Impact of Omeprazole and Fluvoxamine on Platelet Response to Clopidogrel

NCT01269333 | Completed Phase 1

• 1 other identifier: 0330-HMO-CTIL
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

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.

Conditions

Drug Interaction of Clopidogrel

Outcome Measures

Primary Outcomes (1)

• platlet reactivity in response to clopidogrel

  6 months

Study Arms (3)

fluvoxamine

ACTIVE COMPARATOR

Drug: fluvoxamine

omeprazole

EXPERIMENTAL

Drug: omeprazole

placebo

PLACEBO COMPARATOR

Drug: placebo

Interventions

omeprazole DRUG

omeprazole 20mg for 7 days

omeprazole

fluvoxamine DRUG

fluvoxamine 50mg for 7 days

fluvoxamine

placebo DRUG

placebo for 7 days

placebo

Eligibility Criteria

• Age: 20 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy volunteers

You may not qualify if:

• Bleeding tendency

Sponsors & Collaborators

• Hadassah Medical Organization: lead

Study Sites (1)

Hadassah Medical Organization

Jerusalem, Israel

Location

MeSH Terms

Interventions

Omeprazole; Fluvoxamine

Intervention Hierarchy (Ancestors)

2-Pyridinylmethylsulfinylbenzimidazoles; Sulfoxides; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Oximes; Hydroxylamines; Amines

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Cardiologist

Study Record Dates

• First Submitted: January 3, 2011
• First Posted: January 4, 2011
• Study Start: January 1, 2011
• Primary Completion: July 1, 2012
• Last Updated: August 19, 2015

Record last verified: 2015-08

Locations

IL (1)