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Edoxaban in Peripheral Arterial Disease (ePAD)

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ClinicalTrials.gov Identifier: NCT01802775
Recruitment Status : Completed
First Posted : March 1, 2013
Results First Posted : January 12, 2018
Last Update Posted : January 12, 2018
Sponsor:
Collaborator:
UMC Utrecht
Information provided by (Responsible Party):
Daiichi Sankyo, Inc.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Peripheral Arterial Disease
Interventions Drug: edoxaban
Drug: Clopidogrel
Drug: Aspirin
Enrollment 203
Recruitment Details  
Pre-assignment Details A total of 275 subjects were screened, of these 203 subjects were randomized into the study, with 101 subjects in the edoxaban group and 102 subjects in the clopidogrel group.
Arm/Group Title Clopidogrel Edoxaban
Hide Arm/Group Description Open-label clopidogrel with aspirin Open-label edoxaban with aspirin
Period Title: Overall Study
Started 102 101
Received Drug (Safety Analysis Set) 101 100
Completed 96 89
Not Completed 6 12
Reason Not Completed
Death             0             3
Reason not provided             0             1
Physician Decision             1             0
Adverse Event             1             1
Withdrawal by Subject             3             5
Lost to Follow-up             1             2
Arm/Group Title Clopidogrel Edoxaban Total
Hide Arm/Group Description Open-label clopidogrel with aspirin Open-label edoxaban with aspirin Total of all reporting groups
Overall Number of Baseline Participants 102 101 203
Hide Baseline Analysis Population Description
Intention to treat - all participants enrolled in the trial
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 102 participants 101 participants 203 participants
66.7  (8.55) 68  (10.36) 67.4  (9.49)
Age, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 102 participants 101 participants 203 participants
Adults 18-64 years of age
33
  32.4%
30
  29.7%
63
  31.0%
From 65 to 84 years of age
68
  66.7%
65
  64.4%
133
  65.5%
85 years of age and over
1
   1.0%
6
   5.9%
7
   3.4%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 102 participants 101 participants 203 participants
Female
24
  23.5%
34
  33.7%
58
  28.6%
Male
78
  76.5%
67
  66.3%
145
  71.4%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 102 participants 101 participants 203 participants
Austria 13 15 28
Netherlands 5 8 13
Belgium 6 9 15
United States 47 42 89
Israel 7 5 12
Switzerland 13 12 25
Germany 11 10 21
1.Primary Outcome
Title Percentage of Participants With Clinically Relevant Bleeding During Treatment
Hide Description Percentage of participants with clinically relevant bleeding, defined as major bleeding or clinical relevant non-major bleeding, in the on-treatment period based on International Society of Thrombosis and Haemostasis (ISTH)
Time Frame at 3 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety Analysis Set, defined as all participants who received at least one dose of study drug
Arm/Group Title Clopidogrel Edoxaban
Hide Arm/Group Description:
Open-label clopidogrel with aspirin
Open-label edoxaban with aspirin
Overall Number of Participants Analyzed 101 100
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
Including Access Site Bleeding (IASB)
8
(3.5 to 15.0)
11
(5.6 to 18.8)
Excluding Access Site Bleed (EASB)
6
(2.2 to 12.5)
6
(2.2 to 12.6)
2.Primary Outcome
Title Percentage of Participants With First Re-stenosis / Re-occlusion
Hide Description Percentage of participants with re-stenosis/re-occlusion during treatment within 6 months - only the first occurrence of re-stenosis / re-occlusion was counted for each participant
Time Frame within 6 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Modified Intent-to-Treat (mITT), defined as all randomized subjects who received at least one dose of the study study and had at least one post-dose duplex scanning
Arm/Group Title Clopidogrel Edoxaban
Hide Arm/Group Description:
Open-label clopidogrel with aspirin
Open-label edoxaban with aspirin
Overall Number of Participants Analyzed 95 94
Measure Type: Number
Unit of Measure: percentage of participants
34.7 30.9
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Clopidogrel, Edoxaban
Comments Treatment difference was edoxaban - clopidogrel. For the treatment difference, 95% Confidence interval was calculated using a normal approximation to the binomial distribution.
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value -3.9
Confidence Interval (2-Sided) 95%
-17.3 to 9.5
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Percentage of Participants With Major, Clinically Relevant Non-major (CRNM), and Minor Bleeding During Treatment
Hide Description The percentage of participants with major, clinically relevant non-major, and minor bleeding occurring during treatment, within 3 months
Time Frame within 3 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety Analysis Set, defined as all participants who received at least one dose of study drug
Arm/Group Title Clopidogrel Edoxaban
Hide Arm/Group Description:
Open-label clopidogrel with aspirin
Open-label edoxaban with aspirin
Overall Number of Participants Analyzed 101 100
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
IASB : Major Bleeding
5
(1.6 to 11.2)
1
(0 to 5.4)
IASB: CRNM Bleeding
4
(1.1 to 9.8)
10
(4.9 to 17.6)
IASB: Minor Bleeding
20.8
(13.4 to 30)
20
(12.7 to 29.2)
EASB : Major Bleeding
4
(1.1 to 9.8)
1
(0 to 5.4)
EASB : CRNM Bleeding
3
(0.6 to 8.4)
5
(1.6 to 11.3)
EASB : Minor Bleeding
17.8
(10.9 to 26.7)
19
(11.8 to 28.1)
4.Secondary Outcome
Title Safety Assessments
Hide Description

Number of participants with serious adverse events (SAEs) within 6 months

Note: Based on changes to the database structure, clinically significant changes in physical or laboratory parameters are recorded as adverse events (AEs). Details of non-serious adverse events are reported at the 5% reporting threshold in the AE module, as is all-cause mortality.

Time Frame within 6 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety Analysis Set
Arm/Group Title Clopidogrel Edoxaban
Hide Arm/Group Description:
Open-label clopidogrel with aspirin
Open-label edoxaban with aspirin
Overall Number of Participants Analyzed 101 100
Measure Type: Count of Participants
Unit of Measure: Participants
30
  29.7%
31
  31.0%
5.Secondary Outcome
Title Number of Adjudicated Major Adverse Cardiovascular Events During the Overall Study Period
Hide Description Number of Adjudicated Major Adverse Cardiovascular Events (MACE) which is a composite of non-fatal myocardial infarction (MI), non-fatal stroke and cardiovascular death
Time Frame within 6 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
mITT Set 1 (Safety Analysis Set), defined as the participants who received at least 1 dose of study drug
Arm/Group Title Clopidogrel Edoxaban
Hide Arm/Group Description:
Open-label clopidogrel with aspirin
Open-label edoxaban with aspirin
Overall Number of Participants Analyzed 101 100
Measure Type: Count of Participants
Unit of Measure: Participants
1
   1.0%
3
   3.0%
6.Secondary Outcome
Title Number of Participants With Amputations
Hide Description Number of participants with amputations within 6 months
Time Frame within 6 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety Analysis Set
Arm/Group Title Clopidogrel Edoxaban
Hide Arm/Group Description:
Open-label clopidogrel with aspirin
Open-label edoxaban with aspirin
Overall Number of Participants Analyzed 101 100
Measure Type: Count of Participants
Unit of Measure: Participants
3
   3.0%
1
   1.0%
Time Frame From the first dose to the end of the study (6 months)
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Clopidogrel Edoxaban
Hide Arm/Group Description Open-label clopidogrel with aspirin Open-label edoxaban with aspirin
All-Cause Mortality
Clopidogrel Edoxaban
Affected / at Risk (%) Affected / at Risk (%)
Total   0/101 (0.00%)   3/100 (3.00%) 
Show Serious Adverse Events Hide Serious Adverse Events
Clopidogrel Edoxaban
Affected / at Risk (%) Affected / at Risk (%)
Total   30/101 (29.70%)   31/100 (31.00%) 
Blood and lymphatic system disorders     
ANAEMIA  1  0/101 (0.00%)  1/100 (1.00%) 
IRON DEFICIENCY ANAEMIA * 1  1/101 (0.99%)  0/100 (0.00%) 
Cardiac disorders     
ACUTE MYOCARDIAL INFARCTION * 1  0/101 (0.00%)  2/100 (2.00%) 
ANGINA PECTORIS * 1  1/101 (0.99%)  1/100 (1.00%) 
ATRIAL FIBRILLATION * 1  1/101 (0.99%)  1/100 (1.00%) 
BRADYCARDIA * 1  1/101 (0.99%)  1/100 (1.00%) 
CARDIAC FAILURE ACUTE * 1  0/101 (0.00%)  1/100 (1.00%) 
CARDIO-RESPIRATORY ARREST * 1  0/101 (0.00%)  1/100 (1.00%) 
CARDIOGENIC SHOCK  1  1/101 (0.99%)  0/100 (0.00%) 
CORONARY ARTERY DISEASE * 1  1/101 (0.99%)  2/100 (2.00%) 
CORONARY ARTERY STENOSIS * 1  0/101 (0.00%)  1/100 (1.00%) 
Gastrointestinal disorders     
INTESTINAL ISCHAEMIA * 1  1/101 (0.99%)  0/100 (0.00%) 
General disorders     
CHEST PAIN  1  2/101 (1.98%)  2/100 (2.00%) 
NECROSIS * 1  1/101 (0.99%)  0/100 (0.00%) 
Hepatobiliary disorders     
CHOLELITHIASIS * 1  0/101 (0.00%)  1/100 (1.00%) 
Infections and infestations     
CELLULITIS * 1  0/101 (0.00%)  1/100 (1.00%) 
CLOSTRIDIUM COLITIS  1  1/101 (0.99%)  0/100 (0.00%) 
GANGRENE  1  1/101 (0.99%)  2/100 (2.00%) 
INFECTED SKIN ULCER  1  0/101 (0.00%)  1/100 (1.00%) 
LOCALISED INFECTION  1  1/101 (0.99%)  0/100 (0.00%) 
PNEUMONIA  1  0/101 (0.00%)  1/100 (1.00%) 
UROSEPSIS  1  1/101 (0.99%)  0/100 (0.00%) 
Injury, poisoning and procedural complications     
ARTERIAL RESTENOSIS  1  0/101 (0.00%)  1/100 (1.00%) 
FEMUR FRACTURE * 1  0/101 (0.00%)  1/100 (1.00%) 
PERIPHERAL ARTERY RESTENOSIS  1  1/101 (0.99%)  3/100 (3.00%) 
POST PROCEDURAL HAEMATOMA  1  1/101 (0.99%)  0/100 (0.00%) 
POST PROCEDURAL HAEMORRHAGE  1  2/101 (1.98%)  0/100 (0.00%) 
VASCULAR PSEUDOANEURYSM  1  0/101 (0.00%)  4/100 (4.00%) 
WOUND  1  1/101 (0.99%)  0/100 (0.00%) 
Metabolism and nutrition disorders     
FLUID OVERLOAD  1  1/101 (0.99%)  0/100 (0.00%) 
Musculoskeletal and connective tissue disorders     
COMPARTMENT SYNDROME  1  1/101 (0.99%)  1/100 (1.00%) 
PAIN IN EXTREMITY  1  1/101 (0.99%)  1/100 (1.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
LUNG NEOPLASM MALIGNANT  1  1/101 (0.99%)  0/100 (0.00%) 
PANCREATIC CARCINOMA METASTATIC * 1  0/101 (0.00%)  1/100 (1.00%) 
Nervous system disorders     
CAROTID ARTERY STENOSIS  1  1/101 (0.99%)  0/100 (0.00%) 
HAEMORRHAGIC STROKE * 1  0/101 (0.00%)  1/100 (1.00%) 
PRESYNCOPE * 1  1/101 (0.99%)  0/100 (0.00%) 
Psychiatric disorders     
ALCOHOL ABUSE  1  0/101 (0.00%)  1/100 (1.00%) 
Renal and urinary disorders     
HAEMATURIA  1  0/101 (0.00%)  1/100 (1.00%) 
RENAL FAILURE ACUTE * 1  0/101 (0.00%)  1/100 (1.00%) 
RENAL TUBULAR NECROSIS  1  1/101 (0.99%)  0/100 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
ACUTE RESPIRATORY FAILURE  1  0/101 (0.00%)  1/100 (1.00%) 
EPISTAXIS  1  1/101 (0.99%)  0/100 (0.00%) 
Skin and subcutaneous tissue disorders     
SKIN ULCER  1  1/101 (0.99%)  1/100 (1.00%) 
Vascular disorders     
FEMORAL ARTERY OCCLUSION  1  0/101 (0.00%)  2/100 (2.00%) 
HAEMORRHAGE  1  0/101 (0.00%)  1/100 (1.00%) 
HYPERTENSION  1  1/101 (0.99%)  0/100 (0.00%) 
INTERMITTENT CLAUDICATION * 1  4/101 (3.96%)  2/100 (2.00%) 
PERIPHERAL ARTERIAL OCCLUSIVE DISEASE  1  3/101 (2.97%)  1/100 (1.00%) 
PERIPHERAL ARTERY STENOSIS * 1  2/101 (1.98%)  2/100 (2.00%) 
PERIPHERAL ARTERY THROMBOSIS  1  2/101 (1.98%)  3/100 (3.00%) 
PERIPHERAL EMBOLISM  1  1/101 (0.99%)  0/100 (0.00%) 
PERIPHERAL ISCHAEMIA * 1  2/101 (1.98%)  1/100 (1.00%) 
1
Term from vocabulary, MedDRA (15.1)
Indicates events were collected by systematic assessment
*
Indicates events were collected by non-systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Clopidogrel Edoxaban
Affected / at Risk (%) Affected / at Risk (%)
Total   23/101 (22.77%)   32/100 (32.00%) 
Gastrointestinal disorders     
Nausea * 1  4/101 (3.96%)  6/100 (6.00%) 
Injury, poisoning and procedural complications     
Post procedural haematoma * 1  3/101 (2.97%)  6/100 (6.00%) 
Investigations     
Creatinine renal clearance decreased * 1  3/101 (2.97%)  6/100 (6.00%) 
Musculoskeletal and connective tissue disorders     
Arthralgia * 1  2/101 (1.98%)  6/100 (6.00%) 
Pain in extremity * 1  7/101 (6.93%)  9/100 (9.00%) 
Nervous system disorders     
Dizziness * 1  1/101 (0.99%)  5/100 (5.00%) 
Headache * 1  0/101 (0.00%)  5/100 (5.00%) 
Respiratory, thoracic and mediastinal disorders     
Epistaxis * 1  7/101 (6.93%)  7/100 (7.00%) 
1
Term from vocabulary, MedDRA (15.1)
*
Indicates events were collected by non-systematic assessment
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 site may publish the results with proper regard to the protection of subjects’ identities, provided that sponsor (including legal and intellectual property) has had the opportunity to review and comment on the proposed publication prior to its being submitted for publication.
Results Point of Contact
Name/Title: Clinical Trial Information
Organization: Daiichi Sankyo Development Inc.
Phone: +44 1753482800
Responsible Party: Daiichi Sankyo, Inc.
ClinicalTrials.gov Identifier: NCT01802775     History of Changes
Other Study ID Numbers: DU176b-E-U210
2012-003009-88 ( EudraCT Number )
First Submitted: February 25, 2013
First Posted: March 1, 2013
Results First Submitted: December 11, 2017
Results First Posted: January 12, 2018
Last Update Posted: January 12, 2018