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)

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

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.

Study Overview

• Status: Completed
• Conditions: Venous Thromboembolism
• Intervention / Treatment: Drug: Rivaroxaban (Xarelto, BAY59-7939); Drug: Placebo: syringes of Enoxaparin; Drug: Enoxaparin; Drug: Placebo: tablet of Rivaroxaban

• Study Type: Interventional
• Enrollment (Actual): 3148
• Phase: Phase 3

Contacts and Locations

Study Locations

• Bulgaria
  • Pleven, Bulgaria, 5800
  • Plovdiv, Bulgaria, 4002
  • Sofia, Bulgaria, 1431
• Canada
  • Alberta
    • Red Deer, Alberta, Canada, T4N 6V7
  • British Columbia
    • Kelowna, British Columbia, Canada, V1W 4V5
    • Penticton, British Columbia, Canada, V2A 5C8
  • New Brunswick
    • Fredericton, New Brunswick, Canada, E3B 5N5
  • Ontario
    • Ajax, Ontario, Canada, L1S 2J4
    • Brantford, Ontario, Canada, N3R 1G9
    • Oakville, Ontario, Canada, L6J 3M5
    • Oshawa, Ontario, Canada, L1G 2B9
    • Ottawa, Ontario, Canada, K1Y 4E9
    • Peterborough, Ontario, Canada, K9J 7C6
    • Scarborough, Ontario, Canada, M1P 2V5
    • Scarborough, Ontario, Canada, M1M 3W3
    • Sudbury, Ontario, Canada, P3A 1Y8
    • Thunder Bay, Ontario, Canada, P7B 6V4
    • Woodstock, Ontario, Canada, N4S 5B2
  • Prince Edward Island
    • Charlottetown, Prince Edward Island, Canada, C1A 8T5
  • Quebec
    • Montreal, Quebec, Canada, H3T 1E2
    • Montreal, Quebec, Canada, H3G 1A4
• Denmark
  • Hellerup, Denmark, DK-2900
  • Herlev, Denmark, 2730
  • Hvidovre, Denmark, 2650
  • Hørsholm, Denmark, 2970
  • Silkeborg, Denmark, 8600
  • Viborg, Denmark, 8800
• India
  • Bangalore, India, 560034
  • Bangalore, India, 560001
  • Baroda, India, 390007
  • Hyderabad, India
  • New Delhi, India, 110029
  • Andhra Pradesh
    • Hyderabad, Andhra Pradesh, India, 500004
    • Secunderabad, Andhra Pradesh, India, 500 003
    • Secundrabad, Andhra Pradesh, India, 500003
  • Gujarat
    • Ahmedabad, Gujarat, India, 380006
    • Ahmedabad, Gujarat, India, 380054
  • Maharashtra
    • Pune, Maharashtra, India, 411001
    • Pune, Maharashtra, India, 411009
  • Punjab
    • Ludhiana, Punjab, India, 141001
  • Tamil Nadu
    • Chennai, Tamil Nadu, India, 600 006
• Israel
  • Beer Sheva, Israel, 85025
  • Holon, Israel, 58100
  • Kfar Saba, Israel, 44281
  • Petach Tikva, Israel, 49100
  • Tel Aviv, Israel, 64239
  • Zerifin, Israel, 70300
• Lithuania
  • Kaunas, Lithuania, LT-50009
  • Kaunas, Lithuania, 44320
  • Klaipeda, Lithuania, 92288
  • Panevezys, Lithuania, 35144
  • Vilnius, Lithuania, LT-04130
• Mexico
  • Edo. de Mexico, Mexico, 53120
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 44200
    • Guadalajara, Jalisco, Mexico, 44350
    • Zapopan, Jalisco, Mexico, 45100
  • Nuevo Leon
    • Monterrey, Nuevo Leon, Mexico, 64000
    • Monterrey, Nuevo Leon, Mexico, 64380
  • Yucatán
    • Mérida, Yucatán, Mexico, 97150
• Norway
  • Baerum postterminal, Norway, 1306
  • Gjövik, Norway, 2819
  • Kongsvinger, Norway, 2212
  • Lillehammer, Norway, 2609
• Pakistan
  • Sindh
    • Karachi, Sindh, Pakistan, 74800
    • Karachi, Sindh, Pakistan
• Poland
  • Bydgoszcz, Poland, 85-094
  • Elblag, Poland, 82-300
  • Gdansk, Poland, 80-803
  • Kielce, Poland
  • Konskie, Poland, 26-200
  • Krakow, Poland, 31-913
  • Lublin, Poland, 20-718
  • Sosnowiec, Poland, 41-200
  • Warszawa, Poland, 02-507
  • Warszawa, Poland, 02-005
• Sri Lanka
  • Colombo-80, Sri Lanka
  • Kotte, Sri Lanka
  • Ragama, Sri Lanka
• Sweden
  • Göteborg, Sweden, 416 85
  • Hässleholm, Sweden, 281 25
  • Stockholm, Sweden, 112 81
  • Västervik, Sweden, 593 81
  • Växjö, Sweden, 351 85
  • Örebro, Sweden, 701 85
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35209
    • Tuscaloosa, Alabama, United States, 35406
  • Arizona
    • Phoenix, Arizona, United States, 85023
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
  • California
    • Bakersfield, California, United States, 93309
    • Encinitas, California, United States, 92024
    • Fountain Valley, California, United States, 92708
    • La Jolla, California, United States, 92037
    • Torrance, California, United States, 90502-2004
    • Yuba City, California, United States, 95991
  • Colorado
    • Centennial, Colorado, United States, 80112
    • Denver, Colorado, United States, 80230
    • Englewood, Colorado, United States, 80110
  • Florida
    • Boynton Beach, Florida, United States, 33472-2952
    • Clearwater, Florida, United States, 33756
    • DeLand, Florida, United States, 32720
    • Hollywood, Florida, United States, 33021
    • Jacksonville, Florida, United States, 32216
    • Pensacola, Florida, United States, 32501
    • Pinellas Park, Florida, United States, 33781
  • Georgia
    • Decatur, Georgia, United States, 30033
  • Idaho
    • Boise, Idaho, United States, 83702
    • Meridian, Idaho, United States, 83642
  • Maryland
    • Towson, Maryland, United States, 21204
  • Montana
    • Missoula, Montana, United States, 59802
  • New Jersey
    • Teaneck, New Jersey, United States, 07666
  • North Carolina
    • Greensboro, North Carolina, United States, 27401
  • Ohio
    • Cincinnati, Ohio, United States, 45242
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73162
  • Pennsylvania
    • Johnstown, Pennsylvania, United States, 15901
    • State College, Pennsylvania, United States, 16801
  • South Carolina
    • Charleston, South Carolina, United States, 29414
  • Texas
    • Dallas, Texas, United States, 75231
    • Grapevine, Texas, United States, 76051
    • Houston, Texas, United States, 77030
    • Lubbock, Texas, United States, 79410
    • Plano, Texas, United States, 75093
    • San Antonio, Texas, United States, 78233
    • San Antonio, Texas, United States, 78205
  • Washington
    • Spokane, Washington, United States, 99218

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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	Up to 16 days after surgery
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.	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	Up to 16 days after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of the Composite Endpoint Comprising Proximal DVT, Non-fatal PE and VTE- Related Death (Major VTE) Per Protocol Population of Major VTE	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	Up to 16 days after surgery
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.	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	Up to 16 days after surgery
Incidence of Symptomatic VTE (DVT, PE) Per Protocol Population.	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	Up to 16 days after surgery
Incidence of Symptomatic VTE (DVT, PE) Per Modified Intent to Treat Population.	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	Up to 16 days after surgery
Incidence of DVT (Proximal, Distal) Per Protocol Population.	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	Up to 16 days after surgery
Incidence of DVT (Proximal, Distal) Per Modified Intent to Treat Population.	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	Up to 16 days after surgery
Incidence of Symptomatic VTE During Follow-up Per Protocol Population.	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	Up to 47 days after surgery
Incidence of Symptomatic VTE During Follow-up Per Modified Intent to Treat Population.	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	Up to 47 days after surgery
The Composite Endpoint Comprising Major VTE and Treatment-emergent Major Bleeding Per Subjects Valid for Analysis of Net Clinical Benefit	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	Up to 47 days after surgery
Incidence of the Composite Endpoint That Results From the Primary Endpoint by Substituting VTE Related Death for All Death Per Protocol Population.	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	Up to 16 days after surgery
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.	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	Up to 16 days after surgery
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.	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	Up to 16 days after surgery
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.	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	Up to 16 days after surgery
Treatment-emergent Major Bleedings Per Safety Population.	Blinded, adjudicated assessments of all available information (eg, anesthesia and surgery reports, laboratory results, number of transfusions, autopsy report)	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).

Collaborators and Investigators

• Sponsor: Bayer

Publications and helpful links

General Publications

• Turpie AG, Lassen MR, Davidson BL, Bauer KA, Gent M, Kwong LM, Cushner FD, Lotke PA, Berkowitz SD, Bandel TJ, Benson A, Misselwitz F, Fisher WD; RECORD4 Investigators. Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty (RECORD4): a randomised trial. Lancet. 2009 May 16;373(9676):1673-80. doi: 10.1016/S0140-6736(09)60734-0. Epub 2009 May 4. Erratum In: Lancet. 2022 Dec 10;400(10368):2048.

Helpful Links

• Click here and search for information of Bayer products for Europe

Study record dates

Study Major Dates

• Study Start: June 1, 2006
• Primary Completion (Actual): January 1, 2007
• Study Completion (Actual): January 1, 2008

Study Registration Dates

• First Submitted: August 8, 2006
• First Submitted That Met QC Criteria: August 8, 2006
• First Posted (Estimate): August 9, 2006

Study Record Updates

• Last Update Posted (Estimate): November 4, 2014
• Last Update Submitted That Met QC Criteria: October 28, 2014
• Last Verified: October 1, 2014

More Information

Terms related to this study

• Keywords: Prevention of venous thromboembolism
• 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; Enoxaparin sodium
• Other Study ID Numbers: 11355; 2006-002402-60 (EudraCT Number)