Reduced-dosed Rivaroxaban in the Long-term Prevention of Recurrent Symptomatic VTE(Venous Thromboembolism) (EinsteinChoice)

Reduced-dosed Rivaroxaban and Standard-dosed Rivaroxaban Versus ASA in the Long-term Prevention of Recurrent Symptomatic Venous Thromboembolism in Patients With Symptomatic Deep-vein Thrombosis and/or Pulmonary Embolism

This is a multicenter, randomized, double-blind, 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 of anticoagulation are eligible for this trial

Study Overview

• Status: Completed
• Conditions: Thrombosis; Venous Thrombosis; Thromboembolism; Venous Thromboembolism; Pulmonary Embolism
• Intervention / Treatment: Drug: BAY 59-7939; Drug: BAY 59-7939; Drug: ASA

• Study Type: Interventional
• Enrollment (Actual): 3365
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Box Hill, Australia, 3128
  • Melbourne, Australia, 3004
  • Redcliffe, Australia, 4020
  • Australian Capital Territory
    • Garran, Australian Capital Territory, Australia, 2605
  • New South Wales
    • Concord, New South Wales, Australia, 2139
    • Kogarah, New South Wales, Australia, 2217
    • Lismore, New South Wales, Australia, 2480
    • Randwick, New South Wales, Australia, 2031
    • St Leonards, New South Wales, Australia, 2065
    • Westmead, New South Wales, Australia, 2145
  • Queensland
    • Brisbane, Queensland, Australia, 4029
  • Victoria
    • Clayton, Victoria, Australia, 3168
• Austria
  • Wien, Austria, 1090
  • Steiermark
    • Graz, Steiermark, Austria, 8036
  • Tirol
    • Innsbruck, Tirol, Austria, 6020
• Belgium
  • Aalst, Belgium, 9300
  • Bruxelles - Brussel, Belgium, 1070
  • Bruxelles - Brussel, Belgium, 1200
  • Hasselt, Belgium, 3500
  • Leuven, Belgium, 3000
• Brazil
  • Rio de Janeiro, Brazil
  • Sao Paulo, Brazil, 05403-900
  • Minas Gerais
    • Belo Horizonte, Minas Gerais, Brazil, 30150-221
  • Rio Grande Do Sul
    • Porto Alegre, Rio Grande Do Sul, Brazil
  • Sao Paulo
    • Campinas, Sao Paulo, Brazil, 13083-970
    • Santo André, Sao Paulo, Brazil, 09060-650
    • Santo André, Sao Paulo, Brazil, 09190-615
    • São Paulo, Sao Paulo, Brazil, 01323-001
    • São Paulo, Sao Paulo, Brazil, 04039-004
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 2B7
  • British Columbia
    • Victoria, British Columbia, Canada, V8R 4R2
  • New Brunswick
    • Saint John, New Brunswick, Canada, E2L 4L2
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 3A7
  • Ontario
    • Hamilton, Ontario, Canada, L8L 2X2
    • Hamilton, Ontario, Canada, L8N 4A6
    • Hamilton, Ontario, Canada, L8V 1C3
    • London, Ontario, Canada, N6A 4G5
    • Ottawa, Ontario, Canada, K1H 8L6
  • Quebec
    • Montreal, Quebec, Canada, H1T 2M4
    • Montreal, Quebec, Canada, H3T 1E2
    • Montreal, Quebec, Canada, H3T 1M5
    • St. Jerome, Quebec, Canada, J7Z 5T3
• China
  • Beijing, China, 100730
  • Beijing, China, 100020
  • Beijing, China, 100029
  • Beijing, China, 100037
  • Beijing, China, 100053
  • Shanghai, China, 200032
  • Shanghai, China, 200233
  • Shanghai, China, 200025
  • Shanghai, China, 200001
  • Shanghai, China, 200433
  • Tianjin, China, 300052
  • Tianjin, China, 300121
  • Tianjin, China, 300211
  • Fujian
    • Fuzhou, Fujian, China, 350025
  • Guangdong
    • Guangzhou, Guangdong, China, 510080
    • Guangzhou, Guangdong, China, 510120
  • Guangxi
    • Nanning, Guangxi, China, 530021
  • Hebei
    • Shijiazhuang, Hebei, China, 050000
  • Heilongjiang
    • Harbin, Heilongjiang, China
  • Hubei
    • Wuhan, Hubei, China, 430032
  • Hunan
    • Changsha, Hunan, China, 410011
    • Changsha, Hunan, China, 410013
  • Jiangsu
    • Nantong, Jiangsu, China, 226001
    • Suzhou, Jiangsu, China, 215004
  • Jilin
    • Changchun, Jilin, China, 130000
  • Liaoning
    • Shengyang, Liaoning, China, 110004
    • Shenyang, Liaoning, China, 110001
  • Ningxia
    • Yinchuan, Ningxia, China, 750004
  • Shaanxi
    • Xi'an, Shaanxi, China, 710032
    • Xi'an, Shaanxi, China, 710061
  • Shandong
    • Jinan, Shandong, China, 250012
    • Qingdao, Shandong, China, 266000
  • Shanxi
    • Taiyuan, Shanxi, China, 030001
  • Sichuan
    • Chengdu, Sichuan, China, 610041
  • Yunnan
    • Kunming, Yunnan, China, 650032
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310003
    • Hangzhou, Zhejiang, China, 310016
    • Wenzhou, Zhejiang, China, 325000
• Czechia
  • Kladno, Czechia, 27259
  • Liberec, Czechia, 46063
  • Litomysl, Czechia, 570 14
  • Ostrava, Czechia, 708 52
  • Ostrava, Czechia, 728 80
  • Prague, Czechia, 118 33
  • Praha 1, Czechia, 110 00
  • Praha 5, Czechia, 150 06
  • Usti nad Labem, Czechia, 401 13
• Denmark
  • Aarhus N, Denmark, 8200
  • Copenhagen, Denmark, 2300
  • Glostrup, Denmark, 2600
  • Hellerup, Denmark, 2900
  • Herning, Denmark, 7400
  • København NV, Denmark, 2400
  • Svendborg, Denmark, 5700
• France
  • Angers, France, 49933
  • Arras, France, 62000
  • BREST Cedex 9, France, 29240
  • Besancon, France, 25030
  • Bois-guillaume, France, 76320
  • Brest Cedex, France, 29609
  • Castelnau Le Lez, France, 34170
  • Clermont Ferrand, France, 63000
  • Colombes Cedex, France, 92701
  • Dijon, France, 21000
  • Grenoble, France, 38043
  • Le Kremlin Bicetre Cedex, France, 94275
  • Le Mans, France, 72037
  • Limoges Cedex, France, 87042
  • Nice, France, 06002
  • Paris, France, 75475
  • Paris, France, 75674
  • Paris Cedex 15, France, 75908
  • Quimper, France, 29000
  • Saint Etienne, France, 42055
  • Strasbourg Cedex, France, 67091
  • Toulon, France, 83056
  • Toulouse, France, 31403
  • Vernon, France, 27200
• Germany
  • Berlin, Germany, 10787
  • Karlsbad, Germany, 76307
  • Baden-Württemberg
    • Heidelberg, Baden-Württemberg, Germany, 69120
  • Bayern
    • München, Bayern, Germany, 80336
  • Hessen
    • Darmstadt, Hessen, Germany, 64297
  • Nordrhein-Westfalen
    • Witten, Nordrhein-Westfalen, Germany, 58448
  • Rheinland-Pfalz
    • Mainz, Rheinland-Pfalz, Germany, 55131
  • Sachsen
    • Dresden, Sachsen, Germany, 01067
    • Dresden, Sachsen, Germany, 01307
  • Sachsen-Anhalt
    • Magdeburg, Sachsen-Anhalt, Germany, 39112
  • Thüringen
    • Erfurt, Thüringen, Germany, 99089
• Hungary
  • Baja, Hungary, 6500
  • Budapest, Hungary, 1115
  • Debrecen, Hungary, 4032
  • Gyula, Hungary, 5700
  • Kecskemet, Hungary, 6000
  • Miskolc, Hungary, 3526
  • Pecs, Hungary, 7624
  • Szentes, Hungary, 6600
  • Szombathely, Hungary, 9700
  • Zalaegerszeg, Hungary, 8900
• Israel
  • Afula, Israel, 1834111
  • Haifa, Israel, 3109601
  • Haifa, Israel, 3339419
  • Holon, Israel, 5810001
  • Kfar Saba, Israel, 4428164
  • Nahariya, Israel, 2210001
  • Petah Tikva, Israel, 4941492
  • Tel-Aviv, Israel, 64239
  • Zefat, Israel, 1311001
• Italy
  • Abruzzo
    • Chieti, Abruzzo, Italy, 66013
  • Calabria
    • Cosenza, Calabria, Italy, 87100
  • Emilia-Romagna
    • Piacenza, Emilia-Romagna, Italy, 29121
    • Reggio Emilia, Emilia-Romagna, Italy, 42100
  • Lombardia
    • Varese, Lombardia, Italy, 21100
  • Umbria
    • Perugia, Umbria, Italy, 06156
  • Veneto
    • Padova, Veneto, Italy, 35128
    • Treviso, Veneto, Italy, 31029
    • Treviso, Veneto, Italy, 31033
• Korea, Republic of
  • Busan, Korea, Republic of, 602-739
  • Daegu, Korea, Republic of, 705-718
  • Seoul, Korea, Republic of, 03080
  • Seoul, Korea, Republic of, 120-752
  • Seoul, Korea, Republic of, 135-710
  • Gwangju Gwang''yeogsi
    • Donggu,, Gwangju Gwang''yeogsi, Korea, Republic of, 501-757
• Mexico
  • Aguascalientes, Mexico, 20230
  • Chihuahua, Mexico, 31203
  • Guanajuato
    • Leon, Guanajuato, Mexico, 37000
    • León, Guanajuato, Mexico, 37000
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 44280
    • Guadalajara, Jalisco, Mexico, 44340
  • Nuevo Leon
    • Monterrey, Nuevo Leon, Mexico, 64718
  • Veracruz
    • Xalapa, Veracruz, Mexico, 91020
  • Yucatán
    • Merida, Yucatán, Mexico, 97129
• Netherlands
  • Alkmaar, Netherlands, 1815 JD
  • Almere, Netherlands, 1315 RA
  • Amsterdam, Netherlands, 1105 AZ
  • Assen, Netherlands, 9401 RK
  • Dordrecht, Netherlands, 3318 AT
  • Groningen, Netherlands, 9713 GZ
  • Hoofddorp, Netherlands, 2134 TM
  • Maastricht, Netherlands, 6229 HX
  • Sittard, Netherlands, 6131 BK
  • Zwolle, Netherlands, 8025 AB
• New Zealand
  • Auckland, New Zealand, 1023
  • Auckland, New Zealand, 1309
  • Auckland, New Zealand, 2024
  • Christchurch, New Zealand, 8011
  • Palmerston North, New Zealand, 4414
  • Wellington, New Zealand, 6021
• Norway
  • Fredrikstad, Norway, 1603
  • Oslo, Norway, 0450
• Philippines
  • Quezon City, Philippines, NCR 1100
• Poland
  • Bialystok, Poland, 15-276
  • Bydgoszcz, Poland, 85-681
  • Poznan, Poland, 60-631
  • Warszawa, Poland, 01-138
  • Wroclaw, Poland, 51-124
• Russian Federation
  • Barnaul, Russian Federation, 656045
  • Moscow, Russian Federation, 111539
  • Moscow, Russian Federation, 121552
  • Novosibirsk, Russian Federation, 630055
  • Novosibirsk, Russian Federation, 630087
  • Rostov-on-Don, Russian Federation, 344022
  • Ryazan, Russian Federation, 390026
  • Sochi, Russian Federation, 354057
  • St. Petersburg, Russian Federation
  • St. Petersburg, Russian Federation, 197022
  • Tver, Russian Federation, 170036
• South Africa
  • Bloemfontein, South Africa, 9301
  • Gauteng
    • Johannesburg, Gauteng, South Africa, 2132
    • Johannesburg, Gauteng, South Africa, 2191
    • Pretoria, Gauteng, South Africa, 0181
    • Pretoria West, Gauteng, South Africa, 0082
    • Roodepoort, Gauteng, South Africa, 1724
  • Western Cape
    • Worcester, Western Cape, South Africa, 6850
• Spain
  • Girona, Spain, 17007
  • Madrid, Spain, 28007
  • Alicante
    • Torrevieja, Alicante, Spain, 03186
  • Barcelona
    • L'Hospitalet de Llobregat, Barcelona, Spain, 08907
  • Madrid
    • San Sebastián de los Reyes, Madrid, Spain, 28702
• Sweden
  • Göteborg, Sweden, 416 85
  • Kristianstad, Sweden, 29185
• Switzerland
  • Bern, Switzerland, 3010
  • Fribourg, Switzerland, 1700
  • Genève, Switzerland, 1205
  • Luzern, Switzerland, 6000
  • Basel-Stadt
    • Basel, Basel-Stadt, Switzerland, 4031
  • Vaud
    • Lausanne, Vaud, Switzerland, 1011
• Taiwan
  • New Taipei City, Taiwan, 220
  • Taichung, Taiwan, 40447
  • Taipei, Taiwan, 11217
• Thailand
  • Bangkok, Thailand, 10400
  • Khon Kaen, Thailand, 40002
• Turkey
  • Istanbul, Turkey, 34-300
  • Istanbul, Turkey, 34760
• United Kingdom
  • Cardiff, United Kingdom, CF14 4XW
  • London, United Kingdom, SE1 7EH
  • Devon
    • Plymouth, Devon, United Kingdom, PL6 8DH
  • Humberside
    • Hull, Humberside, United Kingdom, HU3 2JZ
  • Tyne And Wear
    • Newcastle Upon Tyne, Tyne And Wear, United Kingdom, NE1 4LP
• United States
  • California
    • Beverly Hills, California, United States, 90211
    • La Jolla, California, United States, 92037
    • Ventura, California, United States, 93003
  • Colorado
    • Denver, Colorado, United States, 80262
  • Florida
    • Jacksonville, Florida, United States, 32207
  • Georgia
    • Columbus, Georgia, United States, 31904
  • Illinois
    • Joliet, Illinois, United States, 60435
  • Maine
    • Rockport, Maine, United States, 04856
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
    • Boston, Massachusetts, United States, 02114-2696
    • Boston, Massachusetts, United States, 02115
  • Michigan
    • Detroit, Michigan, United States, 48202
  • Montana
    • Butte, Montana, United States, 59701
  • Nevada
    • Las Vegas, Nevada, United States, 89169
  • North Carolina
    • Raleigh, North Carolina, United States, 27607
  • Ohio
    • Columbus, Ohio, United States, 43210-1240
    • Toledo, Ohio, United States, 43606
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
  • Texas
    • San Antonio, Texas, United States, 78229
  • Virginia
    • Fredericksburg, Virginia, United States, 22401
  • Washington
    • Bellevue, Washington, United States, 98004
    • Seattle, Washington, United States, 98104
    • Spokane, Washington, United States, 99216
    • Tacoma, Washington, United States, 98405-2433
• Vietnam
  • Ha Noi, Vietnam
  • Ho Chi Minh, Vietnam, 70000

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 and/or DVT who have been treated for 6 to 12 months and did not interrupt anticoagulation for longer than 1 week

Exclusion Criteria:

• Legal lower age limitations (country specific) Indication for therapeutic-dosed anticoagulants Indication for antiplatelet therapy or a conventional non-steroid anti-inflammatory drug (NSAID) Hepatic disease which is associated with coagulopathy leading to a clinically relevant bleeding risk Calculated creatinine clearance < 30 mL/min

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1; Rivaroxaban 10 mg once daily for 12 months	Drug: BAY 59-7939; 10 mg tablet once daily for 12 months; Drug: BAY 59-7939; 20 mg tablet once daily for 12 months
Experimental: Arm 2; Rivaroxaban 20 mg once daily for 12 months	Drug: BAY 59-7939; 10 mg tablet once daily for 12 months; Drug: BAY 59-7939; 20 mg tablet once daily for 12 months
Active Comparator: Arm 3; ASA (Acetylsalicylic Acid) 100 mg once daily for 12 months	Drug: ASA; 100 mg tablet once daily for 12 months

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With the Composite of Fatal or Non-fatal Symptomatic Recurrent Venous Thromboembolism	The primary efficacy outcomes (i.e., recurrent venous thromboembolism [VTE] defined as composite of fatal or non-fatal symptomatic recurrent VTE, including unexplained death for which pulmonary embolism [PE] could not be ruled out) as confirmed by the central independent adjudication committee (CIAC) were considered up to the end of the individual intended duration of treatment. Incidence of the composite of the primary and secondary efficacy outcome and its components are based on the first occurrence to participant.	Up to 12 months, at least 6 months
Number of Participants With First Treatment-emergent Major Bleeding	The principal safety outcome was major bleeding which was defined according to the criteria of the International Society on Thrombosis and Hemostasis (ISTH) as clinically overt bleeding and associated with a fall in hemoglobin of 2 gram per deciliter (g/dL) or more, or leading to a transfusion of 2 or more units of packed red blood cells or whole blood, or occurring in a critical site, e.g. intracranial, intraspinal, intraocular, pericardial, intra articular, intramuscular with compartment syndrome, retroperitoneal, or contributing to death. Incidence of the composite of the primary and secondary efficacy outcome and its components are based on the first occurrence to participant.	Up to 12 months, at least 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With the Composite of the Primary Efficacy Outcome, Myocardial Infarction, Ischemic Stroke or Systemic Non-CNS Embolism	The secondary efficacy outcome is the composite of the primary efficacy outcome, myocardial infarction (MI), ischemic stroke or non-central nervous system (CNS) systemic embolism. Incidence of the composite of the primary and secondary efficacy outcome and its components are based on the first occurrence to participant.	Up to 12 months, at least 6 months
Number of Participants With Non-major Bleeding Associated With Study Drug Interruption for > 14 Days	The secondary safety outcome was clinically relevant non-major (CRNM) bleeding, which was adjudicated by the CIAC using the ASA criteria: the bleeding was non-major and the bleeding was associated with a study medication interruption of more than 14 days.	Up to 12 months, at least 6 months

Collaborators and Investigators

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

Publications and helpful links

General Publications

• Weitz JI, Bauersachs R, Beyer-Westendorf J, Bounameaux H, Brighton TA, Cohen AT, Davidson BL, Holberg G, Kakkar A, Lensing AW, Prins M, Haskell L, van Bellen B, Verhamme P, Wells PS, Prandoni P; EINSTEIN CHOICE Investigators. Two doses of rivaroxaban versus aspirin for prevention of recurrent venous thromboembolism. Rationale for and design of the EINSTEIN CHOICE study. Thromb Haemost. 2015 Aug 31;114(3):645-50. doi: 10.1160/TH15-02-0131. Epub 2015 May 21.
• Flumignan CD, Nakano LC, Baptista-Silva JC, Flumignan RL. Antiplatelet agents for the treatment of deep venous thrombosis. Cochrane Database Syst Rev. 2022 Jul 25;7(7):CD012369. doi: 10.1002/14651858.CD012369.pub2.
• Weitz JI, Lensing AWA, Prins MH, Bauersachs R, Beyer-Westendorf J, Bounameaux H, Brighton TA, Cohen AT, Davidson BL, Decousus H, Freitas MCS, Holberg G, Kakkar AK, Haskell L, van Bellen B, Pap AF, Berkowitz SD, Verhamme P, Wells PS, Prandoni P; EINSTEIN CHOICE Investigators. Rivaroxaban or Aspirin for Extended Treatment of Venous Thromboembolism. N Engl J Med. 2017 Mar 30;376(13):1211-1222. doi: 10.1056/NEJMoa1700518. Epub 2017 Mar 18.

Study record dates

Study Major Dates

• Study Start (Actual): March 5, 2014
• Primary Completion (Actual): September 22, 2016
• Study Completion (Actual): November 4, 2016

Study Registration Dates

• First Submitted: February 14, 2014
• First Submitted That Met QC Criteria: February 14, 2014
• First Posted (Estimate): February 17, 2014

Study Record Updates

• Last Update Posted (Actual): December 19, 2017
• Last Update Submitted That Met QC Criteria: December 17, 2017
• Last Verified: November 1, 2017

More Information

Terms related to this study

• Keywords: deep vein thrombosis; pulmonary embolism; long-term prevention of recurrent symptomatic VTE
• 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: 16416; 2013-000619-26 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No