Once - Daily Oral Direct Factor Xa Inhibitor Rivaroxaban In The Long-Term Prevention Of Recurrent Symptomatic Venous Thromboembolism In Patients With Symptomatic Deep-Vein Thrombosis Or Pulmonary Embolism. The Einstein-Extension Study

Once-daily Oral Direct Factor Xa Inhibitor Rivaroxaban in the Long-term Prevention of Recurrent Symptomatic Venous Thromboembolism in Patients With Symptomatic Deep-vein Thrombosis or Pulmonary Embolism. The Einstein-Extension Study

This is a multicenter, randomized, double-blind, placebo-controlled, event-driven, superiority study for efficacy. Patients with confirmed symptomatic DVT (deep vein thrombosis) or PE (pulmonary embolism) who completed 6 or 12 months of treatment with rivaroxaban or VKA (vitamin K antagonist) are eligible for this trial (Einstein-Extension study).

Study Overview

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

Detailed Description

Within the US 'Johnson & Johnson Pharmaceutical Research & Development, L.L.C.' is sponsor.

The treatment period was followed by an observational period of 30 days starting the day after the last intake of study medication, regardless of the actual duration of study drug administration. Participants who did not complete the treatment period also entered the observational period. It was also possible that participants did not enter the observational period, e.g. due to withdrawal of consent or termination of study participation.

• Study Type: Interventional
• Enrollment (Actual): 1197
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Australian Capital Territory
    • Garran, Australian Capital Territory, Australia, 2605
  • New South Wales
    • Gosford, New South Wales, Australia, 2250
    • Kogarah, New South Wales, Australia, 2217
    • Lismore, New South Wales, Australia, 2480
    • St Leonards, New South Wales, Australia, 2065
    • Sydney, New South Wales, Australia, 2031
    • Sydney, New South Wales, Australia, 2229
    • Sydney, New South Wales, Australia, 2139
    • Sydney, New South Wales, Australia, 2010
  • Queensland
    • Brisbane, Queensland, Australia, 4029
    • Redcliffe, Queensland, Australia, 4020
    • Southport, Queensland, Australia, 4215
    • Woolloongabba, Queensland, Australia, 4102
  • South Australia
    • Adelaide, South Australia, Australia, 5042
    • Adelaide, South Australia, Australia, 5011
  • Victoria
    • Box Hill, Victoria, Australia, 3128
    • Clayton, Victoria, Australia, 3168
    • Geelong, Victoria, Australia, 3220
    • Melbourne, Victoria, Australia, 3135
    • Melbourne, Victoria, Australia, 3181
    • Prahran, Victoria, Australia, 3181
  • Western Australia
    • Fremantle, Western Australia, Australia, 6160
    • Perth, Western Australia, Australia, 6000
• Austria
  • Salzburg, Austria, 5020
  • Wien, Austria, 1090
  • Wien, Austria, 1140
  • Steiermark
    • Graz, Steiermark, Austria, 8036
  • Tirol
    • Innsbruck, Tirol, Austria, 6020
  • Vorarlberg
    • Feldkirch, Vorarlberg, Austria, 6807
• Belgium
  • Bruxelles - Brussel, Belgium, 1070
  • Bruxelles - Brussel, Belgium, 1200
  • Duffel, Belgium, 2570
  • Genk, Belgium, 3600
  • Gent, Belgium, 9000
  • Hasselt, Belgium, 3500
  • Leuven, Belgium, 3000
  • Liege, Belgium, 4000
  • Lier, Belgium, 2500
  • Namur, Belgium, 5000
  • Sint-Truiden, Belgium, 3800
  • Yvoir, Belgium, 5530
  • Zottegem, Belgium, 9620
• Brazil
  • Rio de Janeiro, Brazil
  • Sao Paulo, Brazil, 04023-061
  • Minas Gerais
    • Uberaba, Minas Gerais, Brazil, 38010 380
  • Parana
    • Curitiba, Parana, Brazil, 80050-350
    • Londrina, Parana, Brazil, 86038440
  • Rio Grande do Sul
    • Porto Alegre, Rio Grande do Sul, Brazil
  • Sao Paulo
    • Botucatu, Sao Paulo, Brazil, 18618 000
    • Sorocaba, Sao Paulo, Brazil, 18031-000
    • São Paulo, Sao Paulo, Brazil, 01323-001
    • São Paulo, Sao Paulo, Brazil, 04039-004
    • São Paulo, Sao Paulo, Brazil, 01509-900
• Canada
  • Manitoba
    • Winnipeg, Manitoba, Canada, R2H 2A6
  • Ontario
    • Toronto, Ontario, Canada, M6R 1B5
• China
  • Beijing, China, 100044
  • Beijing, China, 100730
  • Beijing, China, 100020
  • Beijing, China, 100029
  • Beijing, China, 100037
  • Beijing, China, 100038
  • Beijing, China, 100853
  • Shanghai, China, 200032
  • Shanghai, China, 200001
  • Shanghai, China, 200433
  • Guangdong
    • Guangzhou, Guangdong, China, 510080
  • Heilongjiang
    • Harbin, Heilongjiang, China, 150086
  • Hubei
    • Wuhan, Hubei, China, 430022
  • Jiangsu
    • Suzhou, Jiangsu, China, 215004
  • Liaoning
    • Shenyang, Liaoning, China, 110016
• Czech Republic
  • Brno, Czech Republic, 65691
  • Karlovy Vary, Czech Republic, 360 00
  • Kladno, Czech Republic, 27259
  • Ostrava, Czech Republic, 728 80
  • Ostrava-Poruba, Czech Republic, 708 52
  • Prague 5, Czech Republic, 150 00
  • Praha 1, Czech Republic, 110 00
  • Praha 2, Czech Republic, 12800
  • Praha 4, Czech Republic, 140 21
  • Usti nad Lebem, Czech Republic, 401 13
• Denmark
  • Aarhus C, Denmark, 8000
  • Braedstrup, Denmark, 8740
  • Frederiksberg, Denmark, 2000F
  • Hellerup, Denmark, 2900
• Finland
  • Seinäjoki, Finland, 60220
• France
  • Agen Cedex 9, France, 47923
  • Amiens, France, 80000
  • Angers Cedex 01, France, 49033
  • Arras, France, 62000
  • Bordeaux, France, 33075
  • Brest Cedex, France, 29609
  • Castelnau Le Lez, France, 34170
  • Clamart, France, 92141
  • Clermont Ferrand, France, 63000
  • Colombes, France, 92700
  • Creteil, France, 94000
  • Dijon, France, 21000
  • Grenoble, France, 38043
  • Grenoble, France, 38028
  • Lille Cedex, France, 59037
  • Limoges, France, 87042
  • Montpellier Cedex, France, 34295
  • Nantes, France, 44000
  • Nimes Cedex 9, France, 30029
  • Orthez, France, 64300
  • Paris, France, 75475
  • Paris, France, 75877
  • Paris, France, 75004
  • Paris Cedex 15, France, 75908
  • Pierre Benite, France, 69495
  • Roanne, France, 42328
  • Rouen Cedex, France, 76031
  • Saint Etienne, France, 42055
  • Strasbourg Cedex, France, 67091
  • Toulon, France, 83000
  • Toulouse, France, 31403
  • Tours, France, 37044
  • Valenciennes Cedex, France, 59322
  • Vandoeuvre Les Nancy, France, 54511
  • Vernon, France, 27200
• Germany
  • Berlin, Germany, 10713
  • Berlin, Germany, 12099
  • Hamburg, Germany, 20251
  • Baden-Württemberg
    • Bruchsal, Baden-Württemberg, Germany, 76646
    • Heidelberg, Baden-Württemberg, Germany, 69115
    • Karlsbad, Baden-Württemberg, Germany, 76307
    • Mannheim, Baden-Württemberg, Germany, 68167
    • Neckargemünd, Baden-Württemberg, Germany, 69151
    • Tübingen, Baden-Württemberg, Germany, 72076
  • Bayern
    • Augsburg, Bayern, Germany, 86156
    • München, Bayern, Germany, 81377
    • München, Bayern, Germany, 80331
    • Würzburg, Bayern, Germany, 97080
  • Hessen
    • Darmstadt, Hessen, Germany, 64297
    • Frankfurt, Hessen, Germany, 60596
    • Gießen, Hessen, Germany, 35392
    • Wiesbaden, Hessen, Germany, 65183
  • Mecklenburg-Vorpommern
    • Greifswald, Mecklenburg-Vorpommern, Germany, 17475
  • Niedersachsen
    • Hannover, Niedersachsen, Germany, 30625
    • Rotenburg, Niedersachsen, Germany, 27342
  • Nordrhein-Westfalen
    • Düsseldorf, Nordrhein-Westfalen, Germany, 40225
    • Essen, Nordrhein-Westfalen, Germany, 45122
    • Paderborn, Nordrhein-Westfalen, Germany, 33098
    • Soest, Nordrhein-Westfalen, Germany, 59494
    • Witten, Nordrhein-Westfalen, Germany, 58455
  • Rheinland-Pfalz
    • Mainz, Rheinland-Pfalz, Germany, 55131
  • Saarland
    • Homburg, Saarland, Germany, 66424
    • Homburg, Saarland, Germany, 66421
  • Sachsen
    • Dresden, Sachsen, Germany, 01307
    • Leipzig, Sachsen, Germany, 04289
  • Sachsen-Anhalt
    • Halle, Sachsen-Anhalt, Germany, 06120
    • Magdeburg, Sachsen-Anhalt, Germany, 39112
• Hong Kong
  • Hong Kong, Hong Kong
• Hungary
  • Budapest, Hungary, 1115
  • Budapest, Hungary, 1096
  • Debrecen, Hungary, 4032
  • Kecskemet, Hungary, 6000
  • Kistarcsa, Hungary, 2143
  • Miskolc, Hungary, 3526
  • Nyiregyhaza, Hungary, 4400
  • Szentes, Hungary, 6600
  • Szombathely, Hungary, 9700
• India
  • Hyderabad, India, 500082
  • Kolkata, India, 700029
  • New Delhi, India, 110060
  • Pune, India, 411001
  • Kerala
    • Kochi, Kerala, India, 682026
    • Vellore, Kerala, India, 632004
  • Maharashtra
    • Mumbai, Maharashtra, India, 400016
    • Mumbai, Maharashtra, India, 400022
    • Mumbai, Maharashtra, India, 400008
• Indonesia
  • Bandung, Indonesia, 40161
  • Jakarta, Indonesia, 10430
  • Medan, Indonesia, 20152
  • Semarang, Indonesia, 50241
• Israel
  • Afula, Israel, 18101
  • Ashkelon, Israel, 78278
  • Beer Sheva, Israel, 84101
  • Haifa, Israel, 31048
  • Haifa, Israel, 34362
  • Haifa, Israel, 31096
  • Holon, Israel, 58100
  • Jerusalem, Israel, 91120
  • Kfar Saba, Israel, 44281
  • Petach Tikva, Israel, 49100
  • Rehovot, Israel, 76100
  • Safed, Israel, 13100
  • Tel Aviv, Israel, 64239
• Italy
  • Bologna, Italy, 40138
  • Chieti, Italy, 66013
  • Milano, Italy, 20132
  • Milano, Italy, 20142
  • Napoli, Italy, 80131
  • Padova, Italy, 35128
  • Palermo, Italy, 90127
  • Parma, Italy, 43100
  • Pavia, Italy, 27100
  • Piacenza, Italy, 29100
  • Venezia, Italy, 30122
• Korea, Republic of
  • Daegu, Korea, Republic of, 705-718
  • Seoul, Korea, Republic of, 137-701
  • Seoul, Korea, Republic of, 120-752
  • Taegu, Korea, Republic of, 700-712
  • Daegu Gwang'yeogsi
    • Daegu, Daegu Gwang'yeogsi, Korea, Republic of, 700721
  • Seoul Teugbyeolsi
    • Seoul, Seoul Teugbyeolsi, Korea, Republic of, 110-744
• Malaysia
  • Selangor, Malaysia, 68000
• Netherlands
  • Amsterdam, Netherlands, 1105 AZ
  • Arnhem, Netherlands, 6815 AD
  • Den Bosch, Netherlands, 5223 GZ
  • Dordrecht, Netherlands, 3318 AT
  • Enschede, Netherlands, 7511 JX
  • Groningen, Netherlands, 9713 GZ
  • Hoofddorp, Netherlands, 2134 TM
  • Maastricht, Netherlands, 6229 HX
  • Rotterdam, Netherlands, 3083 AN
  • Zwijndrecht, Netherlands, 3331 LZ
  • Zwolle, Netherlands, 8025 AB
• New Zealand
  • Auckland, New Zealand, 1023
  • Auckland, New Zealand, 0622
  • Christchurch, New Zealand, 8011
  • Palmerston North, New Zealand, 4414
  • Wellington South, New Zealand, 6021
• Norway
  • Fredrikstad, Norway, 1603
  • Oslo, Norway, 0407
  • Oslo, Norway, 0514
  • Rud, Norway, 1309
• Philippines
  • Quezon City, Philippines, 1102
  • Quezon City, Philippines, 0850
• Poland
  • Bialystok, Poland, 15-276
  • Bydgoszcz, Poland, 85-168
  • Gdansk, Poland, 80-952
  • Katowice, Poland, 40-365
  • Krakow, Poland, 31-066
  • Lodz, Poland, 90-153
  • Lublin, Poland, 20-081
  • Poznan, Poland, 60-631
  • Poznan, Poland, 61-848
  • Torun, Poland, 87-100
  • Warszawa, Poland, 01-138
  • Warszawa, Poland, 02-097
  • Warszawa, Poland, 04-479
  • Wroclaw, Poland, 51-124
  • Wroclaw, Poland, 50-326
• Singapore
  • Singapore, Singapore, 169608
  • Singapore, Singapore, 308433
• South Africa
  • Cape
    • Cape Town, Cape, South Africa, 7500
  • Gauteng
    • Johannesburg, Gauteng, South Africa, 2132
    • Johannesburg, Gauteng, South Africa, 2191
    • Johannesburg, Gauteng, South Africa, 2193
    • Johannesburg, Gauteng, South Africa, 2157
    • Pretoria, Gauteng, South Africa, 0181
    • Pretoria, Gauteng, South Africa, 0084
    • Pretoria, Gauteng, South Africa, 0157
    • Roodepoort, Gauteng, South Africa, 1724
  • Western Cape
    • Cape Town, Western Cape, South Africa, 7460
    • Somerset West, Western Cape, South Africa, 7130
    • Worcester, Western Cape, South Africa, 6850
• Spain
  • Barcelona, Spain, 08036
  • Barcelona, Spain, 08025
  • Girona, Spain, 17007
  • Madrid, Spain, 28034
  • Pamplona, Spain, 31008
  • Barcelona
    • Terrassa, Barcelona, Spain, 08221
  • Madrid
    • Alcorcón, Madrid, Spain, 28922
    • Fuenlabrada, Madrid, Spain, 28942
  • Valencia
    • Xàtiva, Valencia, Spain, 46800
• Sweden
  • Borås, Sweden, 501 82
  • Göteborg, Sweden, 416 85
  • Göteborg, Sweden, 413 45
  • Jönköping, Sweden, 551 85
  • Sundsvall, Sweden, 851 86
  • Västervik, Sweden, 593 81
• Switzerland
  • Lugano, Switzerland, 6903
  • Luzern, Switzerland, 6000
  • Zürich, Switzerland, 8091
  • Basel-Landschaft
    • Bruderholz, Basel-Landschaft, Switzerland, 4101
  • Genève 14
    • Genéve 14, Genève 14, Switzerland, 1211
  • Graubünden
    • Chur, Graubünden, Switzerland, 7000
  • Valais
    • Brig, Valais, Switzerland, 3900
• Taiwan
  • Kaohsiung, Taiwan, 80756
  • Tainan, Taiwan, 704
  • Taipei, Taiwan, 11217
  • Taipei, Taiwan, 10002
  • Taoyuan, Taiwan, 333
• Thailand
  • Bangkok, Thailand, 10400
  • Bangkok, Thailand, 10700
  • Pathumwan, Bangkok, Thailand, 10330
• United Kingdom
  • London, United Kingdom
  • London, United Kingdom, SE5 9RS
  • London, United Kingdom, SE1 7EH
  • London, United Kingdom, W1T 4EU
  • Devon
    • Plymouth, Devon, United Kingdom, PL6 8DH
  • Essex
    • Chelmsford, Essex, United Kingdom, CM1 5ET
    • Romford, Essex, United Kingdom, RM7 0AG
  • London
    • Isleworth, London, United Kingdom, TW7 6AF
  • Lothian
    • Edinburgh, Lothian, United Kingdom, EH16 4SA
  • Merseyside
    • Liverpool, Merseyside, United Kingdom, L7 8XP
• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
  • California
    • Los Angeles, California, United States, 90095
    • Redlands, California, United States, 92373
  • Florida
    • Bay Pines, Florida, United States, 33744
    • Melbourne, Florida, United States, 32901
    • Miami, Florida, United States, 33136
    • Miami, Florida, United States, 33136-1096
  • Georgia
    • Decatur, Georgia, United States, 30033
  • Idaho
    • Idaho Falls, Idaho, United States, 83404
  • Louisiana
    • Covington, Louisiana, United States, 70433
  • Maryland
    • Baltimore, Maryland, United States, 21215-5271
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
  • New Mexico
    • Albuquerque, New Mexico, United States, 87108
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599-7035
    • Greensboro, North Carolina, United States, 27401
    • Greensboro, North Carolina, United States, 27403
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15224
  • Texas
    • Corsicana, Texas, United States, 75110
    • San Antonio, Texas, United States, 78229
  • Utah
    • Murray, Utah, United States, 84107
    • Salt Lake City, Utah, United States, 84132
  • Vermont
    • Burlington, Vermont, United States, 05401
  • Virginia
    • Fredericksburg, Virginia, United States, 22401
  • Washington
    • Spokane, Washington, United States, 99204

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:

• Patients with confirmed symptomatic PE or DVT who have been treated for 6 or 12 months with VKA or rivaroxaban

Exclusion Criteria:

• Legal lower age limitations (country specific)
• Indication for VKA other than DVT and/or PE
• Patients in whom anticoagulant treatment for their index PE or DVT should be continued
• Childbearing potential without proper contraceptive measures, pregnancy or breast feeding. Proper contraceptive measures are defined as a method of contraception with a failure rate < 1 % during the course of the study (including the observational period). These methods of contraception according to the note for guidance on non-clinical safety studies for the conduct of human trials for pharmaceuticals (CPMP [Committee for Proprietary Medicinal Products]/ICH [International Conference on Harmonization]/286/95, modification) include consistent and correct use of hormone containing implants and injectables, combined oral contraceptives, hormone containing intrauterine devices, surgical sterilization, sexual abstinence and vasectomy

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Rivaroxaban (Xarelto, BAY59-7939); Participants were to receive rivaroxaban 20 mg oral tablet once daily	Drug: Rivaroxaban (Xarelto, BAY59-7939); Patients randomized to rivaroxaban will receive rivaroxaban 20 mg once-daily.
Placebo Comparator: Placebo; Participants were to receive matching placebo oral tablet once daily	Drug: Placebo; Patients allocated to placebo will receive a matching placebo tablet once daily.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Symptomatic Recurrent Venous Thromboembolism [VTE] (i.e. the Composite of Recurrent Deep Vein Thrombosis [DVT] or Fatal or Non-fatal Pulmonary Embolism [PE]) Until the Intended End of Study Treatment	All events were adjudicated and confirmed by a central independent adjudication committee blinded to treatment. Events were assessed based on either compression ultrasound (for DVT), venography (for DVT), spiral computed tomography (CT) scanning (for PE), pulmonary angiography (for PE), ventilation/perfusion lung scan (for PE), lung scintigraphy (for PE), autopsy (for fatal PE) or unexplained death for which DVT/PE could not be ruled out (for fatal PE), and/or case summaries. For definition of DVT/PE, kindly refer to the link in the Protocol section.	6- or 12-month study treatment period

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With the Composite Variable Comprising Recurrent DVT, Non-fatal PE and All Cause Mortality Until the Intended End of Study Treatment	All events were adjudicated and confirmed by a central independent adjudication committee blinded to treatment. Events were assessed based on either compression ultrasound (for DVT), venography (for DVT), spiral computed tomography (CT) scanning (for PE), pulmonary angiography (for PE), ventilation/perfusion lung scan (for PE), or lung scintigraphy (for PE), and/or case summaries.	6- or 12-month study treatment period
Percentage of Participants With the Composite Variable Comprising Recurrent DVT, Non-fatal PE, All Cause Mortality, Strokes and Myocardial Infarctions Until the Intended End of Study Treatment	All events were adjudicated and confirmed by a central independent adjudication committee blinded to treatment. Events were assessed based on either compression ultrasound (for DVT), venography (for DVT), spiral computed tomography (CT) scanning (for PE), pulmonary angiography (for PE), ventilation/perfusion lung scan (for PE), lung scintigraphy (for PE), results/films/images of confirmatory testing, and/or case summaries.	6- or 12-month study treatment period
Percentage of Participants With Net Clinical Benefit as Composite of Recurrent DVT or Non-fatal or Fatal PE and Major Bleeding Events Until the Intended End of Study Treatment	All events were adjudicated and confirmed by a central independent adjudication committee blinded to treatment, based on either compression ultrasound, venography, spiral computed tomography scanning, pulmonary angiography, ventilation/perfusion lung scan, lung scintigraphy, autopsy or unexplained death for which DVT/PE could not be ruled out, results/films/images of confirmatory testing, and/or case summaries. Major bleeding was overt bleeding associated with 2 g/dL or greater fall in hemoglobin, leading to a transfusion of ≥2 units, occurring in a critical site or contributing to death.	6- or 12-month study treatment period
Percentage of Participants With Recurrent VTE (PE or DVT) Until the Intended End of Study Treatment	All events were adjudicated and confirmed by a central independent adjudication committee blinded to treatment. Events were assessed based on either compression ultrasound (for DVT), venography (for DVT), spiral computed tomography (CT) scanning (for PE), pulmonary angiography (for PE), ventilation/perfusion lung scan (for PE), lung scintigraphy (for PE), results/films/images of confirmatory testing, and/or case summaries.	6- or 12-month study treatment period
Percentage of Participants With Recurrent DVT Until the Intended End of Study Treatment	All events were adjudicated and confirmed by a central independent adjudication committee blinded to treatment. Events were assessed based on either compression ultrasound, venography, results/films/images of confirmatory testing, and/or case summaries.	6- or 12-month study treatment period
Percentage of Participants With Major Bleeding	All events were adjudicated and confirmed by a central independent adjudication committee (CIAC) blinded to treatment. Major bleeding event was overt bleeding associated with a 2 g/dL or greater fall in hemoglobin, leading to a transfusion of 2 or more units of packed red blood cells or whole blood, occurring in a critical site or contributing to death. Treatment-emergent [after intake of first tablet of study medication as randomized but not more than 2 days after stop of study medication (referred to as time window: 2 days)] events and all events post randomization were reported.	6- or 12-month study treatment period
Percentage of Participants With Clinically Relevant Bleeding	All events adjudicated/confirmed by CIAC blinded to treatment. Clinically relevant bleeding included major bleeding (definition: see outcome 7) and non-major bleeding associated with medical intervention, unscheduled physician contact, (temporary) cessation of study treatment, discomfort for the participants such as pain, or impairment of daily life activities. Treatment-emergent events (after intake of 1st study medication tablet as randomized up to 2 days after stop of study medication ['time window: 2 days']) and all events post randomization were reported	6- or 12-month study treatment period
Percentage of Participants With All Death	All events were adjudicated and confirmed by a central independent adjudication committee blinded to treatment. Events were assessed based on either autopsy, results/films/images of confirmatory testing, and/or case summaries. Treatment-emergent events and all events post randomization were reported. Treatment-emergent: after intake of first tablet of study medication as randomized but not more than 2 days after stop of study medication (referred to as time window: 2 days)	6- or 12-month study treatment period
Percentage of Participants With Other Vascular Events	All pre-defined vascular events (acute coronary syndromes, ischemic stroke, transient ischemic attack, non-central nervous system systemic embolism and vascular death) were adjudicated/confirmed by a central independent adjudication committee blinded to treatment, based on results/films/images of confirmatory testing, and/or case summaries. On treatment events and all events post randomization were reported. On treatment: after intake of first tablet of study medication as randomized but not more than 1 day after stop of study medication (referred to as time window: 1 day)	6- or 12-month study treatment period

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Death (PE) Until the Intended End of Study Treatment	All events were adjudicated and confirmed by a central independent adjudication committee blinded to treatment. Events were assessed based on either autopsy, results/films/images of confirmatory testing, and/or case summaries.	6- or 12-month study treatment period
Percentage of Participants With Death (PE Cannot be Excluded) Until the Intended End of Study Treatment	All events were adjudicated and confirmed by a central independent adjudication committee blinded to treatment. Events were assessed based on unexplained death for which DVT/PE could not be ruled out, results/films/images of confirmatory testing, and/or case summaries.	6- or 12-month study treatment period
Percentage of Participants With Symptomatic Recurrent PE Until the Intended End of Study Treatment	All events were adjudicated and confirmed by a central independent adjudication committee blinded to treatment. Events were assessed based on either spiral computed tomography (CT) scanning, pulmonary angiography, ventilation/perfusion lung scan, lung scintigraphy, results/films/images of confirmatory testing, and/or case summaries.	6- or 12-month study treatment period
Percentage of Participants With Symptomatic Recurrent Venous Thromboembolism [VTE] (i.e. the Composite of Recurrent Deep Vein Thrombosis [DVT] or Fatal or Non-fatal Pulmonary Embolism [PE]) During Observational Period	All events were adjudicated and confirmed by a central independent adjudication committee blinded to treatment. Events were assessed based on either compression ultrasound (for DVT), venography (for DVT), spiral computed tomography (CT) scanning (for PE), pulmonary angiography (for PE), ventilation/perfusion lung scan (for PE), lung scintigraphy (for PE), autopsy (for fatal PE) or unexplained death for which DVT/PE could not be ruled out (for fatal PE), results/films/images of confirmatory testing, and/or case summaries.	30 days observational period after last intake of study medication
Percentage of Participants With Symptomatic Recurrent PE During Observational Period	All events were adjudicated and confirmed by a central independent adjudication committee blinded to treatment. Events were assessed based on either spiral computed tomography (CT) scanning, pulmonary angiography, ventilation/perfusion lung scan, lung scintigraphy, results/films/images of confirmatory testing, and/or case summaries.	30 days observational period after last intake of study medication
Percentage of Participants With the Composite Variable Comprising Recurrent DVT, Non-fatal PE and All Cause Mortality During Observational Period	All events were adjudicated and confirmed by a central independent adjudication committee blinded to treatment. Events were assessed based on either compression ultrasound (for DVT), venography (for DVT), spiral computed tomography (CT) scanning (for PE), pulmonary angiography (for PE), ventilation/perfusion lung scan (for PE), lung scintigraphy (for PE), autopsy (for deaths), results/films/images of confirmatory testing, and/or case summaries.	30 days observational period after last intake of study medication
Percentage of Participants With the Composite Variable Comprising Recurrent DVT, Non-fatal PE, All Cause Mortality, Strokes and Myocardial Infarctions During Observational Period	All events were adjudicated and confirmed by a central independent adjudication committee blinded to treatment. Events were assessed based on either compression ultrasound (for DVT), venography (for DVT), spiral computed tomography (CT) scanning (for PE), pulmonary angiography (for PE), ventilation/perfusion lung scan (for PE), lung scintigraphy (for PE), autopsy (for fatal PE) or unexplained death for which DVT/PE could not be ruled out (for fatal PE), results/films/images of confirmatory testing, and/or case summaries.	30 days observational period after last intake of study medication
Percentage of Participants With Net Clinical Benefit as Composite of Recurrent DVT or Non-fatal or Fatal PE and Major Bleeding Events During Observational Period	Events were adjudicated/confirmed by a central independent adjudication committee blinded to treatment, based on either compression ultrasound, venography, spiral CT scanning, pulmonary angiography, ventilation/perfusion lung scan, lung scintigraphy, autopsy or unexplained death for which DVT/PE could not be ruled out, results/films/images of confirmatory testing, and/or case summaries. Major bleeding was overt bleeding associated with 2 g/dL or greater fall in hemoglobin, leading to a transfusion of 2 or more units, occurring in a critical site or contributing to death.	30 days observational period after last intake of study medication
Percentage of Participants With Recurrent VTE (PE or DVT) During Observational Period	All events were adjudicated and confirmed by a central independent adjudication committee blinded to treatment. Events were assessed based on either compression ultrasound (for DVT), venography (for DVT), spiral computed tomography (CT) scanning (for PE), pulmonary angiography (for PE), ventilation/perfusion lung scan (for PE), lung scintigraphy (for PE), results/films/images of confirmatory testing, and/or case summaries.	30 days observational period after last intake of study medication
Percentage of Participants With Recurrent DVT During Observational Period	All events were adjudicated and confirmed by a central independent adjudication committee blinded to treatment. Events were assessed based on either compression ultrasound or venography, results/films/images of confirmatory testing, and/or case summaries.	30 days observational period after last intake of study medication

Collaborators and Investigators

• Sponsor: Bayer
• Collaborators: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Publications and helpful links

General Publications

• Cohen AT, Dobromirski M. The use of rivaroxaban for short- and long-term treatment of venous thromboembolism. Thromb Haemost. 2012 Jun;107(6):1035-43. doi: 10.1160/TH11-12-0859. Epub 2012 Feb 28.
• Wells PS, Gebel M, Prins MH, Davidson BL, Lensing AW. Influence of statin use on the incidence of recurrent venous thromboembolism and major bleeding in patients receiving rivaroxaban or standard anticoagulant therapy. Thromb J. 2014 Nov 26;12:26. doi: 10.1186/1477-9560-12-26. eCollection 2014.
• EINSTEIN Investigators; Bauersachs R, Berkowitz SD, Brenner B, Buller HR, Decousus H, Gallus AS, Lensing AW, Misselwitz F, Prins MH, Raskob GE, Segers A, Verhamme P, Wells P, Agnelli G, Bounameaux H, Cohen A, Davidson BL, Piovella F, Schellong S. Oral rivaroxaban for symptomatic venous thromboembolism. N Engl J Med. 2010 Dec 23;363(26):2499-510. doi: 10.1056/NEJMoa1007903. Epub 2010 Dec 3.
• Wells PS, Prins MH, Levitan B, Beyer-Westendorf J, Brighton TA, Bounameaux H, Cohen AT, Davidson BL, Prandoni P, Raskob GE, Yuan Z, Katz EG, Gebel M, Lensing AWA. Long-term Anticoagulation With Rivaroxaban for Preventing Recurrent VTE: A Benefit-Risk Analysis of EINSTEIN-Extension. Chest. 2016 Nov;150(5):1059-1068. doi: 10.1016/j.chest.2016.05.023. Epub 2016 Jun 1.

Helpful Links

• Click here and search for information of Bayer products for Europe
• Click here to find the definition for Deep Vein Thrombosis [DVT].
• Click here to find the definition for Pulmonary Embolism [PE].

Study record dates

Study Major Dates

• Study Start: February 1, 2007
• Primary Completion (Actual): August 1, 2009
• Study Completion (Actual): September 1, 2009

Study Registration Dates

• First Submitted: February 23, 2007
• First Submitted That Met QC Criteria: February 23, 2007
• First Posted (Estimate): February 26, 2007

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

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Embolism and Thrombosis; Embolism; Thrombosis; Venous Thrombosis; Thromboembolism; Venous Thromboembolism; Pulmonary Embolism; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protease Inhibitors; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Rivaroxaban
• Other Study ID Numbers: 11899; 2006-004494-96 (EudraCT Number)