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

Coronary Artery Disease Clinical Trial

— SPICE  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00930670
• Other study ID #: SPICE
• Status: Completed
• Phase: Phase 4
• First received: June 29, 2009
• Last updated: February 8, 2012
• Start date: June 2009
• Est. completion date: December 2011

Study information

• Verified date: February 2012
• Source: Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Quebec
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Ethics Review Committee
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 320
• Est. completion date: December 2011
• Est. primary completion date: December 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Allocation: Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Factorial Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Coronary Artery Disease
• Coronary Disease
• Myocardial Ischemia

Intervention

Drug:
• Rosuvastatin-omeprazole
Rosuvastatin 20 mg for 1 month. Then rosuvastatin 20mg and omeprazole 20mg for 11 months
• Rosuvastatin-pantoprazole
Rosuvastatin 20 mg for 1 month, then rosuvastatin 20 mg and pantoprazole 40 mg for 11 months
• Rosuvastatin-esomeprazole
Rosuvastatin 20 mg for 1 month, then rosuvastatin 20 mg and esomeprazole 40 mg for 11 months
• Rosuvastatin-ranitidine
Rosuvastatin 20 mg for 1 month, then rosuvastatin 20 mg and ranitidine 300mg for 11 months
• Atorvastatin-omeprazole
Atorvastatin 80mg for 1 month, then atorvastatin 80 mg and omeprazole 20 mg for 11 months
• Atorvastatin-pantoprazole
Atorvastatin 80mg for 1 month, then atorvastatin 80 mg and pantoprazole 40 mg for 11 months
• Atorvastatin-esomeprazole
Atorvastatin 80mg for 1 month, then atorvastatin 80 mg and esomeprazole 40 mg for 11 months
• Atorvastatin-ranitidine
Atorvastatin 80mg for 1 month, then atorvastatin 80 mg and ranitidine 300mg for 11 months

Locations

Country	Name	City	State
Canada	Institut Universitaire de Cardiologie et de Pneumologie de Quebec	Quebec City	Quebec

Sponsors (1)

Lead Sponsor	Collaborator
Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Quebec

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percent change in residual platelet aggregation by light transmittance aggregometry and percent change in platelet reactivity index by VASP		At 30 and 60 days	No
Secondary	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	No
Secondary	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	No
Secondary	The composite of death from all causes, myocardial infarction, ischemia-driven repeat revascularization, and stroke		30 days, 60 days and 1 year	No
Secondary	Need to stop any antiplatelet medication for gastrointestinal bleeding or peptic ulcer disease		30 days, 60 days and one year	Yes

External Links

•   Centre de recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Quebec