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PharmacOdynamic compaRison of piTavastatin Versus atOrvastatin on Platelet Reactivity (PORTO)

This study is not yet open for participant recruitment.
Verified March 2013 by University of Roma La Sapienza
Sponsor:
Information provided by (Responsible Party):
Francesco Pelliccia, University of Roma La Sapienza
ClinicalTrials.gov Identifier:
NCT01648829
First received: July 19, 2012
Last updated: March 6, 2013
Last verified: March 2013
History of Changes
  Purpose

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 Intervention Phase
Coronary Artery Disease
 Drug: Atorvastatin
Drug: Pitavastatin
 Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by University of Roma La Sapienza:

Primary Outcome Measures:
  • Assessment of platelet reaction units [ Time Frame: After 30 days of treatment with each drug ] [ Designated as safety issue: No ]
    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 [ Time Frame: After 30 days of treatment with each drug ] [ Designated as safety issue: No ]
    Frequency of high platelet reactivity with the 2 study treatments (as defined by a Platelet Reaction Unit value>208)


Estimated Enrollment: 100
Study Start Date: January 2014
Estimated Study Completion Date: December 2017
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: Livalo, Kowa Pharmaceuticals, Japan

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.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01648829

Contacts
Contact: Francesco Pelliccia, MD +39064997 ext 123 f.pelliccia@mclink.it

Locations
Italy
Sapienza University Not yet recruiting
Rome, Italy, 00166
Contact: Francesco Pelliccia, MD     +39064997 ext 123     f.pelliccia@mclink.it    
Principal Investigator: Francesco Pelliccia, MD            
Sponsors and Collaborators
University of Roma La Sapienza
Investigators
Principal Investigator: Francesco Pelliccia, MD Sapienza University
  More Information

No publications provided

Responsible Party: Francesco Pelliccia, Assistant Professor, University of Roma La Sapienza
ClinicalTrials.gov Identifier: NCT01648829     History of Changes
Other Study ID Numbers: 449/2012/D
Study First Received: July 19, 2012
Last Updated: March 6, 2013
Health Authority: Italy: National Institute of Health

Additional relevant MeSH terms:
Coronary Artery Disease
Myocardial Ischemia
Coronary Disease
Heart Diseases
Cardiovascular Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Atorvastatin
Pitavastatin
 Hydroxymethylglutaryl-CoA Reductase Inhibitors
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Enzyme Inhibitors
Lipid Regulating Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on May 16, 2013