A Randomized, Open-Label, Parallel-Group, Multi-Center Study for the Evaluation of Efficacy and Safety of Edoxaban Monotherapy Versus Low Molecular Weight (LMW) Heparin/Warfarin in Subjects With Symptomatic Deep-Vein Thrombosis
Condition: Deep Vein Thrombosis; Venous Thrombosis
MeSH terms: Thrombosis; Venous Thrombosis
Intervention: edoxaban tosylate; enoxaparin/unfractionated heparin; warfarin
Intervention description: edoxaban tosylate (DU-176b), film-coated for oral use, 90 mg once daily (QD) for 10 days (±2 days) followed by 60 mg QD for a total of approximately 90 days of edoxaban treatment; enoxaparin - administered by subcutaneous injection;1 mg/kg/ twice daily or 1.5 mg/kg once daily unfractionated heparin - started with 5000 IU bolus intravenous administration, 1300 IU/h continuous infusion, minimum of 5 days of treatment and stopped when target INR (2.0 - 3.0) is achieved.; tablet for oral use; daily dosage, adjusted to maintain international normalized ratio (INR) between 2.0 and 3.0; 90 days treatment.
Intervention MeSH terms: Heparin; Enoxaparin; Calcium heparin; Warfarin; Edoxaban
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 85.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      Assess the relative change in thrombus volume as determined by two assessments (Baseline and
      Day 14-21) with magnetic resonance venography (MRV) in subjects with deep-vein thrombosis
      (DVT) treated with either an edoxaban monotherapy regimen or a low molecular weight (LMW)
      heparin/warfarin regimen.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male or female subjects older than the minimum legal adult age (country specific)

          -  Acute symptomatic proximal DVT involving the popliteal, femoral or iliac veins
             confirmed by compression ultrasonography (CUS) or other appropriate imaging techniques
             (such as venography or spiral/contrast CT) with symptom onset < or = 1week prior to
             randomization

          -  Able to provide signed informed consent

        Exclusion Criteria:

          -  Concomitant pulmonary embolism known to the investigator at the time of randomization

          -  Thrombectomy, insertion of a caval filter, or use of a fibrinolytic agent to treat the
             current episode of DVT

          -  Indication for warfarin other than DVT

          -  More than 48 hours pre-treatment with therapeutic dosages of anti-coagulant treatment
             [low molecular weight heparin (LMWH), unfractionated heparin (UFH), fondaparinux, VKA,
             factor Xa inhibitor or other anti coagulant per local labeling] prior to randomization
             to treat the current episode

          -  Treatment with any investigational drug within 30 days prior to randomization

          -  Calculated creatinine clearance (CrCL) < 30 mL/min

          -  Significant liver disease (e.g., acute hepatitis, chronic active hepatitis, cirrhosis)
             or alanine aminotransferase (ALT) > or = 2 times the upper limit of normal (ULN), or
             total bilirubin (TBL) > or = to 1.5 times the ULN (however subjects whose elevated TBL
             is due to known Gilbert's syndrome may be included in the study)

          -  Subjects with active cancer for whom long term treatment with (LMW) heparin is
             anticipated

          -  Life expectancy < 3 months

          -  Active bleeding or high risk for bleeding contraindicating treatment with (LMW)
             heparin or warfarin

          -  Uncontrolled hypertension as judged by the Investigator (e.g., systolic blood pressure
             > 170 mmHg or diastolic blood pressure > 100 mmHg despite antihypertensive medications
             confirmed by repeat measurement)

          -  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

          -  Any contraindication listed in the local labeling of LMWH, UFH, or warfarin

          -  Chronic treatment with non-aspirin non-steroidal anti-inflammatory drugs (NSAIDs)
             including both cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX- 2) inhibitors for >
             or = 4 days/week anticipated to continue during the study.

          -  Treatment with aspirin in a dosage of more than 100 mg/per day or dual antiplatelet
             therapy (any two antiplatelet agents including aspirin plus any other oral or
             intravenous [IV] antiplatelet drug) anticipated to continue during the study

          -  Treatment with P-gp inhibitors is not permitted at the time of randomization;
             subsequent use is permitted, with a dose reduction in the edoxaban monotherapy
             treatment arm.

          -  Known history of positive Hepatitis B antigen or Hepatitis C antibody

          -  Subjects with any condition that, as judged by the investigator, would put the subject
             at increased risk of harm if he/she participated in the study; including, but not
             limited to, subjects at increased risk of harm if given a gadolinium-based contrast
             agent such as gadofosveset trisodium (Ablavar®)

          -  Subjects for whom MRI would be contraindicated (e.g., subjects with metal implants) or
             for whom the use of a gadolinium-based contrast agent such as gadofosveset trisodium
             (Ablavar®) would be contraindicated

          -  Subject has previously entered this study or another edoxaban study