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Trial record 1 of 5 for:    "Arteriosclerosis" | "Pantoprazole"
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"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- (dOPPLER)

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ClinicalTrials.gov Identifier: NCT02028234
Recruitment Status : Unknown
Verified January 2014 by Polacco Marina, University of Roma La Sapienza.
Recruitment status was:  Not yet recruiting
First Posted : January 7, 2014
Last Update Posted : January 8, 2014
Sponsor:
Information provided by (Responsible Party):
Polacco Marina, University of Roma La Sapienza

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.


Condition or disease Intervention/treatment Phase
Coronary Artery Disease Drug: Pantoprazole, Drug: Omeprazole Phase 4

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 150 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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"
Study Start Date : February 2014
Estimated Primary Completion Date : March 2015
Estimated Study Completion Date : April 2016

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: 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.
Drug: Pantoprazole,
os, 20 mg, once per day, for 30 days
Other Name: pantorc

Drug: Omeprazole
os, 20 mg, once per day, for 30 days
Other Name: lansox

Active Comparator: 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.
Drug: Pantoprazole,
os, 20 mg, once per day, for 30 days
Other Name: pantorc

Drug: Omeprazole
os, 20 mg, once per day, for 30 days
Other Name: lansox




Primary Outcome Measures :
  1. Assessment of platelet reaction units [ Time Frame: After 30 days of treatment with each drug ]
    Absolute changes in platelet reactivity (expressed as P2Y(12) reaction units by the point-of-care VerifyNow assay [Accumetrics, San Diego, California]


Secondary Outcome Measures :
  1. Frequency of high platelet reactivity [ Time Frame: After 30 days of treatment with each drug ]
    Frequency of high platelet reactivity with the 2 study treatments (as defined by a Platelet Reaction Unit value>240



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02028234


Contacts
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Contact: MD MARINA POLACCO +393333347960 dott.mpolacco@gmail.com

Locations
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Italy
Sapienza Univeristy of Rome Not yet recruiting
Rome, Italy, 00166
Contact: MD Marina Polacco    +393333347960    dott.mpolacco@gmail.com   
Principal Investigator: MD Marina Polacco         
Sponsors and Collaborators
University of Roma La Sapienza

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Responsible Party: Polacco Marina, MD, University of Roma La Sapienza
ClinicalTrials.gov Identifier: NCT02028234     History of Changes
Other Study ID Numbers: 010114
First Posted: January 7, 2014    Key Record Dates
Last Update Posted: January 8, 2014
Last Verified: January 2014
Additional relevant MeSH terms:
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Arteriosclerosis
Pantoprazole
Coronary Artery Disease
Acute Coronary Syndrome
Coronary Disease
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Arterial Occlusive Diseases
Vascular Diseases
Omeprazole
Anti-Ulcer Agents
Gastrointestinal Agents
Proton Pump Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action