Modeling Genotype and Other Factors to Enhance the Safety of Coumadin Prescribing

NCT00484640 | Unknown DMC

• 1 other identifier: R01HS016335-01
• Study Type: interventional
• Target: 260
• Locations: 1 country
• Sites: 2

Brief Summary

The study goal is to conduct a randomized controlled trial to compare safety and accuracy of dosing based on clinical information including the clinical reason for your taking coumadin, your age, gender, your body surface area, and other medical conditions you may have with dosing estimated by a dosing calculator which adjusts for factors affecting coumadin dosing variability including genotypes for genes important in Coumadin metabolism and response. The hypothesis to be tested by this trial states that:when compared to patients managed with a best practices standard-of-care coumadin dosing regimen, patients randomized to coumadin dosing based on genetically programmed metabolic capacity and other known clinical and environmental factors affecting dose will: 1)show reduced risk of adverse events (using surrogate measures of such events); and 2)more rapidly achieve Coumadin dosing.

Conditions

Atrial Fibrillation; Deep Venous Thrombosis; Heart Valve Replacement; Pulmonary Embolism

Outcome Measures

Primary Outcomes (2)

• weighted time in therapeutic range

• absolute deviation from clinically optimal dose

Secondary Outcomes (3)

• time to stable dose in therapeutic target range

• warfarin related adverse drug events

• time to first INR above 4

Interventions

Coumadin DRUG

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Caucasian male and female patients(including Hispanic white) greater than or equal to 40 years of age;
• Patients initiating coumadin therapy without a documented history of stabilized dose of coumadin therapy;
• Target INR of 2 to 3.5;
• Women of childbearing potential must use an effective method of birth control(e.g. condom,oral contraceptives, indwelling intrauterine device, abstinence.

You may not qualify if:

• Age less than 40 years;
• Patients of known Native American, Asian, or African descent;
• Patients with thrombocytopenia(platelet count\<50x10 cells/ml);
• Patient has previously received coumadin and information on dosing of the patient is known at time of restarting coumadin;
• Patients with severe to moderate hepatic insufficiency (AST or ALT less than 2x the upper limit of normal;
• Clinical contraindication for coumadin therapy;
• Female patients with a positive pregnancy test or women who are breastfeeding

Sponsors & Collaborators

• Agency for Healthcare Research and Quality (AHRQ): lead
• Marshfield Clinic Research Foundation: collaborator

Study Sites (2)

Third Wave Molecular Diagnostics

Madison, Wisconsin, 53719, United States

Location

Marshfield Clinic

Marshfield, Wisconsin, 54449, United States

Location

Related Publications (4)

• Hillman MA, Wilke RA, Caldwell MD, Berg RL, Glurich I, Burmester JK. Relative impact of covariates in prescribing warfarin according to CYP2C9 genotype. Pharmacogenetics. 2004 Aug;14(8):539-47. doi: 10.1097/01.fpc.0000114760.08559.dc.

  PMID: 15284536 BACKGROUND

• Greenlee RT, Vidaillet H. Recent progress in the epidemiology of atrial fibrillation. Curr Opin Cardiol. 2005 Jan;20(1):7-14.

  PMID: 15596953 BACKGROUND

• Wilke RA, Berg RL, Vidaillet HJ, Caldwell MD, Burmester JK, Hillman MA. Impact of age, CYP2C9 genotype and concomitant medication on the rate of rise for prothrombin time during the first 30 days of warfarin therapy. Clin Med Res. 2005 Nov;3(4):207-13. doi: 10.3121/cmr.3.4.207.

  PMID: 16303885 BACKGROUND

• Hillman MA, Wilke RA, Yale SH, Vidaillet HJ, Caldwell MD, Glurich I, Berg RL, Schmelzer J, Burmester JK. A prospective, randomized pilot trial of model-based warfarin dose initiation using CYP2C9 genotype and clinical data. Clin Med Res. 2005 Aug;3(3):137-45. doi: 10.3121/cmr.3.3.137.

  PMID: 16160068 BACKGROUND

MeSH Terms

Conditions

Atrial Fibrillation; Venous Thrombosis; Pulmonary Embolism

Interventions

Warfarin

Condition Hierarchy (Ancestors)

Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Thrombosis; Embolism and Thrombosis; Vascular Diseases; Lung Diseases; Respiratory Tract Diseases; Embolism

Intervention Hierarchy (Ancestors)

4-Hydroxycoumarins; Coumarins; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Michael Caldwell, Physician

  Marshfield Clinic Research Foundation

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Deborah J Hilgemann, Res. Coord.

CONTACT

715-389-3774; hilgemann.deborah@marshfieldclinic.org

Sandra K Strey, Res. Coord.

CONTACT

715-389-4030; strey.sandra@marshfieldclinic.org

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: FED

Study Record Dates

• First Submitted: June 4, 2007
• First Posted: June 11, 2007
• Study Start: June 1, 2007
• Study Completion: May 1, 2008
• Last Updated: June 11, 2007

Record last verified: 2007-06

Locations

US (2)