Prolonged Clinical Follow-up of OPTIMA-5

Phase 4

Completed

• Conditions: ST-segment Elevation Myocardial Infarction (STEMI)
• Interventions: Drug: Recombinant Staphylokinase; Drug: Normal Saline

• Registration Number: NCT05649696
• Lead Sponsor: The First Affiliated Hospital with Nanjing Medical University

Brief Summary

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.

Detailed 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.

Study Timeline

• Study Start: 2021-10-29
• Study First Submitted: 2022-11-24
• Study First Submitted QC: 2022-12-12
• Study First Posted: 2022-12-14
• Primary Completion: 2023-09-14
• Study Completion: 2023-10-01
• Status Verified: 2024-02
• Last Update Submitted: 2024-02-22
• Last Update Posted: 2024-02-26

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 210

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
r-SAK group	Recombinant Staphylokinase	intravenous injection of single bolus 5 mg r-SAK in 3min
normal saline group	Normal Saline	intravenous injection of 10ml saline in 3min, r-SAK and saline are the same in appearance

Primary Outcome Measures

Name	Time	Method
MACE	Within 360 days	A composite of all-cause death, reinfarction, unplanned target vessel revascularization, heart failure or cardiogenic shock, major ventricular arrhythmia

Secondary Outcome Measures

Name	Time	Method
Adverse cardiac and cerebrovascular events	Within 360 days	Each of the above independent MACE events, cardiovascular death, cardiac mechanical complications and stroke.

Trial Locations

Locations (8)

The First Affiliated Hospital of Nanjing Medical University; 🇨🇳 Nanjing, Jiangsu, China

Changzhou Second People's Hospital; 🇨🇳 Changzhou, China

The second Affiliated Hospital of Dalian Medical University; 🇨🇳 Dalian, China

Lianyungang First People's Hospital; 🇨🇳 Lianyungang, China

Affiliated Hospital of Jiangnan University; 🇨🇳 Wuxi, China

Taizhou People's Hospital; 🇨🇳 Taizhou, China

The Second Affiliated Hospital of Zhejiang University Medical College; 🇨🇳 Zhejiang, China

Huai 'an Second People's Hospital affiliated to Nanjing Medical University; 🇨🇳 Huai'an, China