- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01964794
Improving Anticoagulant Therapy Through Warfarin Metabolite Profiling
Study Overview
Status
Conditions
Detailed Description
Coumadin (R/S-warfarin) is a commonly prescribed anticoagulant for over 20 million Americans for the treatment of atrial fibrillation, mechanical heart valves, venous thromboembolism and other coagulopathies. While highly efficacious, warfarin treatment is challenging due to a narrow therapeutic range and high inter-individual variations in response. Optimal warfarin dosage relies on a potentially lengthy trial-and-error process to optimize dosage for a desired anticoagulant response as measured by the international normalization ratio (INR), a prothrombin test. Even when a maintenance dose is achieved, patients are prone to testing out of the target INR range, and thus are at risk of hemorrhaging (over-dosing) or thromboembolism (under-dosing). In fact, warfarin is among the top ten drug-related causes of serious adverse drug events and increased health care costs. The progressive increase in warfarin use necessitates a better understanding of the mechanisms underlying inter-individual variability in responses to anticoagulant therapy. Our long-term goal is to identify metabolic biomarkers correlating with clinical responses to warfarin therapy and then utilize this knowledge to predict safe and effective dosing for patients based on a single blood draw.
Therapeutic outcomes for patients involve a balance between warfarin dosing and its metabolism to maintain a stable target INR. There is an initial lengthy titration stage in which dosing is increased to achieve but not surpass a target INR range. The potency of this effect depends on warfarin metabolism, which counters the dosing effect on patients by inactivating the drug. Warfarin undergoes extensive metabolism through distinct enantio- and regio-specific metabolic pathways to yield a complex array of essentially inactive isomeric metabolites. Warfarin is clinically available as an equal mixture of R and S enantiomers. S-Warfarin is about four times more potent than R-warfarin, and presumably dominates the anticoagulant response to therapy. During maintenance dosing, a longer metabolic half-life for R-warfarin leads to higher accumulation levels in plasma than those observed for S-warfarin. Variations in R-and S-warfarin plasma levels may potentiate the anticoagulant effect of both drug isomers and the corresponding responses to therapy. For our exploratory study, we will identify biomarkers within patient metabolic profiles for R-and S-warfarin that predict clinical outcomes for the patients.
Study Type
Enrollment (Actual)
Contacts and Locations
Study Locations
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Arkansas
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Little Rock, Arkansas, United States, 72205
- University of Arkansas for Medical Sciences
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Little Rock, Arkansas, United States, 72205
- Central Arkansas Veterans Healthcare System
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Sampling Method
Study Population
Description
Inclusion Criteria:
- Males aged 60 - 69 originally. Opened inclusion criteria age to include 18-79 years of age.
- Potential participant received a warfarin maintenance dose with a stable INR (defined as within target range over a two month (60 day) period that includes a minimum of two clinical visits).
- Potential participant has taken warfarin as prescribed over the past three days.
Exclusion Criteria:
- Female
- Potential participant receiving a warfarin while not achieving a stable INR (defined as within target range over a two month (60 day) period that includes a minimum of two clinical visits).
- Potential participant has not received any warfarin over the past three days.
Study Plan
How is the study designed?
Design Details
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Metabolite Profiling
Time Frame: Up to 24 months
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Based on a single blood draw, identify metabolite biomarkers for achieving a stable target anticoagulant response among patients at a maintenance dose of warfarin.
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Up to 24 months
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Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Grover P Miller, PhD, University of Arkansas
- Principal Investigator: Eugene Smith, III, MD, Dentral Arkansas Veterans Healthcare System
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Other Study ID Numbers
- 135288
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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