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

This study has been completed.
Sponsor:
Collaborator:
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Information provided by:
Bayer
ClinicalTrials.gov Identifier:
NCT00439725
First received: February 23, 2007
Last updated: March 7, 2013
Last verified: March 2013
History of Changes
Results First Received: January 31, 2012  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor);   Primary Purpose: Prevention
Condition: Venous Thromboembolism
Interventions: Drug: Rivaroxaban (Xarelto, BAY59-7939)
Drug: Placebo

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Participants with confirmed symptomatic deep vein thrombosis or pulmonary embolism, who either had been treated for 6 or 12 months with warfarin or acenocoumarol or rivaroxaban in study NCT00440193, or who had been treated for 6 to 14 months with warfarin or acenocoumarol outside study NCT00440193, were recruited at specialized study sites.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Out of 1200 participants screened, 3 failed screening (2 due to withdrawal of consent and 1 due to a protocol violation), and 1197 participants were randomized (602 to rivaroxaban and 595 to placebo).

Reporting Groups
  Description
Rivaroxaban (Xarelto, BAY59-7939) Participants were to receive rivaroxaban 20 mg oral tablet once daily
Placebo Participants were to receive matching placebo oral tablet once daily

Participant Flow for 2 periods

 Period 1:   Treatment Period
    Rivaroxaban (Xarelto, BAY59-7939)     Placebo  
STARTED     602     595  
Participants Received Treatment     598 [1]   590 [1]
COMPLETED     366     349  
NOT COMPLETED     236     246  
Withdrawal by Subject                 22                 19  
Study terminated by sponsor                 156                 148  
Site closed by investigator                 1                 2  
Adverse Event                 39                 18  
Physician Decision                 1                 1  
Protocol Violation                 2                 1  
Clinical endpoint reached                 6                 50  
Technical problems                 1                 0  
Lost to Follow-up                 1                 1  
Participant convenience                 1                 0  
Protocol driven decision point                 1                 1  
Death                 1                 1  
Participant did not receive treatment                 4                 4  
[1] Safety population

Period 2:   Observational Period
    Rivaroxaban (Xarelto, BAY59-7939)     Placebo  
STARTED     577 [1]   560 [1]
COMPLETED     569     553  
NOT COMPLETED     8     7  
Withdrawal by Subject                 2                 2  
Lost to Follow-up                 0                 1  
Death                 0                 2  
Study termination by sponsor                 1                 1  
Clinical endpoint reached                 3                 1  
Technical problems                 1                 0  
Participant convenience                 1                 0  
[1] All participants who took any study medication and entered the observational period.



  Baseline Characteristics
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Reporting Groups
  Description
Rivaroxaban (Xarelto, BAY59-7939) Participants were to receive rivaroxaban 20 mg oral tablet once daily
Placebo Participants were to receive matching placebo oral tablet once daily
Total Total of all reporting groups

Baseline Measures
    Rivaroxaban (Xarelto, BAY59-7939)     Placebo     Total  
Number of Participants  
[units: participants]
 		  602     594     1196  
Age [1]
[units: years]
Mean ± Standard Deviation 		  58.2  ± 15.6     58.4  ± 16.0     58.3  ± 15.8  
Age, Customized [1]
[units: participants]
 		     
18 - 40 years     87     94     181  
>40 - <65 years     273     280     553  
65 - 75 years     153     121     274  
>75 years     89     99     188  
Gender [1]
[units: participants]
 		     
Female     248     255     503  
Male     354     339     693  
[1] Number of participants analyzed for Baseline is intention-to-treat (ITT) population.



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   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   [ Time Frame: 6- or 12-month study treatment period ]
  Show Outcome Measure 1

2.  Secondary:   Percentage of Participants With the Composite Variable Comprising Recurrent DVT, Non-fatal PE and All Cause Mortality Until the Intended End of Study Treatment   [ Time Frame: 6- or 12-month study treatment period ]
  Show Outcome Measure 2

3.  Secondary:   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   [ Time Frame: 6- or 12-month study treatment period ]
  Show Outcome Measure 3

4.  Secondary:   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   [ Time Frame: 6- or 12-month study treatment period ]
  Show Outcome Measure 4

5.  Secondary:   Percentage of Participants With Recurrent VTE (PE or DVT) Until the Intended End of Study Treatment   [ Time Frame: 6- or 12-month study treatment period ]
  Show Outcome Measure 5

6.  Secondary:   Percentage of Participants With Recurrent DVT Until the Intended End of Study Treatment   [ Time Frame: 6- or 12-month study treatment period ]
  Show Outcome Measure 6

7.  Secondary:   Percentage of Participants With Major Bleeding   [ Time Frame: 6- or 12-month study treatment period ]
  Show Outcome Measure 7

8.  Secondary:   Percentage of Participants With Clinically Relevant Bleeding   [ Time Frame: 6- or 12-month study treatment period ]
  Show Outcome Measure 8

9.  Secondary:   Percentage of Participants With All Death   [ Time Frame: 6- or 12-month study treatment period ]
  Show Outcome Measure 9

10.  Secondary:   Percentage of Participants With Other Vascular Events   [ Time Frame: 6- or 12-month study treatment period ]
  Show Outcome Measure 10

11.  Other Pre-specified:   Percentage of Participants With Death (PE) Until the Intended End of Study Treatment   [ Time Frame: 6- or 12-month study treatment period ]
  Show Outcome Measure 11

12.  Other Pre-specified:   Percentage of Participants With Death (PE Cannot be Excluded) Until the Intended End of Study Treatment   [ Time Frame: 6- or 12-month study treatment period ]
  Show Outcome Measure 12

13.  Other Pre-specified:   Percentage of Participants With Symptomatic Recurrent PE Until the Intended End of Study Treatment   [ Time Frame: 6- or 12-month study treatment period ]
  Show Outcome Measure 13

14.  Other Pre-specified:   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   [ Time Frame: 30 days observational period after last intake of study medication ]
  Show Outcome Measure 14

15.  Other Pre-specified:   Percentage of Participants With Symptomatic Recurrent PE During Observational Period   [ Time Frame: 30 days observational period after last intake of study medication ]
  Show Outcome Measure 15

16.  Other Pre-specified:   Percentage of Participants With the Composite Variable Comprising Recurrent DVT, Non-fatal PE and All Cause Mortality During Observational Period   [ Time Frame: 30 days observational period after last intake of study medication ]
  Show Outcome Measure 16

17.  Other Pre-specified:   Percentage of Participants With the Composite Variable Comprising Recurrent DVT, Non-fatal PE, All Cause Mortality, Strokes and Myocardial Infarctions During Observational Period   [ Time Frame: 30 days observational period after last intake of study medication ]
  Show Outcome Measure 17

18.  Other Pre-specified:   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   [ Time Frame: 30 days observational period after last intake of study medication ]
  Show Outcome Measure 18

19.  Other Pre-specified:   Percentage of Participants With Recurrent VTE (PE or DVT) During Observational Period   [ Time Frame: 30 days observational period after last intake of study medication ]
  Show Outcome Measure 19

20.  Other Pre-specified:   Percentage of Participants With Recurrent DVT During Observational Period   [ Time Frame: 30 days observational period after last intake of study medication ]
  Show Outcome Measure 20


  Serious Adverse Events
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  Other Adverse Events
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  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed.


Limitations and Caveats
Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.  


Results Point of Contact:  
Name/Title: Therapeutic Area Head
Organization: BAYER
e-mail: clinical-trials-contact@bayerhealthcare.com


Publications of Results:


Responsible Party: Therapeutic Area Head, Bayer HealthCare Pharmaceuticals Inc.
ClinicalTrials.gov Identifier: NCT00439725     History of Changes
Other Study ID Numbers: 11899, 2006-004494-96
Study First Received: February 23, 2007
Results First Received: January 31, 2012
Last Updated: March 7, 2013
Health Authority: United States: Food and Drug Administration