Evaluation of the Influence of Statins and Proton Pump Inhibitors on Clopidogrel Antiplatelet Effects

Phase 4

Completed

• Conditions: Coronary Artery Disease
• Interventions: Drug: Rosuvastatin-omeprazole; Drug: Rosuvastatin-pantoprazole; Drug: Rosuvastatin-esomeprazole; Drug: Rosuvastatin-ranitidine; Drug: Atorvastatin-omeprazole; Drug: Atorvastatin-pantoprazole; Drug: Atorvastatin-esomeprazole; Drug: Atorvastatin-ranitidine

• Registration Number: NCT00930670
• Lead Sponsor: Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Quebec

Brief Summary

There is conflicting evidence in the literature suggesting that the use of proton pump inhibitors (PPIs), and/or some statins can interfere with clopidogrel antiplatelet effect and result in adverse cardiovascular outcomes in patients treated with coronary artery stents and dual antiplatelet therapy.

The primary aim of the study is to determine the effect of various currently used PPI on platelet aggregation in patients undergoing percutaneous coronary intervention (PCI) and treated with dual antiplatelet therapy.

The secondary aim of the study is to evaluate how statins and 2C19\*2 polymorphism modulate the effect of PPI on clopidogrel efficacy.

Detailed Description

Not available

Study Timeline

• Study Start: 2009-06
• Study First Submitted: 2009-06-29
• Study First Submitted QC: 2009-06-29
• Study First Posted: 2009-06-30
• Primary Completion: 2011-12
• Study Completion: 2011-12
• Status Verified: 2012-02
• Last Update Submitted: 2012-02-08
• Last Update Posted: 2012-02-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 320

Inclusion Criteria

• Subject must be 18 years of age or older
• Bare metal stent implantation
• Discharged with dual antiplatelet therapy for at least 60 days
• Written informed consent

Exclusion Criteria

• Patients who do not consent to participate in the study
• Premenopausal women not using contraceptive methods or without a negative pregnancy test in the past week
• Patients treated or planned to be treated with oral anticoagulants
• Present treatment with or clear indication for treatment with a PPI or H2 antagonists
• Allergy or intolerance to study medications including ranitidine, Proton pump inhibitors, atorvastatin, rosuvastatin, aspirin and/or clopidogrel
• Patient treated with a strong CYP2C19 interacting drug
• History of a bleeding diathesis, or evidence of active abnormal bleeding within 30 days before enrollment
• History of intracranial hemorrhage or intracranial surgery in the last 3 months
• History of gastro-intestinal ulcers in the last 3 months
• Any serious illness or any condition that the investigator feels would influence the impact of this therapy on the subject
• Known platelet count < 100000/mm3 at time of enrollment or within 24 hours prior to enrollment

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: FACTORIAL

Arm && Interventions

Group	Intervention	Description
Rosuvastatin-omeprazole	Rosuvastatin-omeprazole	Rosuvastatin-omeprazole
Rosuvastatin-pantoprazole	Rosuvastatin-pantoprazole	Rosuvastatin 20 mg for 1 month, then rosuvastatin 20 mg and pantoprazole 40 mg for 11 months
Rosuvastatin-esomeprazole	Rosuvastatin-esomeprazole	Rosuvastatin 20 mg for 1 month, then rosuvastatin 20 mg and esomeprazole 40 mg for 11 months
Rosuvastatin-ranitidine	Rosuvastatin-ranitidine	Rosuvastatin 20 mg for 1 month, then rosuvastatin 20 mg and ranitidine 300 mg for 11 months
Atorvastatin-omeprazole	Atorvastatin-omeprazole	Atorvastatin 80mg for 1 month, then atorvastatin 80 mg and omeprazole 20 mg for 11 months
Atorvastatin-pantoprazole	Atorvastatin-pantoprazole	Atorvastatin 80mg for 1 month, then atorvastatin 80 mg and pantoprazole 40mg for 11 months
Atorvastatin-esomeprazole	Atorvastatin-esomeprazole	Atorvastatin 80mg for 1 month, then atorvastatin 80 mg and esomeprazole 40 mg for 11 months
Atorvastatin-ranitidine	Atorvastatin-ranitidine	Atorvastatin 80mg for 1 month, then atorvastatin 80 mg and ranitidine 300mg for 11 months

Primary Outcome Measures

Name	Time	Method
Percent change in residual platelet aggregation by light transmittance aggregometry and percent change in platelet reactivity index by VASP	At 30 and 60 days

Secondary Outcome Measures

Name	Time	Method
The composite of death from all causes, myocardial infarction, ischemia-driven repeat revascularization, and stroke	30 days, 60 days and 1 year
Prevalence and role of CYP 2C19*2 polymorphism on the effect of PPIs and statins on the antiplatelet activity of clopidogrel	30 and 60 days
Need to stop any antiplatelet medication for gastrointestinal bleeding or peptic ulcer disease	30 days, 60 days and one year
Resistance to clopidogrel by light transmittance aggregometry (defined by RPA >55%), resistance to clopidogrel by vasodilator-stimulated phosphoprotein (VASP) (defined by PRI >55%)	30 and 60 days

Trial Locations

Locations (1)

Institut Universitaire de Cardiologie et de Pneumologie de Quebec; 🇨🇦 Quebec City, Quebec, Canada