Improving Anticoagulant Therapy Through Warfarin Metabolite Profiling

This study is currently recruiting participants.
Verified October 2013 by University of Arkansas
Sponsor:
Collaborator:
Central Arkansas Veterans Healthcare System
Information provided by (Responsible Party):
University of Arkansas
ClinicalTrials.gov Identifier:
NCT01964794
First received: October 9, 2013
Last updated: October 14, 2013
Last verified: October 2013
  Purpose

Clinically relevant biomarkers for warfarin identified in this study will provide crucial leads for subsequent studies to assess their predictive value during anticoagulant therapy. This knowledge will aid stratifying risk among patients to improve therapeutic outcomes and decrease adverse drug events and associated health care costs. Collectively, these efforts will provide a critical foundation for future research using a metabolite biomarker strategy in a clinical setting to revolutionize warfarin therapy. Through its application, a real−time assessment of warfarin metabolism for each patient could lead to a truly personalized dosing strategy and improve patient safety for this life−saving drug.


Condition
Stable Target INR

Study Type: Observational
Study Design: Observational Model: Case-Only
Time Perspective: Cross-Sectional
Official Title: Improving Anticoagulant Therapy Through Warfarin Metabolite Profiling

Resource links provided by NLM:


Further study details as provided by University of Arkansas:

Primary Outcome Measures:
  • Metabolite Profiling [ Time Frame: Up to 24 months ] [ Designated as safety issue: No ]
    Based on a single blood draw, identify metabolite biomarkers for achieving a stable target anticoagulant response among patients at a maintenance dose of warfarin.


Biospecimen Retention:   Samples With DNA

Blood specimens to identify coumadin genetic and metabolic biomarkers.


Estimated Enrollment: 150
Study Start Date: May 2012
Estimated Primary Completion Date: May 2014 (Final data collection date for primary outcome measure)
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.

  Eligibility

Ages Eligible for Study:   60 Years to 69 Years
Genders Eligible for Study:   Male
Sampling Method:   Non-Probability Sample
Study Population

For this pilot study, we chose a sample population size of 150 with a focus on veterans from the Korean War.

Criteria

Inclusion Criteria:

  1. Males aged 60 - 69
  2. 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).
  3. Potential participant has taken warfarin as prescribed over the past three days.

Exclusion Criteria:

  1. Female
  2. 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).
  3. Potential participant has not received any warfarin over the past three days.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01964794

Contacts
Contact: Shawna Owens 501-526-7657 OwensShawnaS@uams.edu

Locations
United States, Arkansas
Central Arkansas Veterans Healthcare System Recruiting
Little Rock, Arkansas, United States, 72205
Contact: Shawna Owens, BSB, CCRP    501-526-7657    OwensShawnaS@uams.edu   
Principal Investigator: Eugene Smith, III, MD         
University of Arkansas for Medical Sciences Recruiting
Little Rock, Arkansas, United States, 72205
Contact: Shawna Owens, BSB, CCRP    501-526-7657    OwensShawnaS@uams.edu   
Principal Investigator: Grover P Miller, PhD         
Sponsors and Collaborators
University of Arkansas
Central Arkansas Veterans Healthcare System
Investigators
Principal Investigator: Grover P Miller, PhD University of Arkansas
Principal Investigator: Eugene Smith, III, MD Dentral Arkansas Veterans Healthcare System
  More Information

No publications provided

Responsible Party: University of Arkansas
ClinicalTrials.gov Identifier: NCT01964794     History of Changes
Other Study ID Numbers: 135288
Study First Received: October 9, 2013
Last Updated: October 14, 2013
Health Authority: United States: University of Arkansas for Medical Sciences Institutional Review Board
United States: Department of Veterans Affairs Institutional Review Board Central Arkansas Veterans Heathcare System

Keywords provided by University of Arkansas:
Warfarin

Additional relevant MeSH terms:
Anticoagulants
Warfarin
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 17, 2014