PACT (Platelet Activity After Clopidogrel Termination)

Study Overview
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Brief Summary
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Clopidogrel is a medication that is used to decrease the ability of platelets to form blood clots. The theory has been proposed that, in patients with coronary artery disease or stroke, increased platelet function after discontinuation of clopidogrel therapy is associated with an increased clotting risk. However, this theory has never been rigorously tested. The goal of this research is to determine whether discontinuation of clopidogrel results in increased platelet function.

Detailed Description
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In this study, we will address the question: does discontinuation of clopidogrel result in platelet hyperreactivity? We will perform a double-blind, placebo-controlled, crossover study in normal subjects, in whom platelet reactivity will be measured before clopidogrel or placebo, during clopidogrel or placebo, and at various time points after discontinuation of clopidogrel or placebo. The dose of clopidogrel will be the standard, FDA-approved dose: 75 mg daily. All subjects will be treated with aspirin 81 mg daily throughout the 57 days of study assessment in both the clopidogrel arm and the placebo arm, because the clinically relevant question is: in patients who remain on aspirin, does discontinuation of clopidogrel result in platelet hyperreactivity?

Official Title
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PACT (Platelet Activity After Clopidogrel Termination)

Conditions
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Clopidogrel, Blood Platelets

Intervention / Treatment
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* Drug: clopidogrel + aspirin
* Drug: placebo
* Drug: Aspirin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Must be a normal healthy subject Must be between 21-70 years old Must be able to take aspirin and clopidogrel. Must be able to have blood drawn 16 times over approximately 3 months. Exclusion Criteria: Subject who is currently taking aspirin or another anti-platelet drug such as clopidogrel. Subject must be free of these medications for 10 days before enrolling in this study. Subject who is currently taking a non-steroidal anti-inflammatory drug such as ibuprofen or naproxen. Subject must be free of these medications for 3 days before enrolling in this study. Subject who is currently taking medications for depression or medications that lower blood pressure or lower blood sugar. Subject who are pregnant or may become pregnant during the study or who is breast feeding. Subject with a known allergy to aspirin or clopidogrel. Cigarette smoking or use of other nicotine product. Subject with a history of any of the following: coronary artery disease; stroke; bleeding disorder; ongoing bleeding; previous life-threatening hemorrhage; stomach ulcers; gastrointestinal bleeding within the past 1 month; major surgery within the past 1 month; minor surgery within the past 2 weeks; or platelet transfusion within the past 7 days. Subject with a blood count, measured on the pre-study drug blood sample, that is not in the normal range. Subject who is enrolled in another clinical trial of an investigational drug.

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Clopidogrel + aspirin<br>The subjects will be randomized to clopidogrel 75 mg plus aspirin 81 mg orally daily for 14 days. The study drug (i.e., clopidogrel) will then be discontinued and aspirin continued for another 43 days. | Drug: clopidogrel + aspirin<br>* Clopidogrel 75mg plus aspirin 81mg, tablet by mouth daily for 14 days.<br>* Other names: aspirin;Drug: Aspirin<br>* Aspirin 81mg tablet by mouth continued daily alone for 43 days after day 14.<br>|
| Placebo Comparator: Placebo + aspirin<br>The subjects will be randomized to placebo plus aspirin 81 mg orally daily for 14 days. The study drug (i.e., placebo) will then be discontinued and aspirin continued for another 43 days. | Drug: placebo<br>* Placebo plus aspirin 81 mg, tablet by mouth daily for 14 days.<br>* Other names: aspirin;Drug: Aspirin<br>* Aspirin 81mg tablet by mouth continued daily alone for 43 days after day 14.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Platelet Surface Activated GPIIb-IIIa Complex at 45 Days After Intervention. | Value at 45 days after intervention minus value at baseline in platelet surface activated GPIIb-IIIa complex using flow cytometry.The types and concentrations of agonists used in the flow cytometry assays reported here were: ADP 0.5, 1, and 20 µmol/L; thrombin receptor activating peptide (TRAP) 1 and 20 µmol/L; and a combination of collagen 5 µg/mL and epinephrine 5 µmol/L. Mean Florescence Intensity (MFI) is used as unit of measure. MFI indicates relative degree of shift in fluorescence intensity of a population of platelets in arbitrary units. | Baseline and 45 days after intervention | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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blood platelets, platelet aggregation inhibitors, antiplatelet drugs, clopidogrel