Arthroplasty, Replacement, Hip, Deep Vein Thrombosis, Embolism and Thrombosis, Thromboembolism, Thrombosis, Venous Thromboembolism
Conditions
Keywords
prevention, venous thromboembolism, edoxaban, anticoagulants
Brief summary
The objective of this study is to compare the efficacy, safety of DU-176b 30mg or DU-176b 15mg versus enoxaparin sodium for the prevention of venous thromboembolism in patients after elective total hip arthroplasty.
Interventions
DRUGDU-176b 15mg
DU-176b 15 mg tablets oral, once daily for 2 weeks initiated within 6 to 24 hours after surgery.
DRUGDU-176b 30mg
DU-176b 30 mg tablets, oral once daily for 2 weeks initiated within 6 to 24 hours after surgery.
DRUGEnoxaparin sodium 20 mg (=2000IU)
Enoxaparin sodium 20 mg (=2000IU) / 0.2ml twice daily, subcutaneous injection for 2 weeks initiated within 24 to 36 hours after surgery.
Sponsors
Daiichi Sankyo Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
20 Years to 84 Years
Healthy volunteers
No
Inclusion criteria
1. Patients undergoing unilateral total hip arthroplasty 2. Patients who are 20-84 years olds
Exclusion criteria
1. Subjects with risks of hemorrhage 2. Subjects with thromboembolic risks 3. Subjects who weigh less than 40 kg 4. Subjects who are pregnant or suspect pregnancy, or subjects who want to become pregnant
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects With Venous Thromboembolism Events | 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. * Lower extremity DVT confirmed by bilateral venography at the end of study treatment * Definite diagnosis of symptomatic PE * Symptomatic DVT confirmed before the venography at the end of study treatment The objectives were to verify the non-inferiority of edoxaban to enoxaparin with regard to prevention of VTE |
Secondary
| Measure | Time frame |
|---|---|
| Incidence of Major Bleeding or Clinically Relevant Non-major Bleedings. | 2 weeks |
Countries
Japan, Taiwan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| DU-176b 15 mg DU-176b 15 mg tablets, oral once daily for 2 weeks | 78 |
| DU-176b 30 mg DU-176b 30 mg tablets oral, once daily for 2 weeks | 72 |
| Enoxaparin Sodium 20mg (2000IU) Enoxaparin sodium 20 mg (=2000IU) / 0.2ml twice daily, subcutaneous injection for 2 weeks | 74 |
| Total | 224 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 3 | 1 | 7 |
| Overall Study | Lost to Follow-up | 0 | 0 | 1 |
| Overall Study | Physician Decision | 2 | 2 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 1 | 3 |
Baseline characteristics
| Characteristic | DU-176b 15 mg | DU-176b 30 mg | Enoxaparin Sodium 20mg (2000IU) | Total |
|---|---|---|---|---|
| Age, Continuous | 61.3 years STANDARD_DEVIATION 10.3 | 60.6 years STANDARD_DEVIATION 9.6 | 58.9 years STANDARD_DEVIATION 10.7 | 60.3 years STANDARD_DEVIATION 10.2 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 78 Participants | 72 Participants | 74 Participants | 224 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 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 |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment Japan | 75 participants | 70 participants | 70 participants | 215 participants |
| Region of Enrollment Taiwan | 3 participants | 2 participants | 4 participants | 9 participants |
| Sex: Female, Male Female | 63 Participants | 69 Participants | 59 Participants | 191 Participants |
| Sex: Female, Male Male | 15 Participants | 3 Participants | 15 Participants | 33 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 58 / 89 | 60 / 85 | 72 / 87 |
| serious Total, serious adverse events | 1 / 89 | 2 / 85 | 1 / 87 |
Outcome results
Primary
Percentage of Subjects With Venous Thromboembolism Events
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. * Lower extremity DVT confirmed by bilateral venography at the end of study treatment * Definite diagnosis of symptomatic PE * Symptomatic DVT confirmed before the venography at the end of study treatment The objectives were to verify the non-inferiority of edoxaban to enoxaparin with regard to prevention of VTE
Time frame: 2 weeks
Population: The FAS was defined as all subjects enrolled in the study, but excluded those who had significant GCP violations, who had not received any doses of the study drug, or those who did not develop symptomatic DVT or PE, but in whom venography was not appropriately performed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| DU-176b 15 mg | Percentage of Subjects With Venous Thromboembolism Events | 3.8 percent of participants with VTE event |
| DU-176b 30 mg | Percentage of Subjects With Venous Thromboembolism Events | 2.8 percent of participants with VTE event |
| Enoxaparin Sodium 20mg (2000IU) | Percentage of Subjects With Venous Thromboembolism Events | 4.1 percent of participants with VTE event |
Comparison: Primary analyses were performed on proportion of subjects who experienced thromboembolic events defined as primary efficacy endpoint (incidence of thromboembolic events); incidence of thromboembolic events and its 95% confidence interval (CI) were calculated by treatment group, and difference between DU-176b 15 mg and 30 mg groups and its 95% CI were also calculated. For reference, difference between enoxaparin group and each DU-176b group and its 95% CI of each were calculated.95% CI: [-7.2, 4.6]
Comparison: Primary analyses were performed on proportion of subjects who experienced thromboembolic events defined as primary efficacy endpoint (incidence of thromboembolic events); incidence of thromboembolic events and its 95% confidence interval (CI) were calculated by treatment group, and difference between DU-176b 15 mg and 30 mg groups and its 95% CI were also calculated. For reference, difference between enoxaparin group and each DU-176b group and its 95% CI of each were calculated.95% CI: [-4.6, 6.8]
Secondary
Incidence of Major Bleeding or Clinically Relevant Non-major Bleedings.
Time frame: 2 weeks
Population: The Safety Analysis Set was defined as all subjects who were enrolled in the study, but excluded those who had significant GCP violations, who did not receive any doses of the study drug, or who had no safety data after the start of study treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| DU-176b 15 mg | Incidence of Major Bleeding or Clinically Relevant Non-major Bleedings. | 2.2 percentage of subjects with bleeds |
| DU-176b 30 mg | Incidence of Major Bleeding or Clinically Relevant Non-major Bleedings. | 1.2 percentage of subjects with bleeds |
| Enoxaparin Sodium 20mg (2000IU) | Incidence of Major Bleeding or Clinically Relevant Non-major Bleedings. | 2.3 percentage of subjects with bleeds |