Clinical trial NCT00930670: Evaluation of the Influence of Statins and Proton Pump Inhibitors on Clopidogrel Antiplatelet Effects
Official title: Evaluation of the Influence of Statins and Proton Pump Inhibitors on Clopidogrel Antiplatelet Effects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Coronary Artery Disease
Keywords: ranitidine
pantoprazole
esomeprazole
omeprazole
atorvastatin
rosuvastatin
statin
clopidogrel resistance
antiplatelet therapy
coronary artery disease
percutaneous coronary intervention
stent
clopidogrel
proton pump inhibitors
drug interactions
drug resistance
genetic polymorphism
Lead sponsor: Institut universitaire de cardiologie et de pneumologie de Québec, University Laval
Sponsor class: OTHER
First posted: 2009-06-30
Enrollment: 320
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Percent change in residual platelet aggregation by light transmittance aggregometry and percent change in platelet reactivity index by VASP
timeFrame: At 30 and 60 days
Secondary outcomes:
measure: Resistance to clopidogrel by light transmittance aggregometry (defined by RPA >55%), resistance to clopidogrel by vasodilator-stimulated phosphoprotein (VASP) (defined by PRI >55%)
timeFrame: 30 and 60 days
measure: Prevalence and role of CYP 2C19*2 polymorphism on the effect of PPIs and statins on the antiplatelet activity of clopidogrel
timeFrame: 30 and 60 days
measure: The composite of death from all causes, myocardial infarction, ischemia-driven repeat revascularization, and stroke
timeFrame: 30 days, 60 days and 1 year
measure: Need to stop any antiplatelet medication for gastrointestinal bleeding or peptic ulcer disease
timeFrame: 30 days, 60 days and one year
Other outcomes:
Locations:
city: Quebec City
country: Canada
facility: Institut Universitaire de Cardiologie et de Pneumologie de Quebec
state: Quebec
Study officials:
affiliation: Institut universitaire de cardiologie et de pneumologie de Québec, University Laval
name: Jean-Pierre Dery, MD, MHS
role: PRINCIPAL_INVESTIGATOR
References:
citation: Harvey A, Modak A, Dery U, Roy M, Rinfret S, Bertrand OF, Larose E, Rodes-Cabau J, Barbeau G, Gleeton O, Nguyen CM, Proulx G, Noel B, Roy L, Paradis JM, De Larochelliere R, Dery JP. Changes in CYP2C19 enzyme activity evaluated by the [(13)C]-pantoprazole breath test after co-administration of clopidogrel and proton pump inhibitors following percutaneous coronary intervention and correlation to platelet reactivity. J Breath Res. 2016 Jan 27;10(1):017104. doi: 10.1088/1752-7155/10/1/017104.