Pharmacodynamic Effects of Ranolazine Versus Amlodipine on Platelet Reactivity

Study Overview
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Brief Summary
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No previous study has assessed the potential of ranolazine to interfere with levels of platelet reactivity in patients with coronary artery disease who are treated with dual antiplatelet therapy. Aim of this study is to compare the pharmacodynamic effects of maintenance doses of ranolazine versus amlodipine on platelet reactivity in patients with coronary artery disease who are treated with dual antiplatelet therapy.

Detailed Description
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Patients with coronary artery disease (CAD) are often treated with dual antiplatelet therapy (DAT), including aspirin and clopidogrel, to prevent from recurrent atherothrombotic events. Levels of platelet reactivity in patients on DAT can be influenced by concomitant treatment with medications that inhibit the CYP3A4 system involved in the activation of clopidogrel, such as calcium channel blockers, potentially interfering with its clinical benefits. Importantly, calcium channel blockers, such as amlodipine, are commonly used for relief of ischemic symptoms in patients with CAD. Ranolazine is a novel antianginal drug that reduces intracellular sodium and calcium accumulation and constitutes a pharmacologic alternative to calcium channel blockade. However, no previous study has assessed the potential of ranolazine to interfere with levels of platelet reactivity in CAD patients on DAT. The primary objective of this study is to compare the pharmacodynamic effects of maintenance doses of ranolazine versus amlodipine on platelet reactivity in patients with CAD on DAT.

Official Title
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Comparison of the Pharmacodynamic Effects of RanOlazine Versus aMlodipine on Platelet Reactivity in Stable Patients With Coronary Artery Disease Treated With Dual ANtiplatelet Therapy - The ROMAN Randomized Study

Conditions
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Coronary Artery Disease

Intervention / Treatment
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* Drug: Ranolazine
* Drug: Amlodipine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Angiographically-proven coronary artery disease Class I indication to dual antiplatelet therapy because of recent (<12 months) percutaneous coronary intervention and/or recent acute coronary syndrome (<12 months) Stable clinical conditions Able to understand and willing to sign the informed consent form Exclusion Criteria: Use of other drug interfering with CYP activity such as proton pump inhibitors Women of child bearing potential patients must demonstrate a negative pregnancy test performed within 24 hours before
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: Diagnostic
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Ranolazine<br>Patients will receive ranolazine (750 mg bid) for 15 days | Drug: Ranolazine<br>* os, 750 mg, twice per day, for 15 days<br>* Other names: Ranexa®, Gilead, USA;|
| Active Comparator: Amlodipine<br>Patients will receive amlodipine (10 mg once daily) for 15 days | Drug: Amlodipine<br>* os, 10 mg, once daily, 15 days<br>* Other names: Norvasc®, Pfizer, USA;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of platelet reaction units | Absolute changes in platelet reactivity (expressed as P2Y(12) reaction units by the point-of-care VerifyNow assay [Accumetrics, San Diego, California]) | After 15 days of treatment with each drug | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of high platelet reactivity | Frequency of high platelet reactivity with the two study treatments (as defined by a Platelet Reaction Unit value>240 | After 15 days of treatment with each drug | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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platelet reactivity, aspirin, clopidogrel