Pharmacodynamic Effects of Ranolazine Versus Amlodipine on Platelet Reactivity

Phase 4

• Conditions: Coronary Artery Disease
• Interventions: Drug: Ranolazine; Drug: Amlodipine

• Registration Number: NCT01490255
• Lead Sponsor: University of Roma La Sapienza

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2011-12-08
• Study First Submitted QC: 2011-12-09
• Study First Posted: 2011-12-12
• Study Start: 2012-01
• Status Verified: 2014-03
• Last Update Submitted: 2014-03-23
• Last Update Posted: 2014-03-26
• Primary Completion: 2014-06
• Study Completion: 2014-06

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 100

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Ranolazine	Ranolazine	Patients will receive ranolazine (750 mg bid) for 15 days
Amlodipine	Amlodipine	Patients will receive amlodipine (10 mg once daily) for 15 days

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Frequency of high platelet reactivity	After 15 days of treatment with each drug	Frequency of high platelet reactivity with the two study treatments (as defined by a Platelet Reaction Unit value\>240

Trial Locations

Locations (2)

San Raffaele Pisana; 🇮🇹 Rome, Italy

University La Sapienza; 🇮🇹 Rome, Italy