PORTO: PharmacOdynamic compaRison of piTavastatin Versus atOrvastatin on Platelet Reactivity

Sponsor

University of Roma La Sapienza (Other)

Overall Status

Unknown status

CT.gov ID

NCT01648829

Collaborator

(none)

100

Enrollment

Location

Arms

Duration (Months)

2.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Coronary Artery Disease	Drug: Atorvastatin Drug: Pitavastatin	Phase 4

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

100 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Diagnostic

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

Study Start Date :

Jan 1, 2014

Anticipated Primary Completion Date :

Dec 1, 2015

Anticipated Study Completion Date :

Dec 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Atorvastatin os, 20 mg, once per day, for 30 days	Drug: Atorvastatin Patients will receive randomly atorvastatin (20 mg day) for 30 days Other Names: Torvast, Pfizer, USA
Active Comparator: Pitavastatin os, 4 mg, once per day, for 30 days	Drug: Pitavastatin Patients will receive randomly pitavastatin (4 mg day) for 30 days Other Names: Livalo, Kowa Pharmaceuticals, Japan

Arm

Intervention/Treatment

Active Comparator: Atorvastatin

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

Drug: Atorvastatin

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

Other Names:

Torvast, Pfizer, USA

Active Comparator: Pitavastatin

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

Drug: Pitavastatin

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

Other Names:

Livalo, Kowa Pharmaceuticals, Japan

Outcome Measures

Primary Outcome Measures

Assessment of platelet reaction units [After 30 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

Frequency of high platelet reactivity [After 30 days of treatment with each drug]
Frequency of high platelet reactivity with the 2 study treatments (as defined by a Platelet Reaction Unit value>208)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Sapienza University	Rome		Italy	00166

Sponsors and Collaborators

University of Roma La Sapienza

Investigators

Principal Investigator: Francesco Pelliccia, MD, Sapienza University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Francesco Pelliccia, Assistant Professor, University of Roma La Sapienza

ClinicalTrials.gov Identifier:

NCT01648829

Other Study ID Numbers:

449/2012/D

First Posted:

Jul 24, 2012

Last Update Posted:

Mar 7, 2013

Last Verified:

Mar 1, 2013

Additional relevant MeSH terms:

Coronary Artery Disease

Study Results

No Results Posted as of Mar 7, 2013