Deep Vein Thrombosis, Total Knee Arthroplasty, Venous Thromboembolism
Conditions
Keywords
prevention, venous thromboembolism, edoxaban, factor Xa
Brief summary
The objective of this study is to assess the efficacy, safety and dose-response relationship of DU-176b compared with placebo for the prevention of venous thromboembolism in patients after elective total knee arthroplasty.
Interventions
DRUGDU-176b
DU-176b 5mg tablets oral, once daily for 2 weeks
DRUGPlacebo
Matching placebo oral tablets, once daily for 2 weeks
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
* risks of hemorrhage * thromboembolic risks * weight less than 40 kg * pregnant, suspect pregnancy, or subjects who want to become pregnant
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion 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 | Description |
|---|---|---|
| Incidence of Major Bleeding or Clinically Relevant Non-major Bleeding | 2 weeks | Incidence of Major Bleeding or Clinically Relevant Non-major Bleeding. Related to the study drug |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| DU-176b 5 mg DU-176b: DU-176b 5mg tablets oral, once daily for 2 weeks | 88 |
| DU-176b 15 mg DU-176b: DU-176b 15mg tablets, oral once daily for 2 weeks | 92 |
| DU-176b 30 mg DU-176b: DU-176b 30 mg tablets, oral, once daily for 2 weeks | 88 |
| DU-176b 60 mg DU-176b: DU-176b 60 mg tablets, oral, once daily for 2 weeks | 88 |
| Placebo Placebo: Matching placebo oral tablets, once daily for 2 weeks | 89 |
| Total | 445 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 5 | 3 | 2 | 4 | 2 |
| Overall Study | Lack of Efficacy | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Lost to Follow-up | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Protocol Violation | 2 | 0 | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 2 | 2 | 1 | 2 | 3 |
Baseline characteristics
| Characteristic | DU-176b 5 mg | Total | Placebo | DU-176b 60 mg | DU-176b 30 mg | DU-176b 15 mg |
|---|---|---|---|---|---|---|
| Age, Continuous | 70.2 years STANDARD_DEVIATION 7.7 | 71.2 years STANDARD_DEVIATION 7.3 | 70.3 years STANDARD_DEVIATION 6.5 | 72.1 years STANDARD_DEVIATION 7 | 71.6 years STANDARD_DEVIATION 8.1 | 71.7 years STANDARD_DEVIATION 7 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 88 Participants | 445 Participants | 89 Participants | 88 Participants | 88 Participants | 92 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 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 |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment Japan | 88 participants | 445 participants | 89 participants | 88 participants | 88 participants | 92 participants |
| Sex: Female, Male Female | 67 Participants | 347 Participants | 68 Participants | 69 Participants | 69 Participants | 74 Participants |
| Sex: Female, Male Male | 21 Participants | 98 Participants | 21 Participants | 19 Participants | 19 Participants | 18 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 |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 78 / 103 | 85 / 106 | 78 / 103 | 78 / 106 | 67 / 102 |
| serious Total, serious adverse events | 2 / 103 | 1 / 106 | 1 / 103 | 3 / 106 | 5 / 102 |
Outcome results
Primary
Proportion 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 5 mg | Proportion of Subjects With Venous Thromboembolism Events. | 29.5 percentage of participants |
| DU-176b 15 mg | Proportion of Subjects With Venous Thromboembolism Events. | 26.1 percentage of participants |
| DU-176b 30 mg | Proportion of Subjects With Venous Thromboembolism Events. | 12.5 percentage of participants |
| DU-176b 60 mg | Proportion of Subjects With Venous Thromboembolism Events. | 9.1 percentage of participants |
| Placebo | Proportion of Subjects With Venous Thromboembolism Events. | 48.3 percentage of participants |
Comparison: As the primary analysis, the dose-response relationship in the incidence of thromboembolic event was verified using the Cochran-Armitage test.p-value: <0.001Cochran-Armitage
Secondary
Incidence of Major Bleeding or Clinically Relevant Non-major Bleeding
Incidence of Major Bleeding or Clinically Relevant Non-major Bleeding. Related to the study drug
Time frame: 2 weeks
Population: Safety Analysis Set is defined as subjects secondarily enrolled in study, but excluded those with significant GCP violations, did not receive any doses of study drug, or had no safety data after start of study treatment. Subjects with significant GCP violations, but received at least one dose of study drug, safety data were assessed individually
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| DU-176b 5 mg | Incidence of Major Bleeding or Clinically Relevant Non-major Bleeding | 1.9 percentage of subjects with bleeds |
| DU-176b 15 mg | Incidence of Major Bleeding or Clinically Relevant Non-major Bleeding | 3.8 percentage of subjects with bleeds |
| DU-176b 30 mg | Incidence of Major Bleeding or Clinically Relevant Non-major Bleeding | 3.9 percentage of subjects with bleeds |
| DU-176b 60 mg | Incidence of Major Bleeding or Clinically Relevant Non-major Bleeding | 4.7 percentage of subjects with bleeds |
| Placebo | Incidence of Major Bleeding or Clinically Relevant Non-major Bleeding | 3.9 percentage of subjects with bleeds |