Evaluation of the Influence of Statins and Proton Pump Inhibitors on Clopidogrel Antiplatelet Effects - Full Text View

Sponsor:	Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Quebec
Information provided by (Responsible Party):	Jean-Pierre Dery, MD, MSc, Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Quebec
ClinicalTrials.gov Identifier:	NCT00930670

Purpose

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.

Condition	Intervention	Phase
Coronary Artery Disease	Drug: Rosuvastatin-omeprazole Drug: Rosuvastatin-pantoprazole Drug: Rosuvastatin-esomeprazole Drug: Rosuvastatin-ranitidine Drug: Atorvastatin-omeprazole Drug: Atorvastatin-pantoprazole Drug: Atorvastatin-esomeprazole Drug: Atorvastatin-ranitidine	Phase IV

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Pharmacodynamics Study Intervention Model: Factorial Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Evaluation of the Influence of Statins and Proton Pump Inhibitors on Clopidogrel Antiplatelet Effects

Resource links provided by NLM:

Further study details as provided by Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Quebec:

Primary Outcome Measures:

Percent change in residual platelet aggregation by light transmittance aggregometry and percent change in platelet reactivity index by VASP [ Time Frame: At 30 and 60 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Resistance to clopidogrel by light transmittance aggregometry (defined by RPA >55%), resistance to clopidogrel by vasodilator-stimulated phosphoprotein (VASP) (defined by PRI >55%) [ Time Frame: 30 and 60 days ] [ Designated as safety issue: No ]
Prevalence and role of CYP 2C19*2 polymorphism on the effect of PPIs and statins on the antiplatelet activity of clopidogrel [ Time Frame: 30 and 60 days ] [ Designated as safety issue: No ]
The composite of death from all causes, myocardial infarction, ischemia-driven repeat revascularization, and stroke [ Time Frame: 30 days, 60 days and 1 year ] [ Designated as safety issue: No ]
Need to stop any antiplatelet medication for gastrointestinal bleeding or peptic ulcer disease [ Time Frame: 30 days, 60 days and one year ] [ Designated as safety issue: Yes ]

Enrollment:	320
Study Start Date:	June 2009
Study Completion Date:	December 2011
Primary Completion Date:	December 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Rosuvastatin-omeprazole Rosuvastatin-omeprazole	Drug: Rosuvastatin-omeprazole Rosuvastatin 20 mg for 1 month. Then rosuvastatin 20mg and omeprazole 20mg for 11 months
Experimental: Rosuvastatin-pantoprazole Rosuvastatin 20 mg for 1 month, then rosuvastatin 20 mg and pantoprazole 40 mg for 11 months	Drug: Rosuvastatin-pantoprazole Rosuvastatin 20 mg for 1 month, then rosuvastatin 20 mg and pantoprazole 40 mg for 11 months
Experimental: Rosuvastatin-esomeprazole Rosuvastatin 20 mg for 1 month, then rosuvastatin 20 mg and esomeprazole 40 mg for 11 months	Drug: Rosuvastatin-esomeprazole Rosuvastatin 20 mg for 1 month, then rosuvastatin 20 mg and esomeprazole 40 mg for 11 months
Active Comparator: Rosuvastatin-ranitidine Rosuvastatin 20 mg for 1 month, then rosuvastatin 20 mg and ranitidine 300 mg for 11 months	Drug: Rosuvastatin-ranitidine Rosuvastatin 20 mg for 1 month, then rosuvastatin 20 mg and ranitidine 300mg for 11 months
Experimental: Atorvastatin-omeprazole Atorvastatin 80mg for 1 month, then atorvastatin 80 mg and omeprazole 20 mg for 11 months	Drug: Atorvastatin-omeprazole Atorvastatin 80mg for 1 month, then atorvastatin 80 mg and omeprazole 20 mg for 11 months
Experimental: Atorvastatin-pantoprazole Atorvastatin 80mg for 1 month, then atorvastatin 80 mg and pantoprazole 40mg for 11 months	Drug: Atorvastatin-pantoprazole Atorvastatin 80mg for 1 month, then atorvastatin 80 mg and pantoprazole 40 mg for 11 months
Experimental: Atorvastatin-esomeprazole Atorvastatin 80mg for 1 month, then atorvastatin 80 mg and esomeprazole 40 mg for 11 months	Drug: Atorvastatin-esomeprazole Atorvastatin 80mg for 1 month, then atorvastatin 80 mg and esomeprazole 40 mg for 11 months
Active Comparator: Atorvastatin-ranitidine Atorvastatin 80mg for 1 month, then atorvastatin 80 mg and ranitidine 300mg for 11 months	Drug: Atorvastatin-ranitidine Atorvastatin 80mg for 1 month, then atorvastatin 80 mg and ranitidine 300mg for 11 months

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00930670

Locations

Canada, Quebec
Institut Universitaire de Cardiologie et de Pneumologie de Quebec
Quebec City, Quebec, Canada, G1V4G5

Sponsors and Collaborators

Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Quebec

Investigators

Principal Investigator:

Jean-Pierre Dery, MD, MHS

Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Quebec

More Information

Additional Information:

Centre de recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Quebec This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Jean-Pierre Dery, MD, MSc, Interventional Cardiologist, Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Quebec
ClinicalTrials.gov Identifier:	NCT00930670 History of Changes
Other Study ID Numbers:	SPICE
Study First Received:	June 29, 2009
Last Updated:	February 8, 2012
Health Authority:	Canada: Ethics Review Committee

Keywords provided by Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Quebec:

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

Additional relevant MeSH terms:

Coronary Artery Disease
Myocardial Ischemia
Coronary Disease
Heart Diseases
Cardiovascular Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Omeprazole
Ranitidine
Ranitidine bismuth citrate
Pantoprazole
Atorvastatin
Rosuvastatin
Clopidogrel

Proton Pump Inhibitors
Anti-Ulcer Agents
Gastrointestinal Agents
Therapeutic Uses
Pharmacologic Actions
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Histamine H2 Antagonists
Histamine Antagonists
Histamine Agents
Neurotransmitter Agents
Physiological Effects of Drugs
Platelet Aggregation Inhibitors
Hematologic Agents
Purinergic P2Y Receptor Antagonists

ClinicalTrials.gov processed this record on February 09, 2012