Completed

NCT Number: NCT01341600

Clopidogrel Pharmacogenetics (PGX) Bench to Bedside

Clopidogrel (also known as Plavix) is used commonly in patients to prevent heart attacks and conditions caused by blood clots. Although clopidogrel works in many individuals, some people do not respond as well to this drug. The variation in treatment response may be linked to genetics. This study will examine the effects of clopidogrel in a population in which sequencing for certain genes has been performed in order to determine the role that genes play in the response to various clopidogrel maintenance doses.

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Key information

Conditions

Metabolism of Clopidogrel

Age range

20 year–70 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Amish Research Clinic

Lancaster, Pennsylvania, 17601, United States

About this study

Clopidogrel is a prodrug with high inter-individual response variability. Clopidogrel is converted to an active drug in part through an enzyme encoded by the gene named CYP2C19. Individuals with genetically-impaired CYP2C19 metabolism have lower capacity to convert the prodrug to its active form. Consequently, these individuals have lower blood levels of the activated form of clopidogrel, diminished antiplatelet responses, and higher rates of cardiovascular events and stent thrombosis. Increasing doses of clopidogrel in such patients represents a possible approach to managing the gene-drug interaction.

The purpose of this study is to evaluate whether increasing the dose of clopidogrel increases antiplatelet responses and active metabolite exposure in individuals with genetically reduced CYP2C19 metabolism relative to those with normal CYP2C19 metabolism.

The primary objective is to assess changes in clopidogrel response and exposure at three clopidogrel dose levels and with coadministration of omeprazole.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

Amish men or women between 20 and 70 years of age who participated in PAPI

Exclusion criteria

Severe hypertension (bp > 160/95 mm Hg)
Co-existing malignancy
Aspartate Aminotransferase (AST) or Alanine Aminotransferase (ALT) > 2 times normal
Creatinine >2.0
Hct < 32 or Hct > 50
Thyroid Stimulating Hormone (TSH) < 0.40 or >5.50
History of bleeding disorder or gastrointestinal bleeding
History of unstable angina, myocardial infarction (MI), angioplasty, coronary artery bypass surgery
History of atrial fibrillation, stroke or transient ischemic attacks or deep vein thrombosis
Type 2 diabetes
Thrombocytosis (platelet count > 500,000) or thrombocytopenia (platelet count < 150,000)
Surgery within six months
Clopidogrel allergy
Pregnant women
Currently breast feeding
Omeprazole allergy
Prospective participants taking medications that would affect the outcome(s) to be measured and who cannot willingly and safely, in the opinion of the treating physician and study physician, discontinue these medications for 1 week prior to protocol initiation, or who are taking vitamins and/or other supplements and who are unwilling to discontinue their use for at least 1 week prior to study

Treatment and study plan

clopidogrel

Drug

Over a 6 week period participants will be given: 75 mg of clopidogrel for 8 days, at least 1 week washout, 150 mg of clopidogrel for eight days, at least 1 week washout, 300 mg of clopidogrel for eight days.

Other names: Plavix

Omeprazole/Clopidogrel

Drug

After a washout of at least 1 week, participants will have the option to participate in a final intervention in which they will be given 75 mg of clopidogrel together with 20 mg of omeprazole daily for eight days.

Other names: Prilosec, Plavix

Primary outcomes

Change in Platelet Aggregation Following Therapy With Clopidogrel

Time frame: Day 1, 4 hours post clopidogrel dose

Adenosine diphosphate (ADP) mediated platelet aggregation measured 4 hours post-dose of clopidogrel on Day 1.
Change in Platelet Aggregation Following Therapy With Clopidogrel

Time frame: 4 hours post Day 8 dose

ADP mediated platelet aggregation measured 4 hours post Day 8 clopidogrel dose

Secondary outcomes

Change in Platelet Aggregation Following Therapy With Clopidogrel and Omeprazole

Time frame: Baseline, Day 8

The change in maximum platelet aggregation in response to ADP 4-hours post dose on day 8 of therapy with clopidogrel and omeprazole will be compared to the baseline measure of platelet aggregation at day 1 prior to drug therapy
Level of Active Clopidogrel Metabolite

Time frame: Baseline, 0.25, 0.5, 1, 2, and 4 hours

The level of the active clopidogrel metabolite will be measured at at 0.25, 0.5, 1, 2, and 4 hours after the Day One dose is administered for pharmacokinetic analysis. The analysis will measure the Area Under the Curve.

Sponsors and collaborators

Lead sponsor

University of Maryland, Baltimore

Other

Collaborators

Food and Drug Administration (FDA)
National Cancer Institute (NCI)
National Heart, Lung, and Blood Institute (NHLBI)
National Institute of General Medical Sciences (NIGMS)

Registry information

Official study title

Clopidogrel Pharmacogenetics Bench to Bedside - A Practical Application

Acronym: PGXB2B

Important dates

Study start: 2010
Primary completion: 2011
Study completion: 2011
First posted: Apr 25, 2011
Registry last updated: Jan 30, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.