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

NCT00930670 | Completed Phase 4

• 1 other identifier: SPICE
• Study Type: interventional
• Target: 320
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Coronary Artery Disease

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Percent change in residual platelet aggregation by light transmittance aggregometry and percent change in platelet reactivity index by VASP

  At 30 and 60 days

Secondary Outcomes (4)

• 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

• 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

• The composite of death from all causes, myocardial infarction, ischemia-driven repeat revascularization, and stroke

  30 days, 60 days and 1 year

• Need to stop any antiplatelet medication for gastrointestinal bleeding or peptic ulcer disease

  30 days, 60 days and one year

Study Arms (8)

Rosuvastatin-omeprazole

EXPERIMENTAL

Rosuvastatin-omeprazole

Drug: Rosuvastatin-omeprazole

Rosuvastatin-pantoprazole

EXPERIMENTAL

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

Drug: Rosuvastatin-pantoprazole

Rosuvastatin-esomeprazole

EXPERIMENTAL

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

Drug: Rosuvastatin-esomeprazole

Rosuvastatin-ranitidine

ACTIVE COMPARATOR

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

Drug: Rosuvastatin-ranitidine

Atorvastatin-omeprazole

EXPERIMENTAL

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

Drug: Atorvastatin-omeprazole

Atorvastatin-pantoprazole

EXPERIMENTAL

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

Drug: Atorvastatin-pantoprazole

Atorvastatin-esomeprazole

EXPERIMENTAL

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

Drug: Atorvastatin-esomeprazole

Atorvastatin-ranitidine

ACTIVE COMPARATOR

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

Drug: Atorvastatin-ranitidine

Interventions

Rosuvastatin-omeprazole DRUG

Rosuvastatin 20 mg for 1 month. Then rosuvastatin 20mg and omeprazole 20mg for 11 months

Rosuvastatin-omeprazole

Rosuvastatin-pantoprazole DRUG

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

Rosuvastatin-pantoprazole

Rosuvastatin-esomeprazole DRUG

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

Rosuvastatin-esomeprazole

Rosuvastatin-ranitidine DRUG

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

Rosuvastatin-ranitidine

Atorvastatin-omeprazole DRUG

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

Atorvastatin-omeprazole

Atorvastatin-pantoprazole DRUG

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

Atorvastatin-pantoprazole

Atorvastatin-esomeprazole DRUG

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

Atorvastatin-esomeprazole

Atorvastatin-ranitidine DRUG

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

Atorvastatin-ranitidine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Quebec: lead

Study Sites (1)

Institut Universitaire de Cardiologie et de Pneumologie de Quebec

Québec, Quebec, G1V4G5, Canada

Location

Related Publications (1)

• Harvey A, Modak A, Dery U, Roy M, Rinfret S, Bertrand OF, Larose E, Rodes-Cabau J, Barbeau G, Gleeton O, Nguyen CM, Proulx G, Noel B, Roy L, Paradis JM, De Larochelliere R, Dery JP. Changes in CYP2C19 enzyme activity evaluated by the [(13)C]-pantoprazole breath test after co-administration of clopidogrel and proton pump inhibitors following percutaneous coronary intervention and correlation to platelet reactivity. J Breath Res. 2016 Jan 27;10(1):017104. doi: 10.1088/1752-7155/10/1/017104.

  PMID: 26815196 DERIVED

MeSH Terms

Conditions

Coronary Artery Disease

Condition Hierarchy (Ancestors)

Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases

Study Officials

• Jean-Pierre Dery, MD, MHS

  Institut universitaire de cardiologie et de pneumologie de Québec, University Laval

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Interventional Cardiologist

Study Record Dates

• First Submitted: June 29, 2009
• First Posted: June 30, 2009
• Study Start: June 1, 2009
• Primary Completion: December 1, 2011
• Study Completion: December 1, 2011
• Last Updated: February 9, 2012

Record last verified: 2012-02

Locations

CA (1)