PharmacOdynamic compaRison of piTavastatin Versus atOrvastatin on Platelet Reactivity — PORTO  

Coronary Artery Disease Clinical Trial

Official title: Pharmacodynamic Comparison of Pitavastatin Versus Atorvastatin on Platelet Reactivity in Patients With Coronary Artery Disease Treated With Dual Antiplatelet Therapy - The PORTO Trial

Status Not yet recruiting

Clinical Trial Summary

Levels of platelet reactivity in patients on Dual Antiplatelet Therapy (DAPT) can be influenced by concomitant treatment with medications (i.e. statins) that inhibit the CYP3A4 system involved in the activation of clopidogrel. Atorvastatin and simvastatin are metabolized by CYP3A4. Pitavastatin, unlike other statins, is little metabolized, most of the dose being excreted unchanged in bile, and biotransformation through the cytochrome P450 system is minimal. Indeed, pitavastatin's cyclopropyl group diverts the drug away from metabolism by CYP3A4 and allows only a small amount of clinically insignificant metabolism by CYP2C9.

The primary objective of this study is to compare the pharmacodynamic effects of a CYP3A4-metabolized statin (atorvastatin) versus a non-CYP3A4-metabolized statin (pitavastatin) in patients showing high platelet reactivity while on DAPT.

Clinical Trial Description

Patients with coronary artery disease (CAD) are often treated with dual anti-platelet therapy (DAPT), including aspirin and clopidogrel, to prevent from recurrent atherothrombotic events.

Levels of platelet reactivity in patients on DAPT can be influenced by concomitant treatment with medications (i.e. statins) that inhibit the CYP3A4 system involved in the activation of clopidogrel.

Atorvastatin and simvastatin are metabolized by CYP3A4. Pitavastatin, unlike other statins, is little metabolized, most of the dose being excreted unchanged in bile, and biotransformation through the cytochrome P450 system is minimal. Indeed, pitavastatin's cyclopropyl group diverts the drug away from metabolism by CYP3A4 and allows only a small amount of clinically insignificant metabolism by CYP2C9.

At least 1 month after starting DAT (clopidogrel 75 mg and aspirin 100 mg), patients will receive randomly atorvastatin (20 mg day, N=50) or pitavastatin (4 mg day, N=50) for 30 days (until T-1).

At this time-point, there will be a wash-out period of 15 days after the first treatment with atorvastatin or pitavastatin in order to avoid any carry-over effect.

Afterwards, a cross-over will be performed, and patients will be switched to the other drug which will be continued for further 30 days (until T-2).

No previous studies have evaluated the influence of pitavastatin as compared with other statins on platelet reactivity in patients receiving DAPT.

The primary objective of this study is to compare the pharmacodynamic effects of a CYP3A4-metabolized statin (atorvastatin) versus a non-CYP3A4-metabolized statin (pitavastatin) in patients showing high platelet reactivity while on DAPT. ;

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Diagnostic

Related Conditions & MeSH terms

• Coronary Artery Disease
• Coronary Disease
• Myocardial Ischemia

• NCT number: NCT01648829
• Study type: Interventional
• Source: University of Roma La Sapienza
• Contact: Francesco Pelliccia, MD
• Phone: +39064997
• Email: f.pelliccia@mclink.it
• Status: Not yet recruiting
• Phase: Phase 4
• Start date: January 2014
• Completion date: December 2017