Trial Outcomes & Findings for A Study of DU-176b, Prevention of Venous Thromboembolism in Patients After Total Hip Arthroplasty (NCT NCT01181167)

NCT ID: NCT01181167

Last Updated: 2019-03-05

Results Overview

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

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

610 participants

Primary outcome timeframe

2 weeks

Results posted on

2019-03-05

Participant Flow

Participant milestones

Participant milestones
Measure
DU-176b
DU-176b oral tablets, 30 mg., taken once daily for 2 weeks edoxaban
Enoxaparin Sodium
enoxaparin sodium 20mg(=2000IU)/0.2ml twice daily, subcutaneous injection for 2 weeks enoxaparin sodium
Overall Study
STARTED
307
303
Overall Study
Efficacy Analysis Population
255
248
Overall Study
COMPLETED
284
271
Overall Study
NOT COMPLETED
23
32

Reasons for withdrawal

Reasons for withdrawal
Measure
DU-176b
DU-176b oral tablets, 30 mg., taken once daily for 2 weeks edoxaban
Enoxaparin Sodium
enoxaparin sodium 20mg(=2000IU)/0.2ml twice daily, subcutaneous injection for 2 weeks enoxaparin sodium
Overall Study
Adverse Event
11
21
Overall Study
Lost to Follow-up
1
0
Overall Study
Physician Decision
2
3
Overall Study
Protocol Violation
3
0
Overall Study
Withdrawal by Subject
6
8

Baseline Characteristics

A Study of DU-176b, Prevention of Venous Thromboembolism in Patients After Total Hip Arthroplasty

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
DU-176b
n=255 Participants
DU-176b oral tablets, 30 mg., taken once daily for 2 weeks edoxaban
Enoxaparin Sodium
n=248 Participants
enoxaparin sodium 20mg(=2000IU)/0.2ml twice daily, subcutaneous injection for 2 weeks enoxaparin sodium
Total
n=503 Participants
Total of all reporting groups
Age, Continuous
62.8 years
STANDARD_DEVIATION 9.61 • n=5 Participants
62.8 years
STANDARD_DEVIATION 9.72 • n=7 Participants
62.8 years
STANDARD_DEVIATION 9.65 • n=5 Participants
Sex: Female, Male
Female
220 Participants
n=5 Participants
212 Participants
n=7 Participants
432 Participants
n=5 Participants
Sex: Female, Male
Male
35 Participants
n=5 Participants
36 Participants
n=7 Participants
71 Participants
n=5 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Race (NIH/OMB)
Asian
255 Participants
n=5 Participants
248 Participants
n=7 Participants
503 Participants
n=5 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
Race (NIH/OMB)
Black or African American
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Race (NIH/OMB)
White
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Race (NIH/OMB)
More than one race
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Race (NIH/OMB)
Unknown or Not Reported
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Region of Enrollment
Japan
255 participants
n=5 Participants
248 participants
n=7 Participants
503 participants
n=5 Participants

PRIMARY outcome

Timeframe: 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.

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

Outcome measures

Outcome measures
Measure
DU-176b
n=255 Participants
DU-176b oral tablets, 30 mg., taken once daily for 2 weeks edoxaban
Enoxaparin Sodium
n=248 Participants
enoxaparin sodium 20mg(=2000IU)/0.2ml twice daily, subcutaneous injection for 2 weeks enoxaparin sodium
Incidence of Subjects With Venous Thromboembolism Events
2.4 percentage of subjects with vte events
Interval 1.1 to 5.0
6.9 percentage of subjects with vte events
Interval 4.3 to 10.7

SECONDARY outcome

Timeframe: 2 weeks

Population: Safety analyses were performed for the Safety Analysis Set, which was defined as all subjects who were secondarily enrolled in the study, but excluded those who had significant GCP violations, who had not received any doses of the study drug, or who had no safety data after the start of study treatment.

Outcome measures

Outcome measures
Measure
DU-176b
n=303 Participants
DU-176b oral tablets, 30 mg., taken once daily for 2 weeks edoxaban
Enoxaparin Sodium
n=301 Participants
enoxaparin sodium 20mg(=2000IU)/0.2ml twice daily, subcutaneous injection for 2 weeks enoxaparin sodium
Incidence of Major Bleeding or Clinically Relevant Non-major Bleeding
2.6 percentage of subjects with bleeds
Interval 1.3 to 5.1
3.7 percentage of subjects with bleeds
Interval 2.1 to 6.7

Adverse Events

DU-176b

Serious events: 9 serious events
Other events: 197 other events
Deaths: 0 deaths

Enoxaparin Sodium

Serious events: 9 serious events
Other events: 232 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
DU-176b
n=303 participants at risk
DU-176b oral tablets, 30 mg., taken once daily for 2 weeks edoxaban
Enoxaparin Sodium
n=301 participants at risk
enoxaparin sodium 20mg(=2000IU)/0.2ml twice daily, subcutaneous injection for 2 weeks enoxaparin sodium
Vascular disorders
deep vein thrombosis
0.33%
1/303 • Number of events 1
0.33%
1/301 • Number of events 1
Injury, poisoning and procedural complications
femur fracture
0.66%
2/303 • Number of events 2
0.33%
1/301 • Number of events 1
Injury, poisoning and procedural complications
pelvic fracture
0.33%
1/303 • Number of events 1
0.00%
0/301
Infections and infestations
herpes zoster
0.33%
1/303 • Number of events 1
0.00%
0/301
Vascular disorders
otrhostatic hypotension
0.33%
1/303 • Number of events 1
0.00%
0/301
Injury, poisoning and procedural complications
Dislocation of joint prosthesis
0.66%
2/303 • Number of events 2
0.33%
1/301 • Number of events 1
Nervous system disorders
lacunar infarction
0.33%
1/303 • Number of events 1
0.00%
0/301
Gastrointestinal disorders
intestinal obstruction
0.00%
0/303
0.33%
1/301 • Number of events 1
Infections and infestations
postoperative wound infection
0.00%
0/303
0.33%
1/301 • Number of events 1
Injury, poisoning and procedural complications
hip fracture
0.00%
0/303
0.33%
1/301 • Number of events 1
Infections and infestations
abcess jaw
0.00%
0/303
0.33%
1/301 • Number of events 1
Nervous system disorders
Transient ischaemic attack
0.00%
0/303
0.33%
1/301 • Number of events 1
Nervous system disorders
Subarachnoid haemorrhage
0.00%
0/303
0.33%
1/301 • Number of events 1
Gastrointestinal disorders
gastroenteritis
0.00%
0/303
0.33%
1/301 • Number of events 1

Other adverse events

Other adverse events
Measure
DU-176b
n=303 participants at risk
DU-176b oral tablets, 30 mg., taken once daily for 2 weeks edoxaban
Enoxaparin Sodium
n=301 participants at risk
enoxaparin sodium 20mg(=2000IU)/0.2ml twice daily, subcutaneous injection for 2 weeks enoxaparin sodium
Investigations
Aspartate aminotransferase increased
5.6%
17/303 • Number of events 17
32.2%
97/301 • Number of events 98
Investigations
Gamma-glutamyltransferase increased
14.5%
44/303 • Number of events 45
26.2%
79/301 • Number of events 81
Investigations
Alanine aminotransferase increased
11.9%
36/303 • Number of events 37
41.9%
126/301 • Number of events 128
Investigations
Blood urine present
12.5%
38/303 • Number of events 39
11.3%
34/301 • Number of events 37
Investigations
Blood alkaline phosphatase increased
4.6%
14/303 • Number of events 15
13.3%
40/301 • Number of events 41
Skin and subcutaneous tissue disorders
Haemorrhage subcutaneous
4.0%
12/303 • Number of events 12
7.0%
21/301 • Number of events 23
Investigations
Blood bilirubin increased
3.6%
11/303 • Number of events 11
3.3%
10/301 • Number of events 10
Nervous system disorders
headache
3.6%
11/303 • Number of events 12
4.0%
12/301 • Number of events 12
Gastrointestinal disorders
Abdominal discomfort
3.0%
9/303 • Number of events 10
1.7%
5/301 • Number of events 5
Gastrointestinal disorders
Diarrhoea
3.3%
10/303 • Number of events 10
3.3%
10/301 • Number of events 10
Renal and urinary disorders
Haematuria
3.6%
11/303 • Number of events 12
0.66%
2/301 • Number of events 2

Additional Information

Masayuki Fukuzawa, Associate Director

Daiichi Sankyo Co., Ltd.

Phone: 81-90-5584-2197

Results disclosure agreements

  • Principal investigator is a sponsor employee PI shall not publish the results of the Study at any time without the prior written approval of Sponsor.
  • Publication restrictions are in place

Restriction type: OTHER