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

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

Status and phase: Completed; Phase 4

Conditions: Coronary Artery Disease

Treatments: Drug: Atorvastatin-esomeprazole; Drug: Rosuvastatin-esomeprazole; Drug: Rosuvastatin-pantoprazole; Drug: Atorvastatin-pantoprazole; Drug: Atorvastatin-omeprazole; Drug: Rosuvastatin-omeprazole; Drug: Rosuvastatin-ranitidine; Drug: Atorvastatin-ranitidine

Study type: Interventional

Funder types: Other

Identifiers

NCT00930670

SPICE

Details and patient eligibility

About

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.

Enrollment: 320 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Factorial Assignment

Masking: None (Open label)

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320 participants in 8 patient groups

Rosuvastatin-omeprazole

Experimental group

Description:

Rosuvastatin-omeprazole

Treatment:

Drug: Rosuvastatin-omeprazole

Rosuvastatin-pantoprazole

Experimental group

Description:

Rosuvastatin 20 mg for 1 month, then rosuvastatin 20 mg and pantoprazole 40 mg for 11 months

Treatment:

Drug: Rosuvastatin-pantoprazole

Rosuvastatin-esomeprazole

Experimental group

Description:

Rosuvastatin 20 mg for 1 month, then rosuvastatin 20 mg and esomeprazole 40 mg for 11 months

Treatment:

Drug: Rosuvastatin-esomeprazole

Rosuvastatin-ranitidine

Active Comparator group

Description:

Rosuvastatin 20 mg for 1 month, then rosuvastatin 20 mg and ranitidine 300 mg for 11 months

Treatment:

Drug: Rosuvastatin-ranitidine

Atorvastatin-omeprazole

Experimental group

Description:

Atorvastatin 80mg for 1 month, then atorvastatin 80 mg and omeprazole 20 mg for 11 months

Treatment:

Drug: Atorvastatin-omeprazole

Atorvastatin-pantoprazole

Experimental group

Description:

Atorvastatin 80mg for 1 month, then atorvastatin 80 mg and pantoprazole 40mg for 11 months

Treatment:

Drug: Atorvastatin-pantoprazole

Atorvastatin-esomeprazole

Experimental group

Description:

Atorvastatin 80mg for 1 month, then atorvastatin 80 mg and esomeprazole 40 mg for 11 months

Treatment:

Drug: Atorvastatin-esomeprazole

Atorvastatin-ranitidine

Active Comparator group

Description:

Atorvastatin 80mg for 1 month, then atorvastatin 80 mg and ranitidine 300mg for 11 months

Treatment:

Drug: Atorvastatin-ranitidine