Prolonged Clinical Follow-up of OPTIMA-5

Nanjing Medical University

Status and phase: Completed; Phase 4

Conditions: ST-segment Elevation Myocardial Infarction (STEMI)

Treatments: Drug: Normal Saline; Drug: Recombinant Staphylokinase

Study type: Interventional

Funder types: Other

Identifiers

NCT05649696

020

Details and patient eligibility

About

The OPTIMA-5 trial is a prospective, multi-center, randomized, patient blinded, controlled trial comparing a single bolus of half-dose recombinant staphylokinase (r-SAK) with normal saline (NS) in patients with ST-segment elevation myocardial infarction (STEMI) presenting ≤12 hours of symptom onset and expected to undergo primary percutaneous coronary intervention (PPCI) within 120 minutes. The results of OPTIMA-5 showed that a single bolus r-SAK prior to PPCI for STEMI improves infarct related artery (IRA) patency and reduces infarct size without increasing major bleeding. On this basis, this study was designed to investigate the effect of the novel reperfusion strategy on 1-year outcomes of patients with STEMI.

Full description

Acute myocardial infarction (AMI) is one of the leading causes of death all over the world, and accounted for more than 100 thousand deaths in the US in 2019. Early PPCI reduces mortality in patients with STEMI. If PPCI cannot be performed within 120 minutes of presentation, guidelines recommend the use of thrombolytic therapy. However, it remains uncertain whether adjunctive thrombolytic therapy administered immediately prior to PPCI improves outcomes in patients undergoing the procedure within 120 minutes.

SAK is a fibrin specific fibrinolytic agent produced by Staphylococcus aureus that was first discovered in 1948. A recombinant form of SAK was approved by China Food and Drug Administration (CFDA) for treatment of patients with STEMI. It has been demonstrated that r-SAK is more potent than urokinase and recombinant streptokinase in rabbit models.

The OPTIMA-5 trial is an investigator-initiated, prospective, multi-center, randomized, patient blinded, controlled trial comparing a single bolus of half-dose r-SAK with NS in patients with STEMI presenting ≤12 hours of symptom onset and expected to undergo PPCI within 120 minutes. Between October 29, 2021 and August 14, 2022, 283 STEMI patients were screened in 8 centers in China and 200 were randomized to r-SAK group or control in a 1:1 ratio using a computer-generated randomization sequence.

On this basis, this study was aimed to conduct a 1-year follow-up study to further confirm the efficacy and safety of this novel reperfusion strategy for patients with STEMI.

Enrollment: 210 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Arm 1 and 2 inclusion and exclusion criteria

Inclusion Criteria:

1. Age 18-75 years, weight ≥45 kg;

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

   i. Ischemic chest pain lasts ≥30 minutes; ii. Electrocardiogram indicates that ST-segment elevation ≥2 mm in 2 or more contiguous precordial leads or ≥1 mm in 2 or more peripheral leads;

3. Time from onset of persistent chest pain to randomization <12 hours;

4. Primary PCI expected to be performed within 120 minutes.

Exclusion Criteria:

1. Cardiogenic shock;
2. Active bleeding or 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. Platelet count <100×109/L or hemoglobin <100 g/L;
6. Known intracranial aneurysm;
7. Severe trauma, surgery or head injury within 1 month;
8. Suspected aortic dissection or infective endocarditis;
9. Recent puncture with difficult hemostasis by compression (eg, visceral biopsy, compartment puncture);
10. Currently taking anticoagulants;
11. Poorly controlled hypertension ( ≥180/110 mmHg);
12. Hepatic or renal impairment (glutamic-pyruvic transaminase, glutamic oxalacetic transaminase, or γ -glutamyl transferase >2.5 times upper limit of normal value; creatinine >1.5 times upper limit of normal value);
13. Known allergy to r-SAK;
14. Pregnancy, lactation, or planning for pregnancy;
15. History of myocardial infarction or CABG;
16. Having taken antiplatelet drugs other than aspirin and ticagrelor, such as clopidogrel, prasugrel or cilostazol after the symptom onset;
17. Patients with other conditions that made them unsuitable to be recruited at the discretion of the investigators.

Arm 3 inclusion and exclusion criteria Inclusion criteria

1. Age ≥18, ≤75 years old, weight ≥45kg, gender is not limited；
2. Taking maintenance dose of aspirin and ticagrelor for more than 3 days, or taking loading dose of aspirin (300mg) and ticagrelor (180mg);
3. Inpatients with suspected coronary atherosclerotic heart disease scheduled for coronary angiography or interventional therapy.

Exclusion criteria

1. Patients who had received r-SAK thrombolytic therapy before;
2. Previous diagnosis of Staphylococcus aureus infection;
3. Patients who were participating in other clinical trials;
4. Other patients considered unsuitable for inclusion by the investigators.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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210 participants in 3 patient groups, including a placebo group

r-SAK group

Experimental group

Description:

intravenous injection of single bolus 5 mg r-SAK in 3min

Treatment:

Drug: Recombinant Staphylokinase

normal saline group

Placebo Comparator group

Description:

intravenous injection of 10ml saline in 3min, r-SAK and saline are the same in appearance

Treatment:

Drug: Normal Saline

patients with coronary artery disease

No Intervention group

Description:

20 ml arterial blood samples and 5 ml venous blood samples were collected from patients before coronary angiography