Back to resultsProspective Genotyping For Total Hip or Knee Replacement Patients Receiving Warfarin (Coumadin)
Primary Purpose
Venous Thromboembolism, Bleeding
Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Pharmacogenetic-based warfarin dosing
Usual care warfarin dosing
Sponsored by
About this trial
This is an interventional treatment trial for Venous Thromboembolism focused on measuring Genotyping, Warfarin dosing, arthroplasty
Eligibility 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.
Sites / Locations
- University of Utah Health Care
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Pharmacogenetic-based warfarin dosing
Standard of care (control)
Arm Description
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.
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.
Outcomes
Primary Outcome Measures
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)
Secondary Outcome Measures
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.
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.
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00634907
Brief Title
Prospective Genotyping For Total Hip or Knee Replacement Patients Receiving Warfarin (Coumadin)
Official Title
Prospective CYP2C9 And VKORC1 Genotyping For Total Hip or Knee Replacement Patients Receiving Warfarin (Coumadin)For Anticoagulation
Study Type
Interventional
2. Study Status
Record Verification Date
April 2017
Overall Recruitment Status
Completed
Study Start Date
September 2006 (undefined)
Primary Completion Date
October 2008 (Actual)
Study Completion Date
October 2008 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Gwen McMillin
4. Oversight
Data Monitoring Committee
Yes
5. 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.
Detailed Description
This study was completed in 2008 and was published. Consult the citation link for more details.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Venous Thromboembolism, Bleeding
Keywords
Genotyping, Warfarin dosing, arthroplasty
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
263 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Pharmacogenetic-based warfarin dosing
Arm Type
Experimental
Arm Description
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.
Arm Title
Standard of care (control)
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Genetic
Intervention Name(s)
Pharmacogenetic-based warfarin dosing
Intervention Description
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.
Intervention Type
Other
Intervention Name(s)
Usual care warfarin dosing
Intervention Description
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.
Primary Outcome Measure Information:
Title
The Number of Participants With Adverse Events Associated With Warfarin Anticoagulation Following Total Hip and Total Knee Replacement
Description
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)
Time Frame
90 days post surgery
Secondary Outcome Measure Information:
Title
Percentage of Determinations in Therapuetic Range (INR 1.8-2.9)
Description
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.
Time Frame
2 weeks (knee arthroplasty) or 4 weeks (hip arthroplasty)
Title
Percentage of Determinations Subtherapeutic (INR<1.8)
Description
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.
Time Frame
2 weeks (knee arthroplasty) or 4 weeks (hop arthroplasty)
Title
Percentage of Determinations Supratherapeutic (INR>2.9)
Description
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.
Time Frame
2 weeks (knee arthroplasty) or 4 weeks (hip arthroplasty)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gwen McMillin, PhD
Organizational Affiliation
ARUP Laboratories
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Utah Health Care
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84132
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
20386359
Citation
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.
Results Reference
result
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Prospective Genotyping For Total Hip or Knee Replacement Patients Receiving Warfarin (Coumadin)
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