Coronary Artery DiseasePhase 4SPICENCT00930670
Evaluation of the Influence of Statins and Proton Pump Inhibitors on Clopidogrel Antiplatelet Effects
A Phase 4 study testing Rosuvastatin-omeprazole, Rosuvastatin-pantoprazole and Rosuvastatin-esomeprazole in people with Coronary Artery Disease, run by Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Quebec at 1 site in Canada.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Coronary Artery Disease
- What is being tested?
- Rosuvastatin-omeprazole, Rosuvastatin-pantoprazole and Rosuvastatin-esomeprazole
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 320 participants
- Where
- 1 siteCanada
- Study dates
- Jun 2009to Dec 2011
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 11Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
Canada1 site
Institut Universitaire de Cardiologie et de Pneumologie de Quebec
Québec, Quebec, G1V4G5
About this study
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
- Being tested
- Rosuvastatin-omeprazole, Rosuvastatin-pantoprazole, Rosuvastatin-esomeprazole, Rosuvastatin-ranitidine, Atorvastatin-omeprazole
- 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
- Medical subject headings
- Coronary Artery Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Rosuvastatin-omeprazoleDrug
Rosuvastatin 20 mg for 1 month. Then rosuvastatin 20mg and omeprazole 20mg for 11 months
Rosuvastatin-pantoprazoleDrug
Rosuvastatin 20 mg for 1 month, then rosuvastatin 20 mg and pantoprazole 40 mg for 11 months
Rosuvastatin-esomeprazoleDrug
Rosuvastatin 20 mg for 1 month, then rosuvastatin 20 mg and esomeprazole 40 mg for 11 months
Rosuvastatin-ranitidineDrug
Rosuvastatin 20 mg for 1 month, then rosuvastatin 20 mg and ranitidine 300mg for 11 months
Atorvastatin-omeprazoleDrug
Atorvastatin 80mg for 1 month, then atorvastatin 80 mg and omeprazole 20 mg for 11 months
Atorvastatin-pantoprazoleDrug
Atorvastatin 80mg for 1 month, then atorvastatin 80 mg and pantoprazole 40 mg for 11 months
Atorvastatin-esomeprazoleDrug
Atorvastatin 80mg for 1 month, then atorvastatin 80 mg and esomeprazole 40 mg for 11 months
Atorvastatin-ranitidineDrug
Atorvastatin 80mg for 1 month, then atorvastatin 80 mg and ranitidine 300mg for 11 months
| Study group | Role | What they receive |
|---|---|---|
| Rosuvastatin-omeprazole | Experimental | Rosuvastatin-omeprazole Receives: Drug: Rosuvastatin-omeprazole |
| Rosuvastatin-pantoprazole | Experimental | Rosuvastatin 20 mg for 1 month, then rosuvastatin 20 mg and pantoprazole 40 mg for 11 months Receives: Drug: Rosuvastatin-pantoprazole |
| Rosuvastatin-esomeprazole | Experimental | Rosuvastatin 20 mg for 1 month, then rosuvastatin 20 mg and esomeprazole 40 mg for 11 months Receives: Drug: Rosuvastatin-esomeprazole |
| Rosuvastatin-ranitidine | Active comparator | Rosuvastatin 20 mg for 1 month, then rosuvastatin 20 mg and ranitidine 300 mg for 11 months Receives: Drug: Rosuvastatin-ranitidine |
| Atorvastatin-omeprazole | Experimental | Atorvastatin 80mg for 1 month, then atorvastatin 80 mg and omeprazole 20 mg for 11 months Receives: Drug: Atorvastatin-omeprazole |
| Atorvastatin-pantoprazole | Experimental | Atorvastatin 80mg for 1 month, then atorvastatin 80 mg and pantoprazole 40mg for 11 months Receives: Drug: Atorvastatin-pantoprazole |
| Atorvastatin-esomeprazole | Experimental | Atorvastatin 80mg for 1 month, then atorvastatin 80 mg and esomeprazole 40 mg for 11 months Receives: Drug: Atorvastatin-esomeprazole |
| Atorvastatin-ranitidine | Active comparator | Atorvastatin 80mg for 1 month, then atorvastatin 80 mg and ranitidine 300mg for 11 months Receives: Drug: Atorvastatin-ranitidine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percent change in residual platelet aggregation by light transmittance aggregometry and percent change in platelet reactivity index by VASP
Measured: 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%)
Measured: 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
Measured: 30 and 60 days
The composite of death from all causes, myocardial infarction, ischemia-driven repeat revascularization, and stroke
Measured: 30 days, 60 days and 1 year
Need to stop any antiplatelet medication for gastrointestinal bleeding or peptic ulcer disease
Measured: 30 days, 60 days and one year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jun 2009 (estimated)
- Study startJun 2009
- Primary completionDec 2011
- Study completionDec 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Coronary Artery DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- None (open label)
- Enrolment
- 320 participants (actual)
Sponsor and investigators
- Lead sponsor
- Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Quebec
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jean-Pierre Dery, MD, MSc, Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Quebec
- Investigators
- Jean-Pierre Dery, MD, MHS, Principal investigator, Institut universitaire de cardiologie et de pneumologie de Québec, University Laval
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00930670
- Sponsor's protocol ID
- SPICE
- Acronym
- SPICE
- Status last verified
- Feb 2012
- First submitted
- 29 Jun 2009
- Last updated
- 9 Feb 2012
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 26815196
Study at a glance
From the registry record, last updated by the sponsor on 9 Feb 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of the Influence of Statins and Proton Pump Inhibitors on Clopidogrel Antiplatelet Effects
- ClinicalTrials.gov ID
- NCT00930670
- Acronym / sponsor ID
- SPICE / SPICE
- Conditions
- Coronary Artery Disease
- Keywords
- ranitidine, pantoprazole, esomeprazole, omeprazole, atorvastatin, rosuvastatin, statin, clopidogrel resistance
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 320 participants (actual)
- Lead sponsor
- Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de QuebecUniversity, hospital or other
- Study start
- Jun 2009
- Primary completion
- Dec 2011 (actual)
- Study completion
- Dec 2011 (actual)
- First posted
- 30 Jun 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- None (open label)
- Number of arms
- 8
| Arm | Type | Receives |
|---|---|---|
| Rosuvastatin-omeprazole | Experimental | Drug: Rosuvastatin-omeprazoleRosuvastatin-omeprazole |
| Rosuvastatin-pantoprazole | Experimental | Drug: Rosuvastatin-pantoprazoleRosuvastatin 20 mg for 1 month, then rosuvastatin 20 mg and pantoprazole 40 mg for 11 months |
| Rosuvastatin-esomeprazole | Experimental | Drug: Rosuvastatin-esomeprazoleRosuvastatin 20 mg for 1 month, then rosuvastatin 20 mg and esomeprazole 40 mg for 11 months |
| Rosuvastatin-ranitidine | Active comparator | Drug: Rosuvastatin-ranitidineRosuvastatin 20 mg for 1 month, then rosuvastatin 20 mg and ranitidine 300 mg for 11 months |
| Atorvastatin-omeprazole | Experimental | Drug: Atorvastatin-omeprazoleAtorvastatin 80mg for 1 month, then atorvastatin 80 mg and omeprazole 20 mg for 11 months |
| Atorvastatin-pantoprazole | Experimental | Drug: Atorvastatin-pantoprazoleAtorvastatin 80mg for 1 month, then atorvastatin 80 mg and pantoprazole 40mg for 11 months |
| Atorvastatin-esomeprazole | Experimental | Drug: Atorvastatin-esomeprazoleAtorvastatin 80mg for 1 month, then atorvastatin 80 mg and esomeprazole 40 mg for 11 months |
| Atorvastatin-ranitidine | Active comparator | Drug: Atorvastatin-ranitidineAtorvastatin 80mg for 1 month, then atorvastatin 80 mg and ranitidine 300mg for 11 months |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (11 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Rosuvastatin-omeprazoleRosuvastatin 20 mg for 1 month. Then rosuvastatin 20mg and omeprazole 20mg for 11 months | Drug | Rosuvastatin-omeprazole |
| Rosuvastatin-pantoprazoleRosuvastatin 20 mg for 1 month, then rosuvastatin 20 mg and pantoprazole 40 mg for 11 months | Drug | Rosuvastatin-pantoprazole |
| Rosuvastatin-esomeprazoleRosuvastatin 20 mg for 1 month, then rosuvastatin 20 mg and esomeprazole 40 mg for 11 months | Drug | Rosuvastatin-esomeprazole |
| Rosuvastatin-ranitidineRosuvastatin 20 mg for 1 month, then rosuvastatin 20 mg and ranitidine 300mg for 11 months | Drug | Rosuvastatin-ranitidine |
| Atorvastatin-omeprazoleAtorvastatin 80mg for 1 month, then atorvastatin 80 mg and omeprazole 20 mg for 11 months | Drug | Atorvastatin-omeprazole |
| Atorvastatin-pantoprazoleAtorvastatin 80mg for 1 month, then atorvastatin 80 mg and pantoprazole 40 mg for 11 months | Drug | Atorvastatin-pantoprazole |
| Atorvastatin-esomeprazoleAtorvastatin 80mg for 1 month, then atorvastatin 80 mg and esomeprazole 40 mg for 11 months | Drug | Atorvastatin-esomeprazole |
| Atorvastatin-ranitidineAtorvastatin 80mg for 1 month, then atorvastatin 80 mg and ranitidine 300mg for 11 months | Drug | Atorvastatin-ranitidine |
Primary outcome
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
4 secondary outcomes
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
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
The composite of death from all causes, myocardial infarction, ischemia-driven repeat revascularization, and stroke
Time frame: 30 days, 60 days and 1 year
Need to stop any antiplatelet medication for gastrointestinal bleeding or peptic ulcer disease
Time frame: 30 days, 60 days and one year
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Feb 2012.
- Derived from this study: PubMed 26815196Harvey 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jean-Pierre Dery, MD, MHS principal investigator
Institut universitaire de cardiologie et de pneumologie de Québec, University Laval
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Rosuvastatin-omeprazole, Rosuvastatin-pantoprazole and Rosuvastatin-esomeprazole in people with Coronary Artery Disease, run by Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Quebec at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Feb 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the 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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00930670, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Feb 2012.