Comparison of Antiplatelet Effect of Ticagrelor vs Tirofiban in Patients With Non-ST Elevation Acute Coronary Syndrome

Study Overview
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Brief Summary
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This is a single-center, open-label prospective randomized pharmacodynamic investigation of two anti platelet regimens in patients who are planned to undergo PCI for non-ST segment elevation acute coronary syndrome(NSTE-ACS) for 24 hours Ticagrelor : loading dose(180mg) followed by maintenance dose(90mg bid) Tirofiban : 0.4ug/kg/min for 30min followed by 0.1ug/kg/min both agents will be given on top of aspirin

Detailed Description
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In combination with aspirin, P2Y12 receptor antagonist or glycoprotein IIb/IIIa inhibitor(GPI) is now a recommended drug as the standard dual antiplatelet regimen in patients with acute coronary syndrome(1). Ticagrelor is a newly developed oral P2Y12 receptor inhibitor. It shows faster, greater and more consistent platelet inhibition as compared with previous P2Y12 receptor antagonist clopidogrel(2) and it also shows better clinical outcome and similar risk for bleeding as compared with clopidogrel(3).Interestingly, pharmacodynamic data of some studies showed excellent effect of ticagrelor in terms of inhibiting platelet activation apparently as high as that of GPI(2,4). Primary hypothesis: Ticagrelor have a comparable efficacy in platelet inhibition to GPI in patients with non-ST segment elevation acute coronary syndrome. Statistical design : non-inferiority test

Official Title
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Ticagrelor vs. Tirofiban, Comparison of Anti-platelet Effects in Patients With Non-ST Elevation Acute Coronary Syndrome(TE-CLOT Trial : Ticagrelor's Effect for CLOT Prevention) ; A Single Center, Open-label Randomized Controlled Study

Conditions
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Non-ST Segment Elevation Acute Coronary Syndrome

Intervention / Treatment
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* Drug: Tirofiban
* Drug: Ticagrelor


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with recent or current ischemic symptoms at the time of randomization will be eligible if 2 of the following criteria are met: ST-T change indicating ischemia; a positive test of biomarker indication myocardial necrosis; or one of several risk factors(age ≥60 years Previous myocardial infarction or coronary artery bypass grafting [CABG] Coronary artery disease with stenosis of ≥50% in at least two vessels Previous ischemic stroke, transient ischemic attack, carotid stenosis of at least 50%, or cerebral revascularization Diabetes mellitus Peripheral arterial disease; or chronic renal dysfunction, defined as a creatinine clearance of <60 ml per minute per 1.73 m2 of body surface area) Exclusion Criteria: Administration of fibrinolytic or any GP IIb/IIIa inhibitors for the treatment of current AMI 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 hemodialysis Documented allergy/intolerance or contraindication to tirofiban or P2Y12 inhibitor 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
Maximum Age: 80 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ticagrelor<br>loading dose(180mg) followed by maintenance dose(90mg bid) | Drug: Ticagrelor<br>* loading dose(180mg) followed by maintenance dose(90mg bid)<br>|
| Active Comparator: Tirofiban<br>0.4ug/kg/min for 30min followed by 0.1ug/kg/min | Drug: Tirofiban<br>* 0.4ug/kg/min for 30min followed by 0.1ug/kg/min<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage IPA after 20µmol/l ADP at 2 hour | 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 15 min at 100 g, will be stimulated with 20 µmol/l ADP and aggregation will be assessed using a light transmittance aggregometer(Chronolog, USA). | 2 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage IPA at 8 hours after 20µMol ADP, TRAP, Arachidonic acid, Collagen | 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 15 min at 100 g, will be stimulated with 20 µmol/l ADP, TRAP, arachidonic acid and collagen and aggregation will be assessed using a light transmittance aggregometer(Chrono-log, USA). | 8 hours | 
| Percentage IPA at 8 hours after 20µMol ADP, TRAP, Arachidonic acid, Collagen | Blood samples with 0.129 mol/l sodium citrate will be collected for platelet reactivity. Platelet-rich plasma, obtained by centrifuging whole blood for 15 min at 100 g, will be stimulated with 20 µmol/l ADP, TRAP, arachidonic acid and collagen and aggregation will be assessed using a light transmittance aggregometer(Chrono-log, USA). | 24 hours | 
| periprocedural bleeding | Periprocedural bleeding will be monitored and described according to BARC and TIMI definition | 0 24 hours | 
| Peak cardiac enzyme level | From blood samples at 0, 2H, 8H and 24H, CK-MB and Troponin I will be measured | 0 24 hours | 
| Percentage IPA after TRAP, arachidonic acid, collagen at 2 hours | 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 15 min at 100 g, will be stimulated with TRAP, arachidonic acid and collagen and aggregation will be assessed using a light transmittance aggregometer(Chrono-log, USA). | 2 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ticagrelor, tirofiban, glycoprotein IIa/IIIa inhibitors, P2Y12 blockers, acute coronary syndrome