Trial Outcomes & Findings for A Study of DU-176b in Preventing Blood Clots After Hip Replacement Surgery (NCT NCT00398216)
NCT ID: NCT00398216
Last Updated: 2019-02-26
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
903 participants
Primary outcome timeframe
end of treatment
Results posted on
2019-02-26
Participant Flow
Participant milestones
| Measure |
Edoxaban 15mg QD
edoxaban 15mg QD (once daily) orally (PO)
|
Edoxaban 30mg QD
edoxaban 30mg QD PO
|
Edoxaban 60mg QD
edoxaban 60mg QD PO
|
Edoxaban 90mg QD
edoxaban 90mg QD PO
|
Dalteparin
dalteparin 2500 IU/mL initial dose followed by 5000 IU once daily subcutaneously
|
|---|---|---|---|---|---|
|
Overall Study
STARTED
|
192
|
170
|
185
|
177
|
172
|
|
Overall Study
COMPLETED
|
181
|
151
|
164
|
155
|
157
|
|
Overall Study
NOT COMPLETED
|
11
|
19
|
21
|
22
|
15
|
Reasons for withdrawal
| Measure |
Edoxaban 15mg QD
edoxaban 15mg QD (once daily) orally (PO)
|
Edoxaban 30mg QD
edoxaban 30mg QD PO
|
Edoxaban 60mg QD
edoxaban 60mg QD PO
|
Edoxaban 90mg QD
edoxaban 90mg QD PO
|
Dalteparin
dalteparin 2500 IU/mL initial dose followed by 5000 IU once daily subcutaneously
|
|---|---|---|---|---|---|
|
Overall Study
Adverse Event
|
4
|
2
|
5
|
7
|
2
|
|
Overall Study
Protocol Violation
|
2
|
4
|
5
|
7
|
5
|
|
Overall Study
Lost to Follow-up
|
1
|
6
|
4
|
4
|
1
|
|
Overall Study
Death
|
0
|
3
|
0
|
0
|
0
|
|
Overall Study
Withdrawal by Subject
|
1
|
0
|
3
|
1
|
2
|
|
Overall Study
administrative reasons
|
3
|
4
|
4
|
3
|
3
|
|
Overall Study
entrance criteria
|
0
|
0
|
0
|
0
|
2
|
Baseline Characteristics
A Study of DU-176b in Preventing Blood Clots After Hip Replacement Surgery
Baseline characteristics by cohort
| Measure |
Edoxaban 15mg QD
n=192 Participants
edoxaban 15mg QD (once daily) orally (PO)
|
Edoxaban 30mg QD
n=170 Participants
edoxaban 30mg QD PO
|
Edoxaban 60mg QD
n=185 Participants
edoxaban 60mg QD PO
|
Edoxaban 90mg QD
n=177 Participants
edoxaban 90mg QD PO
|
Dalteparin
n=172 Participants
dalteparin 2500 IU/mL initial dose followed by 5000 IU once daily subcutaneously
|
Total
n=896 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
126 Participants
n=5 Participants
|
111 Participants
n=7 Participants
|
126 Participants
n=5 Participants
|
114 Participants
n=4 Participants
|
110 Participants
n=21 Participants
|
587 Participants
n=10 Participants
|
|
Age, Categorical
>=65 years
|
66 Participants
n=5 Participants
|
59 Participants
n=7 Participants
|
59 Participants
n=5 Participants
|
63 Participants
n=4 Participants
|
62 Participants
n=21 Participants
|
309 Participants
n=10 Participants
|
|
Age, Continuous
|
57.3 years
STANDARD_DEVIATION 12.49 • n=5 Participants
|
57.2 years
STANDARD_DEVIATION 12.28 • n=7 Participants
|
58.3 years
STANDARD_DEVIATION 11.52 • n=5 Participants
|
58.5 years
STANDARD_DEVIATION 12.27 • n=4 Participants
|
57.5 years
STANDARD_DEVIATION 12.43 • n=21 Participants
|
57.8 years
STANDARD_DEVIATION 12.13 • n=10 Participants
|
|
Sex: Female, Male
Female
|
113 Participants
n=5 Participants
|
111 Participants
n=7 Participants
|
118 Participants
n=5 Participants
|
93 Participants
n=4 Participants
|
105 Participants
n=21 Participants
|
540 Participants
n=10 Participants
|
|
Sex: Female, Male
Male
|
79 Participants
n=5 Participants
|
59 Participants
n=7 Participants
|
67 Participants
n=5 Participants
|
84 Participants
n=4 Participants
|
67 Participants
n=21 Participants
|
356 Participants
n=10 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
3 Participants
n=10 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
4 Participants
n=21 Participants
|
10 Participants
n=10 Participants
|
|
Race (NIH/OMB)
White
|
188 Participants
n=5 Participants
|
167 Participants
n=7 Participants
|
178 Participants
n=5 Participants
|
176 Participants
n=4 Participants
|
165 Participants
n=21 Participants
|
874 Participants
n=10 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
2 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
3 Participants
n=21 Participants
|
9 Participants
n=10 Participants
|
|
Region of Enrollment
North America
|
33 participants
n=5 Participants
|
20 participants
n=7 Participants
|
33 participants
n=5 Participants
|
33 participants
n=4 Participants
|
29 participants
n=21 Participants
|
148 participants
n=10 Participants
|
|
Region of Enrollment
Europe
|
159 participants
n=5 Participants
|
150 participants
n=7 Participants
|
152 participants
n=5 Participants
|
144 participants
n=4 Participants
|
143 participants
n=21 Participants
|
748 participants
n=10 Participants
|
PRIMARY outcome
Timeframe: end of treatmentPopulation: per protocol analysis set
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.
Outcome measures
| Measure |
Edoxaban 15mg QD
n=162 Participants
edoxaban 15mg QD (once daily) orally (PO)
|
Edoxaban 30mg QD
n=143 Participants
edoxaban 30mg QD PO
|
Edoxaban 60mg QD
n=153 Participants
edoxaban 60mg QD PO
|
Edoxaban 90mg QD
n=139 Participants
edoxaban 90mg QD PO
|
Dalteparin
n=137 Participants
dalteparin 2500 IU/mL initial dose followed by 5000 IU once daily subcutaneously
|
|---|---|---|---|---|---|
|
Adjudicated Incidence of VTE
|
29.0 percentage of participants with VTE
Interval 22.2 to 36.7
|
20.3 percentage of participants with VTE
Interval 14.0 to 27.8
|
15.7 percentage of participants with VTE
Interval 10.3 to 22.4
|
11.5 percentage of participants with VTE
Interval 6.7 to 18.0
|
46.0 percentage of participants with VTE
Interval 37.4 to 54.7
|
SECONDARY outcome
Timeframe: end of treatmentPopulation: perp protocol analysis set
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
Outcome measures
| Measure |
Edoxaban 15mg QD
n=153 Participants
edoxaban 15mg QD (once daily) orally (PO)
|
Edoxaban 30mg QD
n=137 Participants
edoxaban 30mg QD PO
|
Edoxaban 60mg QD
n=146 Participants
edoxaban 60mg QD PO
|
Edoxaban 90mg QD
n=134 Participants
edoxaban 90mg QD PO
|
Dalteparin
n=132 Participants
dalteparin 2500 IU/mL initial dose followed by 5000 IU once daily subcutaneously
|
|---|---|---|---|---|---|
|
Change in Prothrombin Time (PT) From Baseline
|
.90 seconds
Standard Deviation 3.205
|
1.07 seconds
Standard Deviation 1.875
|
2.87 seconds
Standard Deviation 6.279
|
2.74 seconds
Standard Deviation 5.821
|
.67 seconds
Standard Deviation 1.88
|
SECONDARY outcome
Timeframe: end of treatmentPopulation: perp protocol analysis set
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
Outcome measures
| Measure |
Edoxaban 15mg QD
n=149 Participants
edoxaban 15mg QD (once daily) orally (PO)
|
Edoxaban 30mg QD
n=137 Participants
edoxaban 30mg QD PO
|
Edoxaban 60mg QD
n=145 Participants
edoxaban 60mg QD PO
|
Edoxaban 90mg QD
n=134 Participants
edoxaban 90mg QD PO
|
Dalteparin
n=131 Participants
dalteparin 2500 IU/mL initial dose followed by 5000 IU once daily subcutaneously
|
|---|---|---|---|---|---|
|
Change in Activated Partial Thromboplastin Time (aPTT) From Baseline
|
-0.33 seconds
Standard Deviation 6.562
|
1.67 seconds
Standard Deviation 13.092
|
4.39 seconds
Standard Deviation 16.930
|
3.26 seconds
Standard Deviation 13.169
|
2.34 seconds
Standard Deviation 12.396
|
SECONDARY outcome
Timeframe: 10 days after first dosePopulation: safety analysis dataset
adjudicated incidence of major or clinically relevant non-major bleeding events through 10 days after first dose
Outcome measures
| Measure |
Edoxaban 15mg QD
n=192 Participants
edoxaban 15mg QD (once daily) orally (PO)
|
Edoxaban 30mg QD
n=170 Participants
edoxaban 30mg QD PO
|
Edoxaban 60mg QD
n=185 Participants
edoxaban 60mg QD PO
|
Edoxaban 90mg QD
n=177 Participants
edoxaban 90mg QD PO
|
Dalteparin
n=172 Participants
dalteparin 2500 IU/mL initial dose followed by 5000 IU once daily subcutaneously
|
|---|---|---|---|---|---|
|
Adjudicated Incidence of Major or Clinically Relevant Non-major Bleeding Events
|
1.6 percentage of subjects with bleed events
Interval 0.3 to 4.5
|
1.8 percentage of subjects with bleed events
Interval 0.4 to 5.1
|
2.2 percentage of subjects with bleed events
Interval 0.6 to 5.4
|
2.3 percentage of subjects with bleed events
Interval 0.6 to 5.7
|
0 percentage of subjects with bleed events
Interval 0.0 to 2.1
|
Adverse Events
Edoxaban 15mg QD
Serious events: 8 serious events
Other events: 30 other events
Deaths: 0 deaths
Edoxaban 30mg QD
Serious events: 6 serious events
Other events: 16 other events
Deaths: 0 deaths
Edoxaban 60mg QD
Serious events: 8 serious events
Other events: 22 other events
Deaths: 0 deaths
Edoxaban 90mg QD
Serious events: 10 serious events
Other events: 25 other events
Deaths: 0 deaths
Dalteparin
Serious events: 3 serious events
Other events: 22 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Edoxaban 15mg QD
n=192 participants at risk
edoxaban 15mg QD (once daily) orally (PO)
|
Edoxaban 30mg QD
n=170 participants at risk
edoxaban 30mg QD PO
|
Edoxaban 60mg QD
n=185 participants at risk
edoxaban 60mg QD PO
|
Edoxaban 90mg QD
n=177 participants at risk
edoxaban 90mg QD PO
|
Dalteparin
n=172 participants at risk
dalteparin 2500 IU/mL initial dose followed by 5000 IU once daily subcutaneously
|
|---|---|---|---|---|---|
|
Cardiac disorders
acute myocardial infarction
|
0.00%
0/192
|
0.00%
0/170
|
0.00%
0/185
|
0.56%
1/177 • Number of events 1
|
0.00%
0/172
|
|
Cardiac disorders
angina pectoris
|
0.52%
1/192 • Number of events 1
|
0.00%
0/170
|
0.00%
0/185
|
0.00%
0/177
|
0.00%
0/172
|
|
Cardiac disorders
cardiopulmonary failure
|
0.52%
1/192 • Number of events 1
|
0.00%
0/170
|
0.00%
0/185
|
0.00%
0/177
|
0.00%
0/172
|
|
Cardiac disorders
myocardial infarction
|
0.52%
1/192 • Number of events 1
|
0.59%
1/170 • Number of events 1
|
0.00%
0/185
|
0.00%
0/177
|
0.00%
0/172
|
|
Cardiac disorders
myocardial ischemia
|
0.00%
0/192
|
0.59%
1/170 • Number of events 1
|
0.00%
0/185
|
0.00%
0/177
|
0.00%
0/172
|
|
Cardiac disorders
supraventricular tachycardia
|
0.00%
0/192
|
0.00%
0/170
|
0.00%
0/185
|
0.56%
1/177 • Number of events 1
|
0.00%
0/172
|
|
Gastrointestinal disorders
upper gastrointestinal haemorrhage
|
0.52%
1/192 • Number of events 1
|
0.00%
0/170
|
0.00%
0/185
|
0.00%
0/177
|
0.00%
0/172
|
|
General disorders
death
|
0.00%
0/192
|
0.59%
1/170 • Number of events 1
|
0.00%
0/185
|
0.00%
0/177
|
0.00%
0/172
|
|
General disorders
secretion of discharge
|
0.00%
0/192
|
0.00%
0/170
|
0.00%
0/185
|
0.56%
1/177 • Number of events 1
|
0.00%
0/172
|
|
Immune system disorders
anaphylactic reaction
|
0.00%
0/192
|
0.00%
0/170
|
0.00%
0/185
|
0.56%
1/177 • Number of events 1
|
0.00%
0/172
|
|
Immune system disorders
drug hypersensitivity
|
0.00%
0/192
|
0.00%
0/170
|
0.00%
0/185
|
0.00%
0/177
|
0.58%
1/172 • Number of events 1
|
|
Infections and infestations
gastroenteritis
|
0.52%
1/192 • Number of events 1
|
0.00%
0/170
|
0.00%
0/185
|
0.00%
0/177
|
0.00%
0/172
|
|
Infections and infestations
paronychia
|
0.52%
1/192 • Number of events 1
|
0.00%
0/170
|
0.00%
0/185
|
0.00%
0/177
|
0.00%
0/172
|
|
Injury, poisoning and procedural complications
dislocation of joint prosthesis
|
0.00%
0/192
|
0.59%
1/170 • Number of events 1
|
0.54%
1/185 • Number of events 1
|
0.00%
0/177
|
0.58%
1/172 • Number of events 1
|
|
Injury, poisoning and procedural complications
fat embolism
|
0.52%
1/192 • Number of events 1
|
0.00%
0/170
|
0.00%
0/185
|
0.00%
0/177
|
0.00%
0/172
|
|
Injury, poisoning and procedural complications
hip fracture
|
0.00%
0/192
|
0.00%
0/170
|
0.54%
1/185 • Number of events 1
|
0.00%
0/177
|
0.00%
0/172
|
|
Injury, poisoning and procedural complications
incision site hematoma
|
0.00%
0/192
|
0.00%
0/170
|
0.54%
1/185 • Number of events 1
|
0.56%
1/177 • Number of events 1
|
0.00%
0/172
|
|
Injury, poisoning and procedural complications
post-procedural complication
|
0.00%
0/192
|
0.00%
0/170
|
0.00%
0/185
|
0.56%
1/177 • Number of events 1
|
0.00%
0/172
|
|
Investigations
hepatic enzyme increased
|
0.00%
0/192
|
0.00%
0/170
|
0.00%
0/185
|
0.56%
1/177 • Number of events 1
|
0.00%
0/172
|
|
Nervous system disorders
syncope
|
0.00%
0/192
|
0.00%
0/170
|
0.54%
1/185 • Number of events 1
|
0.00%
0/177
|
0.00%
0/172
|
|
Nervous system disorders
transient ischemic attack
|
0.52%
1/192 • Number of events 1
|
0.00%
0/170
|
0.00%
0/185
|
0.00%
0/177
|
0.00%
0/172
|
|
Respiratory, thoracic and mediastinal disorders
acute respiratory distress syndrome
|
0.52%
1/192 • Number of events 1
|
0.00%
0/170
|
0.00%
0/185
|
0.00%
0/177
|
0.00%
0/172
|
|
Respiratory, thoracic and mediastinal disorders
pulmonary congestion
|
0.00%
0/192
|
0.00%
0/170
|
0.00%
0/185
|
0.56%
1/177 • Number of events 1
|
0.00%
0/172
|
|
Respiratory, thoracic and mediastinal disorders
pulmonary embolism
|
0.00%
0/192
|
0.00%
0/170
|
1.1%
2/185 • Number of events 2
|
0.00%
0/177
|
0.58%
1/172 • Number of events 1
|
|
Vascular disorders
cardiovascular insufficiency
|
0.00%
0/192
|
0.59%
1/170 • Number of events 1
|
0.00%
0/185
|
0.00%
0/177
|
0.00%
0/172
|
|
Vascular disorders
deep vein thrombosis
|
1.0%
2/192 • Number of events 2
|
0.59%
1/170 • Number of events 1
|
1.1%
2/185 • Number of events 2
|
0.56%
1/177 • Number of events 1
|
0.00%
0/172
|
|
Vascular disorders
hematoma
|
0.52%
1/192 • Number of events 1
|
0.00%
0/170
|
0.54%
1/185 • Number of events 1
|
0.00%
0/177
|
0.00%
0/172
|
|
Vascular disorders
wound hemorrhage
|
0.00%
0/192
|
0.00%
0/170
|
0.00%
0/185
|
0.56%
1/177 • Number of events 1
|
0.00%
0/172
|
Other adverse events
| Measure |
Edoxaban 15mg QD
n=192 participants at risk
edoxaban 15mg QD (once daily) orally (PO)
|
Edoxaban 30mg QD
n=170 participants at risk
edoxaban 30mg QD PO
|
Edoxaban 60mg QD
n=185 participants at risk
edoxaban 60mg QD PO
|
Edoxaban 90mg QD
n=177 participants at risk
edoxaban 90mg QD PO
|
Dalteparin
n=172 participants at risk
dalteparin 2500 IU/mL initial dose followed by 5000 IU once daily subcutaneously
|
|---|---|---|---|---|---|
|
Gastrointestinal disorders
constipation
|
2.6%
5/192
|
1.8%
3/170
|
4.3%
8/185
|
7.9%
14/177
|
3.5%
6/172
|
|
Gastrointestinal disorders
nausea
|
6.8%
13/192
|
2.4%
4/170
|
4.3%
8/185
|
4.5%
8/177
|
3.5%
6/172
|
|
General disorders
edema peripheral
|
5.7%
11/192
|
2.9%
5/170
|
3.8%
7/185
|
3.4%
6/177
|
4.7%
8/172
|
|
General disorders
pyrexia
|
7.8%
15/192
|
1.8%
3/170
|
4.3%
8/185
|
3.4%
6/177
|
3.5%
6/172
|
|
Injury, poisoning and procedural complications
procedural pain
|
5.2%
10/192
|
2.9%
5/170
|
4.3%
8/185
|
5.1%
9/177
|
4.7%
8/172
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee A study site may not publish results of a study until after a coordinated multicenter publication has been submitted for publication or until one year after the study has ended, whichever occurs first. The study site will have the opportunity to publish results of the study, provided Daiichi Sankyo has had the opportunity to review and comment on the study site's proposed publication prior to being submitted for publication with the advice of patent council and need for subject protection.
- Publication restrictions are in place
Restriction type: OTHER