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

NCT00634907 | Completed Results DMC

• 1 other identifier: 00019469
• Study Type: interventional
• Target: 263
• Locations: 1 country
• Sites: 1

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.

Conditions

Venous Thromboembolism; Bleeding

Keywords

Genotyping; Warfarin dosing; arthroplasty

Outcome Measures

Primary Outcomes (1)

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

  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)

  90 days post surgery

Secondary Outcomes (3)

• Percentage of Determinations in Therapuetic Range (INR 1.8-2.9)

  2 weeks (knee arthroplasty) or 4 weeks (hip arthroplasty)

• Percentage of Determinations Subtherapeutic (INR<1.8)

  2 weeks (knee arthroplasty) or 4 weeks (hop arthroplasty)

• Percentage of Determinations Supratherapeutic (INR>2.9)

  2 weeks (knee arthroplasty) or 4 weeks (hip arthroplasty)

Study Arms (2)

Pharmacogenetic-based warfarin dosing

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 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

Standard of care (control)

ACTIVE COMPARATOR

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

Interventions

Pharmacogenetic-based warfarin dosing GENETIC

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.

Pharmacogenetic-based warfarin dosing

Usual care warfarin dosing OTHER

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.

Standard of care (control)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Gwen McMillin: lead

Study Sites (1)

University of Utah Health Care

Salt Lake City, Utah, 84132, United States

Location

Related Publications (1)

• 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.

  PMID: 20386359 RESULT

MeSH Terms

Conditions

Venous Thromboembolism; Hemorrhage

Condition Hierarchy (Ancestors)

Thromboembolism; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Limitations and Caveats

Limited by the fact that INR was used to adjust dose at the third dose, which may not have allowed enough time for steady-state concentrations of warfarin to be achieved, nor for the genotype-based dosing to be adequately studied.

Results Point of Contact

• Title: Dr. Gwen McMillin/Principal Investigator
• Organization: University of Utah

gwen.mcmillin@aruplab.com

801-583-2787

Study Officials

• Gwen McMillin, PhD

  ARUP Laboratories

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Medical Director Toxicology and Trace Minterals, Department of Pathology, ARUP Laboratories

Study Record Dates

• First Submitted: February 6, 2008
• First Posted: March 13, 2008
• Study Start: September 1, 2006
• Primary Completion: October 1, 2008
• Study Completion: October 1, 2008
• Last Updated: June 8, 2017
• Results First Posted: June 8, 2017

Record last verified: 2017-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)