Evaluation of the Influence of Statins and Proton Pump Inhibitors on Clopidogrel Antiplatelet Effects (SPICE)
This study has been completed.
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
First received: June 29, 2009
Last updated: February 8, 2012
Last verified: February 2012
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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:
Drug Information available for:
Ranitidine
Ranitidine Hydrochloride
Omeprazole
Omeprazole magnesium
Pantoprazole
Esomeprazole
Clopidogrel bisulfate
Atorvastatin calcium
Pantoprazole sodium
Rosuvastatin calcium
Esomeprazole Sodium
Esomeprazole magnesium
Rosuvastatin
U.S. FDA Resources
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:
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 May 23, 2013