Trial Outcomes & Findings for Prospective Genotyping For Total Hip or Knee Replacement Patients Receiving Warfarin (Coumadin) (NCT NCT00634907)
NCT ID: NCT00634907
Last Updated: 2017-06-08
Results Overview
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)
Recruitment status
COMPLETED
Study phase
NA
Target enrollment
263 participants
Primary outcome timeframe
90 days post surgery
Results posted on
2017-06-08
Participant Flow
Patients planning total hip or knee replacement surgery at the University of Utah Hospital, will be approached about participation in the study by Dr Chris Peters, MD or assigned orthopedic staff at the pre-operative office visit at the University of Utah Orthopaedic Center. Patients were enrolled from 9/27/06 - 10/2/08
Exclusion Criteria: 1. Blood transfusion in previous two weeks 2. Participant is already taking warfarin 3. Pre-operative INR \> 4.0 4. Pre-operative bilirubin \> 2.4 mg/dL 5. Current active cancer diagnosis with ongoing treatment 6. Concomitant medications known to exert a major interaction with warfarin
Participant milestones
| Measure |
2 Genotype Arm
The initial dose of warfarin will be corrected by the AC services team to account for variant genotypes, according to the following:
Sqrt (Dose) = 0.628 - 0.0135(Age) - 0.240(CYP2C9\*2) - 0.370 (CYP2C9\*3) - 0.241(VKORC1) + 0.0162(Height) Age: input age in years CYP2C9: input 0, 1, or 2 based on the number of variant alleles VKORC1: input 1 for GG, 2 for GA, and 3 for AA Height: input height in centimeters Patients in this study group will be managed by designated AC services physicians, different from those in managing patients in the Control Arm of this study. Dosing adjustments will be made based on post-surgical INR values obtained initially on POD#2 daily during hospital stay, and 2 times weekly, or as needed, thereafter.
|
1 Control Arm
This is a two-armed parallel study with randomized assignment designed to test the hypothesis that selection of the initial warfarin dose based on CYP2C9 and VKORC1 genotypes will improve warfarin pharmacotherapy outcomes. Initial dose of warfarin will be given as per standard protocol for the Control Arm. Briefly, 3 or 5 mg warfarin will be administered on the day of surgery (post-operative day zero, POD#0) and the subsequent day. Patients in this study group will be managed by designated AC services physicians. Dosing adjustments will be made based on post-surgical INR values obtained initially on POD#2, daily during hospital stay, and 2 times weekly, or as needed, thereafter.
|
|---|---|---|
|
Overall Study
STARTED
|
131
|
132
|
|
Overall Study
COMPLETED
|
114
|
115
|
|
Overall Study
NOT COMPLETED
|
17
|
17
|
Reasons for withdrawal
| Measure |
2 Genotype Arm
The initial dose of warfarin will be corrected by the AC services team to account for variant genotypes, according to the following:
Sqrt (Dose) = 0.628 - 0.0135(Age) - 0.240(CYP2C9\*2) - 0.370 (CYP2C9\*3) - 0.241(VKORC1) + 0.0162(Height) Age: input age in years CYP2C9: input 0, 1, or 2 based on the number of variant alleles VKORC1: input 1 for GG, 2 for GA, and 3 for AA Height: input height in centimeters Patients in this study group will be managed by designated AC services physicians, different from those in managing patients in the Control Arm of this study. Dosing adjustments will be made based on post-surgical INR values obtained initially on POD#2 daily during hospital stay, and 2 times weekly, or as needed, thereafter.
|
1 Control Arm
This is a two-armed parallel study with randomized assignment designed to test the hypothesis that selection of the initial warfarin dose based on CYP2C9 and VKORC1 genotypes will improve warfarin pharmacotherapy outcomes. Initial dose of warfarin will be given as per standard protocol for the Control Arm. Briefly, 3 or 5 mg warfarin will be administered on the day of surgery (post-operative day zero, POD#0) and the subsequent day. Patients in this study group will be managed by designated AC services physicians. Dosing adjustments will be made based on post-surgical INR values obtained initially on POD#2, daily during hospital stay, and 2 times weekly, or as needed, thereafter.
|
|---|---|---|
|
Overall Study
Withdrawal by Subject
|
11
|
8
|
|
Overall Study
Physician Decision
|
3
|
9
|
Baseline Characteristics
Prospective Genotyping For Total Hip or Knee Replacement Patients Receiving Warfarin (Coumadin)
Baseline characteristics by cohort
| Measure |
Genotype-Based Dosing Arm
n=114 Participants
Initial warfarin dose calculated according to published Sconce algorithm
|
Control Arm
n=115 Participants
Standard of care dosing
|
Total
n=229 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
78 Participants
n=5 Participants
|
80 Participants
n=7 Participants
|
158 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
36 Participants
n=5 Participants
|
35 Participants
n=7 Participants
|
71 Participants
n=5 Participants
|
|
Age, Continuous
|
58.18 years
STANDARD_DEVIATION 12.14 • n=5 Participants
|
59.25 years
STANDARD_DEVIATION 12.83 • n=7 Participants
|
58.75 years
STANDARD_DEVIATION 12.49 • n=5 Participants
|
|
Sex: Female, Male
Female
|
68 Participants
n=5 Participants
|
72 Participants
n=7 Participants
|
140 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
46 Participants
n=5 Participants
|
43 Participants
n=7 Participants
|
89 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
114 participants
n=5 Participants
|
115 participants
n=7 Participants
|
229 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 90 days post surgeryAdverse 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)
Outcome measures
| Measure |
2 Genotype Arm
n=114 Participants
The initial dose of warfarin will be corrected by the AC services team to account for variant genotypes, according to the following:
Sqrt (Dose) = 0.628 - 0.0135(Age) - 0.240(CYP2C9\*2) - 0.370 (CYP2C9\*3) - 0.241(VKORC1) + 0.0162(Height) Age: input age in years CYP2C9: input 0, 1, or 2 based on the number of variant alleles VKORC1: input 1 for GG, 2 for GA, and 3 for AA Height: input height in centimeters Patients in this study group will be managed by designated AC services physicians, different from those in managing patients in the Control Arm of this study. Dosing adjustments will be made based on post-surgical INR values obtained initially on POD#2 daily during hospital stay, and 2 times weekly, or as needed, thereafter.
|
1 Control Arm
n=115 Participants
This is a two-armed parallel study with randomized assignment designed to test the hypothesis that selection of the initial warfarin dose based on CYP2C9 and VKORC1 genotypes will improve warfarin pharmacotherapy outcomes. Initial dose of warfarin will be given as per standard protocol for the Control Arm. Briefly, 3 or 5 mg warfarin will be administered on the day of surgery (post-operative day zero, POD#0) and the subsequent day. Patients in this study group will be managed by designated AC services physicians. Dosing adjustments will be made based on post-surgical INR values obtained initially on POD#2, daily during hospital stay, and 2 times weekly, or as needed, thereafter.
|
|---|---|---|
|
The Number of Participants With Adverse Events Associated With Warfarin Anticoagulation Following Total Hip and Total Knee Replacement
|
2 participants
|
4 participants
|
SECONDARY outcome
Timeframe: 2 weeks (knee arthroplasty) or 4 weeks (hip arthroplasty)Population: Determinations were assessed cumulatively throughout the study period, per patient, per arm. The total number of determinations was 804 for the genotype arm and 780 for the control arm
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.
Outcome measures
| Measure |
2 Genotype Arm
n=114 Participants
The initial dose of warfarin will be corrected by the AC services team to account for variant genotypes, according to the following:
Sqrt (Dose) = 0.628 - 0.0135(Age) - 0.240(CYP2C9\*2) - 0.370 (CYP2C9\*3) - 0.241(VKORC1) + 0.0162(Height) Age: input age in years CYP2C9: input 0, 1, or 2 based on the number of variant alleles VKORC1: input 1 for GG, 2 for GA, and 3 for AA Height: input height in centimeters Patients in this study group will be managed by designated AC services physicians, different from those in managing patients in the Control Arm of this study. Dosing adjustments will be made based on post-surgical INR values obtained initially on POD#2 daily during hospital stay, and 2 times weekly, or as needed, thereafter.
|
1 Control Arm
n=115 Participants
This is a two-armed parallel study with randomized assignment designed to test the hypothesis that selection of the initial warfarin dose based on CYP2C9 and VKORC1 genotypes will improve warfarin pharmacotherapy outcomes. Initial dose of warfarin will be given as per standard protocol for the Control Arm. Briefly, 3 or 5 mg warfarin will be administered on the day of surgery (post-operative day zero, POD#0) and the subsequent day. Patients in this study group will be managed by designated AC services physicians. Dosing adjustments will be made based on post-surgical INR values obtained initially on POD#2, daily during hospital stay, and 2 times weekly, or as needed, thereafter.
|
|---|---|---|
|
Percentage of Determinations in Therapuetic Range (INR 1.8-2.9)
|
43.3 percentage of therapeutic INR values
|
44.9 percentage of therapeutic INR values
|
SECONDARY outcome
Timeframe: 2 weeks (knee arthroplasty) or 4 weeks (hop arthroplasty)Population: Determinations were assessed cumulatively throughout the study period, per patient, per arm. The total number of determinations was 804 for the genotype arm and 780 for the control arm
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.
Outcome measures
| Measure |
2 Genotype Arm
n=114 Participants
The initial dose of warfarin will be corrected by the AC services team to account for variant genotypes, according to the following:
Sqrt (Dose) = 0.628 - 0.0135(Age) - 0.240(CYP2C9\*2) - 0.370 (CYP2C9\*3) - 0.241(VKORC1) + 0.0162(Height) Age: input age in years CYP2C9: input 0, 1, or 2 based on the number of variant alleles VKORC1: input 1 for GG, 2 for GA, and 3 for AA Height: input height in centimeters Patients in this study group will be managed by designated AC services physicians, different from those in managing patients in the Control Arm of this study. Dosing adjustments will be made based on post-surgical INR values obtained initially on POD#2 daily during hospital stay, and 2 times weekly, or as needed, thereafter.
|
1 Control Arm
n=115 Participants
This is a two-armed parallel study with randomized assignment designed to test the hypothesis that selection of the initial warfarin dose based on CYP2C9 and VKORC1 genotypes will improve warfarin pharmacotherapy outcomes. Initial dose of warfarin will be given as per standard protocol for the Control Arm. Briefly, 3 or 5 mg warfarin will be administered on the day of surgery (post-operative day zero, POD#0) and the subsequent day. Patients in this study group will be managed by designated AC services physicians. Dosing adjustments will be made based on post-surgical INR values obtained initially on POD#2, daily during hospital stay, and 2 times weekly, or as needed, thereafter.
|
|---|---|---|
|
Percentage of Determinations Subtherapeutic (INR<1.8)
|
48.0 percentage of deteminations
|
47.1 percentage of deteminations
|
SECONDARY outcome
Timeframe: 2 weeks (knee arthroplasty) or 4 weeks (hip arthroplasty)Population: Determinations were assessed cumulatively throughout the study period, per patient, per arm. The total number of determinations was 804 for the genotype arm and 780 for the control arm
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.
Outcome measures
| Measure |
2 Genotype Arm
n=114 Participants
The initial dose of warfarin will be corrected by the AC services team to account for variant genotypes, according to the following:
Sqrt (Dose) = 0.628 - 0.0135(Age) - 0.240(CYP2C9\*2) - 0.370 (CYP2C9\*3) - 0.241(VKORC1) + 0.0162(Height) Age: input age in years CYP2C9: input 0, 1, or 2 based on the number of variant alleles VKORC1: input 1 for GG, 2 for GA, and 3 for AA Height: input height in centimeters Patients in this study group will be managed by designated AC services physicians, different from those in managing patients in the Control Arm of this study. Dosing adjustments will be made based on post-surgical INR values obtained initially on POD#2 daily during hospital stay, and 2 times weekly, or as needed, thereafter.
|
1 Control Arm
n=115 Participants
This is a two-armed parallel study with randomized assignment designed to test the hypothesis that selection of the initial warfarin dose based on CYP2C9 and VKORC1 genotypes will improve warfarin pharmacotherapy outcomes. Initial dose of warfarin will be given as per standard protocol for the Control Arm. Briefly, 3 or 5 mg warfarin will be administered on the day of surgery (post-operative day zero, POD#0) and the subsequent day. Patients in this study group will be managed by designated AC services physicians. Dosing adjustments will be made based on post-surgical INR values obtained initially on POD#2, daily during hospital stay, and 2 times weekly, or as needed, thereafter.
|
|---|---|---|
|
Percentage of Determinations Supratherapeutic (INR>2.9)
|
8.7 percentage of determinations
|
8.0 percentage of determinations
|
POST_HOC outcome
Timeframe: 2 weeks (knee arthroplasty) or 4 weeks (hip arthroplasty)The number of consistent doses administered before the first dose adjustment was required was recorded, per patient. The average number of doses administered before the first dose adjustment is shown.
Outcome measures
| Measure |
2 Genotype Arm
n=114 Participants
The initial dose of warfarin will be corrected by the AC services team to account for variant genotypes, according to the following:
Sqrt (Dose) = 0.628 - 0.0135(Age) - 0.240(CYP2C9\*2) - 0.370 (CYP2C9\*3) - 0.241(VKORC1) + 0.0162(Height) Age: input age in years CYP2C9: input 0, 1, or 2 based on the number of variant alleles VKORC1: input 1 for GG, 2 for GA, and 3 for AA Height: input height in centimeters Patients in this study group will be managed by designated AC services physicians, different from those in managing patients in the Control Arm of this study. Dosing adjustments will be made based on post-surgical INR values obtained initially on POD#2 daily during hospital stay, and 2 times weekly, or as needed, thereafter.
|
1 Control Arm
n=115 Participants
This is a two-armed parallel study with randomized assignment designed to test the hypothesis that selection of the initial warfarin dose based on CYP2C9 and VKORC1 genotypes will improve warfarin pharmacotherapy outcomes. Initial dose of warfarin will be given as per standard protocol for the Control Arm. Briefly, 3 or 5 mg warfarin will be administered on the day of surgery (post-operative day zero, POD#0) and the subsequent day. Patients in this study group will be managed by designated AC services physicians. Dosing adjustments will be made based on post-surgical INR values obtained initially on POD#2, daily during hospital stay, and 2 times weekly, or as needed, thereafter.
|
|---|---|---|
|
Mean Number of Doses Before First Dose Adjustment
|
3.1 doses
Standard Deviation 1.1
|
3.6 doses
Standard Deviation 1.3
|
POST_HOC outcome
Timeframe: 2 weeks (knee arthroplasty) or 4 weeks (hip arthroplasty)The average number of dose adjustments made per patient, per arm, during the study period was calculated
Outcome measures
| Measure |
2 Genotype Arm
n=114 Participants
The initial dose of warfarin will be corrected by the AC services team to account for variant genotypes, according to the following:
Sqrt (Dose) = 0.628 - 0.0135(Age) - 0.240(CYP2C9\*2) - 0.370 (CYP2C9\*3) - 0.241(VKORC1) + 0.0162(Height) Age: input age in years CYP2C9: input 0, 1, or 2 based on the number of variant alleles VKORC1: input 1 for GG, 2 for GA, and 3 for AA Height: input height in centimeters Patients in this study group will be managed by designated AC services physicians, different from those in managing patients in the Control Arm of this study. Dosing adjustments will be made based on post-surgical INR values obtained initially on POD#2 daily during hospital stay, and 2 times weekly, or as needed, thereafter.
|
1 Control Arm
n=115 Participants
This is a two-armed parallel study with randomized assignment designed to test the hypothesis that selection of the initial warfarin dose based on CYP2C9 and VKORC1 genotypes will improve warfarin pharmacotherapy outcomes. Initial dose of warfarin will be given as per standard protocol for the Control Arm. Briefly, 3 or 5 mg warfarin will be administered on the day of surgery (post-operative day zero, POD#0) and the subsequent day. Patients in this study group will be managed by designated AC services physicians. Dosing adjustments will be made based on post-surgical INR values obtained initially on POD#2, daily during hospital stay, and 2 times weekly, or as needed, thereafter.
|
|---|---|---|
|
Mean Number of Dose Adjustments
|
8.4 doses
Standard Deviation 2.18
|
7.0 doses
Standard Deviation 2.48
|
POST_HOC outcome
Timeframe: 2 weeks (knee arthroplasty) or 4 weeks (hip arthroplasty)The percent of patients that required a dose adjustment during the study period was calculated.
Outcome measures
| Measure |
2 Genotype Arm
n=114 Participants
The initial dose of warfarin will be corrected by the AC services team to account for variant genotypes, according to the following:
Sqrt (Dose) = 0.628 - 0.0135(Age) - 0.240(CYP2C9\*2) - 0.370 (CYP2C9\*3) - 0.241(VKORC1) + 0.0162(Height) Age: input age in years CYP2C9: input 0, 1, or 2 based on the number of variant alleles VKORC1: input 1 for GG, 2 for GA, and 3 for AA Height: input height in centimeters Patients in this study group will be managed by designated AC services physicians, different from those in managing patients in the Control Arm of this study. Dosing adjustments will be made based on post-surgical INR values obtained initially on POD#2 daily during hospital stay, and 2 times weekly, or as needed, thereafter.
|
1 Control Arm
n=115 Participants
This is a two-armed parallel study with randomized assignment designed to test the hypothesis that selection of the initial warfarin dose based on CYP2C9 and VKORC1 genotypes will improve warfarin pharmacotherapy outcomes. Initial dose of warfarin will be given as per standard protocol for the Control Arm. Briefly, 3 or 5 mg warfarin will be administered on the day of surgery (post-operative day zero, POD#0) and the subsequent day. Patients in this study group will be managed by designated AC services physicians. Dosing adjustments will be made based on post-surgical INR values obtained initially on POD#2, daily during hospital stay, and 2 times weekly, or as needed, thereafter.
|
|---|---|---|
|
Percent of Patients With Dose Adjustments
|
83.5 percentage of patients
|
78.0 percentage of patients
|
POST_HOC outcome
Timeframe: 2 weeks (knee arthroplasty) or 4 weeks (hip arthroplasty)The number of doses required to achieve a therapeutic INR (1.8-2.9) was determined per patient, per arm. The average was then calculated and is shown here.
Outcome measures
| Measure |
2 Genotype Arm
n=114 Participants
The initial dose of warfarin will be corrected by the AC services team to account for variant genotypes, according to the following:
Sqrt (Dose) = 0.628 - 0.0135(Age) - 0.240(CYP2C9\*2) - 0.370 (CYP2C9\*3) - 0.241(VKORC1) + 0.0162(Height) Age: input age in years CYP2C9: input 0, 1, or 2 based on the number of variant alleles VKORC1: input 1 for GG, 2 for GA, and 3 for AA Height: input height in centimeters Patients in this study group will be managed by designated AC services physicians, different from those in managing patients in the Control Arm of this study. Dosing adjustments will be made based on post-surgical INR values obtained initially on POD#2 daily during hospital stay, and 2 times weekly, or as needed, thereafter.
|
1 Control Arm
n=115 Participants
This is a two-armed parallel study with randomized assignment designed to test the hypothesis that selection of the initial warfarin dose based on CYP2C9 and VKORC1 genotypes will improve warfarin pharmacotherapy outcomes. Initial dose of warfarin will be given as per standard protocol for the Control Arm. Briefly, 3 or 5 mg warfarin will be administered on the day of surgery (post-operative day zero, POD#0) and the subsequent day. Patients in this study group will be managed by designated AC services physicians. Dosing adjustments will be made based on post-surgical INR values obtained initially on POD#2, daily during hospital stay, and 2 times weekly, or as needed, thereafter.
|
|---|---|---|
|
Mean Number of Doses Required for the First Therapeutic INR
|
3.9 doses
Standard Deviation 1.3
|
3.4 doses
Standard Deviation 1.1
|
POST_HOC outcome
Timeframe: 2 weeks (knee arthroplasty) or 4 weeks (hip arthroplasty)The number of warfarin doses administered before a patient INR exceeded the therapeutic range (\>2.9) was recorded. The average was then calculated and is shown here.
Outcome measures
| Measure |
2 Genotype Arm
n=114 Participants
The initial dose of warfarin will be corrected by the AC services team to account for variant genotypes, according to the following:
Sqrt (Dose) = 0.628 - 0.0135(Age) - 0.240(CYP2C9\*2) - 0.370 (CYP2C9\*3) - 0.241(VKORC1) + 0.0162(Height) Age: input age in years CYP2C9: input 0, 1, or 2 based on the number of variant alleles VKORC1: input 1 for GG, 2 for GA, and 3 for AA Height: input height in centimeters Patients in this study group will be managed by designated AC services physicians, different from those in managing patients in the Control Arm of this study. Dosing adjustments will be made based on post-surgical INR values obtained initially on POD#2 daily during hospital stay, and 2 times weekly, or as needed, thereafter.
|
1 Control Arm
n=115 Participants
This is a two-armed parallel study with randomized assignment designed to test the hypothesis that selection of the initial warfarin dose based on CYP2C9 and VKORC1 genotypes will improve warfarin pharmacotherapy outcomes. Initial dose of warfarin will be given as per standard protocol for the Control Arm. Briefly, 3 or 5 mg warfarin will be administered on the day of surgery (post-operative day zero, POD#0) and the subsequent day. Patients in this study group will be managed by designated AC services physicians. Dosing adjustments will be made based on post-surgical INR values obtained initially on POD#2, daily during hospital stay, and 2 times weekly, or as needed, thereafter.
|
|---|---|---|
|
Mean Number of Doses Before the First Supratherapeutic INR
|
5.4 doses administered
Standard Deviation 2.1
|
4.8 doses administered
Standard Deviation 1.9
|
Adverse Events
2 Genotype Arm
Serious events: 2 serious events
Other events: 1 other events
Deaths: 0 deaths
1 Control Arm
Serious events: 4 serious events
Other events: 6 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
2 Genotype Arm
n=114 participants at risk
The initial dose of warfarin will be corrected by the AC services team to account for variant genotypes, according to the following:
Sqrt (Dose) = 0.628 - 0.0135(Age) - 0.240(CYP2C9\*2) - 0.370 (CYP2C9\*3) - 0.241(VKORC1) + 0.0162(Height) Age: input age in years CYP2C9: input 0, 1, or 2 based on the number of variant alleles VKORC1: input 1 for GG, 2 for GA, and 3 for AA Height: input height in centimeters Patients in this study group will be managed by designated AC services physicians, different from those in managing patients in the Control Arm of this study. Dosing adjustments will be made based on post-surgical INR values obtained initially on POD#2 daily during hospital stay, and 2 times weekly, or as needed, thereafter.
|
1 Control Arm
n=115 participants at risk
This is a two-armed parallel study with randomized assignment designed to test the hypothesis that selection of the initial warfarin dose based on CYP2C9 and VKORC1 genotypes will improve warfarin pharmacotherapy outcomes. Initial dose of warfarin will be given as per standard protocol for the Control Arm. Briefly, 3 or 5 mg warfarin will be administered on the day of surgery (post-operative day zero, POD#0) and the subsequent day. Patients in this study group will be managed by designated AC services physicians. Dosing adjustments will be made based on post-surgical INR values obtained initially on POD#2, daily during hospital stay, and 2 times weekly, or as needed, thereafter.
|
|---|---|---|
|
Vascular disorders
Venous thromboembolic event or bleed
|
1.8%
2/114 • Number of events 2 • Adverse events were recorded and investigated as they occurred, throughout the study period.
|
3.5%
4/115 • Number of events 4 • Adverse events were recorded and investigated as they occurred, throughout the study period.
|
Other adverse events
| Measure |
2 Genotype Arm
n=114 participants at risk
The initial dose of warfarin will be corrected by the AC services team to account for variant genotypes, according to the following:
Sqrt (Dose) = 0.628 - 0.0135(Age) - 0.240(CYP2C9\*2) - 0.370 (CYP2C9\*3) - 0.241(VKORC1) + 0.0162(Height) Age: input age in years CYP2C9: input 0, 1, or 2 based on the number of variant alleles VKORC1: input 1 for GG, 2 for GA, and 3 for AA Height: input height in centimeters Patients in this study group will be managed by designated AC services physicians, different from those in managing patients in the Control Arm of this study. Dosing adjustments will be made based on post-surgical INR values obtained initially on POD#2 daily during hospital stay, and 2 times weekly, or as needed, thereafter.
|
1 Control Arm
n=115 participants at risk
This is a two-armed parallel study with randomized assignment designed to test the hypothesis that selection of the initial warfarin dose based on CYP2C9 and VKORC1 genotypes will improve warfarin pharmacotherapy outcomes. Initial dose of warfarin will be given as per standard protocol for the Control Arm. Briefly, 3 or 5 mg warfarin will be administered on the day of surgery (post-operative day zero, POD#0) and the subsequent day. Patients in this study group will be managed by designated AC services physicians. Dosing adjustments will be made based on post-surgical INR values obtained initially on POD#2, daily during hospital stay, and 2 times weekly, or as needed, thereafter.
|
|---|---|---|
|
Vascular disorders
Minor bleed
|
0.88%
1/114 • Number of events 1 • Adverse events were recorded and investigated as they occurred, throughout the study period.
|
5.2%
6/115 • Number of events 6 • Adverse events were recorded and investigated as they occurred, throughout the study period.
|
Additional Information
Dr. Gwen McMillin/Principal Investigator
University of Utah
Phone: 801-583-2787
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place