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

This study has been completed.
Sponsor:
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
First received: June 29, 2009
Last updated: February 8, 2012
Last verified: February 2012

June 29, 2009
February 8, 2012
June 2009
December 2011   (final data collection date for primary outcome measure)
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 ]
Same as current
Complete list of historical versions of study NCT00930670 on ClinicalTrials.gov Archive Site
  • 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 ]
  • Resistance to clopidogrel by light transmittance aggregometry (defined by RPA >55%), resistance to clopidogrel by 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 ]
Not Provided
Not Provided
 
Evaluation of the Influence of Statins and Proton Pump Inhibitors on Clopidogrel Antiplatelet Effects
Evaluation of the Influence of Statins and Proton Pump Inhibitors on Clopidogrel Antiplatelet Effects

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.

Not Provided
Interventional
Phase 4
Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Factorial Assignment
Masking: Open Label
Primary Purpose: Treatment
Coronary Artery Disease
  • Drug: Rosuvastatin-omeprazole
    Rosuvastatin 20 mg for 1 month. Then rosuvastatin 20mg and omeprazole 20mg for 11 months
  • Drug: Rosuvastatin-pantoprazole
    Rosuvastatin 20 mg for 1 month, then rosuvastatin 20 mg and pantoprazole 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
  • Drug: Rosuvastatin-ranitidine
    Rosuvastatin 20 mg for 1 month, then rosuvastatin 20 mg and ranitidine 300mg for 11 months
  • Drug: Atorvastatin-omeprazole
    Atorvastatin 80mg for 1 month, then atorvastatin 80 mg and omeprazole 20 mg for 11 months
  • Drug: Atorvastatin-pantoprazole
    Atorvastatin 80mg for 1 month, then atorvastatin 80 mg and pantoprazole 40 mg for 11 months
  • Drug: Atorvastatin-esomeprazole
    Atorvastatin 80mg for 1 month, then atorvastatin 80 mg and esomeprazole 40 mg for 11 months
  • Drug: Atorvastatin-ranitidine
    Atorvastatin 80mg for 1 month, then atorvastatin 80 mg and ranitidine 300mg for 11 months
  • Experimental: Rosuvastatin-omeprazole
    Rosuvastatin-omeprazole
    Intervention: Drug: Rosuvastatin-omeprazole
  • Experimental: Rosuvastatin-pantoprazole
    Rosuvastatin 20 mg for 1 month, then rosuvastatin 20 mg and pantoprazole 40 mg for 11 months
    Intervention: Drug: Rosuvastatin-pantoprazole
  • Experimental: Rosuvastatin-esomeprazole
    Rosuvastatin 20 mg for 1 month, then rosuvastatin 20 mg and esomeprazole 40 mg for 11 months
    Intervention: Drug: Rosuvastatin-esomeprazole
  • Active Comparator: Rosuvastatin-ranitidine
    Rosuvastatin 20 mg for 1 month, then rosuvastatin 20 mg and ranitidine 300 mg for 11 months
    Intervention: Drug: Rosuvastatin-ranitidine
  • Experimental: Atorvastatin-omeprazole
    Atorvastatin 80mg for 1 month, then atorvastatin 80 mg and omeprazole 20 mg for 11 months
    Intervention: Drug: Atorvastatin-omeprazole
  • Experimental: Atorvastatin-pantoprazole
    Atorvastatin 80mg for 1 month, then atorvastatin 80 mg and pantoprazole 40mg for 11 months
    Intervention: Drug: Atorvastatin-pantoprazole
  • Experimental: Atorvastatin-esomeprazole
    Atorvastatin 80mg for 1 month, then atorvastatin 80 mg and esomeprazole 40 mg for 11 months
    Intervention: Drug: Atorvastatin-esomeprazole
  • Active Comparator: Atorvastatin-ranitidine
    Atorvastatin 80mg for 1 month, then atorvastatin 80 mg and ranitidine 300mg for 11 months
    Intervention: Drug: Atorvastatin-ranitidine
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
320
December 2011
December 2011   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Canada
 
NCT00930670
SPICE
No
Jean-Pierre Dery, MD, MSc, Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Quebec
Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Quebec
Not Provided
Principal Investigator: Jean-Pierre Dery, MD, MHS Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Quebec
Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Quebec
February 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP