Comparative Investigation of Low Molecular Weight (LMW) Heparin/Edoxaban Tosylate (DU176b) Versus (LMW) Heparin/Warfarin in the Treatment of Symptomatic Deep-Vein Blood Clots and/or Lung Blood Clots. (The Edoxaban Hokusai-VTE Study).

Study Overview
=================
Brief Summary
-----------------
Evaluation of heparin/edoxaban tosylate (DU176b) versus heparin/warfarin in preventing recurrence of blood clots in patients with acute symptomatic deep-vein blood clots in the legs and/or blood clots in the lungs.

Official Title
-----------------
A Phase 3, Randomized, Parallel-Group, Multi-Center, Multi-National Study for the Evaluation of Efficacy and Safety of (LMW) Heparin/Edoxaban Versus (LMW) Heparin/Warfarin in Subjects With Symptomatic Deep-Vein Thrombosis (DVT) and or Pulmonary Embolism (PE).

Conditions
-----------------
Venous Thromboembolism, Deep Vein Thrombosis (DVT), Pulmonary Embolism (PE), Thromboembolism, Venous Thrombosis

Intervention / Treatment
-----------------
* Drug: edoxaban tosylate(DU-176b)
* Drug: low molecular weight heparin/unfractionated heparin
* Drug: warfarin


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male or female subjects older than the minimum legal adult age (country specific); Acute symptomatic proximal DVT and/or symptomatic PE confirmed at the site by appropriate diagnostic imaging; Able to provide written informed consent Exclusion Criteria: thrombectomy, insertion of a caval filter, or use of a fibrinolytic agent to treat the current episode of DVT and/or PE; More than 48 hours pre-treatment with anticoagulant therapy prior to randomization; Calculated Creatinine clearance (CrCL) < 30 mL/min; significant liver disease (e.g., acute hepatitis, chronic active hepatitis, cirrhosis) or alanine transaminase (ALT) >\= 2 times the upper limit of normal (ULN), or total bilirubin (TBL) x 1.5 times the ULN; patients with active cancer for whom long term treatment with (LMW) heparin is anticipated; active bleeding or high risk for bleeding contraindicating treatment with (LMW) heparin or warfarin; chronic treatment with non-aspirin non-steroidal anti-inflammatory drugs (NSAIDs); treatment with aspirin in a dosage of more than 100 mg/per day or dual antiplatelet therapy; concurrent treatment with potent P-gp inhibitors; subjects with any condition that, as judged by the investigator, would place the subject at increased risk of harm if he/she participated in the study

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: heparin/edoxaban tosylate<br> | Drug: edoxaban tosylate(DU-176b)<br>* edoxaban tosylate(DU-176b), film-coated tablet for oral use, 30 mg, two tablets (60 mg) once daily, maximum of 12 months treatment<br>Drug: low molecular weight heparin/unfractionated heparin<br>* LMW heparin - subcutaneous injection, 1 mg/Kg twice daily or 1.5 mg/Kg once daily. Unfractionated heparin - 5,000 IU bolus intravenous administration, 1,300 IU/hour continuous infusion, minimum of 5 days and maximum of about 12 days treatment<br>|
| Active Comparator: heparin/warfarin<br> | Drug: low molecular weight heparin/unfractionated heparin<br>* LMW heparin - subcutaneous injection, 1 mg/Kg twice daily or 1.5 mg/Kg once daily. Unfractionated heparin - 5,000 IU bolus intravenous administration, 1,300 IU/hour continuous infusion, minimum of 5 days and maximum of about 12 days treatment<br>Drug: warfarin<br>* tablet for oral use; 0.5 mg, 1 mg, 2.5 mg, 5 mg; daily dosage, adjusted to maintain international normalized ratio (INR) between 2.0 and 3.0; maximum of 12 months treatment<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Symptomatic Recurrent VTE, i.e., the Composite of DVT, Non-fatal PE, and Fatal PE | Symptomatic recurrent Venous Thromboembolism (VTE), i.e., the composite of deep Vein Thrombosis (DVT), non-fatal Pulmonary Embolism (PE), and fatal PE occurring during the Overall Study Period. Overall Study Period defined as The time from the reference date (randomization date/initial dose of study drug date) to the last study follow-up visit. | 12 months from time of randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Composite Clinical Outcome of Symptomatic Recurrent VTE and All-cause Mortality |  | 12 months from time of randomization | 
| Clinically Relevant Bleeding (i.e., Major or Clinically Relevant Non-major Bleeding) Occurring During Treatment | Clinically relevant bleeding (i.e., major or clinically relevant non-major bleeding) occurring during treatment plus 3 days after their last dose for that time period. | 12 months from time of randomization | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Recurrent Thrombosis, Recurrent Pulmonary Embolism, Symptomatic Deep Vein Thrombosis, Symptomatic Pulmonary Embolism, Venous Thromboembolism (VTE)