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

The recruitment status of this study is unknown. The completion date has passed and the status has not been verified in more than two years.
Verified May 2013 by University of Roma La Sapienza.
Recruitment status was:  Recruiting
Information provided by (Responsible Party):
Francesco Pelliccia, University of Roma La Sapienza Identifier:
First received: March 29, 2012
Last updated: May 3, 2013
Last verified: May 2013

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.

Condition Intervention Phase
Coronary Artery Disease
Drug: Atorvastatin
Drug: Rosuvastatin
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Pharmacodynamic Effects of Atorvastatin vs. Rosuvastatin on pLatelet Reactivity in Stable Patients With Coronary Artery Disease Treated With Dual Antiplatelet Therapy

Resource links provided by NLM:

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 ]
    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 ]
    Frequency of high platelet reactivity with the 2 study treatments (as defined by a Platelet Reaction Unit value>240

Estimated Enrollment: 100
Study Start Date: April 2012
Estimated Study Completion Date: June 2015
Estimated Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Atorvastatin
Patients will receive randomly atorvastatin (20 mg day) for 30 days
Drug: Atorvastatin
os, 20 mg, once per day, for 30 days
Other Name: Norvasc, Pfizer, USA
Active Comparator: Rosuvastatin
Patients will receive randomly rosuvastatin (10 mg per day) for 30 days
Drug: Rosuvastatin
os, 10 mg, once per day, for 30 days
Other Name: Crestor, AstraZeneca, UK

Detailed 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).


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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
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Please refer to this study by its identifier: NCT01567774

Sapienza University
Rome, Italy, 00161
University Sapienza
Rome, Italy, 00166
Sponsors and Collaborators
University of Roma La Sapienza
Principal Investigator: Francesco Pelliccia, MD University Sapienza
  More Information

Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: Francesco Pelliccia, Assistant Professor, University of Roma La Sapienza Identifier: NCT01567774     History of Changes
Other Study ID Numbers: 198/2012/D 
Study First Received: March 29, 2012
Last Updated: May 3, 2013

Keywords provided by University of Roma La Sapienza:
Coronary artery disease
dual antiplatelet therapy

Additional relevant MeSH terms:
Coronary Artery Disease
Myocardial Ischemia
Coronary Disease
Heart Diseases
Cardiovascular Diseases
Arterial Occlusive Diseases
Vascular Diseases
Atorvastatin Calcium
Rosuvastatin Calcium
Anticholesteremic Agents
Hypolipidemic Agents
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Enzyme Inhibitors processed this record on February 20, 2017