Clinical trial NCT00439725: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Venous Thromboembolism
Lead sponsor: Bayer
Sponsor class: INDUSTRY
Collaborators: name: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
First posted: 2007-02-26
Enrollment: 1197
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: 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
timeFrame: 6- or 12-month study treatment period
Secondary outcomes:
measure: Percentage of Participants With the Composite Variable Comprising Recurrent DVT, Non-fatal PE and All Cause Mortality Until the Intended End of Study Treatment
timeFrame: 6- or 12-month study treatment period
measure: 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
timeFrame: 6- or 12-month study treatment period
measure: 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
timeFrame: 6- or 12-month study treatment period
measure: Percentage of Participants With Recurrent VTE (PE or DVT) Until the Intended End of Study Treatment
timeFrame: 6- or 12-month study treatment period
measure: Percentage of Participants With Recurrent DVT Until the Intended End of Study Treatment
timeFrame: 6- or 12-month study treatment period
measure: Percentage of Participants With Major Bleeding
timeFrame: 6- or 12-month study treatment period
measure: Percentage of Participants With Clinically Relevant Bleeding
timeFrame: 6- or 12-month study treatment period
measure: Percentage of Participants With All Death
timeFrame: 6- or 12-month study treatment period
measure: Percentage of Participants With Other Vascular Events
timeFrame: 6- or 12-month study treatment period
Other outcomes:
measure: Percentage of Participants With Death (PE) Until the Intended End of Study Treatment
timeFrame: 6- or 12-month study treatment period
measure: Percentage of Participants With Death (PE Cannot be Excluded) Until the Intended End of Study Treatment
timeFrame: 6- or 12-month study treatment period
measure: Percentage of Participants With Symptomatic Recurrent PE Until the Intended End of Study Treatment
timeFrame: 6- or 12-month study treatment period
measure: 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
timeFrame: 30 days observational period after last intake of study medication
measure: Percentage of Participants With Symptomatic Recurrent PE During Observational Period
timeFrame: 30 days observational period after last intake of study medication
measure: Percentage of Participants With the Composite Variable Comprising Recurrent DVT, Non-fatal PE and All Cause Mortality During Observational Period
timeFrame: 30 days observational period after last intake of study medication
measure: Percentage of Participants With the Composite Variable Comprising Recurrent DVT, Non-fatal PE, All Cause Mortality, Strokes and Myocardial Infarctions During Observational Period
timeFrame: 30 days observational period after last intake of study medication
measure: 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
timeFrame: 30 days observational period after last intake of study medication
measure: Percentage of Participants With Recurrent VTE (PE or DVT) During Observational Period
timeFrame: 30 days observational period after last intake of study medication
measure: Percentage of Participants With Recurrent DVT During Observational Period
timeFrame: 30 days observational period after last intake of study medication
Locations:
city: Little Rock
country: United States
state: Arkansas
city: Los Angeles
country: United States
state: California
city: Redlands
country: United States
state: California
city: Bay Pines
country: United States
state: Florida
city: Melbourne
country: United States
state: Florida
city: Miami
country: United States
state: Florida
city: Miami
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state: Florida
city: Decatur
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state: Georgia
city: Idaho Falls
country: United States
state: Idaho
city: Covington
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state: Louisiana
city: Baltimore
country: United States
state: Maryland
city: Boston
country: United States
state: Massachusetts
city: Albuquerque
country: United States
state: New Mexico
city: Chapel Hill
country: United States
state: North Carolina
city: Greensboro
country: United States
state: North Carolina
city: Greensboro
country: United States
state: North Carolina
city: Oklahoma City
country: United States
state: Oklahoma
city: Pittsburgh
country: United States
state: Pennsylvania
city: Corsicana
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state: Texas
city: San Antonio
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state: Texas
city: Murray
country: United States
state: Utah
city: Salt Lake City
country: United States
state: Utah
city: Burlington
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state: Vermont
city: Fredericksburg
country: United States
state: Virginia
city: Spokane
country: United States
state: Washington
city: Garran
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state: Australian Capital Territory
city: Gosford
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state: New South Wales
city: Kogarah
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state: New South Wales
city: Lismore
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state: New South Wales
city: St Leonards
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state: New South Wales
city: Sydney
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state: New South Wales
city: Sydney
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state: New South Wales
city: Sydney
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state: New South Wales
city: Sydney
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state: New South Wales
city: Brisbane
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state: Queensland
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city: Johannesburg
country: South Africa
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city: Pretoria
country: South Africa
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city: Pretoria
country: South Africa
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city: Pretoria
country: South Africa
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city: Roodepoort
country: South Africa
state: Gauteng
city: Cape Town
country: South Africa
state: Western Cape
city: Somerset West
country: South Africa
state: Western Cape
city: Worcester
country: South Africa
state: Western Cape
city: Terrassa
country: Spain
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city: Alcorcón
country: Spain
state: Madrid
city: Fuenlabrada
country: Spain
state: Madrid
city: Xàtiva
country: Spain
state: Valencia
city: Barcelona
country: Spain
city: Barcelona
country: Spain
city: Girona
country: Spain
city: Madrid
country: Spain
city: Pamplona
country: Spain
city: Borås
country: Sweden
city: Göteborg
country: Sweden
city: Göteborg
country: Sweden
city: Jönköping
country: Sweden
city: Sundsvall
country: Sweden
city: Västervik
country: Sweden
city: Bruderholz
country: Switzerland
state: Basel-Landschaft
city: Genéve 14
country: Switzerland
state: Genève 14
city: Chur
country: Switzerland
state: Graubünden
city: Brig
country: Switzerland
state: Valais
city: Lugano
country: Switzerland
city: Luzern
country: Switzerland
city: Zürich
country: Switzerland
city: Kaohsiung
country: Taiwan
city: Tainan
country: Taiwan
city: Taipei
country: Taiwan
city: Taipei
country: Taiwan
city: Taoyuan
country: Taiwan
city: Bangkok
country: Thailand
city: Bangkok
country: Thailand
city: Pathumwan, Bangkok
country: Thailand
city: Plymouth
country: United Kingdom
state: Devon
city: Chelmsford
country: United Kingdom
state: Essex
city: Romford
country: United Kingdom
state: Essex
city: Isleworth
country: United Kingdom
state: London
city: Edinburgh
country: United Kingdom
state: Lothian
city: Liverpool
country: United Kingdom
state: Merseyside
city: London
country: United Kingdom
city: London
country: United Kingdom
city: London
country: United Kingdom
city: London
country: United Kingdom
Study officials:
affiliation: Bayer
name: Bayer Study Director
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.