Venous Thromboembolism
Conditions
Keywords
anticoagulant, venus thromboembolism, thrombosis, thromboembolism, embolism and thrombosis, deep vein thrombosis, DU-176b, Edoxaban, factor Xa, total knee arthroplasty, Enoxaparin sodium
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 knee 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 knee 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 Deep Vein Thrombosis (DVT) confirmed by unilateral venography at the end of study treatment * Definite diagnosis of symptomatic Pulmonary Embolism (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 venous Thromboembolism (VTE) |
Secondary
| Measure | Time frame |
|---|---|
| Incidence of Major Bleeding or Clinically Relevant Non-major Bleeding. | 2 weeks |
Countries
Japan, Taiwan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| DU-176b DU-176b oral tablets, 30 mg., taken once daily for 2 weeks
edoxaban | 299 |
| Enoxaparin Sodium enoxaparin sodium 20mg(=2000IU)/0.2ml twice daily, subcutaneous injection for 2 weeks
enoxaparin sodium | 295 |
| Total | 594 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 28 | 26 |
| Overall Study | Lack of Efficacy | 3 | 1 |
| Overall Study | Lost to Follow-up | 2 | 0 |
| Overall Study | Physician Decision | 3 | 1 |
| Overall Study | Protocol Violation | 5 | 6 |
| Overall Study | Withdrawal by Subject | 10 | 12 |
Baseline characteristics
| Characteristic | DU-176b | Enoxaparin Sodium | Total |
|---|---|---|---|
| Age, Continuous | 72.6 years STANDARD_DEVIATION 7.5 | 72.1 years STANDARD_DEVIATION 7.8 | 72.4 years STANDARD_DEVIATION 7.6 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 299 Participants | 295 Participants | 594 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 | 273 participants | 270 participants | 543 participants |
| Region of Enrollment Taiwan | 26 participants | 25 participants | 51 participants |
| Sex: Female, Male Female | 245 Participants | 229 Participants | 474 Participants |
| Sex: Female, Male Male | 54 Participants | 66 Participants | 120 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 237 / 354 | 256 / 349 |
| serious Total, serious adverse events | 10 / 354 | 11 / 349 |
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 Deep Vein Thrombosis (DVT) confirmed by unilateral venography at the end of study treatment * Definite diagnosis of symptomatic Pulmonary Embolism (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 venous Thromboembolism (VTE)
Time frame: 2 weeks
Population: Efficacy Analysis population. 22 (7.4%) - DU-176b 41 (13.9%) - enoxaparin
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| DU-176b | Incidence of Subjects With Venous Thromboembolism Events. | 7.4 percent of participants with VTE events |
| Enoxaparin Sodium | Incidence of Subjects With Venous Thromboembolism Events. | 13.9 percent of participants with VTE events |
Comparison: The incidence proportion of thromboembolic events in the DU-176b group (P˅DU) = The incidence proportion of thromboembolic events in the enoxaparin group (P˅E) + Δ (5%). Alternative hypothesis H˅11: P˅DU \< P˅E + Δ (level of significance, 0.025; one-sided). If the null hypothesis H˅01 was rejected, the following analysis had to be sequentially performed using the χ2 test statistic. Null hypothesis H˅02: P˅DU = P˅E Alternative hypothesis H˅12: P˅DU ≠ P˅E (level of significance, 0.05; two-sided).p-value: <0.00195% CI: [-11.5, -1.6]non-inferiority:Z test. superiority:χ2 t
Secondary
Incidence of Major Bleeding or Clinically Relevant Non-major Bleeding.
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 | Incidence of Major Bleeding or Clinically Relevant Non-major Bleeding. | 6.2 percentage of subjects with bleeds |
| Enoxaparin Sodium | Incidence of Major Bleeding or Clinically Relevant Non-major Bleeding. | 3.7 percentage of subjects with bleeds |
95% CI: [-0.8, 5.9]