Participants presenting with ST-elevation myocardial infarction Circulatory System
Conditions
Interventions
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
Sponsors
Thrombolytic Science LLC
Eligibility
Sex/Gender
All
Age
18 Years to 100 Years
Inclusion criteria
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
Exclusion criteria
Exclusion criteria: 1. Left bundle branch block (LBBB) or ventricular pacing 2. Currently taking a P2Y12 inhibitor (clopidogrel, ticagrelor or prasugrel) 3. High bleeding risk patients – one major, or two minor criteria on the ARC-HBR criteria 4. Prior percutaneous coronary intervention in the last 3 months 5. Known contraindications to primary PCI or cardiac MRI 6. Cardiogenic shock (Killip Class IV) 7. NYHA Class 3-4 heart failure 8. History of intracranial haemorrhage 9. Known intolerance/hypersensitivity to aspirin, ticagrelor, heparin, limus drugs 10. Patients with current concomitant oral anticoagulant therapy, including vitamin K antagonists (warfarin) and non-vitamin K antagonist oral anticoagulants (NOACS) 11. Recent administration of any intravenous or subcutaneous anticoagulation within 12 h, including unfractionated heparin, enoxaparin, and/or bivalirudin 12. Severe hepatic impairment 13. Non-cardiac co-morbidity with expected survival <1 year 14. Patients of child-bearing potential with either a confirmed positive pregnancy test or those unable to have a pregnancy test conducted prior to inclusion in the study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change from baseline serum fibrinogen levels to 6 h after administration of the IMP | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Reperfusion, thrombus, epicardial patency (coronary angiography) pre and post PCI, and microvascular patency (coronary physiology: index of microcirculatory resistance [IMR]) will be assessed at the end of the index primary 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 index primary 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 index as 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 | — |
Countries
United Kingdom, Wales
Outcome results
None listed