Drug InteractionPhase 1NCT01170533
PPI and Clopidogrel Response
A Phase 1 study testing omeprazole and pantoprazole in people with Drug Interaction, run by University of Florida at 1 site in United States.
Trial summary
Clopidogrel, in combination with aspirin, is currently the recommended treatment for secondary prevention of ischemic events in high-risk patients and for prevention of coronary artery stent thrombosis. Read more about this study
- Who is it for?
- Ages 18 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Drug Interaction
- What is being tested?
- omeprazole and pantoprazole
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2009to Aug 2010
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 to 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Healthy volunteers aged between 18 and 75 years
Who cannot join
- Known allergies to clopidogrel or omeprazole.
- Blood dyscrasia or bleeding diathesis.
- Recent antiplatelet treatment (< 30 days) with a glycoprotein IIb/IIIa antagonist, thienopyridine (ticlopidine, clopidogrel), cilostazol or dipyridamole.
- Treatment with other medications that may interfere with the CYP system (ketoconazole, itraconazole, diltiazem, erythromycin, clarithromycin, fluvoxamine, fluoxetine, nefazodone, or sertraline).
- Platelet count <100x106/microL.
- Diabetes mellitus
Show all 12Show fewer
- History of coronary artery disease, gastrointestinal bleed, gastroesophageal reflux disease (GERD), cerebrovascular event or any active malignancy.
- Active bleeding or hemodynamic instability.
- Serum creatinine >2mg/dL.
- Baseline ALT >2.5 times the upper limit of normal.
- Pregnant females.
- Patients taking omeprazole or any H2 antagonist or proton pump inhibitors
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Effects of PPI Therapy on Clopidogrel-Induced Antiplatelet Effects: A Randomized Study
Clopidogrel, in combination with aspirin, is currently the recommended treatment for secondary prevention of ischemic events in high-risk patients and for prevention of coronary artery stent thrombosis. Patients receiving aspirin and clopidogrel are frequently treated with proton pump inhibitors, such as omeprazole or pantoprazole, in order to prevent the risk of gastrointestinal bleeding, accorded to guidelines. An interaction between proton pump inhibitors and clopidogrel has been suggested, which may lead to a decrease of clopidogrel effects. It remains unclear whether this interaction between PPIs and clopidogrel might be a class effect or if this may be affected by timing regimen.
The objectives of this two-phase investigation are:
- to compare clopidogrel platelet inhibitory effects when taken at the same time versus separated at least 8 hours from omeprazole administration.
- to compare clopidogrel-induced inhibitory effects when taken at the same time versus staggered at least 8 hours from pantoprazole administration.
Read the detailed description
Clopidogrel, in combination with aspirin, is currently the recommended treatment for secondary prevention of ischemic events in high-risk patients and for prevention of coronary artery stent thrombosis. Patients receiving aspirin and clopidogrel are frequently treated with proton pump inhibitors, such as omeprazole or pantoprazole, in order to prevent the risk of gastrointestinal bleeding, accorded to guidelines. An interaction between proton pump inhibitors and clopidogrel has been suggested, which may lead to a decrease of clopidogrel effects. It remains unclear whether this interaction between PPIs and clopidogrel might be a class effect or if this may be affected by timing regimen. The objectives of this two-phase investigation are: 1. to compare clopidogrel platelet inhibitory effects when taken at the same time versus separated at least 8 hours from omeprazole administration. 2. to compare clopidogrel-induced inhibitory effects when taken at the same time versus staggered at least 8 hours from pantoprazole administration. The clopidogrel dose will be a 600mg loading dose followed by a 75mg daily maintenance dose, starting the next day for 7 days. Omeprazole will be used at a daily dose of 40mg and pantoprazole at 80mg.
The proposed study will have a prospective, randomized, cross-over design. Subjects are randomized in a 1:1 fashion to take PPI concomitantly (CONC regimen) or staggered by 8-12 hours (STAG regimen) for one-week on a background of clopidogrel therapy. In particular, in the CONC regimen both drugs were taken in the morning, while in the STAG regimen clopidogrel was taken in the morning and omeprazole in the evening. After a 2-4 week washout period, subjects crossed-over treatment regimen. After completing these two treatment phases, subjects underwent another washout period of 2-4 weeks and were treated for 1 week with clopidogrel alone, without receiving omeprazole therapy (CLOP regimen). The sequence with the PPI pantoprazole will have the same prospective, randomized, cross-over design as the omeprazole sequence. A CLOP regimen in the absence of pantoprazole will be collected before entering randomization phase with adequate wash-out period.
Blood sampling for platelet function assessments were performed at all three phases of the study at the following time points: a) baseline, b) 24 hours after LD (before intake of study medication), and c) 7 days (24 hours after the last MD).
- Conditions
- Drug Interaction
- Being tested
- omeprazole and pantoprazole
- Keywords
- proton pump inhibitor, clopidogrel, platelet function
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
omeprazole and pantoprazoleDrug
The clopidogrel dose will be a 600mg loading dose followed by a 75mg daily maintenance dose, starting the next day for 7 days. Omeprazole will be used at a daily dose of 40mg and pantoprazole at 80mg.
| Study group | Role | What they receive |
|---|---|---|
| Omeprazole | Active comparator | prospective, open-label, two-sequence, three-period, randomized crossover study Receives: Drug: omeprazole and pantoprazole |
| Pantoprazole | Active comparator | prospective, open-label, two-sequence, three-period, randomized crossover study Receives: Drug: omeprazole and pantoprazole |
What is being measured
The primary outcome is the main question the study is designed to answer.
Platelet Function as Assessed by the P2Y12 Reactivity Index
P2Y12 reactivity index which will be assessed by flow cytometry determination of vasodilator-stimulated phosphoprotein (VASP).
Measured: 1 week
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jul 2010 (estimated)
- Study startMar 2009
- Primary completionAug 2010
- Study completionAug 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Drug InteractionStudies of the same condition, open and under way.
- More trials run by University of FloridaThe sponsor's other registered studies.
- 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 1
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Florida
- Sponsor type
- University, hospital or other
- Collaborators
- Bristol-Myers Squibb, Sanofi
- Responsible party
- Sponsor
- Investigators
- Dominick J Angiolillo, MD, PhD, Principal investigator, University of Florida
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01170533
- Sponsor's protocol ID
- UFJ 2009-2
- Status last verified
- Mar 2012
- First submitted
- 23 Jul 2010
- Last updated
- 6 Mar 2012
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Ferreiro JL, Ueno M, Capodanno D, Desai B, Dharmashankar K, Darlington A, Charlton RK, Bass TA, Angiolillo DJ. Pharmacodynamic effects of concomitant versus staggered clopidogrel and omeprazole intake: results of a prospective randomized crossover study. Circ Cardiovasc Interv. 2010 Oct;3(5):436-41. doi: 10.1161/CIRCINTERVENTIONS.110.957829. Epub 2010 Sep 21.
PubMed 20858862Ferreiro JL, Ueno M, Tomasello SD, Capodanno D, Desai B, Dharmashankar K, Seecheran N, Kodali MK, Darlington A, Pham JP, Tello-Montoliu A, Charlton RK, Bass TA, Angiolillo DJ. Pharmacodynamic evaluation of pantoprazole therapy on clopidogrel effects: results of a prospective, randomized, crossover study. Circ Cardiovasc Interv. 2011 Jun;4(3):273-9. doi: 10.1161/CIRCINTERVENTIONS.110.960997. Epub 2011 Apr 26.
PubMed 21521834
Study at a glance
From the registry record, last updated by the sponsor on 6 Mar 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of PPI Therapy on Clopidogrel-Induced Antiplatelet Effects: A Randomized Study
- ClinicalTrials.gov ID
- NCT01170533
- Acronym / sponsor ID
- UFJ 2009-2
- Conditions
- Drug Interaction
- Keywords
- proton pump inhibitor, clopidogrel, platelet function
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- University of FloridaUniversity, hospital or other
- Collaborators
- Bristol-Myers Squibb, Sanofi
- Study start
- Mar 2009
- Primary completion
- Aug 2010 (actual)
- Study completion
- Aug 2010 (actual)
- First posted
- 27 Jul 2010 (estimated)
- Results
- Posted 6 Mar 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Clopidogrel, in combination with aspirin, is currently the recommended treatment for secondary prevention of ischemic events in high-risk patients and for prevention of coronary artery stent thrombosis. Patients receiving aspirin and clopidogrel are frequently treated with proton pump inhibitors, such as omeprazole or pantoprazole, in order to prevent the risk of gastrointestinal bleeding, accorded to guidelines. An interaction between proton pump inhibitors and clopidogrel has been suggested, which may lead to a decrease of clopidogrel effects. It remains unclear whether this interaction between PPIs and clopidogrel might be a class effect or if this may be affected by timing regimen.
The objectives of this two-phase investigation are:
- to compare clopidogrel platelet inhibitory effects when taken at the same time versus separated at least 8 hours from omeprazole administration.
- to compare clopidogrel-induced inhibitory effects when taken at the same time versus staggered at least 8 hours from pantoprazole administration.
Detailed description
Clopidogrel, in combination with aspirin, is currently the recommended treatment for secondary prevention of ischemic events in high-risk patients and for prevention of coronary artery stent thrombosis. Patients receiving aspirin and clopidogrel are frequently treated with proton pump inhibitors, such as omeprazole or pantoprazole, in order to prevent the risk of gastrointestinal bleeding, accorded to guidelines. An interaction between proton pump inhibitors and clopidogrel has been suggested, which may lead to a decrease of clopidogrel effects. It remains unclear whether this interaction between PPIs and clopidogrel might be a class effect or if this may be affected by timing regimen. The objectives of this two-phase investigation are: 1. to compare clopidogrel platelet inhibitory effects when taken at the same time versus separated at least 8 hours from omeprazole administration. 2. to compare clopidogrel-induced inhibitory effects when taken at the same time versus staggered at least 8 hours from pantoprazole administration. The clopidogrel dose will be a 600mg loading dose followed by a 75mg daily maintenance dose, starting the next day for 7 days. Omeprazole will be used at a daily dose of 40mg and pantoprazole at 80mg.
The proposed study will have a prospective, randomized, cross-over design. Subjects are randomized in a 1:1 fashion to take PPI concomitantly (CONC regimen) or staggered by 8-12 hours (STAG regimen) for one-week on a background of clopidogrel therapy. In particular, in the CONC regimen both drugs were taken in the morning, while in the STAG regimen clopidogrel was taken in the morning and omeprazole in the evening. After a 2-4 week washout period, subjects crossed-over treatment regimen. After completing these two treatment phases, subjects underwent another washout period of 2-4 weeks and were treated for 1 week with clopidogrel alone, without receiving omeprazole therapy (CLOP regimen). The sequence with the PPI pantoprazole will have the same prospective, randomized, cross-over design as the omeprazole sequence. A CLOP regimen in the absence of pantoprazole will be collected before entering randomization phase with adequate wash-out period.
Blood sampling for platelet function assessments were performed at all three phases of the study at the following time points: a) baseline, b) 24 hours after LD (before intake of study medication), and c) 7 days (24 hours after the last MD).
Study design
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Omeprazole | Active comparator | Drug: omeprazole and pantoprazoleprospective, open-label, two-sequence, three-period, randomized crossover study |
| Pantoprazole | Active comparator | Drug: omeprazole and pantoprazoleprospective, open-label, two-sequence, three-period, randomized crossover study |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Healthy volunteers aged between 18 and 75 years
Key exclusion criteria (12 listed)
- Known allergies to clopidogrel or omeprazole.
- Blood dyscrasia or bleeding diathesis.
- Recent antiplatelet treatment (< 30 days) with a glycoprotein IIb/IIIa antagonist, thienopyridine (ticlopidine, clopidogrel), cilostazol or dipyridamole.
- Treatment with other medications that may interfere with the CYP system (ketoconazole, itraconazole, diltiazem, erythromycin, clarithromycin, fluvoxamine, fluoxetine, nefazodone, or sertraline).
- Platelet count <100x106/microL.
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 |
|---|---|---|
| omeprazole and pantoprazoleThe clopidogrel dose will be a 600mg loading dose followed by a 75mg daily maintenance dose, starting the next day for 7 days. Omeprazole will be used at a daily dose of 40mg and pantoprazole at 80mg. | Drug | Omeprazole, Pantoprazole |
Primary outcome
Platelet Function as Assessed by the P2Y12 Reactivity Index
Time frame: 1 week
P2Y12 reactivity index which will be assessed by flow cytometry determination of vasodilator-stimulated phosphoprotein (VASP).
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Mar 2012.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 20858862Ferreiro JL, Ueno M, Capodanno D, Desai B, Dharmashankar K, Darlington A, Charlton RK, Bass TA, Angiolillo DJ. Pharmacodynamic effects of concomitant versus staggered clopidogrel and omeprazole intake: results of a prospective randomized crossover study. Circ Cardiovasc Interv. 2010 Oct;3(5):436-41. doi: 10.1161/CIRCINTERVENTIONS.110.957829. Epub 2010 Sep 21.
- Results publication: PubMed 21521834Ferreiro JL, Ueno M, Tomasello SD, Capodanno D, Desai B, Dharmashankar K, Seecheran N, Kodali MK, Darlington A, Pham JP, Tello-Montoliu A, Charlton RK, Bass TA, Angiolillo DJ. Pharmacodynamic evaluation of pantoprazole therapy on clopidogrel effects: results of a prospective, randomized, crossover study. Circ Cardiovasc Interv. 2011 Jun;4(3):273-9. doi: 10.1161/CIRCINTERVENTIONS.110.960997. Epub 2011 Apr 26.
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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.
Dominick J Angiolillo, MD, PhD principal investigator
University of Florida
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing omeprazole and pantoprazole in people with Drug Interaction, run by University of Florida at 1 site in United States.
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 1 inclusion and 12 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 6 Mar 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 United States. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 6 Mar 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Platelet Function as Assessed by the P2Y12 Reactivity Index (time frame: 1 week). 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 NCT01170533, which also lists 2 linked publications.
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 6 Mar 2012.