Oral Direct Factor Xa Inhibitor Rivaroxaban in Patients With Acute Symptomatic Deep Vein Thrombosis - The EINSTEIN DVT Study

NCT ID: NCT00440193

Last Updated: 2014-02-27

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

3449 participants

Study Classification

INTERVENTIONAL

Study Start Date

2007-03-31

Study Completion Date

2010-04-30

Brief Summary

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This is a multicenter, randomized, open-label, assessor-blind, event-driven, non-inferiority program for efficacy with a study treatment duration of 3, 6 or 12 months in patients with confirmed acute symptomatic DVT without symptomatic PE (Einstein-DVT).

Detailed Description

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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. Participants who were transferring from study 11702 DVT (NCT00440193) to the extension study 11899 (NCT00439725) did not enter the observational period.

Conditions

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Venous Thrombosis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Rivaroxaban (Xarelto, BAY59-7939)

Participants were to receive rivaroxaban 15 mg oral tablet twice daily for 3 weeks, followed by 20 mg once daily

Group Type EXPERIMENTAL

Rivaroxaban (Xarelto, BAY59-7939)

Intervention Type DRUG

During the first 3 weeks patients will receive 15 mg rivaroxaban twice-daily. Thereafter, patients will receive rivaroxaban 20 mg once-daily. Rivaroxaban will be administered orally and should be taken with food.

Enoxaparin/VKA

Participants were to receive 1.0 mg/kg enoxaparin twice daily (subcutaneous) for at least 5 days, plus vitamin K antagonist (VKA) (oral) at individually titrated doses to achieve a target international normalized ratio (INR) of 2.5 (range: 2.0 to 3.0)

Group Type ACTIVE_COMPARATOR

Enoxaparin followed by VKA

Intervention Type DRUG

Enoxaparin 1.0 mg/kg twice daily with a minimal duration of 5 days. This 5 days treatment could include the period up to 36 h before randomization if enoxaparin twice-daily was used. VKA should be started as soon as possible but not later than 48 hours after randomization.

Interventions

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Rivaroxaban (Xarelto, BAY59-7939)

During the first 3 weeks patients will receive 15 mg rivaroxaban twice-daily. Thereafter, patients will receive rivaroxaban 20 mg once-daily. Rivaroxaban will be administered orally and should be taken with food.

Intervention Type DRUG

Enoxaparin followed by VKA

Enoxaparin 1.0 mg/kg twice daily with a minimal duration of 5 days. This 5 days treatment could include the period up to 36 h before randomization if enoxaparin twice-daily was used. VKA should be started as soon as possible but not later than 48 hours after randomization.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Confirmed acute symptomatic proximal DVT without symptomatic PE

Exclusion Criteria

* Legal lower age limitations (country specific)
* Thrombectomy, insertion of a caval filter, or use of a fibrinolytic agent to treat the current episode of DVT and/or PE
* Other indication for VKA than DVT and/or PE
* The pre-randomization anti-coagulant treatment (Criteria # 4) has been prolonged from 36 hours to a maximum of 48 hours.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

INDUSTRY

Sponsor Role collaborator

Bayer

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Bayer Study Director

Role: STUDY_DIRECTOR

Bayer

Locations

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Little Rock, Arkansas, United States

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Redlands, California, United States

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Bay Pines, Florida, United States

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Miami, Florida, United States

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Miami, Florida, United States

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Idaho Falls, Idaho, United States

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Covington, Louisiana, United States

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Baltimore, Maryland, United States

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Boston, Massachusetts, United States

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Albuquerque, New Mexico, United States

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Chapel Hill, North Carolina, United States

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Greensboro, North Carolina, United States

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Greensboro, North Carolina, United States

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Oklahoma City, Oklahoma, United States

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Camp Hill, Pennsylvania, United States

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Pittsburgh, Pennsylvania, United States

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Corsicana, Texas, United States

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San Antonio, Texas, United States

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Murray, Utah, United States

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Salt Lake City, Utah, United States

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Fredericksburg, Virginia, United States

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Spokane, Washington, United States

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Tacoma, Washington, United States

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Garran, Australian Capital Territory, Australia

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Darlinghurst, New South Wales, Australia

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Gosford, New South Wales, Australia

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Kogarah, New South Wales, Australia

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Lismore, New South Wales, Australia

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St Leonards, New South Wales, Australia

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Sydney, New South Wales, Australia

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Sydney, New South Wales, Australia

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Sydney, New South Wales, Australia

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Brisbane, Queensland, Australia

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Redcliffe, Queensland, Australia

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Southport, Queensland, Australia

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Woolloongabba, Queensland, Australia

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Adelaide, South Australia, Australia

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Woodville South, South Australia, Australia

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Box Hill, Victoria, Australia

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Clayton, Victoria, Australia

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Geelong, Victoria, Australia

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Melbourne, Victoria, Australia

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Melbourne, Victoria, Australia

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Fremantle, Western Australia, Australia

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Perth, Western Australia, Australia

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Graz, Styria, Austria

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Vienna, Vienna, Austria

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Vienna, Vienna, Austria

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Feldkirch, Vorarlberg, Austria

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Innsbruck, , Austria

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Salzburg, , Austria

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Bruxelles - Brussel, , Belgium

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Bruxelles - Brussel, , Belgium

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Duffel, , Belgium

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Genk, , Belgium

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Ghent, , Belgium

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Hasselt, , Belgium

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Leuven, , Belgium

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Lier, , Belgium

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Liège, , Belgium

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Namur, , Belgium

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Yvoir, , Belgium

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Zottegem, , Belgium

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Uberaba, Minas Gerais, Brazil

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Curitiba, Paraná, Brazil

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Londrina, Paraná, Brazil

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Botucatu, São Paulo, Brazil

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São Paulo, São Paulo, Brazil

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São Paulo, São Paulo, Brazil

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São Paulo, São Paulo, Brazil

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São Paulo, São Paulo, Brazil

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Sorocaba, São Paulo, Brazil

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Rio de Janeiro, , Brazil

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Winnipeg, Manitoba, Canada

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London, Ontario, Canada

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Ottawa, Ontario, Canada

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Toronto, Ontario, Canada

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Toronto, Ontario, Canada

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Guangzhou, Guangdong, China

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Guangzhou, Guangdong, China

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Harbin, Heilongjiang, China

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Wuhan, Hubei, China

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Suzhou, Jiangsu, China

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Shenyang, Liaoning, China

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Hangzhou, Zhejiang, China

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Beijing, , China

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Beijing, , China

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Beijing, , China

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Beijing, , China

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Beijing, , China

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Beijing, , China

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Beijing, , China

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Shanghai, , China

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Shanghai, , China

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Shanghai, , China

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Karlovy Vary, , Czechia

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Kladno, , Czechia

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Ostrava, , Czechia

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Ostrava-Poruba, , Czechia

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Prague, , Czechia

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Prague, , Czechia

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Prague, , Czechia

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Prague, , Czechia

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Usti Nad Lebem, , Czechia

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Aarhus C, , Denmark

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Brædstrup, , Denmark

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Frederiksberg, , Denmark

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Hellerup, , Denmark

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Seinäjoki, , Finland

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Agen, , France

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Amiens, , France

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Angers, , France

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Arras, , France

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Besançon, , France

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Bordeaux, , France

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Brest, , France

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Castelnau-le-Lez, , France

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Clamart, , France

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Clermont-Ferrand, , France

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Colombes, , France

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Créteil, , France

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Dijon, , France

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Grenoble, , France

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Grenoble, , France

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Lille, , France

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Limoges, , France

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Metz-Tessy, , France

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Montpellier, , France

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Nantes, , France

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Nice, , France

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Nîmes, , France

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Orthez, , France

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Paris, , France

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Paris, , France

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Paris, , France

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Paris, , France

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Paris, , France

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Pierre-Bénite, , France

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Roanne, , France

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Rouen, , France

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Saint-Etienne, , France

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Strasbourg, , France

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Toulon, , France

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Toulouse, , France

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Tours, , France

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Valenciennes, , France

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Vandœuvre-lès-Nancy, , France

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Vernon, , France

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Bruchsal, Baden-Wurttemberg, Germany

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Heidelberg, Baden-Wurttemberg, Germany

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Karlsbad, Baden-Wurttemberg, Germany

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Mannheim, Baden-Wurttemberg, Germany

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Neckargemünd, Baden-Wurttemberg, Germany

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Tübingen, Baden-Wurttemberg, Germany

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Augsburg, Bavaria, Germany

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München, Bavaria, Germany

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München, Bavaria, Germany

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Würzburg, Bavaria, Germany

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Hamburg, City state of Hamburg, Germany

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Darmstadt, Hesse, Germany

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Frankfurt am Main, Hesse, Germany

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Frankfurt am Main, Hesse, Germany

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Giessen, Hesse, Germany

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Wiesbaden, Hesse, Germany

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Hanover, Lower Saxony, Germany

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Rotenburg (Wümme), Lower Saxony, Germany

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Greifswald, Mecklenburg-Vorpommern, Germany

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Düsseldorf, North Rhine-Westphalia, Germany

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Essen, North Rhine-Westphalia, Germany

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Paderborn, North Rhine-Westphalia, Germany

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Soest, North Rhine-Westphalia, Germany

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Witten, North Rhine-Westphalia, Germany

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Mainz, Rhineland-Palatinate, Germany

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Homburg, Saarland, Germany

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Homburg, Saarland, Germany

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Dresden, Saxony, Germany

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Leipzig, Saxony, Germany

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Halle, Saxony-Anhalt, Germany

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Magdeburg, Saxony-Anhalt, Germany

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Berlin, State of Berlin, Germany

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Berlin, State of Berlin, Germany

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Hong Kong, , Hong Kong

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Wan Chai, , Hong Kong

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Budapest, , Hungary

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Budapest, , Hungary

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Debrecen, , Hungary

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Kecskemét, , Hungary

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Kistarcsa, , Hungary

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Miskolc, , Hungary

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Szentes, , Hungary

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Szombathely, , Hungary

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Kochi, Kerala, India

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Mumbai, Maharashtra, India

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Hyderabad, , India

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Kolkata, , India

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New Delhi, , India

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Pune, , India

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Jakarta, Indonesia, Indonesia

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Bandung, , Indonesia

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Jakarta, , Indonesia

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Medan, , Indonesia

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Semarang, , Indonesia

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Afula, Israel, Israel

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Ashkelon, Israel, Israel

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Beersheba, Israel, Israel

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Haifa, Israel, Israel

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Haifa, Israel, Israel

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Haifa, Israel, Israel

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Holon, Israel, Israel

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Jerusalem, Israel, Israel

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Kfar Saba, Israel, Israel

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Petah Tikva, Israel, Israel

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Rehovot, Israel, Israel

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Safed, Israel, Israel

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Tel Aviv, Israel, Israel

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Bologna, , Italy

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Chieti, , Italy

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Cremona, , Italy

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Milan, , Italy

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Milan, , Italy

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Milan, , Italy

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Napoli, , Italy

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Padua, , Italy

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Palermo, , Italy

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Parma, , Italy

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Pavia, , Italy

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Piacenza, , Italy

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Reggio Emilia, , Italy

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Varese, , Italy

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Venezia, , Italy

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Kuala Selangor, , Malaysia

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Amsterdam, , Netherlands

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Arnhem, , Netherlands

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Dordrecht, , Netherlands

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Enschede, , Netherlands

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Groningen, , Netherlands

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Hoofddorp, , Netherlands

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Maastricht, , Netherlands

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Rotterdam, , Netherlands

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Zwijndrecht, , Netherlands

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Zwolle, , Netherlands

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Auckland, , New Zealand

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Auckland, , New Zealand

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Auckland, , New Zealand

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Christchurch, , New Zealand

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Palmerston North, , New Zealand

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Wellington South, , New Zealand

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Fredrikstad, , Norway

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Oslo, , Norway

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Rud, , Norway

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Trondheim, , Norway

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Quezon City, , Philippines

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Quezon City, , Philippines

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Bialystok, , Poland

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Bydgoszcz, , Poland

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Gdansk, , Poland

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Katowice, , Poland

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Krakow, , Poland

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Lodz, , Poland

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Lublin, , Poland

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Poznan, , Poland

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Poznan, , Poland

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Torun, , Poland

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Warsaw, , Poland

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Warsaw, , Poland

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Warsaw, , Poland

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Wroclaw, , Poland

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Wroclaw, , Poland

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San Juan, , Puerto Rico

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Singapore, , Singapore

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Singapore, , Singapore

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Cape Town, Cape, South Africa

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Johannesburg, Gauteng, South Africa

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Johannesburg, Gauteng, South Africa

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Johannesburg, Gauteng, South Africa

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Johannesburg, Gauteng, South Africa

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Johannesburg, Gauteng, South Africa

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Pretoria, Gauteng, South Africa

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Pretoria, Gauteng, South Africa

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Pretoria, Gauteng, South Africa

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Cape Town, Western Cape, South Africa

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Somerset West, Western Cape, South Africa

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Worcester, Western Cape, South Africa

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Daegu, Daegu, South Korea

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Seoul, Korea, South Korea

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Daegu, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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Taegu, , South Korea

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Barcelona, Barcelona, Spain

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Barcelona, Barcelona, Spain

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Terrassa, Barcelona, Spain

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Girona, Girona, Spain

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Alcorcón, Madrid, Spain

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Fuenlabrada, Madrid, Spain

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Madrid, Madrid, Spain

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Pamplona, Pamplona, Spain

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Xàtiva, Valencia, Spain

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Borås, , Sweden

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Gothenburg, , Sweden

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Gothenburg, , Sweden

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Jönköping, , Sweden

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Sundsvall, , Sweden

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Västervik, , Sweden

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Lausanne, Canton of Vaud, Switzerland

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Lausanne, Canton of Vaud, Switzerland

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Zurich, Canton of Zurich, Switzerland

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Genéve 14, Genève 14, Switzerland

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Chur, Kanton Graubünden, Switzerland

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Lucerne, , Switzerland

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Kaosiung, Kaoshiong, Taiwan

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Taichung, , Taiwan

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Taipei, , Taiwan

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Taipei, , Taiwan

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Taipei, , Taiwan

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Bangkok, Bangkok, Thailand

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Pathumwan, Bangkok, Thailand, Thailand

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Bangkok, , Thailand

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Plymouth, Devon, United Kingdom

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Chelmsford, Essex, United Kingdom

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Isleworth, Greater London, United Kingdom

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London, Greater London, United Kingdom

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London, Greater London, United Kingdom

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London, , United Kingdom

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Countries

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United States Australia Austria Belgium Brazil Canada China Czechia Denmark Finland France Germany Hong Kong Hungary India Indonesia Israel Italy Malaysia Netherlands New Zealand Norway Philippines Poland Puerto Rico Singapore South Africa South Korea Spain Sweden Switzerland Taiwan Thailand United Kingdom

References

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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.

Reference Type RESULT
PMID: 21128814 (View on PubMed)

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.

Reference Type RESULT
PMID: 22371186 (View on PubMed)

Prins MH, Lensing AW. Derivation of the non-inferiority margin for the evaluation of direct oral anticoagulants in the treatment of venous thromboembolism. Thromb J. 2013 Jul 6;11(1):13. doi: 10.1186/1477-9560-11-13.

Reference Type RESULT
PMID: 23829521 (View on PubMed)

Prins MH, Lensing AW, Bauersachs R, van Bellen B, Bounameaux H, Brighton TA, Cohen AT, Davidson BL, Decousus H, Raskob GE, Berkowitz SD, Wells PS; EINSTEIN Investigators. Oral rivaroxaban versus standard therapy for the treatment of symptomatic venous thromboembolism: a pooled analysis of the EINSTEIN-DVT and PE randomized studies. Thromb J. 2013 Sep 20;11(1):21. doi: 10.1186/1477-9560-11-21.

Reference Type RESULT
PMID: 24053656 (View on PubMed)

Wang Y, Wang C, Chen Z, Zhang J, Liu Z, Jin B, Ying K, Liu C, Shao Y, Jing Z, Meng IL, Prins MH, Pap AF, Muller K, Lensing AW; Chinese EINSTEIN Investigators. Rivaroxaban for the treatment of symptomatic deep-vein thrombosis and pulmonary embolism in Chinese patients: a subgroup analysis of the EINSTEIN DVT and PE studies. Thromb J. 2013 Dec 16;11(1):25. doi: 10.1186/1477-9560-11-25.

Reference Type RESULT
PMID: 24341332 (View on PubMed)

Bamber L, Wang MY, Prins MH, Ciniglio C, Bauersachs R, Lensing AW, Cano SJ. Patient-reported treatment satisfaction with oral rivaroxaban versus standard therapy in the treatment of acute symptomatic deep-vein thrombosis. Thromb Haemost. 2013 Oct;110(4):732-41. doi: 10.1160/TH13-03-0243. Epub 2013 Jul 11.

Reference Type RESULT
PMID: 23846019 (View on PubMed)

van Bellen B, Bamber L, Correa de Carvalho F, Prins M, Wang M, Lensing AW. Reduction in the length of stay with rivaroxaban as a single-drug regimen for the treatment of deep vein thrombosis and pulmonary embolism. Curr Med Res Opin. 2014 May;30(5):829-37. doi: 10.1185/03007995.2013.879439. Epub 2014 Jan 22.

Reference Type RESULT
PMID: 24432872 (View on PubMed)

Cano SJ, Lamping DL, Bamber L, Smith S. The Anti-Clot Treatment Scale (ACTS) in clinical trials: cross-cultural validation in venous thromboembolism patients. Health Qual Life Outcomes. 2012 Sep 26;10:120. doi: 10.1186/1477-7525-10-120.

Reference Type RESULT
PMID: 23013426 (View on PubMed)

Dobesh PP, Volkl AA, Pap AF, Damaraju CV, Levitan B, Yuan Z, Amin AN. Benefit-Risk Assessment of Rivaroxaban in Older Patients With Nonvalvular Atrial Fibrillation or Venous Thromboembolism. Drugs Aging. 2025 May;42(5):469-484. doi: 10.1007/s40266-025-01192-7. Epub 2025 Mar 31.

Reference Type DERIVED
PMID: 40163217 (View on PubMed)

Yang L, Wu J. Cost-effectiveness of rivaroxaban compared with enoxaparin plus warfarin for the treatment of hospitalised acute deep vein thrombosis in China. BMJ Open. 2020 Jul 30;10(7):e038433. doi: 10.1136/bmjopen-2020-038433.

Reference Type DERIVED
PMID: 32737096 (View on PubMed)

Ten Cate H, Lensing AWA, Weitz JI, Middeldorp S, Beyer-Westendorf J, Kubitza D, Brighton T, Raskob GE, Mismetti P, Prandoni P, Gebel M, Prins MH. The prothrombin time does not predict the risk of recurrent venous thromboembolism or major bleeding in rivaroxaban-treated patients. Thromb Res. 2018 Oct;170:75-83. doi: 10.1016/j.thromres.2018.08.008. Epub 2018 Aug 15.

Reference Type DERIVED
PMID: 30121419 (View on PubMed)

Di Nisio M, Vedovati MC, Riera-Mestre A, Prins MH, Mueller K, Cohen AT, Wells PS, Beyer-Westendorf J, Prandoni P, Bounameaux H, Kubitza D, Schneider J, Pisters R, Fedacko J, Fontes-Carvalho R, Lensing AW. Treatment of venous thromboembolism with rivaroxaban in relation to body weight. A sub-analysis of the EINSTEIN DVT/PE studies. Thromb Haemost. 2016 Sep 27;116(4):739-46. doi: 10.1160/TH16-02-0087. Epub 2016 Aug 18.

Reference Type DERIVED
PMID: 27535349 (View on PubMed)

Prins MH, Lensing AW, Brighton TA, Lyons RM, Rehm J, Trajanovic M, Davidson BL, Beyer-Westendorf J, Pap AF, Berkowitz SD, Cohen AT, Kovacs MJ, Wells PS, Prandoni P. Oral rivaroxaban versus enoxaparin with vitamin K antagonist for the treatment of symptomatic venous thromboembolism in patients with cancer (EINSTEIN-DVT and EINSTEIN-PE): a pooled subgroup analysis of two randomised controlled trials. Lancet Haematol. 2014 Oct;1(1):e37-46. doi: 10.1016/S2352-3026(14)70018-3. Epub 2014 Sep 28.

Reference Type DERIVED
PMID: 27030066 (View on PubMed)

Bauersachs RM, Lensing AW, Prins MH, Kubitza D, Pap AF, Decousus H, Beyer-Westendorf J, Prandoni P. Rivaroxaban versus enoxaparin/vitamin K antagonist therapy in patients with venous thromboembolism and renal impairment. Thromb J. 2014 Nov 24;12:25. doi: 10.1186/1477-9560-12-25. eCollection 2014.

Reference Type DERIVED
PMID: 25750589 (View on PubMed)

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.

Reference Type DERIVED
PMID: 25698905 (View on PubMed)

Other Identifiers

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2006-004495-13

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

11702b

Identifier Type: OTHER

Identifier Source: secondary_id

11702a

Identifier Type: -

Identifier Source: org_study_id

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