Hip Replacement, Thrombosis
Conditions
Keywords
Anti-coagulant, hip replacement, hip replacement surgery, unilateral hip replacement surgery, DeepVein Thrombosis, Venous Thromboembolism, pulmonary embolism, Prevention of Blood Clots
Brief summary
This study is to assess if DU176b is effective in prevention of blood clots following hip replacement surgery. The duration is 7-10 days of treatment and 30 and 60 day follow-up visits.
Interventions
DRUGDU176b - action is the prevention of venous thromboembolism by the use of a Factor Xa inhibitor
Sponsors
Daiichi Sankyo
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. 18 years of age or older; male or female. 2. Able to provide written informed consent. 3. Must be scheduled for elective unilateral total hip replacement surgery. Only primary surgeries accepted. 4. If female, must be either one year post-menopausal, surgically sterile, or using medically accepted contraceptive measures as judged by the Investigator and in accordance with local regulatory requirements.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adjudicated Incidence of VTE | end of treatment | Assess the efficacy of DU-176b in the prevention of venous thromboembolism (VTE) from 6 to 8 hours after hip replacement surgery to 7 to 10 days after the surgery. A subject was judged to have a VTE if one or more of the following criteria were met: * Observed lower extremity deep vein thrombosis (DVT) (either proximal, distal, or both ) as assessed by bilateral or unilateral ascending contrast venography prior to or at the end-of-treatment (EOT) visit * Symptomatic and objectively proven pulmonary embolism prior to or at the EOT visit * Symptomatic and objectively proven DVT prior to or at EOT visit end of treatment defined as 6 to 8 hours after after hip replacement surgery to 7 to 10 days after the surgery. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Prothrombin Time (PT) From Baseline | end of treatment | change in prothrombin time (PT) from baseline to end of treatment end of treatment defined as 6-8 hours after hip replacement surgery to 7 to 10 days after the surgery |
| Change in Activated Partial Thromboplastin Time (aPTT) From Baseline | end of treatment | change in Activated Partial Thromboplastin Time (aPTT) from baseline to end of treatment end of treatment defined as 6-8 hours after hip replacement surgery to 7 to 10 days after the surgery |
| Adjudicated Incidence of Major or Clinically Relevant Non-major Bleeding Events | 10 days after first dose | adjudicated incidence of major or clinically relevant non-major bleeding events through 10 days after first dose |
Countries
Canada, Denmark, Hungary, Latvia, Russia, Ukraine, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Edoxaban 15mg QD edoxaban 15mg QD (once daily) orally (PO) | 192 |
| Edoxaban 30mg QD edoxaban 30mg QD PO | 170 |
| Edoxaban 60mg QD edoxaban 60mg QD PO | 185 |
| Edoxaban 90mg QD edoxaban 90mg QD PO | 177 |
| Dalteparin dalteparin 2500 IU/mL initial dose followed by 5000 IU once daily subcutaneously | 172 |
| Total | 896 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | administrative reasons | 3 | 4 | 4 | 3 | 3 |
| Overall Study | Adverse Event | 4 | 2 | 5 | 7 | 2 |
| Overall Study | Death | 0 | 3 | 0 | 0 | 0 |
| Overall Study | entrance criteria | 0 | 0 | 0 | 0 | 2 |
| Overall Study | Lost to Follow-up | 1 | 6 | 4 | 4 | 1 |
| Overall Study | Protocol Violation | 2 | 4 | 5 | 7 | 5 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 3 | 1 | 2 |
Baseline characteristics
| Characteristic | Edoxaban 15mg QD | Edoxaban 30mg QD | Edoxaban 60mg QD | Edoxaban 90mg QD | Dalteparin | Total |
|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 66 Participants | 59 Participants | 59 Participants | 63 Participants | 62 Participants | 309 Participants |
| Age, Categorical Between 18 and 65 years | 126 Participants | 111 Participants | 126 Participants | 114 Participants | 110 Participants | 587 Participants |
| Age, Continuous | 57.3 years STANDARD_DEVIATION 12.49 | 57.2 years STANDARD_DEVIATION 12.28 | 58.3 years STANDARD_DEVIATION 11.52 | 58.5 years STANDARD_DEVIATION 12.27 | 57.5 years STANDARD_DEVIATION 12.43 | 57.8 years STANDARD_DEVIATION 12.13 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 3 Participants | 1 Participants | 4 Participants | 10 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 | 2 Participants | 1 Participants | 3 Participants | 0 Participants | 3 Participants | 9 Participants |
| Race (NIH/OMB) White | 188 Participants | 167 Participants | 178 Participants | 176 Participants | 165 Participants | 874 Participants |
| Region of Enrollment Europe | 159 participants | 150 participants | 152 participants | 144 participants | 143 participants | 748 participants |
| Region of Enrollment North America | 33 participants | 20 participants | 33 participants | 33 participants | 29 participants | 148 participants |
| Sex: Female, Male Female | 113 Participants | 111 Participants | 118 Participants | 93 Participants | 105 Participants | 540 Participants |
| Sex: Female, Male Male | 79 Participants | 59 Participants | 67 Participants | 84 Participants | 67 Participants | 356 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 | 30 / 192 | 16 / 170 | 22 / 185 | 25 / 177 | 22 / 172 |
| serious Total, serious adverse events | 8 / 192 | 6 / 170 | 8 / 185 | 10 / 177 | 3 / 172 |
Outcome results
Primary
Adjudicated Incidence of VTE
Assess the efficacy of DU-176b in the prevention of venous thromboembolism (VTE) from 6 to 8 hours after hip replacement surgery to 7 to 10 days after the surgery. A subject was judged to have a VTE if one or more of the following criteria were met: * Observed lower extremity deep vein thrombosis (DVT) (either proximal, distal, or both ) as assessed by bilateral or unilateral ascending contrast venography prior to or at the end-of-treatment (EOT) visit * Symptomatic and objectively proven pulmonary embolism prior to or at the EOT visit * Symptomatic and objectively proven DVT prior to or at EOT visit end of treatment defined as 6 to 8 hours after after hip replacement surgery to 7 to 10 days after the surgery.
Time frame: end of treatment
Population: per protocol analysis set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Edoxaban 15mg QD | Adjudicated Incidence of VTE | 29.0 percentage of participants with VTE |
| Edoxaban 30mg QD | Adjudicated Incidence of VTE | 20.3 percentage of participants with VTE |
| Edoxaban 60mg QD | Adjudicated Incidence of VTE | 15.7 percentage of participants with VTE |
| Edoxaban 90mg QD | Adjudicated Incidence of VTE | 11.5 percentage of participants with VTE |
| Dalteparin | Adjudicated Incidence of VTE | 46.0 percentage of participants with VTE |
p-value: 0.003Fisher Exact
p-value: <0.001Fisher Exact
p-value: <0.001Fisher Exact
p-value: <0.001Fisher Exact
Secondary
Adjudicated Incidence of Major or Clinically Relevant Non-major Bleeding Events
adjudicated incidence of major or clinically relevant non-major bleeding events through 10 days after first dose
Time frame: 10 days after first dose
Population: safety analysis dataset
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Edoxaban 15mg QD | Adjudicated Incidence of Major or Clinically Relevant Non-major Bleeding Events | 1.6 percentage of subjects with bleed events |
| Edoxaban 30mg QD | Adjudicated Incidence of Major or Clinically Relevant Non-major Bleeding Events | 1.8 percentage of subjects with bleed events |
| Edoxaban 60mg QD | Adjudicated Incidence of Major or Clinically Relevant Non-major Bleeding Events | 2.2 percentage of subjects with bleed events |
| Edoxaban 90mg QD | Adjudicated Incidence of Major or Clinically Relevant Non-major Bleeding Events | 2.3 percentage of subjects with bleed events |
| Dalteparin | Adjudicated Incidence of Major or Clinically Relevant Non-major Bleeding Events | 0 percentage of subjects with bleed events |
p-value: 0.25Fisher Exact
p-value: 0.122Fisher Exact
p-value: 0.124Fisher Exact
p-value: 0.123Fisher Exact
Secondary
Change in Activated Partial Thromboplastin Time (aPTT) From Baseline
change in Activated Partial Thromboplastin Time (aPTT) from baseline to end of treatment end of treatment defined as 6-8 hours after hip replacement surgery to 7 to 10 days after the surgery
Time frame: end of treatment
Population: perp protocol analysis set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Edoxaban 15mg QD | Change in Activated Partial Thromboplastin Time (aPTT) From Baseline | -0.33 seconds | Standard Deviation 6.562 |
| Edoxaban 30mg QD | Change in Activated Partial Thromboplastin Time (aPTT) From Baseline | 1.67 seconds | Standard Deviation 13.092 |
| Edoxaban 60mg QD | Change in Activated Partial Thromboplastin Time (aPTT) From Baseline | 4.39 seconds | Standard Deviation 16.93 |
| Edoxaban 90mg QD | Change in Activated Partial Thromboplastin Time (aPTT) From Baseline | 3.26 seconds | Standard Deviation 13.169 |
| Dalteparin | Change in Activated Partial Thromboplastin Time (aPTT) From Baseline | 2.34 seconds | Standard Deviation 12.396 |
Secondary
Change in Prothrombin Time (PT) From Baseline
change in prothrombin time (PT) from baseline to end of treatment end of treatment defined as 6-8 hours after hip replacement surgery to 7 to 10 days after the surgery
Time frame: end of treatment
Population: perp protocol analysis set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Edoxaban 15mg QD | Change in Prothrombin Time (PT) From Baseline | .90 seconds | Standard Deviation 3.205 |
| Edoxaban 30mg QD | Change in Prothrombin Time (PT) From Baseline | 1.07 seconds | Standard Deviation 1.875 |
| Edoxaban 60mg QD | Change in Prothrombin Time (PT) From Baseline | 2.87 seconds | Standard Deviation 6.279 |
| Edoxaban 90mg QD | Change in Prothrombin Time (PT) From Baseline | 2.74 seconds | Standard Deviation 5.821 |
| Dalteparin | Change in Prothrombin Time (PT) From Baseline | .67 seconds | Standard Deviation 1.88 |