"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-

NCT ID: NCT02028234

Last Updated: 2014-01-08

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 150 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-02-28
• Study Completion Date: 2016-04-30

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.

Conditions

Coronary Artery Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

pantoprazole

Patients were randomly assigned to omeprazole (20 mg day) or pantoprazole (20 mg day) for 30 days. After 1-week wash-out period to avoid any carryover effect, cross-over was performed, and patients were switched to the other drug which was continued for 30 days.

Group Type: ACTIVE_COMPARATOR

Pantoprazole,

Intervention Type: DRUG

os, 20 mg, once per day, for 30 days

Omeprazole

Intervention Type: DRUG

os, 20 mg, once per day, for 30 days

Omeprazole

Patients were randomly assigned to omeprazole (20 mg day) or pantoprazole (20 mg day) for 30 days. After 1-week wash-out period to avoid any carryover effect, cross-over was performed, and patients were switched to the other drug which was continued for 30 days.

Group Type: ACTIVE_COMPARATOR

Pantoprazole,

Intervention Type: DRUG

os, 20 mg, once per day, for 30 days

Omeprazole

Intervention Type: DRUG

os, 20 mg, once per day, for 30 days

Interventions

Pantoprazole,

os, 20 mg, once per day, for 30 days

Intervention Type: DRUG

Omeprazole

os, 20 mg, once per day, for 30 days

Intervention Type: DRUG

Other Intervention Names

pantorc; lansox

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Roma La Sapienza

OTHER

Sponsor Role: lead

Responsible Party

Polacco Marina

MD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Sapienza Univeristy of Rome

Rome, Italy, Italy

Countries

Italy

Central Contacts

MD MARINA POLACCO

Role: CONTACT

dott.mpolacco@gmail.com

+393333347960

Facility Contacts

MD Marina Polacco

Role: primary

dott.mpolacco@gmail.com

+393333347960

Other Identifiers

010114

Identifier Type: -

Identifier Source: org_study_id