Pharmacodynamic Effects of Atorvastatin vs. Rosuvastatin on Platelet Reactivity (PEARL)

This study is currently recruiting participants.
Verified May 2013 by University of Roma La Sapienza
Sponsor:
Information provided by (Responsible Party):
Francesco Pelliccia, University of Roma La Sapienza
ClinicalTrials.gov Identifier:
NCT01567774
First received: March 29, 2012
Last updated: May 3, 2013
Last verified: May 2013

March 29, 2012
May 3, 2013
April 2012
March 2014   (final data collection date for primary outcome measure)
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])
Same as current
Complete list of historical versions of study NCT01567774 on ClinicalTrials.gov Archive Site
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>240
Same as current
Not Provided
Not Provided
 
Pharmacodynamic Effects of Atorvastatin vs. Rosuvastatin on Platelet Reactivity
Pharmacodynamic Effects of Atorvastatin vs. Rosuvastatin on pLatelet Reactivity in Stable Patients With Coronary Artery Disease Treated With Dual Antiplatelet Therapy

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.

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).

Interventional
Phase 4
Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Coronary Artery Disease
  • Drug: Atorvastatin
    os, 20 mg, once per day, for 30 days
    Other Name: Norvasc, Pfizer, USA
  • Drug: Rosuvastatin
    os, 10 mg, once per day, for 30 days
    Other Name: Crestor, AstraZeneca, UK
  • Active Comparator: Atorvastatin
    Patients will receive randomly atorvastatin (20 mg day) for 30 days
    Intervention: Drug: Atorvastatin
  • Active Comparator: Rosuvastatin
    Patients will receive randomly rosuvastatin (10 mg per day) for 30 days
    Intervention: Drug: Rosuvastatin
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
100
June 2015
March 2014   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact: Francesco Pelliccia, MD +39064997 ext 123 f.pelliccia@mclink.it
Contact: Francesco Pelliccia, MD +39064997 ext 123
Italy
 
NCT01567774
198/2012/D
No
Francesco Pelliccia, University of Roma La Sapienza
University of Roma La Sapienza
Not Provided
Principal Investigator: Francesco Pelliccia, MD University Sapienza
University of Roma La Sapienza
May 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP