Prevention, Venous Thromboembolism
Conditions
Keywords
Anticoagulants, Venous thromboembolism, Thromboembolism, Thrombosis, enoxaparin sodium, Embolism, Deep vein thrombosis, DU-176b, edoxaban, factor Xa, total hip arthroplasty
Brief summary
The objective of this study is to assess the efficacy and safety of DU-176b compared with enoxaparin sodium for the prevention of venous thromboembolism in patients after elective total hip arthroplasty.
Interventions
DRUGedoxaban
DRUGenoxaparin sodium
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
* Patients undergoing unilateral total hip arthroplasty
Exclusion criteria
* Subjects with risks of hemorrhage * Subjects with thromboembolic risks * Subjects who weigh less than 40 kg * Subjects who are pregnant or suspect pregnancy, or subjects who want to become pregnant
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence 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 Bleeding | 2 weeks |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| DU-176b DU-176b oral tablets, 30 mg., taken once daily for 2 weeks
edoxaban | 255 |
| Enoxaparin Sodium enoxaparin sodium 20mg(=2000IU)/0.2ml twice daily, subcutaneous injection for 2 weeks
enoxaparin sodium | 248 |
| Total | 503 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 11 | 21 |
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Physician Decision | 2 | 3 |
| Overall Study | Protocol Violation | 3 | 0 |
| Overall Study | Withdrawal by Subject | 6 | 8 |
Baseline characteristics
| Characteristic | DU-176b | Total | Enoxaparin Sodium |
|---|---|---|---|
| Age, Continuous | 62.8 years STANDARD_DEVIATION 9.61 | 62.8 years STANDARD_DEVIATION 9.65 | 62.8 years STANDARD_DEVIATION 9.72 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 255 Participants | 503 Participants | 248 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment Japan | 255 participants | 503 participants | 248 participants |
| Sex: Female, Male Female | 220 Participants | 432 Participants | 212 Participants |
| Sex: Female, Male Male | 35 Participants | 71 Participants | 36 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 197 / 303 | 232 / 301 |
| serious Total, serious adverse events | 9 / 303 | 9 / 301 |
Outcome results
Primary
Incidence 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 | Incidence of Subjects With Venous Thromboembolism Events | 2.4 percentage of subjects with vte events |
| Enoxaparin Sodium | Incidence of Subjects With Venous Thromboembolism Events | 6.9 percentage of subjects with vte events |
Comparison: Hypothesis testing of proportion of subjects who experienced at least one thromboembolic events, defined as primary endpoint, carried out using Farrington-Manning method. Null hypothesis H˅01: Incidence of thromboembolic events in DU-176b group (P˅DU) = Incidence of thromboembolic events in enoxaparin group (P˅E) + Δ (8%). Alternative hypothesis H˅11: P˅DU \< P˅E + Δ (significance level: One-sided, 0.025)p-value: <0.001ANCOVA
Secondary
Incidence of Major Bleeding or Clinically Relevant Non-major Bleeding
Time frame: 2 weeks
Population: Safety analyses were performed for the Safety Analysis Set, which was defined as all subjects who were secondarily enrolled in the study, but excluded those who had significant GCP violations, who had not received any doses of the study drug, or who had no safety data after the start of study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| DU-176b | Incidence of Major Bleeding or Clinically Relevant Non-major Bleeding | 2.6 percentage of subjects with bleeds |
| Enoxaparin Sodium | Incidence of Major Bleeding or Clinically Relevant Non-major Bleeding | 3.7 percentage of subjects with bleeds |