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A Study of DU-176b in Preventing Blood Clots After Hip Replacement Surgery

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00398216
Recruitment Status : Completed
First Posted : November 10, 2006
Results First Posted : February 25, 2015
Last Update Posted : February 26, 2019
Sponsor:
Information provided by:
Daiichi Sankyo, Inc.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double;   Primary Purpose: Prevention
Conditions Thrombosis
Hip Replacement
Intervention Drug: DU176b - action is the prevention of venous thromboembolism by the use of a Factor Xa inhibitor
Enrollment 903
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Edoxaban 15mg QD Edoxaban 30mg QD Edoxaban 60mg QD Edoxaban 90mg QD Dalteparin
Hide Arm/Group Description edoxaban 15mg QD (once daily) orally (PO) edoxaban 30mg QD PO edoxaban 60mg QD PO edoxaban 90mg QD PO dalteparin 2500 IU/mL initial dose followed by 5000 IU once daily subcutaneously
Period Title: Overall Study
Started 192 170 185 177 172
Completed 181 151 164 155 157
Not Completed 11 19 21 22 15
Reason Not Completed
Adverse Event             4             2             5             7             2
Protocol Violation             2             4             5             7             5
Lost to Follow-up             1             6             4             4             1
Death             0             3             0             0             0
Withdrawal by Subject             1             0             3             1             2
administrative reasons             3             4             4             3             3
entrance criteria             0             0             0             0             2
Arm/Group Title Edoxaban 15mg QD Edoxaban 30mg QD Edoxaban 60mg QD Edoxaban 90mg QD Dalteparin Total
Hide Arm/Group Description edoxaban 15mg QD (once daily) orally (PO) edoxaban 30mg QD PO edoxaban 60mg QD PO edoxaban 90mg QD PO dalteparin 2500 IU/mL initial dose followed by 5000 IU once daily subcutaneously Total of all reporting groups
Overall Number of Baseline Participants 192 170 185 177 172 896
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 192 participants 170 participants 185 participants 177 participants 172 participants 896 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
126
  65.6%
111
  65.3%
126
  68.1%
114
  64.4%
110
  64.0%
587
  65.5%
>=65 years
66
  34.4%
59
  34.7%
59
  31.9%
63
  35.6%
62
  36.0%
309
  34.5%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 192 participants 170 participants 185 participants 177 participants 172 participants 896 participants
57.3  (12.49) 57.2  (12.28) 58.3  (11.52) 58.5  (12.27) 57.5  (12.43) 57.8  (12.13)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 192 participants 170 participants 185 participants 177 participants 172 participants 896 participants
Female
113
  58.9%
111
  65.3%
118
  63.8%
93
  52.5%
105
  61.0%
540
  60.3%
Male
79
  41.1%
59
  34.7%
67
  36.2%
84
  47.5%
67
  39.0%
356
  39.7%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 192 participants 170 participants 185 participants 177 participants 172 participants 896 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
1
   0.5%
1
   0.6%
1
   0.5%
0
   0.0%
0
   0.0%
3
   0.3%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
1
   0.5%
1
   0.6%
3
   1.6%
1
   0.6%
4
   2.3%
10
   1.1%
White
188
  97.9%
167
  98.2%
178
  96.2%
176
  99.4%
165
  95.9%
874
  97.5%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
2
   1.0%
1
   0.6%
3
   1.6%
0
   0.0%
3
   1.7%
9
   1.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 192 participants 170 participants 185 participants 177 participants 172 participants 896 participants
North America 33 20 33 33 29 148
Europe 159 150 152 144 143 748
1.Primary Outcome
Title Adjudicated Incidence of VTE
Hide Description

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
Hide Outcome Measure Data
Hide Analysis Population Description
per protocol analysis set
Arm/Group Title Edoxaban 15mg QD Edoxaban 30mg QD Edoxaban 60mg QD Edoxaban 90mg QD Dalteparin
Hide Arm/Group Description:
edoxaban 15mg QD (once daily) orally (PO)
edoxaban 30mg QD PO
edoxaban 60mg QD PO
edoxaban 90mg QD PO
dalteparin 2500 IU/mL initial dose followed by 5000 IU once daily subcutaneously
Overall Number of Participants Analyzed 162 143 153 139 137
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants with VTE
29.0
(22.2 to 36.7)
20.3
(14.0 to 27.8)
15.7
(10.3 to 22.4)
11.5
(6.7 to 18.0)
46.0
(37.4 to 54.7)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Edoxaban 15mg QD, Dalteparin
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.003
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Edoxaban 30mg QD, Dalteparin
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Edoxaban 60mg QD, Dalteparin
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Edoxaban 90mg QD, Dalteparin
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
2.Secondary Outcome
Title Change in Prothrombin Time (PT) From Baseline
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
perp protocol analysis set
Arm/Group Title Edoxaban 15mg QD Edoxaban 30mg QD Edoxaban 60mg QD Edoxaban 90mg QD Dalteparin
Hide Arm/Group Description:
edoxaban 15mg QD (once daily) orally (PO)
edoxaban 30mg QD PO
edoxaban 60mg QD PO
edoxaban 90mg QD PO
dalteparin 2500 IU/mL initial dose followed by 5000 IU once daily subcutaneously
Overall Number of Participants Analyzed 153 137 146 134 132
Mean (Standard Deviation)
Unit of Measure: seconds
.90  (3.205) 1.07  (1.875) 2.87  (6.279) 2.74  (5.821) .67  (1.88)
3.Secondary Outcome
Title Change in Activated Partial Thromboplastin Time (aPTT) From Baseline
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
perp protocol analysis set
Arm/Group Title Edoxaban 15mg QD Edoxaban 30mg QD Edoxaban 60mg QD Edoxaban 90mg QD Dalteparin
Hide Arm/Group Description:
edoxaban 15mg QD (once daily) orally (PO)
edoxaban 30mg QD PO
edoxaban 60mg QD PO
edoxaban 90mg QD PO
dalteparin 2500 IU/mL initial dose followed by 5000 IU once daily subcutaneously
Overall Number of Participants Analyzed 149 137 145 134 131
Mean (Standard Deviation)
Unit of Measure: seconds
-0.33  (6.562) 1.67  (13.092) 4.39  (16.930) 3.26  (13.169) 2.34  (12.396)
4.Secondary Outcome
Title Adjudicated Incidence of Major or Clinically Relevant Non-major Bleeding Events
Hide Description adjudicated incidence of major or clinically relevant non-major bleeding events through 10 days after first dose
Time Frame 10 days after first dose
Hide Outcome Measure Data
Hide Analysis Population Description
safety analysis dataset
Arm/Group Title Edoxaban 15mg QD Edoxaban 30mg QD Edoxaban 60mg QD Edoxaban 90mg QD Dalteparin
Hide Arm/Group Description:
edoxaban 15mg QD (once daily) orally (PO)
edoxaban 30mg QD PO
edoxaban 60mg QD PO
edoxaban 90mg QD PO
dalteparin 2500 IU/mL initial dose followed by 5000 IU once daily subcutaneously
Overall Number of Participants Analyzed 192 170 185 177 172
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of subjects with bleed events
1.6
(0.3 to 4.5)
1.8
(0.4 to 5.1)
2.2
(0.6 to 5.4)
2.3
(0.6 to 5.7)
0
(0.0 to 2.1)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Edoxaban 15mg QD, Dalteparin
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .250
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Edoxaban 30mg QD, Dalteparin
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .122
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Edoxaban 60mg QD, Dalteparin
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .124
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Edoxaban 90mg QD, Dalteparin
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .123
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Edoxaban 15mg QD Edoxaban 30mg QD Edoxaban 60mg QD Edoxaban 90mg QD Dalteparin
Hide Arm/Group Description edoxaban 15mg QD (once daily) orally (PO) edoxaban 30mg QD PO edoxaban 60mg QD PO edoxaban 90mg QD PO dalteparin 2500 IU/mL initial dose followed by 5000 IU once daily subcutaneously
All-Cause Mortality
Edoxaban 15mg QD Edoxaban 30mg QD Edoxaban 60mg QD Edoxaban 90mg QD Dalteparin
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Edoxaban 15mg QD Edoxaban 30mg QD Edoxaban 60mg QD Edoxaban 90mg QD Dalteparin
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   8/192 (4.17%)      6/170 (3.53%)      8/185 (4.32%)      10/177 (5.65%)      3/172 (1.74%)    
Cardiac disorders           
acute myocardial infarction  1  0/192 (0.00%)  0 0/170 (0.00%)  0 0/185 (0.00%)  0 1/177 (0.56%)  1 0/172 (0.00%)  0
angina pectoris  2  1/192 (0.52%)  1 0/170 (0.00%)  0 0/185 (0.00%)  0 0/177 (0.00%)  0 0/172 (0.00%)  0
cardiopulmonary failure  2  1/192 (0.52%)  1 0/170 (0.00%)  0 0/185 (0.00%)  0 0/177 (0.00%)  0 0/172 (0.00%)  0
myocardial infarction  2  1/192 (0.52%)  1 1/170 (0.59%)  1 0/185 (0.00%)  0 0/177 (0.00%)  0 0/172 (0.00%)  0
myocardial ischemia  2  0/192 (0.00%)  0 1/170 (0.59%)  1 0/185 (0.00%)  0 0/177 (0.00%)  0 0/172 (0.00%)  0
supraventricular tachycardia  2  0/192 (0.00%)  0 0/170 (0.00%)  0 0/185 (0.00%)  0 1/177 (0.56%)  1 0/172 (0.00%)  0
Gastrointestinal disorders           
upper gastrointestinal haemorrhage  2  1/192 (0.52%)  1 0/170 (0.00%)  0 0/185 (0.00%)  0 0/177 (0.00%)  0 0/172 (0.00%)  0
General disorders           
death  2  0/192 (0.00%)  0 1/170 (0.59%)  1 0/185 (0.00%)  0 0/177 (0.00%)  0 0/172 (0.00%)  0
secretion of discharge  2  0/192 (0.00%)  0 0/170 (0.00%)  0 0/185 (0.00%)  0 1/177 (0.56%)  1 0/172 (0.00%)  0
Immune system disorders           
anaphylactic reaction  2  0/192 (0.00%)  0 0/170 (0.00%)  0 0/185 (0.00%)  0 1/177 (0.56%)  1 0/172 (0.00%)  0
drug hypersensitivity  2  0/192 (0.00%)  0 0/170 (0.00%)  0 0/185 (0.00%)  0 0/177 (0.00%)  0 1/172 (0.58%)  1
Infections and infestations           
gastroenteritis  2  1/192 (0.52%)  1 0/170 (0.00%)  0 0/185 (0.00%)  0 0/177 (0.00%)  0 0/172 (0.00%)  0
paronychia  2  1/192 (0.52%)  1 0/170 (0.00%)  0 0/185 (0.00%)  0 0/177 (0.00%)  0 0/172 (0.00%)  0
Injury, poisoning and procedural complications           
dislocation of joint prosthesis  1  0/192 (0.00%)  0 1/170 (0.59%)  1 1/185 (0.54%)  1 0/177 (0.00%)  0 1/172 (0.58%)  1
fat embolism  2  1/192 (0.52%)  1 0/170 (0.00%)  0 0/185 (0.00%)  0 0/177 (0.00%)  0 0/172 (0.00%)  0
hip fracture  2  0/192 (0.00%)  0 0/170 (0.00%)  0 1/185 (0.54%)  1 0/177 (0.00%)  0 0/172 (0.00%)  0
incision site hematoma  2  0/192 (0.00%)  0 0/170 (0.00%)  0 1/185 (0.54%)  1 1/177 (0.56%)  1 0/172 (0.00%)  0
post-procedural complication  2  0/192 (0.00%)  0 0/170 (0.00%)  0 0/185 (0.00%)  0 1/177 (0.56%)  1 0/172 (0.00%)  0
Investigations           
hepatic enzyme increased  2  0/192 (0.00%)  0 0/170 (0.00%)  0 0/185 (0.00%)  0 1/177 (0.56%)  1 0/172 (0.00%)  0
Nervous system disorders           
syncope  2  0/192 (0.00%)  0 0/170 (0.00%)  0 1/185 (0.54%)  1 0/177 (0.00%)  0 0/172 (0.00%)  0
transient ischemic attack  2  1/192 (0.52%)  1 0/170 (0.00%)  0 0/185 (0.00%)  0 0/177 (0.00%)  0 0/172 (0.00%)  0
Respiratory, thoracic and mediastinal disorders           
acute respiratory distress syndrome  1  1/192 (0.52%)  1 0/170 (0.00%)  0 0/185 (0.00%)  0 0/177 (0.00%)  0 0/172 (0.00%)  0
pulmonary congestion  2  0/192 (0.00%)  0 0/170 (0.00%)  0 0/185 (0.00%)  0 1/177 (0.56%)  1 0/172 (0.00%)  0
pulmonary embolism  2  0/192 (0.00%)  0 0/170 (0.00%)  0 2/185 (1.08%)  2 0/177 (0.00%)  0 1/172 (0.58%)  1
Vascular disorders           
cardiovascular insufficiency  2  0/192 (0.00%)  0 1/170 (0.59%)  1 0/185 (0.00%)  0 0/177 (0.00%)  0 0/172 (0.00%)  0
deep vein thrombosis  2  2/192 (1.04%)  2 1/170 (0.59%)  1 2/185 (1.08%)  2 1/177 (0.56%)  1 0/172 (0.00%)  0
hematoma  2  1/192 (0.52%)  1 0/170 (0.00%)  0 1/185 (0.54%)  1 0/177 (0.00%)  0 0/172 (0.00%)  0
wound hemorrhage  2  0/192 (0.00%)  0 0/170 (0.00%)  0 0/185 (0.00%)  0 1/177 (0.56%)  1 0/172 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
2
Term from vocabulary, MedDRA (9.0)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Edoxaban 15mg QD Edoxaban 30mg QD Edoxaban 60mg QD Edoxaban 90mg QD Dalteparin
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   30/192 (15.63%)      16/170 (9.41%)      22/185 (11.89%)      25/177 (14.12%)      22/172 (12.79%)    
Gastrointestinal disorders           
constipation  1  5/192 (2.60%)  3/170 (1.76%)  8/185 (4.32%)  14/177 (7.91%)  6/172 (3.49%) 
nausea  2  13/192 (6.77%)  4/170 (2.35%)  8/185 (4.32%)  8/177 (4.52%)  6/172 (3.49%) 
General disorders           
edema peripheral  1  11/192 (5.73%)  5/170 (2.94%)  7/185 (3.78%)  6/177 (3.39%)  8/172 (4.65%) 
pyrexia  1  15/192 (7.81%)  3/170 (1.76%)  8/185 (4.32%)  6/177 (3.39%)  6/172 (3.49%) 
Injury, poisoning and procedural complications           
procedural pain  1  10/192 (5.21%)  5/170 (2.94%)  8/185 (4.32%)  9/177 (5.08%)  8/172 (4.65%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (9.0)
2
Term from vocabulary, MedDRA
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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.
Results Point of Contact
Name/Title: William Maxwell, Assoc. Director
Organization: Daiichi Sankyo, Inc.
Phone: 732-590-5000
Responsible Party: Anne MacDonald, Daiichi Sankyo
ClinicalTrials.gov Identifier: NCT00398216     History of Changes
Other Study ID Numbers: DU176b-PRT011
2006-000758-29 ( EudraCT Number )
First Submitted: November 9, 2006
First Posted: November 10, 2006
Results First Submitted: February 5, 2015
Results First Posted: February 25, 2015
Last Update Posted: February 26, 2019