Dose-confirmatory Bridging Study in Total Knee Replacement

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

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.

Study Overview

• Status: Completed
• Conditions: Venous Thromboembolism
• Intervention / Treatment: Drug: Rivaroxaban (BAY59-7939); Drug: Rivaroxaban (BAY59-7939); Drug: Rivaroxaban (BAY59-7939); Drug: Enoxaparin

• Study Type: Interventional
• Enrollment (Actual): 302
• Phase: Phase 3

Contacts and Locations

Study Locations

• Japan
  • Fukuoka, Japan, 813-0017
  • Fukuoka, Japan, 819-8551
  • Kyoto, Japan, 602-8026
  • Osaka, Japan, 558-8558
  • Osaka, Japan, 530-0012
  • Saga, Japan, 849-8501
  • Saitama, Japan, 336-8522
  • Toyama, Japan, 930-8550
  • Aichi
    • Nagoya, Aichi, Japan, 455-8530
  • Chiba
    • Matsudo, Chiba, Japan, 271-8511
  • Ehime
    • Matsuyama, Ehime, Japan, 790-8524
  • Fukushima
    • Kawanuma, Fukushima, Japan, 969-6593
    • Koriyama, Fukushima, Japan, 963-8501
  • Hokkaido
    • Asahikawa, Hokkaido, Japan, 078-8237
    • Hakodate, Hokkaido, Japan, 040-8611
    • Sapporo, Hokkaido, Japan, 060-8648
  • Hyogo
    • Kakogawa, Hyogo, Japan, 675-8545
    • Kobe, Hyogo, Japan, 657-0068
    • Nishinomiya, Hyogo, Japan, 663-8501
  • Ibaraki
    • Tsukuba, Ibaraki, Japan, 305-0854
  • Nagano
    • Iida, Nagano, Japan, 395-8505
  • Nagasaki
    • Sasebo, Nagasaki, Japan, 857-8575
  • Okinawa
    • Tomigusuku, Okinawa, Japan, 901-0243
  • Osaka
    • Hirakata, Osaka, Japan, 573-8511
    • Izumi, Osaka, Japan, 594-0071
    • Izumisano, Osaka, Japan, 598-8577
    • Kishiwada, Osaka, Japan, 596-8522
    • Kishiwada, Osaka, Japan, 596-8501
    • Osakasayama, Osaka, Japan, 589-8511
    • Sakai, Osaka, Japan, 599-8271
    • Takatsuki, Osaka, Japan, 569-1192
  • Tokyo
    • Adachi, Tokyo, Japan, 121-0064
    • Nerima-ku, Tokyo, Japan, 177-8521

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Bayer
• Collaborators: Janssen Scientific Affairs, LLC

Study record dates

Study Major Dates

• Study Start: October 1, 2010
• Primary Completion (Actual): May 1, 2011
• Study Completion (Actual): June 1, 2011

Study Registration Dates

• First Submitted: September 20, 2010
• First Submitted That Met QC Criteria: September 21, 2010
• First Posted (Estimate): September 22, 2010

Study Record Updates

• Last Update Posted (Estimate): January 18, 2017
• Last Update Submitted That Met QC Criteria: January 17, 2017
• Last Verified: January 1, 2017

More Information

Terms related to this study

• Keywords: prevention; venous thromboembolism; orthopaedic surgery
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Embolism and Thrombosis; Thromboembolism; Venous Thromboembolism; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Fibrinolytic Agents; Fibrin Modulating Agents; Protease Inhibitors; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Rivaroxaban; Enoxaparin
• Other Study ID Numbers: 14398