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
  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 4

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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:
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
Esomeprazole
Proton Pump Inhibitors
Atorvastatin
Rosuvastatin
Clopidogrel
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

ClinicalTrials.gov processed this record on August 28, 2014