Arthroplasty, Replacement, Hip, Thrombosis
Conditions
Keywords
Deep Vein Thrombosis,, Anticoagulant,, Venous thromboembolic
Brief summary
Patients who undergo total hip replacement surgery are at greater risk of getting deep vein thrombosis (blood clots). This study evaluates the safety, tolerability and effectiveness of the study drug, DU-176b, in reducing the occurrence of deep vein thrombosis in patients having total hip replacement surgery.
Detailed description
The primary study objective is to demonstrate prevention of venous thromboembolism in patients undergoing total hip replacement surgery. The secondary objective is to assess the safety and tolerability of DU-176.
Interventions
DRUGDU-176b
Sponsors
Daiichi Sankyo
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Unilateral hip replacement
Exclusion criteria
* Patients scheduled for bilateral hip replacement in same procedure * Patients with increased risk of bleeding * Uncontrolled hypertension (BP greater than 180/100 mmHg) * Patients less than 111 lbs or more than 243 lbs * Patients on long-term anticoagulants * Patients with contraindications to venography * Patients with medical history of venous thromboembolism * Patients with impaired hepatic function * Known to be pregnant * Lactating women
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Prevention of Venous Thromboembolism (VTE) | 2 weeks | The primary efficacy endpoint was the proportion of subjects who experienced at least one of the thromboembolic events listed below during the period from the start of study treatment to the venography at the end of study treatment (approximately 2 weeks post surgery). Confirmed deep vein thrombosis ( both proximal and distal ) as assessed by unilateral or bilateral ascending contrast venograms 7 to 10 days following surgery Symptomatic and objectively proven Pulmonary Embolism (PE) prior to venography Symptomatic and objectively proven Deep Vein Thrombosis (DVT) prior to venography |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline for Prothrombin Time (PT) Results | end of treatment | Intent to Treat (ITT) population |
| Change From Baseline for International Normalized Ratio (INR) Results | end of treatment | Intent to Treat (ITT) population |
| Change From Baseline for Activated Partial Thromboplastin Time (aPTT) Results | end of treatment | Intent to Treat (ITT) population |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 15mg BID 15mg edoxaban administered twice daily (BID) | 85 |
| 30mg QD 30mg edoxaban administered once daily (QD) | 75 |
| 30mg BID 30mg edoxaban administered twice daily (BID) | 129 |
| 60mg QD 60mg edoxaban administered once daily (QD) | 99 |
| 60mg BID 60mg edoxaban administered twice daily (BID) | 115 |
| 120mg QD 120mg edoxaban administered once daily (QD) | 103 |
| Total | 606 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Administrative Reasons | 1 | 0 | 2 | 2 | 2 | 0 |
| Overall Study | Adverse Event | 3 | 2 | 10 | 3 | 5 | 3 |
| Overall Study | Death | 0 | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Lost to Follow-up | 4 | 1 | 3 | 2 | 5 | 5 |
| Overall Study | Protocol Violation | 1 | 0 | 5 | 5 | 7 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 5 | 0 | 1 | 1 |
Baseline characteristics
| Characteristic | 15mg BID | 30mg QD | 30mg BID | 60mg QD | 60mg BID | 120mg QD | Total |
|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 25 Participants | 27 Participants | 56 Participants | 34 Participants | 37 Participants | 31 Participants | 210 Participants |
| Age, Categorical Between 18 and 65 years | 60 Participants | 48 Participants | 73 Participants | 65 Participants | 78 Participants | 72 Participants | 396 Participants |
| Age, Continuous | 57.6 years STANDARD_DEVIATION 10.71 | 59.0 years STANDARD_DEVIATION 11.06 | 60.1 years STANDARD_DEVIATION 13.09 | 58.6 years STANDARD_DEVIATION 11.9 | 58.8 years STANDARD_DEVIATION 12.8 | 56.5 years STANDARD_DEVIATION 12.83 | 58.5 years STANDARD_DEVIATION 12.25 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 6 Participants | 2 Participants | 4 Participants | 0 Participants | 12 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 20 Participants | 11 Participants | 83 Participants | 22 Participants | 31 Participants | 27 Participants | 194 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 65 Participants | 64 Participants | 40 Participants | 75 Participants | 80 Participants | 76 Participants | 400 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 12 Participants | 0 Participants | 3 Participants | 3 Participants | 19 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 2 Participants | 1 Participants | 4 Participants | 0 Participants | 7 Participants |
| Race (NIH/OMB) White | 84 Participants | 75 Participants | 115 Participants | 97 Participants | 108 Participants | 99 Participants | 578 Participants |
| Region of Enrollment Europe | 65 participants | 64 participants | 40 participants | 75 participants | 80 participants | 76 participants | 400 participants |
| Region of Enrollment United States | 20 participants | 11 participants | 89 participants | 24 participants | 35 participants | 27 participants | 206 participants |
| Sex: Female, Male Female | 44 Participants | 48 Participants | 71 Participants | 62 Participants | 69 Participants | 56 Participants | 350 Participants |
| Sex: Female, Male Male | 41 Participants | 27 Participants | 58 Participants | 37 Participants | 46 Participants | 47 Participants | 256 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 24 / 85 | 19 / 75 | 65 / 129 | 56 / 99 | 66 / 115 | 34 / 103 |
| serious Total, serious adverse events | 4 / 85 | 3 / 75 | 9 / 129 | 10 / 99 | 10 / 115 | 4 / 103 |
Outcome results
Primary
Prevention of Venous Thromboembolism (VTE)
The primary efficacy endpoint was the proportion of subjects who experienced at least one of the thromboembolic events listed below during the period from the start of study treatment to the venography at the end of study treatment (approximately 2 weeks post surgery). Confirmed deep vein thrombosis ( both proximal and distal ) as assessed by unilateral or bilateral ascending contrast venograms 7 to 10 days following surgery Symptomatic and objectively proven Pulmonary Embolism (PE) prior to venography Symptomatic and objectively proven Deep Vein Thrombosis (DVT) prior to venography
Time frame: 2 weeks
Population: modified ITT population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 15mg BID | Prevention of Venous Thromboembolism (VTE) | 13 percentage of patients with event |
| 30mg QD | Prevention of Venous Thromboembolism (VTE) | 13 percentage of patients with event |
| 30mg BID | Prevention of Venous Thromboembolism (VTE) | 10 percentage of patients with event |
| 60mg QD | Prevention of Venous Thromboembolism (VTE) | 13 percentage of patients with event |
| 60mg BID | Prevention of Venous Thromboembolism (VTE) | 16 percentage of patients with event |
| 120mg QD | Prevention of Venous Thromboembolism (VTE) | 17 percentage of patients with event |
p-value: 0.238Fisher Exact
Secondary
Change From Baseline for Activated Partial Thromboplastin Time (aPTT) Results
Intent to Treat (ITT) population
Time frame: end of treatment
Population: ITT population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 15mg BID | Change From Baseline for Activated Partial Thromboplastin Time (aPTT) Results | -5.1 seconds | Standard Deviation 22 |
| 30mg QD | Change From Baseline for Activated Partial Thromboplastin Time (aPTT) Results | -1.6 seconds | Standard Deviation 25.3 |
| 30mg BID | Change From Baseline for Activated Partial Thromboplastin Time (aPTT) Results | 2.5 seconds | Standard Deviation 9.8 |
| 60mg QD | Change From Baseline for Activated Partial Thromboplastin Time (aPTT) Results | 4.1 seconds | Standard Deviation 17 |
| 60mg BID | Change From Baseline for Activated Partial Thromboplastin Time (aPTT) Results | 5.8 seconds | Standard Deviation 16.1 |
| 120mg QD | Change From Baseline for Activated Partial Thromboplastin Time (aPTT) Results | 11.3 seconds | Standard Deviation 23.1 |
Secondary
Change From Baseline for International Normalized Ratio (INR) Results
Intent to Treat (ITT) population
Time frame: end of treatment
Population: ITT population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 15mg BID | Change From Baseline for International Normalized Ratio (INR) Results | 0 INR ratio | Standard Deviation 0.2 |
| 30mg QD | Change From Baseline for International Normalized Ratio (INR) Results | 0 INR ratio | Standard Deviation 0.3 |
| 30mg BID | Change From Baseline for International Normalized Ratio (INR) Results | .1 INR ratio | Standard Deviation 0.1 |
| 60mg QD | Change From Baseline for International Normalized Ratio (INR) Results | .1 INR ratio | Standard Deviation 0.2 |
| 60mg BID | Change From Baseline for International Normalized Ratio (INR) Results | .1 INR ratio | Standard Deviation 0.2 |
| 120mg QD | Change From Baseline for International Normalized Ratio (INR) Results | .2 INR ratio | Standard Deviation 0.4 |
Secondary
Change From Baseline for Prothrombin Time (PT) Results
Intent to Treat (ITT) population
Time frame: end of treatment
Population: ITT population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 15mg BID | Change From Baseline for Prothrombin Time (PT) Results | -.2 seconds | Standard Deviation 2.3 |
| 30mg QD | Change From Baseline for Prothrombin Time (PT) Results | -.1 seconds | Standard Deviation 2.7 |
| 30mg BID | Change From Baseline for Prothrombin Time (PT) Results | .7 seconds | Standard Deviation 1.3 |
| 60mg QD | Change From Baseline for Prothrombin Time (PT) Results | .8 seconds | Standard Deviation 2 |
| 60mg BID | Change From Baseline for Prothrombin Time (PT) Results | 1.1 seconds | Standard Deviation 1.9 |
| 120mg QD | Change From Baseline for Prothrombin Time (PT) Results | 1.8 seconds | Standard Deviation 4.3 |