NCT00904293

Brief Summary

The purpose of the investigators' study is to determine the clinical utility of a warfarin-dosing algorithm that incorporates genetic information (VKORC1 and CYP2C9 alleles) for adult patients initiating warfarin therapy.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
109

participants targeted

Target at P25-P50 for not_applicable atrial-fibrillation

Timeline
Completed

Started Aug 2008

Typical duration for not_applicable atrial-fibrillation

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

August 1, 2008

Completed
8 months until next milestone

First Submitted

Initial submission to the registry

April 6, 2009

Completed
1 month until next milestone

First Posted

Study publicly available on registry

May 19, 2009

Completed
2.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 1, 2012

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

January 1, 2012

Completed
Last Updated

May 6, 2016

Status Verified

October 1, 2013

Enrollment Period

3.4 years

First QC Date

April 6, 2009

Last Update Submit

May 5, 2016

Conditions

Atrial FibrillationDeep Vein ThrombosisPulmonary EmbolismArtificial Heart Valve

Keywords

warfarinCYP2C9VKORCoumadinpharmacogeneticspharmacogenomicsanticoagulationgenotype-guided therapy

Outcome Measures

Primary Outcomes (2)

  • Time in therapeutic range (TTR)

    3 months

  • Number of anticoagulation visits

    3 months

Secondary Outcomes (9)

  • Proportion of INRs > 4

    3 months

  • Major bleeding events

    3 months

  • Minor bleeding events

    3 months

  • Thromboembolic complications

    3 months

  • All-cause mortality

    3 months

  • +4 more secondary outcomes

Study Arms (2)

Genotype-guided warfarin dosing

EXPERIMENTAL

A dosing algorithm including clinical factors and genotype information (VKORC1 and CYP2C9) will be used to determine initial warfarin doses.

Other: Genotype-guided dose determination

Non-genotype guided warfarin dosing

ACTIVE COMPARATOR

Initial warfarin dosing will be determined using the same algorithm as in the experimental group, but only including the clinical factors and not including the genotype information

Other: Non-genotype guided warfarin dosing

Interventions

Genotype-guided dose determinationOTHER

Patients in both arms will be treated with warfarin. Those in the experimental group will have initial doses determined using an algorithm (from www.warfarindosing.org) incorporating genetic and clinical factors. Those in the control group will have doses determined using the same algorithm, but without including the genetic factors.

Genotype-guided warfarin dosing
Non-genotype guided warfarin dosingOTHER

Those in the control group will have doses determined using the same algorithm, but without including the genetic factors.

Non-genotype guided warfarin dosing

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Adults ≥18 years old
  • Patients who are beginning warfarin for a variety of diseases or conditions that require long-term oral anticoagulation with target INR \> 2.0 for at least 3 months
  • Subjects that will be following up in UNC anticoagulation clinics at the Ambulatory Care Center or the Family Medicine Center

You may not qualify if:

  • Patients who are unable to complete the study materials (questionnaires) with or without assistance (for example, those with dementia)
  • Non-English speaking patients
  • Patients who are being started on anticoagulation intended to last \< 3 months or whose target INR is \< 2.0
  • Patients who have a history of treatment with warfarin and a known dose requirement will be excluded (as they should be restarted on the previous dose)
  • Pregnant women will be excluded because warfarin is a teratogen and pregnant women should not take the medication
  • Patients will also be excluded if their treating physician does not agree to use the recommended INR dose or feels that the patient should not be enrolled in the study

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

UNC Hospitals, UNC Anticoagulation Clinic at the Ambulatory Care Center (ACC), UNC Family Medicine Center Anti-coagulation Clinic

Chapel Hill, North Carolina, 27599, United States

Location

Related Publications (9)

  • Levine MN, Raskob G, Landefeld S, Kearon C. Hemorrhagic complications of anticoagulant treatment. Chest. 2001 Jan;119(1 Suppl):108S-121S. doi: 10.1378/chest.119.1_suppl.108s.

    PMID: 11157645BACKGROUND

  • Hafner JW Jr, Belknap SM, Squillante MD, Bucheit KA. Adverse drug events in emergency department patients. Ann Emerg Med. 2002 Mar;39(3):258-67. doi: 10.1067/mem.2002.121401.

    PMID: 11867978BACKGROUND

  • McWilliam A, Lutter R, Nardinelli C. Jointcenter; AEI-Brookings Joint Center For Regulatory Studies. Working Paper 06-23, November 2006

    BACKGROUND

  • Rieder MJ, Reiner AP, Gage BF, Nickerson DA, Eby CS, McLeod HL, Blough DK, Thummel KE, Veenstra DL, Rettie AE. Effect of VKORC1 haplotypes on transcriptional regulation and warfarin dose. N Engl J Med. 2005 Jun 2;352(22):2285-93. doi: 10.1056/NEJMoa044503.

    PMID: 15930419BACKGROUND

  • Li T, Lange LA, Li X, Susswein L, Bryant B, Malone R, Lange EM, Huang TY, Stafford DW, Evans JP. Polymorphisms in the VKORC1 gene are strongly associated with warfarin dosage requirements in patients receiving anticoagulation. J Med Genet. 2006 Sep;43(9):740-4. doi: 10.1136/jmg.2005.040410. Epub 2006 Apr 12.

    PMID: 16611750BACKGROUND

  • Sconce EA, Khan TI, Wynne HA, Avery P, Monkhouse L, King BP, Wood P, Kesteven P, Daly AK, Kamali F. The impact of CYP2C9 and VKORC1 genetic polymorphism and patient characteristics upon warfarin dose requirements: proposal for a new dosing regimen. Blood. 2005 Oct 1;106(7):2329-33. doi: 10.1182/blood-2005-03-1108. Epub 2005 Jun 9.

    PMID: 15947090BACKGROUND

  • Millican, E., et al. Blood, Epub ahead of print, Mar 26, 2007

    BACKGROUND

  • Voora D, Eby C, Linder MW, Milligan PE, Bukaveckas BL, McLeod HL, Maloney W, Clohisy J, Burnett RS, Grosso L, Gatchel SK, Gage BF. Prospective dosing of warfarin based on cytochrome P-450 2C9 genotype. Thromb Haemost. 2005 Apr;93(4):700-5. doi: 10.1160/TH04-08-0542.

    PMID: 15841315BACKGROUND

  • Jonas DE, Evans JP, McLeod HL, Brode S, Lange LA, Young ML, Shilliday BB, Bardsley MM, Swinton-Jenkins NJ, Weck KE. Impact of genotype-guided dosing on anticoagulation visits for adults starting warfarin: a randomized controlled trial. Pharmacogenomics. 2013 Oct;14(13):1593-603. doi: 10.2217/pgs.13.145.

    PMID: 24088130DERIVED

MeSH Terms

Conditions

Atrial FibrillationVenous ThrombosisPulmonary Embolism

Condition Hierarchy (Ancestors)

Arrhythmias, CardiacHeart DiseasesCardiovascular DiseasesPathologic ProcessesPathological Conditions, Signs and SymptomsThrombosisEmbolism and ThrombosisVascular DiseasesLung DiseasesRespiratory Tract DiseasesEmbolism

Study Officials

  • Daniel E Jonas, MD, MPH

    UNC Institute for Pharmacogenomics and Individualized Therapy

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, CARE PROVIDER
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

April 6, 2009

First Posted

May 19, 2009

Study Start

August 1, 2008

Primary Completion

January 1, 2012

Study Completion

January 1, 2012

Last Updated

May 6, 2016

Record last verified: 2013-10

Locations

US(1)