Venous ThromboembolismNCT00634907
Prospective Genotyping For Total Hip or Knee Replacement Patients Receiving Warfarin (Coumadin)
A study testing Pharmacogenetic-based warfarin dosing in people with Venous Thromboembolism and Bleeding, run by Gwen McMillin at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Venous Thromboembolism, Bleeding
- What is being tested?
- Pharmacogenetic-based warfarin dosing
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 263 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2006to Oct 2008
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Utah Health Care
Salt Lake City, Utah, 84132
About this study
Official title: Prospective CYP2C9 And VKORC1 Genotyping For Total Hip or Knee Replacement Patients Receiving Warfarin (Coumadin)For Anticoagulation
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.
Read the detailed description
This study was completed in 2008 and was published. Consult the citation link for more details.
- Conditions
- Venous Thromboembolism, Bleeding
- Being tested
- Pharmacogenetic-based warfarin dosing, Usual care warfarin dosing
- Keywords
- Genotyping, Warfarin dosing, arthroplasty
- Medical subject headings
- Venous Thromboembolism, Hemorrhage
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Pharmacogenetic-based warfarin dosingGenetic
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.
Usual care warfarin dosingOther
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Other: Usual care warfarin dosing |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: 90 days post surgery
Secondary outcomes (3)
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.
Measured: 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.
Measured: 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.
Measured: 2 weeks (knee arthroplasty) or 4 weeks (hip arthroplasty)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Mar 2008 (estimated)
- Study startSep 2006
- Primary completionOct 2008
- Study completionOct 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Venous ThromboembolismStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 263 participants (actual)
Sponsor and investigators
- Lead sponsor
- Gwen McMillin
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Gwen McMillin, University of Utah
- Investigators
- Gwen McMillin, PhD, Principal investigator, ARUP Laboratories
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00634907
- Sponsor's protocol ID
- 00019469
- Status last verified
- Apr 2017
- First submitted
- 6 Feb 2008
- Last updated
- 8 Jun 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
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.
PubMed 20386359
Study at a glance
From the registry record, last updated by the sponsor on 8 Jun 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prospective CYP2C9 And VKORC1 Genotyping For Total Hip or Knee Replacement Patients Receiving Warfarin (Coumadin)For Anticoagulation
- ClinicalTrials.gov ID
- NCT00634907
- Acronym / sponsor ID
- 00019469
- Conditions
- Venous Thromboembolism, Bleeding
- Keywords
- Genotyping, Warfarin dosing, arthroplasty
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 263 participants (actual)
- Lead sponsor
- Gwen McMillinUniversity, hospital or other
- Study start
- Sep 2006
- Primary completion
- Oct 2008 (actual)
- Study completion
- Oct 2008 (actual)
- First posted
- 13 Mar 2008 (estimated)
- Results
- Posted 8 Jun 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Pharmacogenetic-based warfarin dosing | Experimental | Genetic: Pharmacogenetic-based warfarin dosingPharmacogenetic-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. |
| Standard of care (control) | Active comparator | Other: Usual care warfarin dosingControl 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- 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.
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Pharmacogenetic-based warfarin dosingPrior 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. | Genetic | Pharmacogenetic-based warfarin dosing |
| Usual care warfarin dosingFor 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. | Other | Standard of care (control) |
Primary outcome
The Number of Participants With Adverse Events Associated With Warfarin Anticoagulation Following Total Hip and Total Knee Replacement
Time frame: 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)
3 secondary outcomes
Percentage of Determinations in Therapuetic Range (INR 1.8-2.9)
Time frame: 2 weeks (knee arthroplasty) or 4 weeks (hip arthroplasty)
Percentage of Determinations Subtherapeutic (INR<1.8)
Time frame: 2 weeks (knee arthroplasty) or 4 weeks (hop arthroplasty)
Percentage of Determinations Supratherapeutic (INR>2.9)
Time frame: 2 weeks (knee arthroplasty) or 4 weeks (hip arthroplasty)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jun 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 20386359McMillin 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gwen McMillin, PhD principal investigator
ARUP Laboratories
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Pharmacogenetic-based warfarin dosing in people with Venous Thromboembolism and Bleeding, run by Gwen McMillin at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Jun 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 8 Jun 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The Number of Participants With Adverse Events Associated With Warfarin Anticoagulation Following Total Hip and Total Knee Replacement (time frame: 90 days post surgery). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00634907, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Jun 2017.