Genetics Informatics Trial (GIFT) of Warfarin to Prevent DVT

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2015 by Washington University School of Medicine
Sponsor:
Collaborators:
Hospital for Special Surgery, New York
Intermountain Health Care, Inc.
University of Utah
Rush University Medical Center
University of Texas Southwestern Medical Center
Information provided by (Responsible Party):
Washington University School of Medicine
ClinicalTrials.gov Identifier:
NCT01006733
First received: October 30, 2009
Last updated: June 3, 2015
Last verified: June 2015
  Purpose

Blood clots contribute to the death of at least 100,000 Americans each year. Because many of these deaths occur suddenly where treatment is impossible, the best treatment is prevention. With this grant, researchers in Missouri, New York, Utah, Illinois, and Texas are developing strategies to improve the safety and effectiveness of clot prevention by customizing a popular blood thinner (warfarin) to each person's genetic and clinical profile. They hypothesize that the use of genetics to guide warfarin therapy will reduce the risk of venous thromboembolism (VTE) postoperatively. They further hypothesize that using a target international normalized ratio (INR) of 1.8 is non-inferior to using a target INR of 2.5 in VTE prevention.


Condition Intervention Phase
Thromboembolism
Genetic: Pharmacogenetic
Drug: Target INR 1.8
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Factorial Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Genetics Informatics Trial (GIFT) of Warfarin to Prevent Deep Venous Thrombosis (DVT)

Resource links provided by NLM:


Further study details as provided by Washington University School of Medicine:

Primary Outcome Measures:
  • For Aim 1: The composite outcome of: non-fatal venous thromboembolism (VTE), non-fatal major hemorrhage, INR>=4.0, and death. [ Time Frame: 30-days, except that VTE may be detected up to day 60 ] [ Designated as safety issue: Yes ]
  • For Aim 2: The composite outcome of: non-fatal venous thromboembolism (VTE) and death. [ Time Frame: 30-days for death; 60 days for VTE ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Percent Time in Therapeutic INR Range [ Time Frame: 3-28 days ] [ Designated as safety issue: No ]
  • Time to first laboratory event (INR > 1.5 + Target INR) [ Time Frame: Maximum of 90 days; median time to last INR is 28 days ] [ Designated as safety issue: Yes ]
  • Ranked Outcomes [ Time Frame: 3-28 days for PTTR (INR variability); 60 days for VTE ] [ Designated as safety issue: No ]
    Outcomes will be ranked using the following tiers in hierarchical order, from worst to best: (1) death; (2) stroke; (3) myocardial infarction (MI); (4) pulmonary edema (PE); (5) symptomatic DVT; (6) INR > 4, (7) atrial fibrillation; (8) DVT detected on screening; and (9) PTTR (with lower percentage time in range ranked lower).

  • Composite Outcomes [ Time Frame: 30 days ] [ Designated as safety issue: No ]
    We will compare the two arms in Aim 2 using the same composite outcome from Aim 1: VTE, major hemorrhage, death, or INR > 4.0.


Estimated Enrollment: 1600
Study Start Date: March 2011
Estimated Study Completion Date: June 2016
Estimated Primary Completion Date: April 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Target INR 1.8 and Pharmacogenetic
The target International Normalized Ratio (INR) is 1.8. Warfarin initiation is via Pharmacogenetic dosing.
Genetic: Pharmacogenetic
The pharmacogenetic arm estimates therapeutic warfarin dose using cytochrome P 450 2C9 (CYP2C9), vitamin K epoxide reductase complex subunit 1 (VKORC1), and cytochrome P 450 4F2 (CYP4F2) genotype and clinical information. The clinical arm estimates warfarin dose from clinical information alone.
Drug: Target INR 1.8
We will randomize patients to a target International Normalized Ratio (INR) of 2.5 or 1.8.
Experimental: Target INR 2.5 and Pharmacogenetic
The target INR is 2.5. Warfarin initiation is via Pharmacogenetic dosing.
Genetic: Pharmacogenetic
The pharmacogenetic arm estimates therapeutic warfarin dose using cytochrome P 450 2C9 (CYP2C9), vitamin K epoxide reductase complex subunit 1 (VKORC1), and cytochrome P 450 4F2 (CYP4F2) genotype and clinical information. The clinical arm estimates warfarin dose from clinical information alone.
Experimental: Target INR 1.8 and Clinical
The target INR is 1.8. Warfarin initiation is via clinical dosing.
Drug: Target INR 1.8
We will randomize patients to a target International Normalized Ratio (INR) of 2.5 or 1.8.
No Intervention: Target INR 2.5 and Clinical
The target INR is 2.5. Warfarin initiation is via clinical dosing.

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   65 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • 65 years of age or older
  • must anticipate taking warfarin for at least 4 weeks for VTE prophylaxis after hip or knee arthroplasty
  • must be able to give written, informed consent
  • must have venous access
  • must not be institutionalized, incarcerated at the time of enrollment (nursing home okay)
  • must have life expectancy > 6 months
  • must have plans to have regular INR monitoring
  • willing/able to follow-up in 3-7 weeks with a Doppler Ultrasound

Exclusion Criteria:

  • Baseline INR > 1.35
  • knowledge of CYP2C9, VKORC1, or CYP4F2 genotype
  • knowledge of warfarin dose requirements from prior warfarin therapy
  • absolute contraindication or allergy to warfarin therapy (e.g. pregnancy)
  • receiving or planning to receive any anticoagulant besides warfarin (if low molecular weight heparin (LMWH) or subcutaneous heparin is deemed necessary by the clinician after enrollment, such patients will be allowed to remain in the study)
  • unlikely to be compliant (e.g. due to history of non-compliance, or alcoholism)
  • known thrombophilia, bleeding disorder, or history of serious bleed in the past 2 years (unless caused by trauma)
  • personal history of venous thromboembolism
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01006733

Contacts
Contact: Hannah Lin, BA 314-454-8369 hlin@dom.wustl.edu
Contact: Brian F Gage, MD, MSc 314-454-8369 bgage@dom.wustl.edu

Locations
United States, Illinois
Rush University Medical Center Recruiting
Chicago, Illinois, United States, 60612
Contact: Eleftheria Steinig, MPH    312-563-2968    Eleftheria_Steinig@rush.edu   
Contact: Amir Jaffer, MD         
Principal Investigator: Amir Jaffer, MD         
United States, Missouri
Washington University in St. Louis, School of Medicine Recruiting
St. Louis, Missouri, United States, 63110
Contact: Hannah Lin, BA    314-454-8369    hlin@dom.wustl.edu   
Contact: Brian F Gage, MD, MSc    314-454-8369    bgage@dom.wustl.edu   
Principal Investigator: Brian F Gage, MD, MSc         
United States, New York
Hospital for Special Surgery, Weill-Cornell Recruiting
NY, New York, United States, 10021
Contact: Kevin Chan, BA    212-774-7043    chanke@HSS.EDU   
Contact: Kerri Merritt, BA    212-774-7043    MerrittK@HSS.EDU   
Principal Investigator: Anne Bass, MD         
United States, Texas
University of Texas Southwestern Recruiting
Dallas, Texas, United States, 75390-8870
Contact: Amy Browning, BA    214-648-2485    Amy.browning@utsouthwestern.edu   
Contact: Michael Huo, MD         
Principal Investigator: Michael Huo, MD         
United States, Utah
Intermountain Medical Center Recruiting
Salt Lake City, Utah, United States, 84157
Contact: Ben Chisum, BS    801-507-4584    Ben.Chisum@imail.org   
Principal Investigator: Scott Woller, MD         
University of Utah Recruiting
Salt Lake City, Utah, United States, 84132
Contact: Lynnae Napoli         
Principal Investigator: Robert Pendleton, MD         
Sponsors and Collaborators
Washington University School of Medicine
Hospital for Special Surgery, New York
Intermountain Health Care, Inc.
University of Utah
Rush University Medical Center
University of Texas Southwestern Medical Center
Investigators
Principal Investigator: Brian F Gage, MD, MSc Washington University in St. Louis, School of Medicine
  More Information

Additional Information:
Publications:

Responsible Party: Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT01006733     History of Changes
Other Study ID Numbers: HL097036-01, R01HL097036
Study First Received: October 30, 2009
Last Updated: June 3, 2015
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration

Keywords provided by Washington University School of Medicine:
pharmacogenetics
arthroplasty
VKORC1
thromboembolism
warfarin

Additional relevant MeSH terms:
Thromboembolism
Cardiovascular Diseases
Embolism and Thrombosis
Thrombosis
Vascular Diseases
Warfarin
Anticoagulants
Hematologic Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on August 30, 2015