Clinical trial NCT01802775: Edoxaban in Peripheral Arterial Disease
Official title: A Randomized, Open-Label, Parallel-Group, Multi-Center Study Of Adding Edoxaban Or Clopidogrel To Aspirin To Maintain Patency In Subjects With Peripheral Arterial Disease Following Femoropopliteal Endovascular Intervention
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Peripheral Arterial Disease
Lead sponsor: Daiichi Sankyo
Sponsor class: INDUSTRY
Collaborators: name: UMC Utrecht
First posted: 2013-03-01
Enrollment: 203
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study is a randomized, open-label, blinded endpoint, parallel-group, active-control, multi-center, proof-of-concept study in subjects with Peripheral Arterial Disease (PAD), designed to assess the safety and potential efficacy of adding edoxaban to aspirin following femoropopliteal endovascular intervention, with or without stent placement, relative to current treatment practice with clopidogrel and aspirin.


Eligibility criteria: Inclusion Criteria:

* Male or female subjects older than the minimum legal adult age (country specific);
* Rutherford stages 2-5 provided there are no ulcerations on the heel and/or exposed tendon and/or bone;
* Superficial femoral above knee-popliteal ( 3 cm proximal to the medial femoral condyle) lesion and ≥ 50% stenosis or occlusion;
* At least one run-off vessel to the foot with or without additional endovascular intervention;
* Successful intervention, defined as angiographic confirmation of ≤ 30% residual stenosis and absence of flow limiting dissection;
* Adequate hemostasis at the vascular access site within 24 hours of intervention;
* A subject is also eligible if they have undergone additional successful endovascular intervention(s) during the index intervention;
* Able to provide signed informed consent.

Exclusion Criteria:

* Calculated Creatinine Clearance \< 30 ml/min;
* Femoral or popliteal aneurysm;
* Adjunctive use of thrombolytics;
* Any extravasation or distal embolization not successfully treated;
* Uncontrolled hypertension as judged by the investigator (e.g., systolic blood pressure \> 170 mmHg or diastolic blood pressure \> 100 mmHg despite antihypertensives);
* Aspirin intolerance;
* Clopidogrel intolerance;
* Contraindication for anticoagulants or antiplatelets and any other contraindication listed in the local labeling of aspirin and/or clopidogrel;
* Active bleeding or known high risk for bleeding or history of intracranial, or spontaneous intraocular, spinal retroperitoneal or intra-articular bleeding; overt gastrointestinal (GI) bleeding or active ulcer within the previous year;
* Subjects receiving dual antiplatelet or anticoagulant therapy at the time of randomization; subjects receiving pre-interventional loading dose of clopidogrel or other P2Y12 receptor antagonists;
* Treatment with cilostazol within 24 hours of randomization;
* Subjects receiving prohibited concomitant medications \[fibrinolytics, chronic use of non steroidal anti-inflammatory drugs (NSAIDS) \> 4 days per week, and oral or parenteral non-aspirin NSAIDs and strong P-gp inhibitors\];
* Prior stroke or myocardial infarction (MI) or acute coronary syndrome within 3 months;
* Chronic liver disease \[alanine transaminase (ALT) and/or aspartate transaminase (AST) ≥ 2 × upper limit of normal; total bilirubin (TBL) ≥ 1.5 × upper limit of normal\]; however, subjects whose elevated TBL is due to known Gilbert"s syndrome may be included in the study;
* Prior history of a positive test for Hepatitis B antigen or Hepatitis C antibody;
* Subjects who received any investigational drug or device within 30 days prior to randomization, or plan to receive such investigational therapy during the study period;
* Subjects previously randomized to an edoxaban (DU-176b) study;
* Women of childbearing potential without proper contraceptive measures (i.e. a method of contraception with a failure rate \< 1 % during the course of the study including the observational period) and women who are pregnant or breast feeding;
* Subjects with the following diagnoses or situations:

Active malignancy except for adequately treated non-melanoma skin cancer or other non-invasive or in-situ neoplasm (e.g., cervical cancer in situ); Concurrent treatment with cancer therapy (drugs, radiation, and/or surgery); Other significant active concurrent medical illness or infection; Life expectancy \< 12 months;

* Subjects who are unlikely to comply with the protocol (e.g., uncooperative attitude, inability to return for subsequent visits, and/or otherwise considered by the Investigator to be unlikely to complete the study);
* Subjects with any condition that, in the opinion of the Investigator, would place the subject at increased risk of harm if he/she participated in the study;
* History of heparin-induced thrombocytopenia

Primary outcomes:
measure: Percentage of Participants With Clinically Relevant Bleeding During Treatment
timeFrame: at 3 months
measure: Percentage of Participants With First Re-stenosis / Re-occlusion
timeFrame: within 6 months
Secondary outcomes:
measure: Percentage of Participants With Major, Clinically Relevant Non-major (CRNM), and Minor Bleeding During Treatment
timeFrame: within 3 months
measure: Safety Assessments
timeFrame: within 6 months
measure: Number of Adjudicated Major Adverse Cardiovascular Events During the Overall Study Period
timeFrame: within 6 months
measure: Number of Participants With Amputations
timeFrame: within 6 months
Other outcomes:
Locations:
city: Birmingham
country: United States
state: Alabama
city: Phoenix
country: United States
state: Arizona
city: Beverly Hills
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: Orange
country: United States
state: California
city: New Haven
country: United States
state: Connecticut
city: Hollywood
country: United States
state: Florida
city: Jacksonville
country: United States
state: Florida
city: Aurora
country: United States
state: Illinois
city: Iowa City
country: United States
state: Iowa
city: New Orleans
country: United States
state: Louisiana
city: Lewiston
country: United States
state: Maine
city: Boston
country: United States
state: Massachusetts
city: Flint
country: United States
state: Michigan
city: Ypsilanti
country: United States
state: Michigan
city: Teaneck
country: United States
state: New Jersey
city: New York
country: United States
state: New York
city: Raleigh
country: United States
state: North Carolina
city: Wilmington
country: United States
state: North Carolina
city: Cleveland
country: United States
state: Ohio
city: Columbus
country: United States
state: Ohio
city: Camp Hill
country: United States
state: Pennsylvania
city: Columbia
country: United States
state: South Carolina
city: Greenville
country: United States
state: South Carolina
city: Austin
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
city: Graz
country: Austria
city: Innsbruck
country: Austria
city: Wien
country: Austria
city: Edegem
country: Belgium
facility: Edgem
city: Ghent
country: Belgium
city: Leuven
country: Belgium
city: Bad Krozingen
country: Germany
city: Leipzig
country: Germany
city: Afula
country: Israel
city: Jerusalem
country: Israel
city: Tel Aviv
country: Israel
city: Tel Hashomer
country: Israel
city: Rotterdam
country: Netherlands
city: Utrecht
country: Netherlands
city: Bern
country: Switzerland
city: Zurich
country: Switzerland
Study officials:
affiliation: Daiichi Sankyo
name: Global Clinical Leader
role: STUDY_DIRECTOR
References:
citation: Moll F, Baumgartner I, Jaff M, Nwachuku C, Tangelder M, Ansel G, Adams G, Zeller T, Rundback J, Grosso M, Lin M, Mercur MF, Minar E; ePAD Investigators. Edoxaban Plus Aspirin vs Dual Antiplatelet Therapy in Endovascular Treatment of Patients With Peripheral Artery Disease: Results of the ePAD Trial. J Endovasc Ther. 2018 Apr;25(2):158-168. doi: 10.1177/1526602818760488.
citation: Tangelder MJ, Nwachuku CE, Jaff M, Baumgartner I, Duggal A, Adams G, Ansel G, Grosso M, Mercuri M, Shi M, Minar E, Moll FL. A review of antithrombotic therapy and the rationale and design of the randomized edoxaban in patients with peripheral artery disease (ePAD) trial adding edoxaban or clopidogrel to aspirin after femoropopliteal endovascular intervention. J Endovasc Ther. 2015 Apr;22(2):261-8. doi: 10.1177/1526602815574687.