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

Study Overview
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Brief Summary
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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
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This study was completed in 2008 and was published. Consult the citation link for more details.

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

Conditions
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Venous Thromboembolism, Bleeding

Intervention / Treatment
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* Genetic: Pharmacogenetic-based warfarin dosing
* Other: Usual care warfarin dosing


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pharmacogenetic-based warfarin dosing<br>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<br>* 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.<br>|
| Active Comparator: Standard of care (control)<br>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<br>* 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.<br>|

What is the study measuring?
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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) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Genotyping, Warfarin dosing, arthroplasty