Impact of Omeprazole and Fluvoxamine on Platelet Response to Clopidogrel
Condition: Drug Interaction of Clopidogrel
Study type: Interventional
Phase: Phase 1

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.
    


Intervention name(s): omeprazole; fluvoxamine; placebo
Intervention type(s): Drug; Drug; Drug
Intervention description(s): omeprazole 20mg for 7 days; fluvoxamine 50mg for 7 days; placebo for 7 days
Intervention MeSH terms: Fluvoxamine; Omeprazole
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment