Pharmacodynamic Effects of Atorvastatin vs. Rosuvastatin on Platelet Reactivity (PEARL)
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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 |
- 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])
- 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 |
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| Contact: Francesco Pelliccia, MD | +39064997 ext 123 | f.pelliccia@mclink.it |
| Contact: Francesco Pelliccia, MD | +39064997 ext 123 |
| 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 | |
| Principal Investigator: | Francesco Pelliccia, MD | University Sapienza |
More Information
No publications provided
| 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 May 23, 2013