A study to test the safety and effectiveness of using mutant pro-urokinase and low-dose alteplase to unblock blood vessels in heart attack patients before receiving treatment at a hospital with PCI capability

INTERVENTION: Patients randomised into the intervention arm will receive sequential fibrinolysis consisting of an alteplase bolus dose followed by an infusion of the study medication. Patients randomised into the standard of care arm will receive either: 1. No fibrinolytic therapy if the anticipated delay to the cardiac cath lab is <2 h 2. Conventional, full‐dose, fibrinolytic therapy if the anticipated delay to the cardiac cath lab is >2 h Randomisation – Randomisation activity will be performed via the use of an online electronic case report form. Patients will be centrally allocated by the eCRF system, stratified by site, to the interventional arm or the standard of care arm. Follow up activity:‐ Patients will be followed up with ECGs and coagulation tests for the 24‐h period following the PCI procedure which include the primary study endpoint. MRIs will be performed at Day 2‐4 and at the end of the study (Day 30) to assess the Salvage Index. CONDITION: Participants presenting with ST‐elevation myocardial infarction ; Circulatory System PRIMARY OUTCOME: Change from baseline serum fibrinogen levels to 6 h after administration of the IMP INCLUSION CRITERIA: 1. Presentation to an investigational site with an acute ST‐elevation myocardial infarction (symptom onset 0‐6 h) requiring mechanical reperfusion with primary PCI to one or more lesions 2. Visually assessed ST‐segment elevation (measured at the J‐point) in at least two contiguous leads with ST‐segment elevation. = 2.5 mm in men <40 years; =2 mm in men =40 years = 1.5 mm in women in leads V2–V3 and/or = 1 mm in the other leads In the absence of left ventricular hypertrophy or left bundle branch block (LBBB) and associated with ongoing ischaemic symptoms 3. Aged =18 years 4. Anticipated delay to primary PCI of at least 1 hour from presentation to being able to be treated with emergency mechanical reperfusion at a PCI‐capable centre 5. Able in person, or with the support of a Next of Kin or legal guardian, to provide informed verbal assent prior to randomisation. 6. Radial artery access for primary PCI procedure SECONDARY OUTCOME: 1. Reperfusion, thrombus, epicardial patency (coronary angiography) pre and post PCI, and microvascular patency (coronary physiology: inde Xof microcirculatory resistance [IMR]) will be assessed at the end of the inde Xprimary PCI procedure. These measures will be analyzed centrally at an independent CoreLab.; 2. Coronary angiography measures of reperfusion and thrombus (pre‐ and post‐primary PCI procedure) will include TIMI flow, TIMI myocardial blush grade, TIMI frame count, and TIMI thrombus grade.; 3. Epicardial patency will be evaluated using parameters like reference vessel diameter, minimum lumen diameter, and percentage diameter stenosis from coronary angiography before (immediately after coronary angiogram) and after the PCI procedure. The analysis will be done centrally at a selected independent CoreLab.; 4. Microvascular patency (coronary physiology ‐ index‐of‐microcirculatory resistance [IMR]) will be assessed at the end of the inde Xprimary PCI procedure, with the site reporting the results.; 5. Percentage ST segment resolution on ECG will be measured at baseline, immediately before the primary PCI procedure, and 1 h after the primary PCI.; 6. Acute infarct characteristics on contrast‐enhanced cardiac MRI will be evaluated at Day 2‐4, including myocardial salvage inde Xas a surrogate measure of therapeutic benefit and late gadolinium enhancement (LGE, % LV mass) volume (acute infarct size).; 7. Incidence and extent of microvascular obstruction (MVO) and/or hemorrhage will be expressed as a percentage of left ventricular mass.; 8. Left ventricular end‐diastolic volume, left ventricular end‐systolic volume, and left ventricular ejection fraction will be assessed as part of the final infarct size on contrast‐enhanced cardiac magnetic resonance imaging (MRI) at Day 30 (range 23‐44 days).; 9. The Selvester score of 30‐day infarct size on the ECG taken at day 30 will be calculated. The Selvester score translates subtle changes in ventricular depolarization on ECG to a surrogate measure of infarct size, with a maximum score of 32 points, where 1 point corresponds to 3% of the left ventricle.; 10. 30‐day mortality, readmission for heart failure, and acute bleeds (BARC =3) will be recorded as outcomes.; 11. Changes in fibrinogen and D‐Dimers levels will be monitored from baseline, immediately pre‐ and post‐primary PCI, 6 hrs, and 24 hrs post randomization. The primary endpoint is the change in fibrinogen from baseline to 6 hours post randomization.; 12. Outcomes will be stratified by transfer times and the dose of the IMP administered.; 13. Patient‐reported outcomes for Heart Related Quality of Life (HRQoL), Medical Outcome Study 36 Item Health Survey (MOS SF‐36), and the Seattle Angina Questionnaires (SAQ) will be collected at Day 30.; 14. Other endpoints will include outcomes stratified by anatomical complexity.; 15. Baseline and residual SYNTA XScores from pre‐ and post‐primary PCI procedures will be calculated. The score will be determined centrally at a selected independent CoreLab.