PharmacOdynamic compaRison of piTavastatin Versus atOrvastatin on Platelet Reactivity

NCT ID: NCT01648829

Last Updated: 2013-03-07

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 100 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-01-31
• Study Completion Date: 2017-12-31

Brief 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.

Detailed 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.

Conditions

Coronary Artery Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: QUADRUPLE

Study Groups

Atorvastatin

os, 20 mg, once per day, for 30 days

Group Type: ACTIVE_COMPARATOR

Atorvastatin

Intervention Type: DRUG

Patients will receive randomly atorvastatin (20 mg day) for 30 days

Pitavastatin

os, 4 mg, once per day, for 30 days

Group Type: ACTIVE_COMPARATOR

Pitavastatin

Intervention Type: DRUG

Patients will receive randomly pitavastatin (4 mg day) for 30 days

Interventions

Atorvastatin

Patients will receive randomly atorvastatin (20 mg day) for 30 days

Intervention Type: DRUG

Pitavastatin

Patients will receive randomly pitavastatin (4 mg day) for 30 days

Intervention Type: DRUG

Other Intervention Names

Torvast, Pfizer, USA; Livalo, Kowa Pharmaceuticals, Japan

Eligibility Criteria

Inclusion Criteria

• Angiographically-proven coronary artery disease
• Class I indication to DAT 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 CF

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 CT

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Roma La Sapienza

OTHER

Sponsor Role: lead

Responsible Party

Francesco Pelliccia

Assistant Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Francesco Pelliccia, MD

Role: PRINCIPAL_INVESTIGATOR

Sapienza University

Locations

Sapienza University

Rome, , Italy

Countries

Italy

Central Contacts

Francesco Pelliccia, MD

Role: CONTACT

f.pelliccia@mclink.it

+39064997 ext. 123

Facility Contacts

Francesco Pelliccia, MD

Role: primary

f.pelliccia@mclink.it

+39064997 ext. 123

Other Identifiers

449/2012/D

Identifier Type: -

Identifier Source: org_study_id