Coronary StentingPhase 4GENIOUSNCT01512953
Effect of Proton Pump Inhibitor on Residual Platelet Reactivity After Clopidogrel in Homogenous Genetic Strata
A Phase 4 study testing Lansoprazole in people with Coronary Stenting, run by Università degli Studi di Ferrara at 1 site in Italy.
Trial summary
This study aims to prospectively assess whether there is an interaction between genetic status in terms of 2C19 activity and residual platelet reactivity after clopidogrel intake in patients who underwent coronary stenting for elective, urgent or emergent intervention. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Coronary Stenting
- What is being tested?
- Lansoprazole
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 522 participants
- Where
- 1 siteItaly
- Study dates
- Jan 2011to Aug 2013
- 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
None listed.
Who cannot join
- Patients who can not give informed consent or have a life expectancy of < 1 year
- Ongoing bleeding or bleeding diathesis or increase bleeding risk or history of bleeding in the last 2 months
- Age > 90
- Previous stroke or TIA or any intracranial pathology
- Major surgery or trauma within the previous six weeks
- Platelet count < 100.000 per cubic mm or HCT ,33% or Hb < 11 gm/dL
Show all 9Show fewer
- Subjects with an allergy or intolerance to prasugrel or to clopidogrel
- Planned elective cardiac or non-cardiac surgery within 1 month.
- Current or planned therapy with coumadin anticoagulation.
Trial locations and contacts
1 site in 1 country.
Italy1 site, 1 recruiting
- Recruiting
University Hospital of Ferrara
Ferrara, ER, 44100
Monia Monti, bSc, 0532-236298 ext. +39, mntmno@unife.it
About this study
Official title: Randomized Comparison of PPI Versus no PPI on Top of Standard Dose Clopidogrel Therapy in Patients Stratified Based on CYC2C19 Activity Via a Genetic Point of Care System.
This study aims to prospectively assess whether there is an interaction between genetic status in terms of 2C19 activity and residual platelet reactivity after clopidogrel intake in patients who underwent coronary stenting for elective, urgent or emergent intervention.
Read the detailed description
In managing patients who undergo percutaneous coronary intervention (PCI), rapid and predictable platelet inhibition for all patients is an important therapeutic goal. Determining the optimal dose of antiplatelet therapy to achieve this goal has been hampered by considerable interpatient variability in response to clopidogrel, which largely reflects gene polymorphism. Most of the evidence is centred around cytochrome 450 2C19.
A substudy of TRITON TIMI 38 has recently shown that among persons treated with clopidogrel, carriers of a reduced-function CYP2C19 allele had significantly lower levels of the active metabolite of clopidogrel, diminished platelet inhibition, and a higher rate of major adverse cardiovascular events, including stent thrombosis, than did noncarriers (N Engl J Med 2009;360:354-62). As a contrary, common functional CYP genetic variants do not affect active drug metabolite levels, inhibition of platelet aggregation, or clinical cardiovascular event rates in persons treated with prasugrel (Circulation. 2009 May 19;119(19):2553-60).
More recently, it has been shown that CYP2C19*17 carrier status is significantly associated with enhanced response to clopidogrel and an increased risk of bleeding. (Circulation. 2010;121:512-518). Whether CYP2C19*17 carrier status enhances response to prasugrel is unknown.
Attention has also been placed on a potential interaction observed between clopidogrel and the widely used proton pump inhibitors (PPIs).
The CYP2C19 isoform is the key enzyme in the metabolism of many of the PPIs, which are also inhibitors of the CYP2C19 isoenzyme in varying degrees. This is important because the antiplatelet effects of clopidogrel rely, to a degree, upon CYP2C19 activity. However, the recent COGENT study and sub-analysis of the TRITON-TIMI 38 have both apparently mitigated this concern. Nevertheless, it is unknown whether PPI can father blunt response to clopidogrel especially in patients carrying the loss of function 2C19 allele.
A recent review paper (Aliment Pharmacol Ther 31, 810-823) included 23 studies covering 93,278 patients. There was substantial heterogeneity in the meta-analyses of major cardiovascular events (19 studies, I2 = 79%) or myocardial infarction (12 studies, I2 = 77%). Analysis of propensity-matched or randomized trial participants showed no associated cardiovascular risk with PPIs, whereas other observational studies generally showed a significant association.
Thus, still today there is an emerging need for more studies, especially prospective randomized studies, to investigate the effect of individual PPI agents on clopidogrel's effectiveness. Such studies should also include a genetic component to stratify response based on the presence of reduced-function alleles of the CYP2C19 enzyme
- Conditions
- Coronary Stenting
- Being tested
- Lansoprazole
- Keywords
- PPI, clopidogrel, 2C19, Lansoprazole
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LansoprazoleDrug
Lansoprazole 30 mg once a day
| Study group | Role | What they receive |
|---|---|---|
| no PPI | No intervention | Patients, stratified according to the genetic stratum, will be randomized not to take any PPI on top of clopidogrel |
| PPI | Experimental | Patients stratified to the genetic stratum will be randomized to take PPI on top of clopidogrel Receives: Drug: Lansoprazole |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximal platelet aggregation at light transmission aggregometry after 20 μmol/l ADP
IPA expressed as maximal platelet aggregation (MPA) after 20 μmol/l ADP according to genetic stratum defined as follows: [(Poor metabolizers: 2C19*2+ and 2C19*17-); (intermediate metabolizers: wild type patients or its carrying both 2C19*2 and *170; (ultra metabolizers: 2c19*2- and 2C19*17+).
Measured: 30 days
maximal platelet aggregation after 5 μmol/l ADP in PPI versus no PPI treated patients
Patients, stratified by genetic stratum, will be randomized to PPI or no PPI. We assume that that will be an interaction in the IPA after 5 μmol/l ADP at 30 days so that PPI will blunt responsiveness to clopidogrel in poor metabolizer patients only but in intermediate or ultra metabolizers.
Measured: 30 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jan 2012 (estimated)
- Study startJan 2011
- Primary completionAug 2012 (estimated)
- Study completionAug 2013 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Coronary StentingStudies 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
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 522 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Università degli Studi di Ferrara
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Marco Valgimigli, Università degli Studi di Ferrara
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01512953
- Sponsor's protocol ID
- GEN-2011-1
- Acronym
- GENIOUS
- Status last verified
- Jan 2012
- First submitted
- 15 Jan 2012
- Last updated
- 20 Jan 2012
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Jan 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Comparison of PPI Versus no PPI on Top of Standard Dose Clopidogrel Therapy in Patients Stratified Based on CYC2C19 Activity Via a Genetic Point of Care System.
- ClinicalTrials.gov ID
- NCT01512953
- Acronym / sponsor ID
- GENIOUS / GEN-2011-1
- Conditions
- Coronary Stenting
- Keywords
- PPI, clopidogrel, 2C19, Lansoprazole
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 522 participants (estimated)
- Lead sponsor
- Università degli Studi di FerraraUniversity, hospital or other
- Study start
- Jan 2011
- Primary completion
- Aug 2012 (estimated)
- Study completion
- Aug 2013 (estimated)
- First posted
- 20 Jan 2012 (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.
This study aims to prospectively assess whether there is an interaction between genetic status in terms of 2C19 activity and residual platelet reactivity after clopidogrel intake in patients who underwent coronary stenting for elective, urgent or emergent intervention.
Detailed description
In managing patients who undergo percutaneous coronary intervention (PCI), rapid and predictable platelet inhibition for all patients is an important therapeutic goal. Determining the optimal dose of antiplatelet therapy to achieve this goal has been hampered by considerable interpatient variability in response to clopidogrel, which largely reflects gene polymorphism. Most of the evidence is centred around cytochrome 450 2C19.
A substudy of TRITON TIMI 38 has recently shown that among persons treated with clopidogrel, carriers of a reduced-function CYP2C19 allele had significantly lower levels of the active metabolite of clopidogrel, diminished platelet inhibition, and a higher rate of major adverse cardiovascular events, including stent thrombosis, than did noncarriers (N Engl J Med 2009;360:354-62). As a contrary, common functional CYP genetic variants do not affect active drug metabolite levels, inhibition of platelet aggregation, or clinical cardiovascular event rates in persons treated with prasugrel (Circulation. 2009 May 19;119(19):2553-60).
More recently, it has been shown that CYP2C19*17 carrier status is significantly associated with enhanced response to clopidogrel and an increased risk of bleeding. (Circulation. 2010;121:512-518). Whether CYP2C19*17 carrier status enhances response to prasugrel is unknown.
Attention has also been placed on a potential interaction observed between clopidogrel and the widely used proton pump inhibitors (PPIs).
The CYP2C19 isoform is the key enzyme in the metabolism of many of the PPIs, which are also inhibitors of the CYP2C19 isoenzyme in varying degrees. This is important because the antiplatelet effects of clopidogrel rely, to a degree, upon CYP2C19 activity. However, the recent COGENT study and sub-analysis of the TRITON-TIMI 38 have both apparently mitigated this concern. Nevertheless, it is unknown whether PPI can father blunt response to clopidogrel especially in patients carrying the loss of function 2C19 allele.
A recent review paper (Aliment Pharmacol Ther 31, 810-823) included 23 studies covering 93,278 patients. There was substantial heterogeneity in the meta-analyses of major cardiovascular events (19 studies, I2 = 79%) or myocardial infarction (12 studies, I2 = 77%). Analysis of propensity-matched or randomized trial participants showed no associated cardiovascular risk with PPIs, whereas other observational studies generally showed a significant association.
Thus, still today there is an emerging need for more studies, especially prospective randomized studies, to investigate the effect of individual PPI agents on clopidogrel's effectiveness. Such studies should also include a genetic component to stratify response based on the presence of reduced-function alleles of the CYP2C19 enzyme
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| no PPI | No intervention | –Patients, stratified according to the genetic stratum, will be randomized not to take any PPI on top of clopidogrel |
| PPI | Experimental | Drug: LansoprazolePatients stratified to the genetic stratum will be randomized to take PPI on top of clopidogrel |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (0 listed)
Key exclusion criteria (9 listed)
- Patients who can not give informed consent or have a life expectancy of < 1 year
- Ongoing bleeding or bleeding diathesis or increase bleeding risk or history of bleeding in the last 2 months
- Age > 90
- Previous stroke or TIA or any intracranial pathology
- Major surgery or trauma within the previous six weeks
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 |
|---|---|---|
| LansoprazoleLansoprazole 30 mg once a day | Drug | PPI |
Primary outcome
Maximal platelet aggregation at light transmission aggregometry after 20 μmol/l ADP
Time frame: 30 days
IPA expressed as maximal platelet aggregation (MPA) after 20 μmol/l ADP according to genetic stratum defined as follows: [(Poor metabolizers: 2C19*2+ and 2C19*17-); (intermediate metabolizers: wild type patients or its carrying both 2C19*2 and *170; (ultra metabolizers: 2c19*2- and 2C19*17+).
maximal platelet aggregation after 5 μmol/l ADP in PPI versus no PPI treated patients
Time frame: 30 days
Patients, stratified by genetic stratum, will be randomized to PPI or no PPI. We assume that that will be an interaction in the IPA after 5 μmol/l ADP at 30 days so that PPI will blunt responsiveness to clopidogrel in poor metabolizer patients only but in intermediate or ultra metabolizers.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Jan 2012.
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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.
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 Lansoprazole in people with Coronary Stenting, run by Università degli Studi di Ferrara at 1 site in Italy.
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 0 inclusion and 9 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: status not confirmed, as of the sponsor's last update on 20 Jan 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 Italy. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Marco Valgimigli, MD, PhD (0532326874 ext. +39, vlgmrc@unife.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximal platelet aggregation at light transmission aggregometry after 20 μmol/l ADP (time frame: 30 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 20 Jan 2012.