Dose-confirmatory Bridging Study in Total Knee Replacement

Study Overview
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Brief Summary
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The objective of this dose-confirmatory bridging study is to investigate the safety and efficacy of rivaroxaban 5 to 10 mg once-daily (od) dosing in the prevention of venous thromboembolism (VTE) in Japanese patients undergoing elective total knee replacement (TKR) and to confirm the extrapolability of global data to Japanese patients by comparing with data from overseas phase III study (RECORD 3 - Study 11356) and phase II studies.

Official Title
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Randomized, Double-blind, Parallel-group, Active-controlled, Dose-confirmatory Bridging Study of Rivaroxaban (BAY59-7939) 5 to 10 mg Once-daily Regimen With a Reference Drug of Enoxaparin in the Prevention of Venous Thromboembolism in Patients Undergoing Elective Total Knee Replacement

Conditions
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Venous Thromboembolism

Intervention / Treatment
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* Drug: Rivaroxaban (BAY59-7939)
* Drug: Rivaroxaban (BAY59-7939)
* Drug: Rivaroxaban (BAY59-7939)
* Drug: Enoxaparin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female patients aged 20 years or above Patients undergoing elective TKR (the first replacement of the applicable knee joint) Patients' written informed consent to participation after receiving detailed verbal and written information on any study specific procedures in advance Exclusion Criteria: Planned, staged major orthopedic surgery within 3 months prior to elective TKR or during this study History of clinically significant active bleeding (e.g. intracranial bleeding, gastrointestinal bleeding*), or high bleeding risk *: within 3 months prior to elective TKR for gastrointestinal bleeding Subjects with hepatic disease which is associated with coagulopathy leading to a clinically relevant bleeding risk Severe impaired renal function (CLCR calculated by Cockcroft-Gault formula: <30 mL/min) Conditions prohibiting bilateral venography (e.g. amputation of 1 leg, allergy to contrast media) Ongoing anticoagulant therapy (e.g. warfarin, heparins and Factor Xa inhibitors other than study medication) that cannot be stopped (in the opinion of the investigator/sub investigator) Subjects for whom epidural catheters are expected to be left in for longer than 18 hours post-operatively Planned intermittent pneumatic compression during treatment period.

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1<br> | Drug: Rivaroxaban (BAY59-7939)<br>* daily dose: 5mg/day (5mg, once daily) for 11 to 12 days (±2 days)<br>|
| Experimental: Arm 2<br> | Drug: Rivaroxaban (BAY59-7939)<br>* daily dose: 7.5mg/day (7.5mg, once daily) for 11 to 12 days (±2 days)<br>|
| Experimental: Arm 3<br> | Drug: Rivaroxaban (BAY59-7939)<br>* daily dose: 10mg/day (10mg, once daily) for 11 to 12 days (±2 days)<br>|
| Active Comparator: Arm 4<br> | Drug: Enoxaparin<br>* daily dose: 40mg/day (20mg, twice daily) for 10 to 11 days (±2 days)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| A composite endpoint of any deep vein thrombosis (proximal and/or distal), non-fatal pulmonary embolism and death from all causes |  | up to Day 13 (±2 days) | 
| Treatment-emergent bleeding (major, non-major clinically relevant, other non-major) |  | from the first intake of study medication to no later than 2 days after the last intake of study drug | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| deep vein thrombosis (total, proximal, distal) |  | up to Day 13 (±2 days) | 
| symptomatic venous thromboembolism |  | up to Day 13 (±2 days) | 
| major venous thromboembolism (proximal deep vein thromboembolism, pulmonary embolism or venous thromboembolism-related death) |  | up to Day 13 (±2 days) | 
| symptomatic venous thromboembolism |  | within 30 days after stop of treatment with study drug | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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venous thromboembolism, prevention, orthopaedic surgery