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

This study is currently recruiting participants. (see Contacts and Locations)
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
  Purpose

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
Endpoint Classification: Safety Study
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 ] [ 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>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).

  Eligibility

Ages Eligible for Study:   18 Years and older
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01567774

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

Locations
Italy
University Sapienza Not yet recruiting
Rome, Italy, 00166
Contact: Francesco Pelliccia, MD    +3906499 ext 123    f.pelliccia@mclink.it   
Sapienza University Recruiting
Rome, Italy, 00161
Contact: Francesco Pelliccia, MD    064997 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 University Sapienza
  More Information

No publications provided by University of Roma La Sapienza

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

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

Additional relevant MeSH terms:
Coronary Artery Disease
Myocardial Ischemia
Coronary Disease
Heart Diseases
Cardiovascular Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Atorvastatin
Rosuvastatin
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 July 20, 2014