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Prospective Genotyping For Total Hip or Knee Replacement Patients Receiving Warfarin (Coumadin)

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ClinicalTrials.gov Identifier: NCT00634907
Recruitment Status : Completed
First Posted : March 13, 2008
Results First Posted : June 8, 2017
Last Update Posted : June 8, 2017
Sponsor:
Information provided by (Responsible Party):

Study Description
Brief Summary:
Several human genes affect how medications are metabolized by the body. It is believed that knowledge of variations of these genes can help health care providers better manage an anticoagulation medicine called warfarin (Coumadin®)and as a result decrease patient problems with bleeding or the development of blood clots. This study was designed to evaluate if genetic testing can improve warfarin initiation better than usual care.

Condition or disease Intervention/treatment
Venous Thromboembolism Bleeding Genetic: Pharmacogenetic-based warfarin dosing Other: Usual care warfarin dosing

Detailed Description:
This study was completed in 2008 and was published. Consult the citation link for more details.

Study Design

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 263 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Prospective CYP2C9 And VKORC1 Genotyping For Total Hip or Knee Replacement Patients Receiving Warfarin (Coumadin)For Anticoagulation
Study Start Date : September 2006
Primary Completion Date : October 2008
Study Completion Date : October 2008

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arms and Interventions

Arm Intervention/treatment
Experimental: Pharmacogenetic-based warfarin dosing

Pharmacogenetic-based warfarin dosing: Warfarin dosing based on formula that incorporates genetic testing results.

NOTE: Standard of care for elective knee and hip replacement at our institution is to receive post-operative warfarin thromboprophylaxis. Administration of warfarin was not specific to this study, nor was the duration of prophylaxis, however, warfarin dosing was influenced by the study arm, as noted above.

Genetic: Pharmacogenetic-based warfarin dosing

Prior to elective joint replacement surgery a blood sample is collected for genetic information(genotyping)which was used for calculating warfarin doses for patients randomized to the cytochrome arm. Outcomes in terms of efficacy, safety, and management of warfarin were compared between this group and the group in which warfarin doses are determined per usual care.

NOTE: Standard of care for elective knee and hip replacement at our institution is to receive post-operative warfarin thromboprophylaxis. Administration of warfarin was not specific to this study, nor was the duration of prophylaxis, however, warfarin dosing was influenced by the study arm as noted above.

Active Comparator: Standard of care (control)

Control or "usual care" warfarin dosing

NOTE: Standard of care ("usual care") for elective knee and hip replacement at our institution is to receive post-operative warfarin thromboprophylaxis. Administration of warfarin was not specific to this study, nor was the duration of prophylaxis, however, warfarin dosing was influenced by the study arm, as noted above.

Other: Usual care warfarin dosing

For patients in arm 2, the control group, warfarin dosing is per usual care. Outcomes in terms of safety, efficacy, and warfarin management was compared to that of patients in the other arm, who receive warfarin dosing based on genotyping.

NOTE: Standard of care for elective knee and hip replacement at our institution is to receive post-operative warfarin thromboprophylaxis. Administration of warfarin was not specific to this study, nor was the duration of prophylaxis, however, warfarin dosing was influenced by the study arm as noted above.



Outcome Measures

Primary Outcome Measures :
  1. The Number of Participants With Adverse Events Associated With Warfarin Anticoagulation Following Total Hip and Total Knee Replacement [ Time Frame: 90 days post surgery ]

    Adverse events were defined as

    1. Major bleeding: fatal bleeding, bleeding into a critical organ, bleeding that requires hospital admission
    2. Minor bleeding: clinically overt bleeding not meeting criteria for major bleeding
    3. Symptomatic deep vein thrombosis (DVT)
    4. Pulmonary embolism (PE)


Secondary Outcome Measures :
  1. Percentage of Determinations in Therapuetic Range (INR 1.8-2.9) [ Time Frame: 2 weeks (knee arthroplasty) or 4 weeks (hip arthroplasty) ]
    Patient response to warfarin was evaluated based on the international normalized ratio (INR), calculated from a prothrombin time blood test. When the INR value was between 1.8 and 2.9, the patient was considered to be "therapeutic." The proportion of INR determinations that fell within the therapeutic range (INR between 1.8-2.9) was calculated, per arm, based on total number of INR determinations that were made during treatment with warfarin.

  2. Percentage of Determinations Subtherapeutic (INR<1.8) [ Time Frame: 2 weeks (knee arthroplasty) or 4 weeks (hop arthroplasty) ]
    Patient response to warfarin was evaluated based on the international normalized ratio (INR), calculated from a prothrombin time blood test. When the INR value was less than 1.8, the patient was considered to be "subtherapeutic." The proportion of INR determination that were subtherapeutic was caluculated, per arm, based on the total number of INR determinations that were made during treatment with warfarin.

  3. Percentage of Determinations Supratherapeutic (INR>2.9) [ Time Frame: 2 weeks (knee arthroplasty) or 4 weeks (hip arthroplasty) ]
    Patient response to warfarin was evaluated based on the international normalized ratio (INR), calculated from a prothrombin time blood test. When the INR value was greater than 2.9, the patient was considered to be "supratherapeutic." The proportion of INR determinations that were supratherapeutic was calculated, per arm, based on total number of INR determinations that were made during treatment with warfarin.


Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Participants were otherwise healthy adults (≥ 18 years of age) who were planning total hip or knee replacement or revision surgery at the University of Utah Hospital, and scheduled a pre-operative office visit at the University of Utah Orthopaedic Center.

Exclusion Criteria:

  • Blood transfusion in previous two weeks
  • Participant is already taking warfarin
  • Pre-operative INR > 4.0
  • Pre-operative bilirubin > 2.4 mg/dL
  • Current active cancer diagnosis with ongoing treatment
  • Concomitant medications known to exert a major interaction with warfarin such as septra, metronidazole, tramadol, amiodarone, ciprofloxacin, or cimetidine.
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00634907


Locations
United States, Utah
University of Utah Health Care
Salt Lake City, Utah, United States, 84132
Sponsors and Collaborators
Gwen McMillin
Investigators
Principal Investigator: Gwen McMillin, PhD ARUP Laboratories
More Information

Publications:
Responsible Party: Gwen McMillin, Medical Director Toxicology and Trace Minterals, Department of Pathology, ARUP Laboratories, University of Utah
ClinicalTrials.gov Identifier: NCT00634907     History of Changes
Other Study ID Numbers: 00019469
First Posted: March 13, 2008    Key Record Dates
Results First Posted: June 8, 2017
Last Update Posted: June 8, 2017
Last Verified: April 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Gwen McMillin, University of Utah:
Genotyping
Warfarin dosing
arthroplasty

Additional relevant MeSH terms:
Thromboembolism
Venous Thromboembolism
Embolism and Thrombosis
Vascular Diseases
Cardiovascular Diseases
Warfarin
Anticoagulants