Impact of Omeprazole and Fluvoxamine on Platelet Response to Clopidogrel

Impact of Omeprazole and Fluvoxamine on Platelet Response to Clopidogrel. a Randomized, Double-blind Placebo Controlled, Crossover Trial

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.

Study Overview

• Status: Completed
• Conditions: Drug Interaction of Clopidogrel
• Intervention / Treatment: Drug: fluvoxamine; Drug: omeprazole; Drug: placebo

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 1

Contacts and Locations

Study Locations

• Israel
  • Jerusalem, Israel
    • Hadassah Medical Organization

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy volunteers

Exclusion Criteria:

• Bleeding tendency

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: placebo	Drug: placebo; placebo for 7 days
Active Comparator: fluvoxamine	Drug: fluvoxamine; fluvoxamine 50mg for 7 days
Experimental: omeprazole	Drug: omeprazole; omeprazole 20mg for 7 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
platlet reactivity in response to clopidogrel	6 months

Collaborators and Investigators

• Sponsor: Hadassah Medical Organization

Study record dates

Study Major Dates

• Study Start: January 1, 2011
• Primary Completion (Actual): July 1, 2012

Study Registration Dates

• First Submitted: January 3, 2011
• First Submitted That Met QC Criteria: January 3, 2011
• First Posted (Estimate): January 4, 2011

Study Record Updates

• Last Update Posted (Estimate): August 19, 2015
• Last Update Submitted That Met QC Criteria: August 18, 2015
• Last Verified: August 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Enzyme Inhibitors; Gastrointestinal Agents; Tranquilizing Agents; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Antidepressive Agents; Anti-Anxiety Agents; Cytochrome P-450 Enzyme Inhibitors; Antidepressive Agents, Second-Generation; Anti-Ulcer Agents; Proton Pump Inhibitors; Cytochrome P-450 CYP1A2 Inhibitors; Cytochrome P-450 CYP2C19 Inhibitors; Omeprazole; Fluvoxamine
• Other Study ID Numbers: 0330-HMO-CTIL