Edoxaban in Peripheral Arterial Disease
Condition: Peripheral Arterial Disease
MeSH terms: Peripheral Arterial Disease; Peripheral Vascular Diseases
Intervention: edoxaban; Clopidogrel; Aspirin
Intervention description: 75mg tablet
Intervention MeSH terms: Aspirin; Edoxaban; Clopidogrel
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 203.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

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