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

Not Applicable

Completed

Conditions: Venous Thromboembolism
Bleeding

Interventions: Other: Usual care warfarin dosing
Genetic: Pharmacogenetic-based warfarin dosing

Registration Number: NCT00634907

Lead Sponsor: Gwen McMillin

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.

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

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 263

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 & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Standard of care (control)	Usual care warfarin dosing	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.
Pharmacogenetic-based warfarin dosing	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.

Primary Outcome Measures

Name	Time	Method
The Number of Participants With Adverse Events Associated With Warfarin Anticoagulation Following Total Hip and Total Knee Replacement	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

Name	Time	Method
Percentage of Determinations in Therapuetic Range (INR 1.8-2.9)	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.
Percentage of Determinations Subtherapeutic (INR<1.8)	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.
Percentage of Determinations Supratherapeutic (INR>2.9)	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.