"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-

Coronary Artery Disease Clinical Trial

— dOPPLER  

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"

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT02028234
• Other study ID #: 010114
• Status: Not yet recruiting
• Phase: Phase 4
• First received: January 2, 2014
• Last updated: January 6, 2014
• Start date: February 2014
• Est. completion date: April 2016

Study information

• Verified date: January 2014
• Source: University of Roma La Sapienza
• Contact: MD MARINA POLACCO
• Phone: +393333347960
• Email: dott.mpolacco[@]gmail.com
• Is FDA regulated: No
• Health authority: Italy: Ministry of Health
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 150
• Est. completion date: April 2016
• Est. primary completion date: March 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 85 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acute Coronary Syndrome
• Coronary Artery Disease
• Coronary Disease
• Myocardial Ischemia

Intervention

Drug:
• Pantoprazole,
os, 20 mg, once per day, for 30 days
• Omeprazole
os, 20 mg, once per day, for 30 days

Locations

Country	Name	City	State
Italy	Sapienza Univeristy of Rome	Rome

Sponsors (1)

Lead Sponsor	Collaborator
University of Roma La Sapienza

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Assessment of platelet reaction units	Absolute changes in platelet reactivity (expressed as P2Y(12) reaction units by the point-of-care VerifyNow assay [Accumetrics, San Diego, California]	After 30 days of treatment with each drug	No
Secondary	Frequency of high platelet reactivity	Frequency of high platelet reactivity with the 2 study treatments (as defined by a Platelet Reaction Unit value>240	After 30 days of treatment with each drug	No