Impact of Omeprazole and Fluvoxamine on Platelet Response to Clopidogrel

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01269333
Recruitment Status : Completed
First Posted : January 4, 2011
Last Update Posted : August 19, 2015
Information provided by (Responsible Party):
RONNY ALCALAI, Hadassah Medical Organization

Brief 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.

Condition or disease Intervention/treatment Phase
Drug Interaction of Clopidogrel Drug: omeprazole Drug: fluvoxamine Drug: placebo Phase 1

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 15 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: Impact of Omeprazole and Fluvoxamine on Platelet Response to Clopidogrel. a Randomized, Double-blind Placebo Controlled, Crossover Trial
Study Start Date : January 2011
Actual Primary Completion Date : July 2012

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Drug Reactions

Arm Intervention/treatment
Active Comparator: fluvoxamine Drug: fluvoxamine
fluvoxamine 50mg for 7 days

Experimental: omeprazole Drug: omeprazole
omeprazole 20mg for 7 days

Placebo Comparator: placebo Drug: placebo
placebo for 7 days

Primary Outcome Measures :
  1. platlet reactivity in response to clopidogrel [ Time Frame: 6 months ]

Information from the National Library of Medicine

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Ages Eligible for Study:   20 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

Inclusion Criteria:

  • Healthy volunteers

Exclusion Criteria:

  • Bleeding tendency

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 identifier (NCT number): NCT01269333

Hadassah Medical Organization
Jerusalem, Israel
Sponsors and Collaborators
Hadassah Medical Organization

Responsible Party: RONNY ALCALAI, Cardiologist, Hadassah Medical Organization Identifier: NCT01269333     History of Changes
Other Study ID Numbers: 0330-HMO-CTIL
First Posted: January 4, 2011    Key Record Dates
Last Update Posted: August 19, 2015
Last Verified: August 2015

Additional relevant MeSH terms:
Platelet Aggregation Inhibitors
Purinergic P2Y Receptor Antagonists
Purinergic P2 Receptor Antagonists
Purinergic Antagonists
Purinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Anti-Ulcer Agents
Gastrointestinal Agents
Proton Pump Inhibitors
Enzyme Inhibitors
Anti-Anxiety Agents
Tranquilizing Agents
Central Nervous System Depressants
Psychotropic Drugs
Serotonin Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Membrane Transport Modulators
Serotonin Agents
Antidepressive Agents, Second-Generation
Antidepressive Agents
Cytochrome P-450 CYP1A2 Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Cytochrome P-450 CYP2C19 Inhibitors