Once-daily Oral Direct Factor Xa Inhibitor BAY59-7939 in Patients With Acute Symptomatic Deep-vein Thrombosis

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to determine the optimal dose of BAY 59-7939 and to compare the safety and effectiveness of this new drug with the standard way of treatment of deep vein thrombosis (heparin infusion plus one of the vitamin K antagonists), taking into account new events of thrombosis and pulmonary embolism and bleeding risk.

Detailed Description
-----------------
Within the U.S., Johnson & Johnson is sponsor.

Official Title
-----------------
Once-daily Oral Direct Factor Xa Inhibitor BAY59-7939 in Patients With Acute Symptomatic Deep-vein Thrombosis The Einstein-DVT Dose-finding Study. A Phase II Evaluation.

Conditions
-----------------
Venous Thromboembolism

Intervention / Treatment
-----------------
* Drug: Xarelto (Rivaroxaban, BAY59-7939)
* Drug: Xarelto (Rivaroxaban, BAY59-7939)
* Drug: Xarelto (Rivaroxaban, BAY59-7939)
* Drug: (LMW) Heparin + Vitamin K Antagonist


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Confirmed acute symptomatic DVT, i.e. proximal or extensive calf-vein thrombosis involving at least the upper third part of the calf veins, without concomitant symptomatic PE Written informed consent Exclusion Criteria: Legal lower age limitations (country specific) Thrombectomy, insertion of a caval filter, or use of a fibrinolytic agent to treat the current episode of DVT Other indication for VKA than PE/DVT More than 36 hours pre-randomization treatment with therapeutic dosages of (LMW) heparin or more than a single dose of VKA prior to randomization Participation in another pharmacotherapeutic study within the prior 30 days Creatinine clearance < 30 mL/min, impaired liver function (transaminases > 2 x ULN), or bacterial endocarditis Life expectancy < 3 months Active bleeding or high risk for bleeding contraindicating treatment with (LMW) heparin Uncontrolled hypertension: systolic blood pressure > 200 mmHg and diastolic blood pressure > 110 mmHg Pregnancy or childbearing potential without proper contraceptive measures Any other contraindication listed in the labeling of warfarin, acenocoumarol, phenprocoumon, fluindione, UFH, enoxaparin, or tinzaparin Systemic treatment with azole compounds or other strong CYP3A4 inhibitors (e.g. ketoconazole, fluconazol, itraconazole, HIV protease inhibitors) within 4 days prior to randomization and during 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Arm 4<br> | Drug: (LMW) Heparin + Vitamin K Antagonist<br>* Low Molecular Weight (LMW) Heparin + Vitamin K Antagonist (VKA) for 5 days, then VKA only for the rest of 12 weeks<br>|
| Experimental: Arm 1<br> | Drug: Xarelto (Rivaroxaban, BAY59-7939)<br>* BAY59-7939 20 mg once daily (od) for 12 weeks<br>|
| Experimental: Arm 2<br> | Drug: Xarelto (Rivaroxaban, BAY59-7939)<br>* BAY59-7939 30 mg od for 12 weeks<br>|
| Experimental: Arm 3<br> | Drug: Xarelto (Rivaroxaban, BAY59-7939)<br>* BAY59-7939 40 mg od for 12 weeks<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary efficacy endpoint was the composite of symptomatic recurrent DVT or symptomatic fatal and non-fatal PE at 12 weeks and deterioration in thrombotic burden, as assessed by CUS and PLS, at baseline and at 12 weeks. |  | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The principal safety outcome is all clinically relevant bleeding (i.e. major bleeding and clinically relevant non-major bleeding) within 12 weeks. |  | 12 weeks | 
| The separate components of the primary efficacy outcome at 12 weeks. |  | 12 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Treatment of venous thromboembolism