic therapy should be performed first and then transported when delivery is expected to be >2 hours to a hospital where PCI can be performed. And thrombolytic therapy is not recommended for patients who can perform PCI within <2 hours. There is a lack of clinical evidence for thrombolysis within 2 hours of first medical contact to Primary PCI. Compared with Primary PCI, early thrombolytic therapy can undoubtedly shorten the implementation time of reperfusion strategy to the maximum. For highly effective thrombolytic drugs, reperfusion time should be shortened, thrombus load should be reduced, and the size of myocardial infarction may be reduced and the prognosis of patients improved. There is a lack of clinical evidence for this. China is a developing country, whose grassroots and rural health resources are still poor. Early thrombolysis treatment plus subsequent reperfusion of interventional therapy not only conform to the Chinese characteristic, but also accord with the international research and the development direction in this field, which is worth further study.
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.
Recombinant SAK (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. R-SAK, a highly effective thrombolytic drug, may shorten the reperfusion time, reduce the size of myocardial infarction and improve the prognosis of the AMI patients.
The aim of this study was to investigate the efficacy of single bolus of r-SAK for thrombolytic therapy at the first contact with the patients who are diagnosed acute ST-segment elevation myocardial infarction. It is hypothesized that this therapy can open the culprit artery very early and effectively, reduce thrombus load, reduce slow flow or no flow caused by subsequent PCI, and improve myocardial tissue perfusion.
- Conditions
- Acute Myocardial Infarction
- Being tested
- Recombinant Staphylokinase, normal saline
- Keywords
- Acute Myocardial Infarction；Recombinant Staphylokinase; thrombolysis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Recombinant StaphylokinaseDrug
Also called r-SAK single intravenous injection for early treatment of acute myocardial infarction
Intravenous injection of r-SAK is administered within 10 minutes after diagnosis of acute ST-segment elevation myocardial infarction
normal salineDrug
Also called normal saline intravenous injection for early treatment of acute myocardial infarction
Intravenous injection of placebo(normal saline ) is administered within 10 minutes after diagnosis of acute ST-segment elevation myocardial infarction
| Study group | Role | What they receive |
|---|---|---|
| r-SAK treatment group | Experimental | intravenous injection of single bolus 5 mg r-SAK in 3min Receives: Drug: Recombinant Staphylokinase |
| saline control group | Placebo comparator | intravenous injection of 10ml saline in 3min,r-SAK and saline are the same in appearance Receives: Drug: normal saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
the percentage of TIMI flow grade 2 and 3 or grade 3 after 60 minutes of the thrombolytic therapy
The primary endpoint
Measured: 60 minutes
the incidence of major bleeding defined as Bleeding Academic Research Consortium (BARC) ≥3 bleeding
The main safety endpoint
Measured: 30 days
Secondary outcomes (8)
The percentage of TIMI flow grade 3 after PCI
The percentage of TIMI flow grade 3 after PCI
Measured: 60 minutes
Clinical net benefits of MACE and major bleeding events during hospitalization
Clinical net benefit of MACE and major bleeding events during hospitalization
Measured: 1 week
MACCEs, defined as composite of all-cause death, myocardial infarction, unplanned revascularization, ischemic stroke and cardiogenic re-hospitalization recorded during 30-day follow-up
MACCEs, defined as composite of all-cause death, myocardial infarction, unplanned revascularization, ischemic stroke and cardiogenic re-hospitalization recorded during 30-day follow-up
Measured: 30 days
Infarct size, Microvascular obstruction, cardiac function (EF) and Intramuscular hemorrhageH detected by MRI 5 days after AMI
Infarct size, Microvascular obstruction, cardiac function (EF) and Intramuscular hemorrhage detected by MRI 5 days after AMI
Measured: 5 days
Major bleeding (BARC ≥3) and minor bleeding (BARC ≤2) events during 30-day follow-up
Major bleeding (BARC ≥3) and minor bleeding (BARC ≤2) events during 30-day follow-up
Measured: 30 days
The occurrence of slow or no reflow during CAG or PCI
The occurrence of slow or no reflow during CAG or PCI
Measured: 60 minutes
Corrected TIMI Frame Count (CTFC) and TIMI Myocardial Perfusion Frame Count (TMPFC) after PCI
Corrected TIMI Frame Count (CTFC) and TIMI Myocardial Perfusion Frame Count (TMPFC) after PCI
Measured: 60 minutes
Malignant arrhythmia after thrombolysis and during hospitalization
Malignant arrhythmia after thrombolysis and during hospitalization
Measured: 1 week
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Aug 2021
- Study start29 Oct 2021
- Primary completion14 Aug 2022
- Study completion14 Sep 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (16)Papers the sponsor has linked to this study.
- Other trials for Acute 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
- 200 participants (actual)
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
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05023681
- Sponsor's protocol ID
- 014
- Status last verified
- Jan 2023
- First submitted
- 22 Aug 2021
- Last updated
- 13 Jan 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Correction to: Heart Disease and Stroke Statistics-2018 Update: A Report From the American Heart Association. Circulation. 2018 Mar 20;137(12):e493. doi: 10.1161/CIR.0000000000000573. No abstract available.
PubMed 29555722Heusch 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 24831770Agnoletti G, Cargnoni A, Agnoletti L, Di Marcello M, Balzarini P, Pasini E, Gitti G, Martina P, Ardesi R, Ferrari R. Experimental ischemic cardiomyopathy: insights into remodeling, physiological adaptation, and humoral response. Ann Clin Lab Sci. 2006 Summer;36(3):333-40.
PubMed 16951276Townsend N, Wilson L, Bhatnagar P, Wickramasinghe K, Rayner M, Nichols M. Cardiovascular disease in Europe: epidemiological update 2016. Eur Heart J. 2016 Nov 7;37(42):3232-3245. doi: 10.1093/eurheartj/ehw334. Epub 2016 Aug 14. No abstract available.
PubMed 27523477Collen D, Lijnen HR. Thrombolytic agents. Thromb Haemost. 2005 Apr;93(4):627-30. doi: 10.1160/TH04-11-0724.
PubMed 15841305Pulicherla KK, Kumar A, Gadupudi GS, Kotra SR, Rao KR. In vitro characterization of a multifunctional staphylokinase variant with reduced reocclusion, produced from salt inducible E. coli GJ1158. Biomed Res Int. 2013;2013:297305. doi: 10.1155/2013/297305. Epub 2013 Aug 13.
PubMed 23998121Ueshima 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 17184583Mehran R, Rao SV, Bhatt DL, Gibson CM, Caixeta A, Eikelboom J, Kaul S, Wiviott SD, Menon V, Nikolsky E, Serebruany V, Valgimigli M, Vranckx P, Taggart D, Sabik JF, Cutlip DE, Krucoff MW, Ohman EM, Steg PG, White H. Standardized bleeding definitions for cardiovascular clinical trials: a consensus report from the Bleeding Academic Research Consortium. Circulation. 2011 Jun 14;123(23):2736-47. doi: 10.1161/CIRCULATIONAHA.110.009449. No abstract available.
PubMed 21670242Thygesen K, Alpert JS, Jaffe AS, Chaitman BR, Bax JJ, Morrow DA, White HD; Executive Group on behalf of the Joint European Society of Cardiology (ESC)/American College of Cardiology (ACC)/American Heart Association (AHA)/World Heart Federation (WHF) Task Force for the Universal Definition of Myocardial Infarction. Fourth Universal Definition of Myocardial Infarction (2018). Glob Heart. 2018 Dec;13(4):305-338. doi: 10.1016/j.gheart.2018.08.004. Epub 2018 Aug 25. No abstract available.
PubMed 30154043Cutlip DE, Windecker S, Mehran R, Boam A, Cohen DJ, van Es GA, Steg PG, Morel MA, Mauri L, Vranckx P, McFadden E, Lansky A, Hamon M, Krucoff MW, Serruys PW; Academic Research Consortium. Clinical end points in coronary stent trials: a case for standardized definitions. Circulation. 2007 May 1;115(17):2344-51. doi: 10.1161/CIRCULATIONAHA.106.685313.
PubMed 17470709Halvorsen S, Storey RF, Rocca B, Sibbing D, Ten Berg J, Grove EL, Weiss TW, Collet JP, Andreotti F, Gulba DC, Lip GYH, Husted S, Vilahur G, Morais J, Verheugt FWA, Lanas A, Al-Shahi Salman R, Steg PG, Huber K; ESC Working Group on Thrombosis. Management of antithrombotic therapy after bleeding in patients with coronary artery disease and/or atrial fibrillation: expert consensus paper of the European Society of Cardiology Working Group on Thrombosis. Eur Heart J. 2017 May 14;38(19):1455-1462. doi: 10.1093/eurheartj/ehw454. No abstract available.
PubMed 27789570
Study at a glance
From the registry record, last updated by the sponsor on 13 Jan 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy and Safety of an Early Phase Single Bolus r-SAK for Acute Myocardial Infarction: a Multi-center Randomized Clinical Trial (OPTIMA-5)
- ClinicalTrials.gov ID
- NCT05023681
- Acronym / sponsor ID
- 014
- Conditions
- Acute Myocardial Infarction
- Keywords
- Acute Myocardial Infarction；Recombinant Staphylokinase; thrombolysis
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 200 participants (actual)
- Lead sponsor
- The First Affiliated Hospital with Nanjing Medical UniversityUniversity, hospital or other
- Study start
- 29 Oct 2021 (actual)
- Primary completion
- 14 Aug 2022 (actual)
- Study completion
- 14 Sep 2022 (actual)
- First posted
- 26 Aug 2021 (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.
This study was a prospective, multicenter, randomized, controlled, excellence clinical trial. Subjects meeting the inclusion/exclusion criteria were randomly assigned 1:1 to r-SAK group or the control group (normal saline). Emergency coronary angiography was performed and cardiac magnetic resonance imaging was performed 5 days after surgery, followed up to 30 days.
At present, there is still a lack of clinical evidence on whether thrombolytic therapy is performed for acute ST-segment elevation myocardial infarction <2 hours after the first medical contact and prime PCI. Compared to prime PCI, early thrombolytic therapy can undoubtedly shorten the implementation time of reperfusion strategy to the maximum. For highly effective thrombolytic drugs, it should also shorten the reperfusion time, reduce thrombotic load, possibly reduce the area of myocardial infarction and improve the prognosis of patients. In this study, normal saline was used as the control. To observe the efficacy of thrombolytic therapy with single intravenous infusion of recombinant glucokinase (r-SAK) at the first time in acute ST-segment elevation myocardial infarction. And the effect of r-SAK on improving myocardial tissue level perfusion, reducing myocardial infarction size, improving cardiac function and clinical prognosis in STEMI patients.
Detailed description
Acute myocardial infarction (AMI) is one of the leading causes of death all over the world. Even if patients with AMI survive the acute period without death, some ones would inevitably develop into chronic heart failure due to myocardial ischemia caused by segmental ventricular wall dyskinesia, myocardial remodeling, etc., which would seriously affect the prognosis of these patients. Early intensive treatment is the decisive factor to reduce the death of patients with AMI. However, the primary hospitals where patients firstly visit do not have the ability of Primary Percutaneous Transluminal Coronary Intervention (PCI) the guidelines recommend. They have to transport patients to a center that has the conditions for emergency interventional treatment. But this transportation will delay a lot of time, resulting in the extension of MI area. More importantly, the thrombus load in coronary arteries would increase with time, and the implantation of stents in vessels with a large thrombus load will often lead to slow flow or no flow, which is a relative contraindication for interventional therapy.
At present, the guidelines recommend loading dose antiplatelet therapy and transport to the superior hospital for prime PCI within 2 hours if the first hospital for acute myocardial infarction does not have the conditions for emergency interventional therapy. Current guidelines recommend that thrombolytic therapy should be performed first and then transported when delivery is expected to be >2 hours to a hospital where PCI can be performed. And thrombolytic therapy is not recommended for patients who can perform PCI within <2 hours. There is a lack of clinical evidence for thrombolysis within 2 hours of first medical contact to Primary PCI. Compared with Primary PCI, early thrombolytic therapy can undoubtedly shorten the implementation time of reperfusion strategy to the maximum. For highly effective thrombolytic drugs, reperfusion time should be shortened, thrombus load should be reduced, and the size of myocardial infarction may be reduced and the prognosis of patients improved. There is a lack of clinical evidence for this. China is a developing country, whose grassroots and rural health resources are still poor. Early thrombolysis treatment plus subsequent reperfusion of interventional therapy not only conform to the Chinese characteristic, but also accord with the international research and the development direction in this field, which is worth further study.
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.
Recombinant SAK (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. R-SAK, a highly effective thrombolytic drug, may shorten the reperfusion time, reduce the size of myocardial infarction and improve the prognosis of the AMI patients.
The aim of this study was to investigate the efficacy of single bolus of r-SAK for thrombolytic therapy at the first contact with the patients who are diagnosed acute ST-segment elevation myocardial infarction. It is hypothesized that this therapy can open the culprit artery very early and effectively, reduce thrombus load, reduce slow flow or no flow caused by subsequent PCI, and improve myocardial tissue perfusion.
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 treatment group | Experimental | Drug: Recombinant Staphylokinaseintravenous injection of single bolus 5 mg r-SAK in 3min |
| saline control group | Placebo comparator | Drug: normal salineintravenous injection of 10ml saline in 3min,r-SAK and saline are the same in appearance |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Age ≥ 18, ≦75 years old, weight ≥45kg, gender is not limited.
- Diagnosis of acute ST-segment elevation myocardial infarction (both of the following) (A) Ischemic chest pain lasting more than 30 minutes; (B) Ecg indicates ST-segment elevation ≥ 0.1mV in 2 or more limb leads, or ST-segment elevation ≥ 0.2mV in 2 or more adjacent chest leads;
- Time from onset of persistent ischemic chest pain to randomization ≤12 hours;
- Coronary angiography and/or PCI are expected to be performed within 2 hours of r-SAK thrombolysis.
Key exclusion criteria (16 listed)
- Non-ST-segment elevation myocardial infarction;
- STEMI with cardiogenic shock;
- active bleeding or bleeding tendency, including Ⅲ, Ⅳ period history of retinopathy, retinal hemorrhage, gastrointestinal tract and urinary tract hemorrhage (1 month), ischemic stroke happened over the past 6 months, transient ischemic attack (TIA) happened over the past 6 weeks, hemorrhagic stroke in the past, unexplained platelet count < 100 x 109 / L or Hemoglobin <100g/L;
- Having a history of central nervous system trauma or known intracranial aneurysm;
- Recent (within 1 month) severe trauma, surgery or head injury;
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 StaphylokinaseAlso: r-SAK single intravenous injection for early treatment of acute myocardial infarctionIntravenous injection of r-SAK is administered within 10 minutes after diagnosis of acute ST-segment elevation myocardial infarction | Drug | r-SAK treatment group |
| normal salineAlso: normal saline intravenous injection for early treatment of acute myocardial infarctionIntravenous injection of placebo(normal saline ) is administered within 10 minutes after diagnosis of acute ST-segment elevation myocardial infarction | Drug | saline control group |
Primary outcome
the percentage of TIMI flow grade 2 and 3 or grade 3 after 60 minutes of the thrombolytic therapy
Time frame: 60 minutes
The primary endpoint
the incidence of major bleeding defined as Bleeding Academic Research Consortium (BARC) ≥3 bleeding
Time frame: 30 days
The main safety endpoint
8 secondary outcomes
The percentage of TIMI flow grade 3 after PCI
Time frame: 60 minutes
Clinical net benefits of MACE and major bleeding events during hospitalization
Time frame: 1 week
MACCEs, defined as composite of all-cause death, myocardial infarction, unplanned revascularization, ischemic stroke and cardiogenic re-hospitalization recorded during 30-day follow-up
Time frame: 30 days
Infarct size, Microvascular obstruction, cardiac function (EF) and Intramuscular hemorrhageH detected by MRI 5 days after AMI
Time frame: 5 days
Major bleeding (BARC ≥3) and minor bleeding (BARC ≤2) events during 30-day follow-up
Time frame: 30 days
The occurrence of slow or no reflow during CAG or PCI
Time frame: 60 minutes
Corrected TIMI Frame Count (CTFC) and TIMI Myocardial Perfusion Frame Count (TMPFC) after PCI
Time frame: 60 minutes
Malignant arrhythmia after thrombolysis and during hospitalization
Time frame: 1 week
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Jan 2023.
- Results publication: PubMed 29555722Correction to: Heart Disease and Stroke Statistics-2018 Update: A Report From the American Heart Association. Circulation. 2018 Mar 20;137(12):e493. doi: 10.1161/CIR.0000000000000573. No abstract available.
- Results publication: 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.
- Results publication: PubMed 16951276Agnoletti G, Cargnoni A, Agnoletti L, Di Marcello M, Balzarini P, Pasini E, Gitti G, Martina P, Ardesi R, Ferrari R. Experimental ischemic cardiomyopathy: insights into remodeling, physiological adaptation, and humoral response. Ann Clin Lab Sci. 2006 Summer;36(3):333-40.
- Results publication: PubMed 27523477Townsend N, Wilson L, Bhatnagar P, Wickramasinghe K, Rayner M, Nichols M. Cardiovascular disease in Europe: epidemiological update 2016. Eur Heart J. 2016 Nov 7;37(42):3232-3245. doi: 10.1093/eurheartj/ehw334. Epub 2016 Aug 14. No abstract available.
- Results publication: PubMed 15841305Collen D, Lijnen HR. Thrombolytic agents. Thromb Haemost. 2005 Apr;93(4):627-30. doi: 10.1160/TH04-11-0724.
- Results publication: PubMed 23998121Pulicherla KK, Kumar A, Gadupudi GS, Kotra SR, Rao KR. In vitro characterization of a multifunctional staphylokinase variant with reduced reocclusion, produced from salt inducible E. coli GJ1158. Biomed Res Int. 2013;2013:297305. doi: 10.1155/2013/297305. Epub 2013 Aug 13.
- Results publication: PubMed 16515501Ueshima S, Matsuo O. Development of new fibrinolytic agents. Curr Pharm Des. 2006;12(7):849-57. doi: 10.2174/138161206776056065.
- Results publication: 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.
- Results publication: PubMed 17549308Szemraj 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.
- Results publication: PubMed 29424308Vakili 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.
- Results publication: PubMed 17184583Li 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.
- Results publication: PubMed 21670242Mehran R, Rao SV, Bhatt DL, Gibson CM, Caixeta A, Eikelboom J, Kaul S, Wiviott SD, Menon V, Nikolsky E, Serebruany V, Valgimigli M, Vranckx P, Taggart D, Sabik JF, Cutlip DE, Krucoff MW, Ohman EM, Steg PG, White H. Standardized bleeding definitions for cardiovascular clinical trials: a consensus report from the Bleeding Academic Research Consortium. Circulation. 2011 Jun 14;123(23):2736-47. doi: 10.1161/CIRCULATIONAHA.110.009449. No abstract available.
- 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. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
9 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 and normal saline in people with Acute Myocardial Infarction, run by The First Affiliated Hospital with Nanjing Medical University at 9 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 4 inclusion and 16 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: finished, as of the sponsor's last update on 13 Jan 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
the percentage of TIMI flow grade 2 and 3 or grade 3 after 60 minutes of the thrombolytic therapy (time frame: 60 minutes). The study lists 2 primary outcomes in all. 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 NCT05023681, which also lists 16 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 13 Jan 2023.