Effect of Amlodipine on Anti-platelet Drug Effect in Patients With Coronary Artery Disease

Study Overview
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Brief Summary
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Clopidogrel can reduce risk of cardiovascular disease by inhibiting platelet aggregation. It is metabolized to an active drug by a liver enzyme. Its efficacy may be measured by blood sampling for platelet activity, analyzed by VerifyNow device. Calcium Channel blocker (CCB) is also commonly used for blood pressure and anginal control in these patients. Dihydropyridine group of calcium channel blocker (e.g. amlodipine) inhibits this enzyme. There are observational studies reporting dihydropyridine CCB reducing clopidogrel effect, but the clinical implication is unclear. This study test the hypothesis that there is no significant effect of dihydropyridines CCB on clopidogrel response compared with control. After giving consent, patients with suboptimal blood pressure or anginal control will be randomized to receive either dihydropyridine CCB or non-CCB as placebo. These patient will be follow-up in 1 month.

Detailed Description
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Clopidogrel is a pro-drug, which requires hepatic transformation by the cytochrome P450 isoform 3A4 to generate the active metabolite. It inhibits adenosine-5-diphosphate (ADP)-induced platelet aggregation by irreversibly blocking the platelet P2Y12 receptor. However, response to clopidogrel shows wide individual variability, and patients with high on-treatment residual ADP-induced platelet reactivity are at an increased risk of adverse cardiovascular events. Previous study suggest co-administration of CCBs is associated with decreased platelet inhibition by clopidogrel, but these observational studies are confounded by patient's characteristics baseline difference such as proportion of hypertension and diabetes. The objective of this randomized controlled study is to compare amlodipine with placebo on anti-platelet effect of clopidogrel.

Official Title
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Effect of Amlodipine on Platelet Inhibition by Clopidogrel in Patients With Ischemic Heart Disease- a Prospective Randomized Controlled Trial

Conditions
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Ischemic Heart Disease

Intervention / Treatment
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* Drug: Amlodipine
* Drug: Amlodipine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ischemic heart disease patient, and given loading or maintenance dose of clopidogrel and in need of it for 1 or more month and in need of additional drug for optimal BP control (aim blood pressure <130/90) or angina control. Exclusion Criteria: existing use of amlodipine thrombocytopenia end stage renal failure allergy to clopidogrel/ amlodipine pregnancy/ lactation strong inhibitor or inducer of cytochrome P450 3A4 enzyme within 7 days before start of the study.

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: non-amlodipine<br>For patient with suboptimal angina control: anti-anginal agent excluding calcium channel blocker | Drug: Amlodipine<br>* For patient with suboptimal angina control: oral 2.5-10mg daily<br>* Other names: Norvasc;|
| Active Comparator: non - amlodipine<br>For patient with suboptimal BP control: anti-hypertensive agent excluding calcium channel blocker | Drug: Amlodipine<br>* For patient with suboptimal BP control: 2.5-10mg daily po<br>* Other names: Norvasc;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Platelet reactivity unit | Platelet reactivity unit as measured by VerifyNow system | baseline and 4 th week | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage inhibition of platelet activity | Percentage inhibition of platelet activity measured by VerifyNow system | baseline and 4th week | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Clopidogrel, Platelet reactivity, Amlodipine