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.

Phase 3

Completed

• Conditions: Venous Thromboembolism
• Interventions: Drug: Rivaroxaban (Xarelto, BAY59-7939); Drug: Enoxaparin

• Registration Number: NCT00362232
• Lead Sponsor: Bayer

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2006-06
• Study First Submitted: 2006-08-08
• Study First Submitted QC: 2006-08-08
• Study First Posted: 2006-08-09
• Primary Completion: 2007-01
• Study Completion: 2008-01
• Results First Submitted: 2012-05-10
• Results First Submitted QC: 2012-05-10
• Results First Posted: 2012-06-13
• Status Verified: 2014-10
• Last Update Submitted: 2014-10-28
• Last Update Posted: 2014-11-04

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 3148

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)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Rivaroxaban 10 mg Once Daily (OD) ((Xarelto, BAY59-7939))	Rivaroxaban (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.
Enoxaparin 30 mg twice a day (bid)	Enoxaparin	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.

Primary Outcome Measures

Name	Time	Method
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	Up to 16 days after surgery	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.	Up to 16 days after surgery	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

Name	Time	Method
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.	Up to 16 days after surgery	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
The Composite Endpoint Comprising Major VTE and Treatment-emergent Major Bleeding Per Subjects Valid for Analysis of Net Clinical Benefit	Up to 47 days after surgery	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.	Up to 16 days after surgery	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.	Up to 16 days after surgery	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 Protocol Population.	Up to 16 days after surgery	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 Comprising Proximal DVT, Non-fatal PE and VTE- Related Death (Major VTE) Per Protocol Population of Major VTE	Up to 16 days after surgery	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 DVT (Proximal, Distal) Per Protocol Population.	Up to 16 days after surgery	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.	Up to 47 days after surgery	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.	Up to 16 days after surgery	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.	Up to 16 days after surgery	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.	Up to 16 days after surgery	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.	Up to 47 days after surgery	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.	Up to 16 days after surgery	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.	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).	Blinded, adjudicated assessments of all available information (eg, anesthesia and surgery reports, laboratory results, number of transfusions, autopsy report)