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

Prospective CYP2C9 And VKORC1 Genotyping For Total Hip or Knee Replacement Patients Receiving Warfarin (Coumadin)For Anticoagulation

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.

Study Overview

• Status: Completed
• Conditions: Bleeding; Venous Thromboembolism
• Intervention / Treatment: 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 Type: Interventional
• Enrollment (Actual): 263
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • University of Utah Health Care

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Number of Participants With Adverse Events Associated With Warfarin Anticoagulation Following Total Hip and Total Knee Replacement	Adverse events were defined as; Major bleeding: fatal bleeding, bleeding into a critical organ, bleeding that requires hospital admission; Minor bleeding: clinically overt bleeding not meeting criteria for major bleeding; Symptomatic deep vein thrombosis (DVT); Pulmonary embolism (PE)	90 days post surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Determinations in Therapuetic Range (INR 1.8-2.9)	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 weeks (knee arthroplasty) or 4 weeks (hip arthroplasty)
Percentage of Determinations Subtherapeutic (INR<1.8)	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.	2 weeks (knee arthroplasty) or 4 weeks (hop arthroplasty)
Percentage of Determinations Supratherapeutic (INR>2.9)	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.	2 weeks (knee arthroplasty) or 4 weeks (hip arthroplasty)

Collaborators and Investigators

• Sponsor: Gwen McMillin
• Investigators: Principal Investigator: Gwen McMillin, PhD, ARUP Laboratories

Publications and helpful links

General Publications

• McMillin GA, Melis R, Wilson A, Strong MB, Wanner NA, Vinik RG, Peters CL, Pendleton RC. Gene-based warfarin dosing compared with standard of care practices in an orthopedic surgery population: a prospective, parallel cohort study. Ther Drug Monit. 2010 Jun;32(3):338-45. doi: 10.1097/FTD.0b013e3181d925bb.

Study record dates

Study Major Dates

• Study Start: September 1, 2006
• Primary Completion (Actual): October 1, 2008
• Study Completion (Actual): October 1, 2008

Study Registration Dates

• First Submitted: February 6, 2008
• First Submitted That Met QC Criteria: March 6, 2008
• First Posted (Estimate): March 13, 2008

Study Record Updates

• Last Update Posted (Actual): June 8, 2017
• Last Update Submitted That Met QC Criteria: April 25, 2017
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Keywords: arthroplasty; Genotyping; Warfarin dosing
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Embolism and Thrombosis; Thromboembolism; Venous Thromboembolism; Anticoagulants; Warfarin
• Other Study ID Numbers: 00019469

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO