Impact of Omeprazole and Fluvoxamine on Platelet Response to Clopidogrel

The recruitment status of this study is unknown because the information has not been verified recently.
Verified December 2010 by Hadassah Medical Organization.
Recruitment status was  Not yet recruiting
Sponsor:
Information provided by:
Hadassah Medical Organization
ClinicalTrials.gov Identifier:
NCT01269333
First received: January 3, 2011
Last updated: July 3, 2011
Last verified: December 2010
  Purpose

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 Intervention Phase
Drug Interaction of Clopidogrel
Drug: omeprazole
Drug: fluvoxamine
Drug: placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Impact of Omeprazole and Fluvoxamine on Platelet Response to Clopidogrel. a Randomized, Double-blind Placebo Controlled, Crossover Trial

Resource links provided by NLM:


Further study details as provided by Hadassah Medical Organization:

Primary Outcome Measures:
  • platlet reactivity in response to clopidogrel [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 20
Study Start Date: January 2011
Estimated Primary Completion Date: July 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   20 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Healthy volunteers

Exclusion Criteria:

  • Bleeding tendency
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01269333

Contacts
Contact: Ronny Alcalai, MD ronny@hadassah.org.il

Locations
Israel
Hadassah Medical Organization Not yet recruiting
Jerusalem, Israel
Contact: Arik Tzukert, DMD       arik@hadassah.org.il   
Contact: Hadas Lamberg       lhadas@hadassah.org.il   
Sponsors and Collaborators
Hadassah Medical Organization
  More Information

No publications provided

Responsible Party: Heart Institute, Hadassah Medical Organization
ClinicalTrials.gov Identifier: NCT01269333     History of Changes
Other Study ID Numbers: 0330-HMO-CTIL
Study First Received: January 3, 2011
Last Updated: July 3, 2011
Health Authority: Israel: Ministry of Health - Director General

Additional relevant MeSH terms:
Omeprazole
Clopidogrel
Fluvoxamine
Anti-Ulcer Agents
Gastrointestinal Agents
Therapeutic Uses
Pharmacologic Actions
Proton Pump Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Platelet Aggregation Inhibitors
Hematologic Agents
Purinergic P2Y Receptor Antagonists
Purinergic P2 Receptor Antagonists
Purinergic Antagonists
Purinergic Agents
Neurotransmitter Agents
Physiological Effects of Drugs
Anti-Anxiety Agents
Tranquilizing Agents
Central Nervous System Depressants
Central Nervous System Agents
Psychotropic Drugs
Serotonin Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Serotonin Agents
Antidepressive Agents, Second-Generation
Antidepressive Agents

ClinicalTrials.gov processed this record on September 15, 2014