Regulation of Coagulation in Orthopedic Surgery to Prevent Deep Vein Thromboembolism (DVT) and Pulmonary Embolism (PE); a Study of BAY59-7939 in the Prevention of Venous Thrombo Embolism (VTE) in Subjects Undergoing Elective Total Knee Replacement (RECORD 4)

This study has been completed.
Sponsor:
Information provided by:
Bayer
ClinicalTrials.gov Identifier:
NCT00362232
First received: August 8, 2006
Last updated: July 18, 2013
Last verified: July 2013
  Purpose

The purpose of this study is to assess if 10 mg BAY59-7939, taken once daily as a tablet, is safe and prevents blood clot which may form after a knee replacement operation.


Condition Intervention Phase
Venous Thromboembolism
Drug: Rivaroxaban (Xarelto, BAY59-7939)
Drug: Enoxaparin
Drug: Placebo: tablet of Rivaroxaban
Drug: Placebo: syringes of Enoxaparin
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Prevention
Official Title: RECORD 4 Study: REgulation of Coagulation in ORthopedic Surgery to Prevent DVT and PE; a Controlled, Double-blind, Randomized Study of BAY59-7939 in the Prevention of VTE in Subjects Undergoing Elective Total Knee Replacement

Resource links provided by NLM:


Further study details as provided by Bayer:

Primary Outcome Measures:
  • Composite Endpoint of Total Venous Thrombo Embolism (VTE) i.e.: Any Deep Vein Thromboembolism (DVT) (Proximal and/or Distal), Non Fatal Pulmonary Embolism (PE), Death of All Causes Per Protocol Population [ Time Frame: Up to 16 days after surgery ] [ Designated as safety issue: No ]
    Blinded, adjudicated assessment of bilateral venography, clinical signs of deep vein thrombosis (DVT) and pulmonary embolism (PE), ultrasound, clinical chemistry and coagulation factors, autopsy report, electrocardiogram (ECG), pulmonary angiography, perfusion/ventilation lung scintigraphy, chest radiography, computed tomography

  • Composite Endpoint of Total VTE i.e.: Any DVT (Proximal and/or Distal), Non Fatal PE, Death of All Causes Per Modified Intent to Treat Population. [ Time Frame: Up to 16 days after surgery ] [ Designated as safety issue: No ]
    Blinded, adjudicated assessment of bilateral venography, clinical signs of deep vein thrombosis (DVT) and pulmonary embolism (PE), ultrasound, clinical chemistry and coagulation factors, autopsy report, electrocardiogram (ECG), pulmonary angiography, perfusion/ventilation lung scintigraphy, chest radiography, computed tomography


Secondary Outcome Measures:
  • Incidence of the Composite Endpoint Comprising Proximal DVT, Non-fatal PE and VTE- Related Death (Major VTE) Per Protocol Population of Major VTE [ Time Frame: Up to 16 days after surgery ] [ Designated as safety issue: No ]
    Blinded, adjudicated assessment of bilateral venography, clinical signs of deep vein thrombosis (DVT) and pulmonary embolism (PE), ultrasound, clinical chemistry and coagulation factors, autopsy report, electrocardiogram (ECG), pulmonary angiography, perfusion/ventilation lung scintigraphy, chest radiography, computed tomography

  • Incidence of the Composite Endpoint Comprising Proximal DVT, Non-fatal PE and VTE- Related Death (Major VTE) Per Modified Intent to Treat Population of Major VTE. [ Time Frame: Up to 16 days after surgery ] [ Designated as safety issue: No ]
    Blinded, adjudicated assessment of bilateral venography, clinical signs of deep vein thrombosis (DVT) and pulmonary embolism (PE), ultrasound, clinical chemistry and coagulation factors, autopsy report, electrocardiogram (ECG), pulmonary angiography, perfusion/ventilation lung scintigraphy, chest radiography, computed tomography

  • Incidence of Symptomatic VTE (DVT, PE) Per Protocol Population. [ Time Frame: Up to 16 days after surgery ] [ Designated as safety issue: No ]
    Blinded, adjudicated assessment of bilateral venography, clinical signs of DVT and PE, ultrasound, clinical chemistry and coagulation factors, autopsy report, electrocardiogram (ECG), pulmonary angiography, perfusion/ventilation lung scintigraphy, chest radiography, computed tomography

  • Incidence of Symptomatic VTE (DVT, PE) Per Modified Intent to Treat Population. [ Time Frame: Up to 16 days after surgery ] [ Designated as safety issue: No ]
    Blinded, adjudicated assessment of bilateral venography, clinical signs of DVT and PE, ultrasound, clinical chemistry and coagulation factors, autopsy report, electrocardiogram (ECG), pulmonary angiography, perfusion/ventilation lung scintigraphy, chest radiography, computed tomography

  • Incidence of DVT (Proximal, Distal) Per Protocol Population. [ Time Frame: Up to 16 days after surgery ] [ Designated as safety issue: No ]
    Blinded, adjudicated assessment of bilateral venography, clinical signs of DVT and PE, ultrasound, clinical chemistry and coagulation factors, autopsy report, electrocardiogram (ECG), pulmonary angiography, perfusion/ventilation lung scintigraphy, chest radiography, computed tomography

  • Incidence of DVT (Proximal, Distal) Per Modified Intent to Treat Population. [ Time Frame: Up to 16 days after surgery ] [ Designated as safety issue: No ]
    Blinded, adjudicated assessment of bilateral venography, clinical signs of DVT and PE, ultrasound, clinical chemistry and coagulation factors, autopsy report, electrocardiogram (ECG), pulmonary angiography, perfusion/ventilation lung scintigraphy, chest radiography, computed tomography

  • Incidence of Symptomatic VTE During Follow-up Per Protocol Population. [ Time Frame: Up to 47 days after surgery ] [ Designated as safety issue: No ]
    Blinded, adjudicated assessment of bilateral venography, clinical signs of DVT and PE, ultrasound, clinical chemistry and coagulation factors, autopsy report, electrocardiogram (ECG), pulmonary angiography, perfusion/ventilation lung scintigraphy, chest radiography, computed tomography

  • Incidence of Symptomatic VTE During Follow-up Per Modified Intent to Treat Population. [ Time Frame: Up to 47 days after surgery ] [ Designated as safety issue: No ]
    Blinded, adjudicated assessment of bilateral venography, clinical signs of DVT and PE, ultrasound, clinical chemistry and coagulation factors, autopsy report, electrocardiogram (ECG), pulmonary angiography, perfusion/ventilation lung scintigraphy, chest radiography, computed tomography

  • The Composite Endpoint Comprising Major VTE and Treatment-emergent Major Bleeding Per Subjects Valid for Analysis of Net Clinical Benefit [ Time Frame: Up to 47 days after surgery ] [ Designated as safety issue: No ]
    Blinded, adjudicated assessment of bilateral venography, clinical signs of DVT and PE, ultrasound, clinical chemistry and coagulation factors, autopsy report, electrocardiogram (ECG), pulmonary angiography, perfusion/ventilation lung scintigraphy, chest radiography, computed tomography, anesthesia and surgery reports, number of transfusions

  • Incidence of the Composite Endpoint That Results From the Primary Endpoint by Substituting VTE Related Death for All Death Per Protocol Population. [ Time Frame: Up to 16 days after surgery ] [ Designated as safety issue: No ]
    Blinded, adjudicated assessment of bilateral venography, clinical signs of DVT and PE, ultrasound, clinical chemistry and coagulation factors, autopsy report, electrocardiogram (ECG), pulmonary angiography, perfusion/ventilation lung scintigraphy, chest radiography, computed tomography

  • Incidence of the Composite Endpoint That Results From the Primary Endpoint by Substituting VTE Related Death for All Death Per Modified Intent to Treat Population. [ Time Frame: Up to 16 days after surgery ] [ Designated as safety issue: No ]
    Blinded, adjudicated assessment of bilateral venography, clinical signs of DVT and PE, ultrasound, clinical chemistry and coagulation factors, autopsy report, electrocardiogram (ECG), pulmonary angiography, perfusion/ventilation lung scintigraphy, chest radiography, computed tomography

  • Incidence of the Composite Endpoint That Results From Major VTE by Substituting All Cause Mortality for VTE-related Death Per Protocol of Major VTE Population. [ Time Frame: Up to 16 days after surgery ] [ Designated as safety issue: No ]
    Blinded, adjudicated assessment of bilateral venography, clinical signs of DVT and PE, ultrasound, clinical chemistry and coagulation factors, autopsy report, electrocardiogram (ECG), pulmonary angiography, perfusion/ventilation lung scintigraphy, chest radiography, computed tomography

  • Incidence of the Composite Endpoint That Results From Major VTE by Substituting All Cause Mortality for VTE-related Death Per Modified Intent to Treat of Major VTE Population. [ Time Frame: Up to 16 days after surgery ] [ Designated as safety issue: No ]
    Blinded, adjudicated assessment of bilateral venography, clinical signs of DVT and PE, ultrasound, clinical chemistry and coagulation factors, autopsy report, electrocardiogram (ECG), pulmonary angiography, perfusion/ventilation lung scintigraphy, chest radiography, computed tomography

  • Treatment-emergent Major Bleedings Per Safety Population. [ Time Frame: from start of double-blind study medication to last dose of double-blind study medication plus two days. The average duration of double-blind treatment was 12 days in each treatment group (safety population). ] [ Designated as safety issue: Yes ]
    Blinded, adjudicated assessments of all available information (eg, anesthesia and surgery reports, laboratory results, number of transfusions, autopsy report)


Enrollment: 3148
Study Start Date: June 2006
Study Completion Date: January 2008
Primary Completion Date: January 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Rivaroxaban 10 mg Once Daily (OD) ((Xarelto, BAY59-7939))
Rivaroxaban (Xarelto, BAY59-7939) 10 mg tablet administered once daily (od) in the evening plus placebo syringes of enoxaparin twice a day (bid) administered once in the morning and once in the evening.
Drug: Rivaroxaban (Xarelto, BAY59-7939)
Rivaroxaban (Xarelto, BAY59-7939) 10 mg tablet administered once daily (od) in the evening.
Drug: Placebo: syringes of Enoxaparin
Placebo syringes of enoxaparin twice a day (bid) administered once in the morning and once in the evening.
Active Comparator: Enoxaparin 30 mg twice a day (bid)
Placebo tablet of rivaroxaban administered once daily in the evening plus syringes of enoxaparin active substance 30 mg twice a day administered once in the morning and once in the evening.
Drug: Enoxaparin
Syringes of enoxaparin active substance 30 mg twice a day administered once in the morning and once in the evening.
Drug: Placebo: tablet of Rivaroxaban
Placebo tablet of rivaroxaban administered once daily in the evening.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male and female patients aged 18 years or above
  • Patients scheduled for elective total knee replacement

Exclusion Criteria:

  • Active bleeding or high risk of bleeding contraindicating treatment with Low Molecular Weight Heparin (LMWH)
  • Contraindication listed in the labeling or conditions precluding subject treatment with enoxaparin or requiring dose adjustment (e.g. severe renal impairment, please refer to the local label of enoxaparin in your country)
  • Conditions prohibiting bilateral venography (e.g. amputation of 1 leg, allergy to contrast media)
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00362232

  Show 124 Study Locations
Sponsors and Collaborators
Bayer
Investigators
Study Director: Bayer Study Director Bayer
  More Information

Additional Information:
Publications:
Responsible Party: Therapeutic Area Head, Bayer HealthCare Pharmaceuticals Inc.
ClinicalTrials.gov Identifier: NCT00362232     History of Changes
Other Study ID Numbers: 11355, 2006-002402-60
Study First Received: August 8, 2006
Results First Received: May 10, 2012
Last Updated: July 18, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Bayer:
Prevention of venous thromboembolism

Additional relevant MeSH terms:
Pulmonary Embolism
Thromboembolism
Venous Thromboembolism
Venous Thrombosis
Lung Diseases
Respiratory Tract Diseases
Embolism
Embolism and Thrombosis
Vascular Diseases
Cardiovascular Diseases
Thrombosis
Enoxaparin
Anticoagulants
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Cardiovascular Agents

ClinicalTrials.gov processed this record on April 23, 2014