Impact of Omeprazole and Fluvoxamine on Platelet Response to Clopidogrel
Information source: Hadassah Medical Organization
Information obtained from ClinicalTrials.gov on February 07, 2013
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Drug Interaction of Clopidogrel
Intervention: omeprazole (Drug); fluvoxamine (Drug); placebo (Drug)
Phase: Phase 1
Status: Not yet recruiting
Sponsored by: Hadassah Medical Organization Overall contact:
Ronny Alcalai, MD, Email: ronny@hadassah.org.il
Summary
Clopidogrel is a platelets inhibitor that is widely used particularly during and after acute
coronary events and coronary interventions. Several studies have shown that some patients
are resistant to clopidogrel. The resistance mechanism is not entirely clear yet, but at
least in part it is related to interactions between medications.
Omeprazole is a member in the family of gastric proton pump inhibitor (PPI) that are widely
used in patients who receive combination of aspirin and clopidogrel in order to protect the
stomach lining and prevent GI bleeding. Data from studies on platelet aggregation indicate
that treatment with omeprazole may cause partial resistance to clopidogrel and increase risk
for recurrent cardiovascular events in patients after coronary interventions. Recently the
FDA published struck to avoid cross clopidogrel and omeprazole treatment for fear of
reduction efficiency. Nevertheless there are several studies that do not support increased
risk of cardiovascular events among patients taking omeprazole and clopidogrel, as the
COGENT trial which is the single prospective controlled study that assessed the clinical
implication of this drugs interaction.
The accepted Mechanism of interaction between omeprazole and clopidogrel is disturbance to
create clopidogrel active metabolite through CYP2C19 inhibition by omeprazole. fluvoxamine -
is a member in SSRIs family and a potent inhibitor of the CYP2C19. In vivo studies compared
the degree of decomposition proguanil (a CYP2C19 indicator) by fluvoxamine and omeprazole
found constant inhibition- Ki = 10 Micromol / L for of Omeprazole versus constant
inhibition- Ki = 0. 69 Micromol / L for fluvoxamine. This indicates a more potent inhibition
of CYP2C19 in vivo of fluvoxamine compared to omeprazole. It is important to note that so
far there is no date in literature studies demonstrates that there is any interaction
between fluvoxamine and other CYP2C19 inhibitors and Clopidogrel.
Research goals:
- To assess the impact of fluvoxamine and omeprazole on platelet reactivity in healthy
individuals treated with clopidogrel.
- To verify weather the mechanism of omeprazole-clopidogrel interaction is related to
CYP2C19 inhibition.
Study design:
Randomized blinded placebo-controlled crossover trial on healthy volunteers. The response to
clopidogrel will be assessed using two methods in subjects receiving clopidogrel and one of
the study drugs: fluvoxamine, omeprazole or placebo.
Clinical Details
Official title: Impact of Omeprazole and Fluvoxamine on Platelet Response to Clopidogrel. a Randomized, Double-blind Placebo Controlled, Crossover Trial
Study design: Allocation: Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment
Primary outcome: platlet reactivity in response to clopidogrel
Eligibility
Minimum age: 20 Years.
Maximum age: 60 Years.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- Healthy volunteers
Exclusion Criteria:
- Bleeding tendency
Locations and Contacts
Ronny Alcalai, MD, Email: ronny@hadassah.org.il
Hadassah Medical Organization, Jerusalem, Israel; Not yet recruiting
Arik Tzukert, DMD, Email: arik@hadassah.org.il
Hadas Lamberg, Email: lhadas@hadassah.org.il
Additional Information
Starting date: January 2011
Last updated: July 3, 2011
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