The OPTIMA-5 Trail
Condition: Acute Myocardial Infarction
MeSH terms: Myocardial Infarction; Infarction
Study type: Interventional
Phase: Phase 4

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). 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.
    

Intervention name(s): Recombinant Staphylokinase; normal saline
Intervention type(s): Drug; Drug
Intervention description(s): Intravenous injection of r-SAK is administered within 10 minutes after diagnosis of acute ST-segment elevation myocardial infarction; Intravenous injection of placebo(normal saline ) is administered within 10 minutes after diagnosis of acute ST-segment elevation myocardial infarction
Other intervention name(s): r-SAK single intravenous injection for early treatment of acute myocardial infarction; normal saline intravenous injection for early treatment of acute myocardial infarction
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Acute Myocardial Infarction；Recombinant Staphylokinase; thrombolysis