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

NCT ID: NCT00439725

Last Updated: 2014-11-04

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

1197 participants

Study Classification

INTERVENTIONAL

Study Start Date

2007-02-28

Study Completion Date

2009-09-30

Brief Summary

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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).

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.

Conditions

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Venous Thromboembolism

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Rivaroxaban (Xarelto, BAY59-7939)

Participants were to receive rivaroxaban 20 mg oral tablet once daily

Group Type EXPERIMENTAL

Rivaroxaban (Xarelto, BAY59-7939)

Intervention Type DRUG

Patients randomized to rivaroxaban will receive rivaroxaban 20 mg once-daily.

Placebo

Participants were to receive matching placebo oral tablet once daily

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Patients allocated to placebo will receive a matching placebo tablet once daily.

Interventions

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Rivaroxaban (Xarelto, BAY59-7939)

Patients randomized to rivaroxaban will receive rivaroxaban 20 mg once-daily.

Intervention Type DRUG

Placebo

Patients allocated to placebo will receive a matching placebo tablet once daily.

Intervention Type DRUG

Eligibility Criteria

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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
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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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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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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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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Nyíregyháza, , Hungary

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Szentes, , Hungary

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Szombathely, , Hungary

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Kochi, Kerala, India

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Vellore, Kerala, India

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Mumbai, Maharashtra, India

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Mumbai, Maharashtra, 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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Bandung, , Indonesia

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Jakarta, , Indonesia

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Medan, , Indonesia

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Semarang, , Indonesia

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Haifa, Israel, Israel

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Petah Tikva, Israel, Israel

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Afula, , Israel

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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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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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Montpellier, , France

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Nantes, , 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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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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Little Rock, Arkansas, United States

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Los Angeles, California, United States

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Redlands, California, United States

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Bay Pines, Florida, United States

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Melbourne, Florida, United States

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Miami, Florida, United States

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Miami, Florida, United States

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Decatur, Georgia, 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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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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Burlington, Vermont, United States

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Fredericksburg, Virginia, United States

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Spokane, Washington, United States

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Garran, Australian Capital Territory, 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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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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Adelaide, 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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Prahran, Victoria, Australia

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Fremantle, Western Australia, Australia

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Perth, Western Australia, Australia

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Salzburg, Salzburg, Austria

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Graz, Styria, Austria

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Innsbruck, Tyrol, 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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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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Sint-Truiden, , 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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Porto Alegre, Rio Grande do Sul, 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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Toronto, Ontario, Canada

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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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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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Brno, , Czechia

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Karlovy Vary, , Czechia

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Kladno, , Czechia

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Ashkelon, , Israel

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Beersheba, , Israel

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Haifa, , Israel

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Haifa, , Israel

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Holon, , Israel

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Jerusalem, , Israel

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Kfar Saba, , Israel

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Rehovot, , Israel

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Safed, , Israel

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Tel Aviv, , Israel

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Bologna, , Italy

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Chieti, , 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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Venezia, , Italy

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Kuala Selangor, , Malaysia

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's-Hertogenbosch, , Netherlands

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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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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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Oslo, , Norway

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Rud, , 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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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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Pretoria, Gauteng, South Africa

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Pretoria, Gauteng, South Africa

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Pretoria, Gauteng, South Africa

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Roodepoort, 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 Gwang'yeogsi, South Korea

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Seoul, Seoul Teugbyeolsi, 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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Bruderholz, Basel-Landschaft, 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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Brig, Valais, Switzerland

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Lucerne, , Switzerland

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Lugano, , Switzerland

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Kaohsiung City, , Taiwan

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Tainan City, , Taiwan

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Taipei, , Taiwan

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Taipei, , Taiwan

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Taoyuan District, , 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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Romford, Essex, United Kingdom

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Isleworth, London, United Kingdom

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London, London, United Kingdom

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London, London, United Kingdom

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Edinburgh, Lothian, United Kingdom

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Liverpool, Merseyside, United Kingdom

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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 Singapore South Africa South Korea Spain Sweden Switzerland Taiwan Thailand United Kingdom

References

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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)

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)

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)

Yamada N, Fu W, Shi Z, Park KH, Kim HS, Dai X, Lensing AW, Pap AF, Kohno T, Tajima T, Watakabe T, Mitsumori T. Risk of recurrent venous thromboembolism and major bleeding according to risk factor profiles in Asian patients: a subgroup analysis EINSTEIN-Extension and EINSTEIN-CHOICE. Thromb J. 2024 Jun 6;22(1):48. doi: 10.1186/s12959-024-00609-4.

Reference Type DERIVED
PMID: 38844941 (View on PubMed)

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.

Reference Type DERIVED
PMID: 27262225 (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)

Related Links

Access external resources that provide additional context or updates about the study.

http://www.nhlbi.nih.gov/health/health-topics/topics/dvt/

Click here to find the definition for Deep Vein Thrombosis \[DVT\].

http://www.nhlbi.nih.gov/health/health-topics/topics/pe/

Click here to find the definition for Pulmonary Embolism \[PE\].

http://www.clinicaltrialsregister.eu

Click here and search for information of Bayer products for Europe

Other Identifiers

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2006-004494-96

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

11899

Identifier Type: -

Identifier Source: org_study_id

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