Prospective Genotyping For Total Hip or Knee Replacement Patients Receiving Warfarin (Coumadin) - Full Text View

Sponsor:	University of Utah
Information provided by:	University of Utah
ClinicalTrials.gov Identifier:	NCT00634907

Purpose

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.

Condition	Intervention
Venous Thromboembolism Major Bleeding	Genetic: Pharmacogenetic-based warfarin dosing Other: Usual care warfarin dosing

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study
Official Title:	Prospective CYP2C9 And VKORC1 Genotyping For Total Hip or Knee Replacement Patients Receiving Warfarin (Coumadin)For Anticoagulation

Resource links provided by NLM:

MedlinePlus related topics: Blood Thinners Knee Replacement

Drug Information available for: Warfarin Warfarin sodium Warfarin potassium

U.S. FDA Resources

Further study details as provided by University of Utah:

Primary Outcome 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 ] [ Designated as safety issue: Yes ]

Secondary Outcome 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 ] [ Designated as safety issue: Yes ]

Enrollment:	263
Study Start Date:	October 2006
Study Completion Date:	August 2008
Primary Completion Date:	April 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental 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.	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.
2: Active Comparator 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.	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

Assigned Interventions

1: Experimental

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.

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.

2: Active Comparator

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.

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00634907

Locations

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

Sponsors and Collaborators

University of Utah

Investigators

Principal Investigator:

Gwen McMillin, PhD

ARUP Laboratories

More Information

No publications provided

Responsible Party:	Department of Pathology, ARUP Laboratories ( Gwen McMillin, PhD, Medical Director Toxicology and Trace Minerals )
Study ID Numbers:	00019469
Study First Received:	February 6, 2008
Last Updated:	September 25, 2008
ClinicalTrials.gov Identifier:	NCT00634907 History of Changes
Health Authority:	United States: Institutional Review Board

Keywords provided by University of Utah:

Genotyping
Warfarin dosing
arthroplasty

Additional relevant MeSH terms:

Embolism and Thrombosis
Anticoagulants
Therapeutic Uses
Hematologic Agents
Vascular Diseases
Cardiovascular Diseases

Warfarin
Venous Thromboembolism
Pharmacologic Actions
Thrombosis
Thromboembolism

ClinicalTrials.gov processed this record on February 08, 2010