Antiplatelet Effects of Ticagrelor Versus Clopidogrel in American Indian Patients

Study Overview
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Brief Summary
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Assess the pharmacodynamic effect of ticagrelor vs. Clopidogrel in American Indian patients with stable coronary artery disease.

Detailed Description
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A Single Center, Randomized, Open Label, Multiple Dose, Crossover Study of the Antiplatelet Effects of Ticagrelor Versus Clopidogrel in American Indian Patients With Stable Coronary Artery Disease

Official Title
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A Single Center, Randomized, Open Label, Multiple Dose, Crossover Study of the Antiplatelet Effects of Ticagrelor Versus Clopidogrel in American Indian Patients With Stable Coronary Artery Disease

Conditions
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Coronary Artery Disease

Intervention / Treatment
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* Drug: Ticagrelor
* Drug: Clopidogrel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Documented stable CAD fulfilling any of the following, and taking 81mg ASA daily treatment: Females must be post menopausal for at least one year or surgically sterile for at least 6 months and negative urine pregnancy test Self-identified as American Indian Genetic Inclusion Criteria: must sign the informed consent for genetic and biological sample banking. Exclusion Criteria: Any indication for oral anticoagulant or dual antiplatelet treatment Concomitant therapy with strong CYP3A inhibitors, CYP3A substrates with narrow therapeutic index, or strong CYP3A inducers within 14 days and during study treatment and during: Increased bleeding risk including: Diabetic patients with HbAlC > 10% at screening Contraindication to clopidogrel, ASA, or ticagrelor - A history of alcohol and/or substance abuse that could interfere with conduct of the trial Patients requiring dialysis Patients scheduled for revascularization (e.g., PCI, CABG) during the study period Any acute or chronic unstable condition in the past 30 days Known active or recurrent hepatic disorder Patients who had ACS or stent placed within 12 months of screening History of Uric Acid nephropathy

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: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ticagrelor<br>Ticagrelor 180 mg loading dose followed by 90 mg bid for 7 days ± 2 days | Drug: Ticagrelor<br>* Ticagrelor 180 mg loading dose followed by 90 mg bid for 7 days ± 2 days<br>* Other names: Brand Name: Brilinta;Drug: Clopidogrel<br>* Clopidogrel 600 mg loading dose followed by 75 mg Daily for 7 days ± 2 days<br>* Other names: Brand Name: Plavix;|
| Active Comparator: Clopidogrel<br>Clopidogrel 600 mg Loading Dose followed by 75 mg Daily for 7 days ± 2 days | Drug: Ticagrelor<br>* Ticagrelor 180 mg loading dose followed by 90 mg bid for 7 days ± 2 days<br>* Other names: Brand Name: Brilinta;Drug: Clopidogrel<br>* Clopidogrel 600 mg loading dose followed by 75 mg Daily for 7 days ± 2 days<br>* Other names: Brand Name: Plavix;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Compare ticagrelor's versus clopidogrel's inhibition of the P2Y12 receptor as measured by the decrease in P2Y12 Reaction Units (PRU) using VerifyNow TM. |  | At 2 hour time point after loading dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Compare the decrease of P2Y12 Reaction Units (PRU) by VerifyNow TM from ticagrelor and clopidogrel. |  | 0.5 and 8 hour time points after loading dose | 
| Compare the decrease in P2Y l2 Reaction Units (PRU) by VerifyNow™ from ticagrelor's and clopidogrel's morning dose on Day 7 |  | At the 2, 8, and 24 hours after the last dose | 
| To evaluate and compare the pharmacodynamic effects, measured by the vasodilator-stimulated phosphoprotein (VASP) assay (platelet reactivity index [PRI]), in all subjects |  | Day1: pre-dose, 0.5, 2, and 8 hours post loading dose Day 7: pre-dose, 2 and 8 hours post dose Day 8: 24 hours post final dose | 
| Assess and to compare the percentage of subjects with High on-treatment Platelet Reactivity (HPR) at all time points after randomized study treatment. | The High on-treatment Platelet Reactivity will be defined in accordance with the following platelet inhibition level cut-off. > 208 PRU by the VerifyNow P2Y12 assay > 230 PRU by the VerifyNow P2Y12 assay > 50% PRI by the VASP assay | Day 1: Pre-dose, 0.5, 2 and 8 hours post loading dose Day 7: pre-dose, 2 and 8 hours post dose Day 8: 24 hours after final dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Clopidogrel, Ticagrelor, Coronary Artery Disease, Myocardial Ischemia, Coronary Disease, Heart Diseases, Cardiovascular Diseases, Arteriosclerosis, Arterial Occlusive Diseases, Vascular Diseases, Platelet Aggregation Inhibitors, Hematologic Agents, Therapeutic Uses, Pharmacologic Actions, Purinergic P2Y Receptor Antagonists, Purinergic P2 Receptor Antagonists, Purinergic Antagonists, Purinergic Agents, Physiological Effects of Drugs