Official Title: “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 is designed to evaluate if genetic testing can improve warfarin initiation better than usual care.

Study Type: Interventional

Study Design: Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study

Study Primary Completion Date: April 2008

Intervention(s) in this Clinical Trial

• Genetic: Pharmacogenetic-based warfarin dosing
  • Prior to elective joint replacement surgery a blood sample is collected for genetic information(genotyping)which will be used for calculating warfarin doses for patients randomized to the cytochrome arm. Outcomes in terms of efficacy, safety, and management of warfarin will be 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 is not specific to this study, nor is the duration of prophylaxis, however, warfarin dosing will be 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 will be 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 is not specific to this study, nor is the duration of prophylaxis, however, warfarin dosing will be influenced by the study arm as noted above.

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 1
  • 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 is not specific to this study, nor is the duration of prophylaxis, however, warfarin dosing will be influenced by the study arm, as noted above.
• Active Comparator: 2
  • Control or "usual care" warfarin dosing NOTE: Standard of care for elective knee and hip replacement at our institution is to receive post-operative warfarin thromboprophylaxis. Administration of warfarin is not specific to this study, nor is the duration of prophylaxis, however, warfarin dosing will be influenced by the study arm, as noted above.

Primary Measures

• Reduction in the number of adverse events associated with warfarin anticoagulation following total hip and total knee replacement
  • Time Frame: Time of warfarin initiation to 3 months after completion of warfarin therapy
    Safety Issue?: Yes

Secondary Measures

• Improved anticoagulation management in patients on warfarin following total hip and total knee replacement.
  • Time Frame: Initiation of warfarin therapy to completion of warfarin therapy
    Safety Issue?: Yes

Inclusion Criteria:

• Participants will be otherwise healthy adults (≥ 18 years of age) who are planning total hip or knee replacement or revision surgery at the University of Utah Hospital, and schedule 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.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: University of Utah

Overall Clinical Trial Officials and Contacts

Gwen McMillin, PhD Principal Investigator ARUP Laboratories  

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00634907

Study ID Number: 00019469

ClinicalTrials.gov Identifier: NCT00634907

Health Authority: United States: Institutional Review Board