"Pharmacodynamic Comparison of Omeprazole Versus Pantoprazole on Platelet Reactivity in Patients With Acute Coronary Syndromes on Dual Antiplatelet Therapy With New P2Y12 Inhibitors" -Trial dOPPLER-
Overview[ - collapse ][ - ]
Purpose | Clopidogrel and Prasugrel are pro-drug necessitating conversion in active metabolites through CYP 450 system (CYP), particularly CYP3A and CYP2C19 isoforms. These drugs are platelet purinergic receptor antagonists, known as P2Y12. The link between active metabolite of Clopidogrel and Prasugrel to P2Y12 receptor prevents ADP receptor activation and inhibits several events leading to conformational change of platelets, therefore facilitating their activation and aggregation, that is the basis of acute coronary syndromes. Proton pump inhibitors (PPI) are actually considered principal agents reducing gastroenteric bleeding risk associated to antiplatelet therapy. Nevertheless the interaction between PPI and antiplatelet therapy has been object of interest. Several studies demonstrated PPI reduce efficacy of clopidogrel on platelet reactivity. Only few data about Prasugrel are available showing a minor effect of PPI on its antiplatelet activity than clopidogrel. Differing from prasugrel and clopidogrel, ticagrelor is a direct inhibitor of P2Y12, not necessitating biotransformation in the liver; therefore its interaction with PPI remains unclear. Interaction between omeprazole and clopidogrel seems related to high inhibitory activity of PPI on CYP2C19, interfering with the conversion of clopidogrel in its active metabolite. |
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Condition | Coronary Artery Disease |
Intervention | Drug: Pantoprazole, Drug: Omeprazole |
Phase | Phase 4 |
Sponsor | University of Roma La Sapienza |
Responsible Party | University of Roma La Sapienza |
ClinicalTrials.gov Identifier | NCT02028234 |
First Received | January 2, 2014 |
Last Updated | January 6, 2014 |
Last verified | January 2014 |
Tracking Information[ + expand ][ + ]
First Received Date | January 2, 2014 |
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Last Updated Date | January 6, 2014 |
Start Date | February 2014 |
Estimated Primary Completion Date | April 2016 |
Current Primary Outcome Measures | Assessment of platelet reaction units [Time Frame: After 30 days of treatment with each drug] [Designated as safety issue: No]Absolute changes in platelet reactivity (expressed as P2Y(12) reaction units by the point-of-care VerifyNow assay [Accumetrics, San Diego, California] |
Current Secondary Outcome Measures | Frequency of high platelet reactivity [Time Frame: After 30 days of treatment with each drug] [Designated as safety issue: No]Frequency of high platelet reactivity with the 2 study treatments (as defined by a Platelet Reaction Unit value>240 |
Descriptive Information[ + expand ][ + ]
Brief Title | "Pharmacodynamic Comparison of Omeprazole Versus Pantoprazole on Platelet Reactivity in Patients With Acute Coronary Syndromes on Dual Antiplatelet Therapy With New P2Y12 Inhibitors" -Trial dOPPLER- |
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Official Title | "Pharmacodynamic Comparison of Omeprazole Versus Pantoprazole on Platelet Reactivity in Patients With Acute Coronary Syndromes on Dual Antiplatelet Therapy With New P2Y12 Inhibitors" |
Brief Summary | Clopidogrel and Prasugrel are pro-drug necessitating conversion in active metabolites through CYP 450 system (CYP), particularly CYP3A and CYP2C19 isoforms. These drugs are platelet purinergic receptor antagonists, known as P2Y12. The link between active metabolite of Clopidogrel and Prasugrel to P2Y12 receptor prevents ADP receptor activation and inhibits several events leading to conformational change of platelets, therefore facilitating their activation and aggregation, that is the basis of acute coronary syndromes. Proton pump inhibitors (PPI) are actually considered principal agents reducing gastroenteric bleeding risk associated to antiplatelet therapy. Nevertheless the interaction between PPI and antiplatelet therapy has been object of interest. Several studies demonstrated PPI reduce efficacy of clopidogrel on platelet reactivity. Only few data about Prasugrel are available showing a minor effect of PPI on its antiplatelet activity than clopidogrel. Differing from prasugrel and clopidogrel, ticagrelor is a direct inhibitor of P2Y12, not necessitating biotransformation in the liver; therefore its interaction with PPI remains unclear. Interaction between omeprazole and clopidogrel seems related to high inhibitory activity of PPI on CYP2C19, interfering with the conversion of clopidogrel in its active metabolite. |
Detailed Description | Clopidogrel and Prasugrel are pro-drug necessitating conversion in active metabolites through CYP 450 system (CYP), particularly CYP3A and CYP2C19 isoforms. These drugs are platelet purinergic receptor antagonists, known as P2Y12. The link between active metabolite of Clopidogrel and Prasugrel to P2Y12 receptor prevents ADP receptor activation and inhibits several events leading to conformational change of platelets, therefore facilitating their activation and aggregation, that is the basis of acute coronary syndromes. Despite double antiplatelet drugs are the principle therapy for the treatment and the prevention of atherothrombotic events in cardiovascular diseases, they are the most important cause of bleeding peptic ulcer. Proton pump inhibitors (PPI) are actually considered principal agents reducing gastroenteric bleeding risk associated to antiplatelet therapy. Nevertheless the interaction between PPI and antiplatelet therapy has been object of interest. Several studies demonstrated PPI reduce efficacy of clopidogrel on platelet reactivity, probably through the inhibition of its metabolism, increasing the risk of cardiovascular events. Only few data about Prasugrel are available showing a minor effect of PPI on its antiplatelet activity than clopidogrel. Differing from prasugrel and clopidogrel, ticagrelor is a direct inhibitor of P2Y12, not necessitating biotransformation in the liver; therefore its interaction with PPI remains unclear. Nevertheless actual studies considered only clinical outcomes (MACEs), such as a subgroup analysis of the Platelet Inhibition and Patient Outcomes (PLATO) trial, showing a higher rate of MACEs in clopidogrel and Ticagrelor patients undergone PPI therapy, especially omeprazole treatment. Interaction between omeprazole and clopidogrel seems related to high inhibitory activity of PPI on CYP2C19, interfering with the conversion of clopidogrel in its active metabolite. It is yet unclear the higher rate of MACEs in the ticagrelor group, similarly to clopidogrel, despite it hasn't a hepatic metabolism. |
Study Type | Interventional |
Study Phase | Phase 4 |
Study Design | Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment |
Condition | Coronary Artery Disease |
Intervention | Drug: Pantoprazole, os, 20 mg, once per day, for 30 days Other Names: pantorcDrug: Omeprazole os, 20 mg, once per day, for 30 days Other Names: lansox |
Study Arm (s) |
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Recruitment Information[ + expand ][ + ]
Recruitment Status | Not yet recruiting |
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Estimated Enrollment | 150 |
Estimated Completion Date | April 2016 |
Estimated Primary Completion Date | March 2015 |
Eligibility Criteria | Inclusion Criteria: 1. All consecutive patients undergone PTCA in our institution in the period between July 2013 and December 2013 will be eligible to be enrolled. 2. Positive biomarker indicating myocardial necrosis. 3. All patients with prior myocardial infarction (MI) or coronary artery bypass grafting; coronary artery disease will be included. Exclusion Criteria: 1. Increased risk of bleeding (ex. active bleeding, major surgery <30 days). 2. Allergy or adverse reactions to administered drugs. 3. Other drugs or medications that affect CYP3A4 mediated drug metabolism. 4. Patients with missing follow-up data will be dropped out from the study. |
Gender | Both |
Ages | 18 Years |
Accepts Healthy Volunteers | No |
Contacts | Contact: MD MARINA POLACCO +393333347960 dott.mpolacco@gmail.com |
Location Countries | Italy |
Administrative Information[ + expand ][ + ]
NCT Number | NCT02028234 |
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Other Study ID Numbers | 010114 |
Has Data Monitoring Committee | No |
Information Provided By | University of Roma La Sapienza |
Study Sponsor | University of Roma La Sapienza |
Collaborators | Not Provided |
Investigators | Not Provided |
Verification Date | January 2014 |
Locations[ + expand ][ + ]
Sapienza Univeristy of Rome | Rome, Italy, 00166 Contact: MD Marina Polacco | +393333347960 | dott.mpolacco@gmail.comPrincipal Investigator: MD Marina Polacco Not yet recruiting |
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