Comparison of Low-Dose, Standard-Dose Ticagrelor and Clopidogrel for Inhibition of Platelet Reactivity in Patients With Acute Coronary Syndromes

Study Overview
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Brief Summary
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The purpose of this study is to compare Low-Dose, Standard-Dose Ticagrelor and Clopidogrel for Inhibition of Platelet Reactivity in Patients with Acute Coronary Syndromes

Official Title
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Comparison of Low-Dose, Standard-Dose Ticagrelor and Clopidogrel for Inhibition of Platelet Reactivity in Patients With Acute Coronary Syndromes; Pharmacodynamics and Pharmacokinetics Study

Conditions
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Acute Coronary Syndrome

Intervention / Treatment
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* Drug: ticagrelor
* Drug: clopidogrel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ST elevation or non ST elevation acute coronary syndrome patients of chest pain within 24 hours Exclusion Criteria: Known hypersensitivity to clopidogrel and ticagrelor and aspirin Treatment with anticoagulants Exposure to a thrombolytic agent within 24 hours prior to randomization Use of glycoprotein IIb - IIIa inhibitors at randomization History of major hemorrhage (intracranial, gastrointestinal, etc.) clotting disorder and/or bleeding disorder Any history of Severe renal or hepatic dysfunction Hematologic disorder including a Hemoglobin less than 10 g/L or a platelet count less than 80,000 cells/mm3 Cardiac shock, severe left ventricular dysfunction LVEF less than 30% Sick sinus syndrome or second degree of av block without permanent pacemaker No concurrent cytochrome p450 3a inhibitors and enhancers within 2 weeks Subject has any condition for which, in the opinion of the investigator, participation would not be in the best interest of the subject (eg,drug and alcohol abuse, mental illness) or that could prevent, limit, or confound the protocol-specified assessments. Life expectancy of less than 6 months Pregnancy or lactating Participation in any drug study in the previous 3 months Inability to follow the protocol and comply with follow-up requirements or any other reason that the investigator feels would place the patient at increased risk

Ages Eligible for Study
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Minimum Age: 20 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: Low dose ticagrelor<br>60mg bid | Drug: ticagrelor<br> <br> |
| Active Comparator: standard dose ticagrelor<br>90mg bid | Drug: ticagrelor<br> <br> |
| Active Comparator: standard dose clopidogrel<br>75mg qd | Drug: clopidogrel<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| P2Y12 reaction units(PRU) | P2Y12 Reaction Units (PRU) measured by VerifyNow P2Y12 assay | 8 hours and 30days after first randomized dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage inhibition of platelet aggregation |  | 0, 0.5, 1, 2, 4, 8,24 hours and 30 days after first randomized study treatment | 
| Aggregation units(AU), Area Under the Curve(AUC) | by Multiplate analyzer | 0, 0.5, 1, 2, 4, 8,24 hours and 30 days after first randomized study treatment | 
| Percentage of low-responsive patients | Low-responsive patients is defined as PRU ≥ 235 from VerifyNow P2Y12 and/or percentage of platelet inhibition <15% | 0, 0.5, 1, 2, 4, 8,24 hours and 30 days after first randomized study treatment | 
| Description of the pharmacokinetic (PK) profile for Ticagrelor and its metabolite AR-C124910XX | in terms of maximum concentration (Cmax),time to maximum concentration (tmax) and area under the concentration curve from time zero to infinity (AUC), t1/2, CL/F | 0, 0.5, 1, 2, 4, 8, 10,24 hours after first randomized study treatment | 
| MACE(Major adverse cardiac event) | Death, Myocardial Infarction, stent thrombosis, stroke, | 30 days after first randomized study treatment | 
| Adverse event | including bleeding by TIMI/PLATO criteria, dyspnea, bradycardia, syncope, | 30 days after first randomized study treatment | 
| Drug tolerance | Drug tolerance is evaluated as adverse event following discontinuation of drug administration | 30 days after first randomized study treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Inhibition of Platelet Reactivity, ticagrelor, clopidogrel, Pharmacodynamics, Pharmacokinetics