Trial Outcomes & Findings for Edoxaban in Peripheral Arterial Disease (NCT NCT01802775)

Last Updated: 2019-02-26

Results Overview

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)

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

203 participants

Primary outcome timeframe

at 3 months

Results posted on

2019-02-26

Participant Flow

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.

Participant milestones

Participant milestones
Measure	Clopidogrel Open-label clopidogrel with aspirin	Edoxaban Open-label edoxaban with aspirin
Overall Study STARTED	102	101
Overall Study Received Drug (Safety Analysis Set)	101	100
Overall Study COMPLETED	96	89
Overall Study NOT COMPLETED	6	12

Reasons for withdrawal

Reasons for withdrawal
Measure	Clopidogrel Open-label clopidogrel with aspirin	Edoxaban Open-label edoxaban with aspirin
Overall Study Death	0	3
Overall Study Reason not provided	0	1
Overall Study Physician Decision	1	0
Overall Study Adverse Event	1	1
Overall Study Withdrawal by Subject	3	5
Overall Study Lost to Follow-up	1	2

Baseline Characteristics

Edoxaban in Peripheral Arterial Disease

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Clopidogrel n=102 Participants Open-label clopidogrel with aspirin	Edoxaban n=101 Participants Open-label edoxaban with aspirin	Total n=203 Participants Total of all reporting groups
Age, Continuous	66.7 years STANDARD_DEVIATION 8.55 • n=5 Participants	68 years STANDARD_DEVIATION 10.36 • n=7 Participants	67.4 years STANDARD_DEVIATION 9.49 • n=5 Participants
Age, Customized Adults 18-64 years of age	33 Participants n=5 Participants	30 Participants n=7 Participants	63 Participants n=5 Participants
Age, Customized From 65 to 84 years of age	68 Participants n=5 Participants	65 Participants n=7 Participants	133 Participants n=5 Participants
Age, Customized 85 years of age and over	1 Participants n=5 Participants	6 Participants n=7 Participants	7 Participants n=5 Participants
Sex: Female, Male Female	24 Participants n=5 Participants	34 Participants n=7 Participants	58 Participants n=5 Participants
Sex: Female, Male Male	78 Participants n=5 Participants	67 Participants n=7 Participants	145 Participants n=5 Participants
Region of Enrollment Austria	13 Participants n=5 Participants	15 Participants n=7 Participants	28 Participants n=5 Participants
Region of Enrollment Netherlands	5 Participants n=5 Participants	8 Participants n=7 Participants	13 Participants n=5 Participants
Region of Enrollment Belgium	6 Participants n=5 Participants	9 Participants n=7 Participants	15 Participants n=5 Participants
Region of Enrollment United States	47 Participants n=5 Participants	42 Participants n=7 Participants	89 Participants n=5 Participants
Region of Enrollment Israel	7 Participants n=5 Participants	5 Participants n=7 Participants	12 Participants n=5 Participants
Region of Enrollment Switzerland	13 Participants n=5 Participants	12 Participants n=7 Participants	25 Participants n=5 Participants
Region of Enrollment Germany	11 Participants n=5 Participants	10 Participants n=7 Participants	21 Participants n=5 Participants

PRIMARY outcome

Timeframe: at 3 months

Population: Safety Analysis Set, defined as all participants who received at least one dose of study drug

Outcome measures

Outcome measures
Measure	Clopidogrel n=101 Participants Open-label clopidogrel with aspirin	Edoxaban n=100 Participants Open-label edoxaban with aspirin
Percentage of Participants With Clinically Relevant Bleeding During Treatment Including Access Site Bleeding (IASB)	8 percentage of participants Interval 3.5 to 15.0	11 percentage of participants Interval 5.6 to 18.8
Percentage of Participants With Clinically Relevant Bleeding During Treatment Excluding Access Site Bleed (EASB)	6 percentage of participants Interval 2.2 to 12.5	6 percentage of participants Interval 2.2 to 12.6

PRIMARY outcome

Timeframe: within 6 months

Population: 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

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

Outcome measures

Outcome measures
Measure	Clopidogrel n=95 Participants Open-label clopidogrel with aspirin	Edoxaban n=94 Participants Open-label edoxaban with aspirin
Percentage of Participants With First Re-stenosis / Re-occlusion	34.7 percentage of participants	30.9 percentage of participants

SECONDARY outcome

Timeframe: within 3 months

Population: Safety Analysis Set, defined as all participants who received at least one dose of study drug

The percentage of participants with major, clinically relevant non-major, and minor bleeding occurring during treatment, within 3 months

Outcome measures

Outcome measures
Measure	Clopidogrel n=101 Participants Open-label clopidogrel with aspirin	Edoxaban n=100 Participants Open-label edoxaban with aspirin
Percentage of Participants With Major, Clinically Relevant Non-major (CRNM), and Minor Bleeding During Treatment IASB : Major Bleeding	5 percentage of participants Interval 1.6 to 11.2	1 percentage of participants Interval 0.0 to 5.4
Percentage of Participants With Major, Clinically Relevant Non-major (CRNM), and Minor Bleeding During Treatment IASB: CRNM Bleeding	4 percentage of participants Interval 1.1 to 9.8	10 percentage of participants Interval 4.9 to 17.6
Percentage of Participants With Major, Clinically Relevant Non-major (CRNM), and Minor Bleeding During Treatment IASB: Minor Bleeding	20.8 percentage of participants Interval 13.4 to 30.0	20 percentage of participants Interval 12.7 to 29.2
Percentage of Participants With Major, Clinically Relevant Non-major (CRNM), and Minor Bleeding During Treatment EASB : Major Bleeding	4 percentage of participants Interval 1.1 to 9.8	1 percentage of participants Interval 0.0 to 5.4
Percentage of Participants With Major, Clinically Relevant Non-major (CRNM), and Minor Bleeding During Treatment EASB : CRNM Bleeding	3 percentage of participants Interval 0.6 to 8.4	5 percentage of participants Interval 1.6 to 11.3
Percentage of Participants With Major, Clinically Relevant Non-major (CRNM), and Minor Bleeding During Treatment EASB : Minor Bleeding	17.8 percentage of participants Interval 10.9 to 26.7	19 percentage of participants Interval 11.8 to 28.1

SECONDARY outcome

Timeframe: within 6 months

Population: Safety Analysis Set

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.

Outcome measures

Outcome measures
Measure	Clopidogrel n=101 Participants Open-label clopidogrel with aspirin	Edoxaban n=100 Participants Open-label edoxaban with aspirin
Safety Assessments	30 Participants	31 Participants

SECONDARY outcome

Timeframe: within 6 months

Population: mITT Set 1 (Safety Analysis Set), defined as the participants who received at least 1 dose of study drug

Number of Adjudicated Major Adverse Cardiovascular Events (MACE) which is a composite of non-fatal myocardial infarction (MI), non-fatal stroke and cardiovascular death

Outcome measures

Outcome measures
Measure	Clopidogrel n=101 Participants Open-label clopidogrel with aspirin	Edoxaban n=100 Participants Open-label edoxaban with aspirin
Number of Adjudicated Major Adverse Cardiovascular Events During the Overall Study Period	1 Participants	3 Participants

SECONDARY outcome

Timeframe: within 6 months

Population: Safety Analysis Set

Number of participants with amputations within 6 months

Outcome measures

Outcome measures
Measure	Clopidogrel n=101 Participants Open-label clopidogrel with aspirin	Edoxaban n=100 Participants Open-label edoxaban with aspirin
Number of Participants With Amputations	3 Participants	1 Participants

Adverse Events

Clopidogrel

Serious events: 30 serious events

Other events: 23 other events

Deaths: 0 deaths

Edoxaban

Serious events: 31 serious events

Other events: 32 other events

Deaths: 3 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Clopidogrel n=101 participants at risk Open-label clopidogrel with aspirin	Edoxaban n=100 participants at risk Open-label edoxaban with aspirin
Injury, poisoning and procedural complications Post procedural haematoma	3.0% 3/101 • From the first dose to the end of the study (6 months)	6.0% 6/100 • From the first dose to the end of the study (6 months)
Investigations Creatinine renal clearance decreased	3.0% 3/101 • From the first dose to the end of the study (6 months)	6.0% 6/100 • From the first dose to the end of the study (6 months)
Respiratory, thoracic and mediastinal disorders Epistaxis	6.9% 7/101 • From the first dose to the end of the study (6 months)	7.0% 7/100 • From the first dose to the end of the study (6 months)
Nervous system disorders Dizziness	0.99% 1/101 • From the first dose to the end of the study (6 months)	5.0% 5/100 • From the first dose to the end of the study (6 months)
Nervous system disorders Headache	0.00% 0/101 • From the first dose to the end of the study (6 months)	5.0% 5/100 • From the first dose to the end of the study (6 months)
Gastrointestinal disorders Nausea	4.0% 4/101 • From the first dose to the end of the study (6 months)	6.0% 6/100 • From the first dose to the end of the study (6 months)
Musculoskeletal and connective tissue disorders Arthralgia	2.0% 2/101 • From the first dose to the end of the study (6 months)	6.0% 6/100 • From the first dose to the end of the study (6 months)
Musculoskeletal and connective tissue disorders Pain in extremity	6.9% 7/101 • From the first dose to the end of the study (6 months)	9.0% 9/100 • From the first dose to the end of the study (6 months)

Additional Information

Clinical Trial Information

Daiichi Sankyo Development Inc.

Phone: +44 1753482800

Email: [email protected]

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 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.
Publication restrictions are in place

Restriction type: OTHER

Measure	Clopidogrel n=101 participants at risk Open-label clopidogrel with aspirin	Edoxaban n=100 participants at risk Open-label edoxaban with aspirin
Blood and lymphatic system disorders ANAEMIA	0.00% 0/101 • From the first dose to the end of the study (6 months)	1.0% 1/100 • From the first dose to the end of the study (6 months)
Blood and lymphatic system disorders IRON DEFICIENCY ANAEMIA	0.99% 1/101 • From the first dose to the end of the study (6 months)	0.00% 0/100 • From the first dose to the end of the study (6 months)
Cardiac disorders ACUTE MYOCARDIAL INFARCTION	0.00% 0/101 • From the first dose to the end of the study (6 months)	2.0% 2/100 • From the first dose to the end of the study (6 months)
Cardiac disorders ANGINA PECTORIS	0.99% 1/101 • From the first dose to the end of the study (6 months)	1.0% 1/100 • From the first dose to the end of the study (6 months)
Cardiac disorders ATRIAL FIBRILLATION	0.99% 1/101 • From the first dose to the end of the study (6 months)	1.0% 1/100 • From the first dose to the end of the study (6 months)
Cardiac disorders BRADYCARDIA	0.99% 1/101 • From the first dose to the end of the study (6 months)	1.0% 1/100 • From the first dose to the end of the study (6 months)
Cardiac disorders CARDIAC FAILURE ACUTE	0.00% 0/101 • From the first dose to the end of the study (6 months)	1.0% 1/100 • From the first dose to the end of the study (6 months)
Cardiac disorders CARDIO-RESPIRATORY ARREST	0.00% 0/101 • From the first dose to the end of the study (6 months)	1.0% 1/100 • From the first dose to the end of the study (6 months)
Cardiac disorders CARDIOGENIC SHOCK	0.99% 1/101 • From the first dose to the end of the study (6 months)	0.00% 0/100 • From the first dose to the end of the study (6 months)
Cardiac disorders CORONARY ARTERY DISEASE	0.99% 1/101 • From the first dose to the end of the study (6 months)	2.0% 2/100 • From the first dose to the end of the study (6 months)
Cardiac disorders CORONARY ARTERY STENOSIS	0.00% 0/101 • From the first dose to the end of the study (6 months)	1.0% 1/100 • From the first dose to the end of the study (6 months)
Gastrointestinal disorders INTESTINAL ISCHAEMIA	0.99% 1/101 • From the first dose to the end of the study (6 months)	0.00% 0/100 • From the first dose to the end of the study (6 months)
General disorders CHEST PAIN	2.0% 2/101 • From the first dose to the end of the study (6 months)	2.0% 2/100 • From the first dose to the end of the study (6 months)
General disorders NECROSIS	0.99% 1/101 • From the first dose to the end of the study (6 months)	0.00% 0/100 • From the first dose to the end of the study (6 months)
Hepatobiliary disorders CHOLELITHIASIS	0.00% 0/101 • From the first dose to the end of the study (6 months)	1.0% 1/100 • From the first dose to the end of the study (6 months)
Infections and infestations CELLULITIS	0.00% 0/101 • From the first dose to the end of the study (6 months)	1.0% 1/100 • From the first dose to the end of the study (6 months)
Infections and infestations CLOSTRIDIUM COLITIS	0.99% 1/101 • From the first dose to the end of the study (6 months)	0.00% 0/100 • From the first dose to the end of the study (6 months)
Infections and infestations GANGRENE	0.99% 1/101 • From the first dose to the end of the study (6 months)	2.0% 2/100 • From the first dose to the end of the study (6 months)
Infections and infestations INFECTED SKIN ULCER	0.00% 0/101 • From the first dose to the end of the study (6 months)	1.0% 1/100 • From the first dose to the end of the study (6 months)
Infections and infestations LOCALISED INFECTION	0.99% 1/101 • From the first dose to the end of the study (6 months)	0.00% 0/100 • From the first dose to the end of the study (6 months)
Infections and infestations PNEUMONIA	0.00% 0/101 • From the first dose to the end of the study (6 months)	1.0% 1/100 • From the first dose to the end of the study (6 months)
Infections and infestations UROSEPSIS	0.99% 1/101 • From the first dose to the end of the study (6 months)	0.00% 0/100 • From the first dose to the end of the study (6 months)
Injury, poisoning and procedural complications ARTERIAL RESTENOSIS	0.00% 0/101 • From the first dose to the end of the study (6 months)	1.0% 1/100 • From the first dose to the end of the study (6 months)
Injury, poisoning and procedural complications FEMUR FRACTURE	0.00% 0/101 • From the first dose to the end of the study (6 months)	1.0% 1/100 • From the first dose to the end of the study (6 months)
Injury, poisoning and procedural complications PERIPHERAL ARTERY RESTENOSIS	0.99% 1/101 • From the first dose to the end of the study (6 months)	3.0% 3/100 • From the first dose to the end of the study (6 months)
Injury, poisoning and procedural complications POST PROCEDURAL HAEMATOMA	0.99% 1/101 • From the first dose to the end of the study (6 months)	0.00% 0/100 • From the first dose to the end of the study (6 months)
Injury, poisoning and procedural complications POST PROCEDURAL HAEMORRHAGE	2.0% 2/101 • From the first dose to the end of the study (6 months)	0.00% 0/100 • From the first dose to the end of the study (6 months)
Injury, poisoning and procedural complications VASCULAR PSEUDOANEURYSM	0.00% 0/101 • From the first dose to the end of the study (6 months)	4.0% 4/100 • From the first dose to the end of the study (6 months)
Injury, poisoning and procedural complications WOUND	0.99% 1/101 • From the first dose to the end of the study (6 months)	0.00% 0/100 • From the first dose to the end of the study (6 months)
Metabolism and nutrition disorders FLUID OVERLOAD	0.99% 1/101 • From the first dose to the end of the study (6 months)	0.00% 0/100 • From the first dose to the end of the study (6 months)
Musculoskeletal and connective tissue disorders COMPARTMENT SYNDROME	0.99% 1/101 • From the first dose to the end of the study (6 months)	1.0% 1/100 • From the first dose to the end of the study (6 months)
Musculoskeletal and connective tissue disorders PAIN IN EXTREMITY	0.99% 1/101 • From the first dose to the end of the study (6 months)	1.0% 1/100 • From the first dose to the end of the study (6 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) LUNG NEOPLASM MALIGNANT	0.99% 1/101 • From the first dose to the end of the study (6 months)	0.00% 0/100 • From the first dose to the end of the study (6 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) PANCREATIC CARCINOMA METASTATIC	0.00% 0/101 • From the first dose to the end of the study (6 months)	1.0% 1/100 • From the first dose to the end of the study (6 months)
Nervous system disorders CAROTID ARTERY STENOSIS	0.99% 1/101 • From the first dose to the end of the study (6 months)	0.00% 0/100 • From the first dose to the end of the study (6 months)
Nervous system disorders HAEMORRHAGIC STROKE	0.00% 0/101 • From the first dose to the end of the study (6 months)	1.0% 1/100 • From the first dose to the end of the study (6 months)
Nervous system disorders PRESYNCOPE	0.99% 1/101 • From the first dose to the end of the study (6 months)	0.00% 0/100 • From the first dose to the end of the study (6 months)
Psychiatric disorders ALCOHOL ABUSE	0.00% 0/101 • From the first dose to the end of the study (6 months)	1.0% 1/100 • From the first dose to the end of the study (6 months)
Renal and urinary disorders HAEMATURIA	0.00% 0/101 • From the first dose to the end of the study (6 months)	1.0% 1/100 • From the first dose to the end of the study (6 months)
Renal and urinary disorders RENAL FAILURE ACUTE	0.00% 0/101 • From the first dose to the end of the study (6 months)	1.0% 1/100 • From the first dose to the end of the study (6 months)
Renal and urinary disorders RENAL TUBULAR NECROSIS	0.99% 1/101 • From the first dose to the end of the study (6 months)	0.00% 0/100 • From the first dose to the end of the study (6 months)
Respiratory, thoracic and mediastinal disorders ACUTE RESPIRATORY FAILURE	0.00% 0/101 • From the first dose to the end of the study (6 months)	1.0% 1/100 • From the first dose to the end of the study (6 months)
Respiratory, thoracic and mediastinal disorders EPISTAXIS	0.99% 1/101 • From the first dose to the end of the study (6 months)	0.00% 0/100 • From the first dose to the end of the study (6 months)
Skin and subcutaneous tissue disorders SKIN ULCER	0.99% 1/101 • From the first dose to the end of the study (6 months)	1.0% 1/100 • From the first dose to the end of the study (6 months)
Vascular disorders FEMORAL ARTERY OCCLUSION	0.00% 0/101 • From the first dose to the end of the study (6 months)	2.0% 2/100 • From the first dose to the end of the study (6 months)
Vascular disorders HAEMORRHAGE	0.00% 0/101 • From the first dose to the end of the study (6 months)	1.0% 1/100 • From the first dose to the end of the study (6 months)
Vascular disorders HYPERTENSION	0.99% 1/101 • From the first dose to the end of the study (6 months)	0.00% 0/100 • From the first dose to the end of the study (6 months)
Vascular disorders INTERMITTENT CLAUDICATION	4.0% 4/101 • From the first dose to the end of the study (6 months)	2.0% 2/100 • From the first dose to the end of the study (6 months)
Vascular disorders PERIPHERAL ARTERIAL OCCLUSIVE DISEASE	3.0% 3/101 • From the first dose to the end of the study (6 months)	1.0% 1/100 • From the first dose to the end of the study (6 months)
Vascular disorders PERIPHERAL ARTERY STENOSIS	2.0% 2/101 • From the first dose to the end of the study (6 months)	2.0% 2/100 • From the first dose to the end of the study (6 months)
Vascular disorders PERIPHERAL ARTERY THROMBOSIS	2.0% 2/101 • From the first dose to the end of the study (6 months)	3.0% 3/100 • From the first dose to the end of the study (6 months)
Vascular disorders PERIPHERAL EMBOLISM	0.99% 1/101 • From the first dose to the end of the study (6 months)	0.00% 0/100 • From the first dose to the end of the study (6 months)
Vascular disorders PERIPHERAL ISCHAEMIA	2.0% 2/101 • From the first dose to the end of the study (6 months)	1.0% 1/100 • From the first dose to the end of the study (6 months)