Facilitation Through Aggrastat By drOpping or Shortening Infusion Line in Patients With ST-segment Elevation Myocardial Infarction Compared to or on Top of PRasugrel Loading dOse

Study Overview
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Brief Summary
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This is a single-centre, open-label prospective randomized pharmacodynamic investigation of 2 antiplatelet regimens in patients undergoing coronary intervention for ST segment elevation myocardial infarction(STEMI): Tirofiban bolus only or bolus followed by 2 hour infusion on top of 600 mg clopidogrel or 60 mg prasugrel. Prasugrel given at 60 mg.

Detailed Description
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Primary hypothesis: Percentage IPA after 20uMol/ADP at 30' will be superior in the tirofiban arm (as aggregate) versus prasugrel alone arm Percentage IPA at 30' after 20uMol/ADP 90%±15 and 80%±15 in the tirofiban and prasugrel alone arm, respectively. For a power of 90% and an alpha error set at 5%, 50 patients per group have to be recruited.

Official Title
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Comparison of Multiple Oral and/or Intravenous Anti-platelet Strategies in Patients With ST-segment Elevation Myocardial Infarction Undergoing Primary PCI

Conditions
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ST Segment Elevation Myocardial Infarction

Intervention / Treatment
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* Drug: Prasugrel
* Drug: Tirofiban


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Chest pain for >30 min with an electrocardiographic ST-segment elevation more than 1 mm in two or more contiguous electrocardiogram (ECG) leads, or with a new left bundle-branch block, and admission either within 12 h of symptom onset or between 12 and 24 h after onset with evidence of continuing ischemia Exclusion Criteria: Administration of fibrinolytic or any GP IIbIIIa inhibitors for the treatment of current AMI or within 1 month before history of bleeding diathesis Known sensitivity to abciximab, to any component of the product or to murine monoclonal antibodies Major surgery or trauma within 30 days Active bleeding Previous stroke in the last six months Oral anticoagulant therapy Pre-existing thrombocytopenia Vasculitis Hypertensive retinopathy Severe hepatic failure Severe renal failure requiring haemodialysis Documented allergy/intolerance or contraindication to clopidogrel or inability to assume clopidogrel on a consecutive daily basis for a minimum of 30 days, or to heparin or aspirin Uncontrolled hypertension (systolic or diastolic arterial pressure >180 mmHg or 120, respectively, despite medical therapy) Limited life expectancy, e.g. neoplasms, others Inability to obtain informed consent

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: prasugrel<br>Prasugrel 60 mg loading dose | Drug: Prasugrel<br>* 60 mg loading dose given orally at presentation<br>|
| Active Comparator: Tirofiban<br>Tirofiban will be at a bolus only of 25uM or followed by 2 hour infusion | Drug: Tirofiban<br>* Tirofiban will be given at high bolus dose only of bolus followed by 2 H infusion in a randomized manner (1:1 ratio).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage IPA after 20uMol/ADP at 30' will be superior in the tirofiban arm (as aggregate) versus prasugrel alone arm | Platelet aggregation (PA) will be performed as previously reported [J Am Coll Cardiol 2006;48:2178-85]. Blood samples anticoagulated with 0.129 mol/l sodium citrate will be collected for platelet reactivity. Platelet-rich plasma, obtained by centrifuging whole blood for 10 min at 200 g, will be stimulated with 5 and 20 µmol/l adenosine 5'-diphosphate (ADP) (Alfa Wasserman, Bologna, Italia) and aggregation will be assessed using a AggRAM Advanced Modular System light transmittance aggregometer. | 30 minutes | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage IPA at 15 minutes after ADP or TRAP induced platelet aggregation via traditional light transmission aggregometry. | Blood samples draen at 15', 30', 1H, 2H, 6H and 18-24H, anticoagulated with 0.129 mol/l sodium citrate will be collected for platelet reactivity. Platelet-rich plasma, obtained by centrifuging whole blood for 10 min at 200 g, will be stimulated with 5 and 20 µmol/l adenosine 5'-diphosphate (ADP) and 5 and 15 TRAP. | 15 minutes | 
| Clinical outcomes | Death, Myocardial infarction, stroke and the need for target vessel revascularisation will be monitored up to 1 year | 1 year | 
| Percentage IPA at 1 hour after ADP or TRAP induced platelet aggregation via traditional light transmission aggregometry. | Blood samples draen at 15', 30', 1H, 2H, 6H and 18-24H, anticoagulated with 0.129 mol/l sodium citrate will be collected for platelet reactivity. Platelet-rich plasma, obtained by centrifuging whole blood for 10 min at 200 g, will be stimulated with 5 and 20 µmol/l adenosine 5'-diphosphate (ADP) and 5 and 15 TRAP. | 1 hour | 
| Percentage IPA at 2 hours after ADP or TRAP induced platelet aggregation via traditional light transmission aggregometry. | Blood samples draen at 15', 30', 1H, 2H, 6H and 18-24H, anticoagulated with 0.129 mol/l sodium citrate will be collected for platelet reactivity. Platelet-rich plasma, obtained by centrifuging whole blood for 10 min at 200 g, will be stimulated with 5 and 20 µmol/l adenosine 5'-diphosphate (ADP) and 5 and 15 TRAP. | 2 hours | 
| Percentage IPA at 6 hours after ADP or TRAP induced platelet aggregation via traditional light transmission aggregometry. | Blood samples draen at 15', 30', 1H, 2H, 6H and 18-24H, anticoagulated with 0.129 mol/l sodium citrate will be collected for platelet reactivity. Platelet-rich plasma, obtained by centrifuging whole blood for 10 min at 200 g, will be stimulated with 5 and 20 µmol/l adenosine 5'-diphosphate (ADP) and 5 and 15 TRAP. | 6 hours | 
| Percentage IPA at 18-24 hours after ADP or TRAP induced platelet aggregation via traditional light transmission aggregometry. | Blood samples draen at 15', 30', 1H, 2H, 6H and 18-24H, anticoagulated with 0.129 mol/l sodium citrate will be collected for platelet reactivity. Platelet-rich plasma, obtained by centrifuging whole blood for 10 min at 200 g, will be stimulated with 5 and 20 µmol/l adenosine 5'-diphosphate (ADP) and 5 and 15 TRAP. | 18-24 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Prasugrel, Tirofiban, Clopidogrel, glycoprotein IIa/IIIa inhibitors, P2Y12 blockers