Pharmacodynamic Effects of Atorvastatin vs. Rosuvastatin on Platelet Reactivity

Coronary Artery Disease Clinical Trial

— PEARL  

Official title:

Pharmacodynamic Effects of Atorvastatin vs. Rosuvastatin on pLatelet Reactivity in Stable Patients With Coronary Artery Disease Treated With Dual Antiplatelet Therapy

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01567774
• Other study ID #: 198/2012/D
• Status: Recruiting
• Phase: Phase 4
• First received: March 29, 2012
• Last updated: May 3, 2013
• Start date: April 2012
• Est. completion date: June 2015

Study information

• Verified date: May 2013
• Source: University of Roma La Sapienza
• Contact: Francesco Pelliccia, MD
• Phone: +39064997
• Email: f.pelliccia[@]mclink.it
• Is FDA regulated: No
• Health authority: Italy: Ministry of Health
• Study type: Interventional

Clinical Trial Summary

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.

Atorvastatin and simvastatin are metabolized by CYP3A4 [Clin pharmacokinetic 2002; 41:

343-70], whereas the cytochrome P450 mediated metabolism of rosuvastatin appears to be minimal and principally mediated by the 2C9 isoenzyme, with little involvement of CYP3A4 [Clin Ther 2003; 25: 2822-5.].

Previous studies comparing atorvastatin versus rosuvastatin by means of ex vivo platelet function tests have yielded conflicting results.

Description:

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 rosuvastatin (10 mg bid, 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 rosuvastatin 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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: June 2015
• Est. primary completion date: March 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Coronary Artery Disease
• Coronary Disease
• Myocardial Ischemia

Intervention

Drug:
• Atorvastatin
os, 20 mg, once per day, for 30 days
• Rosuvastatin
os, 10 mg, once per day, for 30 days

Locations

Country	Name	City	State
Italy	Sapienza University	Rome
Italy	University Sapienza	Rome

Sponsors (1)

Lead Sponsor	Collaborator
University of Roma La Sapienza

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Assessment of platelet reaction units	Absolute changes in platelet reactivity (expressed as P2Y(12) reaction units by the point-of-care VerifyNow assay [Accumetrics, San Diego, California])	After 30 days of treatment with each drug	No
Secondary	Frequency of high platelet reactivity	Frequency of high platelet reactivity with the 2 study treatments (as defined by a Platelet Reaction Unit value>240	After 30 days of treatment with each drug	No