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

This study has been completed.
Sponsor:
Collaborator:
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Information provided by (Responsible Party):
Bayer
ClinicalTrials.gov Identifier:
NCT00440193
First received: February 23, 2007
Last updated: January 26, 2014
Last verified: January 2014
Results First Received: November 22, 2012  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Venous Thrombosis
Interventions: Drug: Rivaroxaban (Xarelto, BAY59-7939)
Drug: Enoxaparin followed by VKA

  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 acute proximal symptomatic deep vein thrombosis (DVT) without symptomatic pulmonary embolism (PE) 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 3459 participants screened, 10 failed screening due to protocol violations, and 3449 participants were randomized (1731 to rivaroxaban and 1718 to enoxaparin/VKA).

Reporting Groups
  Description
Rivaroxaban (Xarelto, BAY59-7939) Participants were to receive rivaroxaban 15 mg oral tablet twice daily for 3 weeks, followed by 20 mg once daily
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)

Participant Flow for 2 periods

Period 1:   Treatment Period
    Rivaroxaban (Xarelto, BAY59-7939)     Enoxaparin/VKA  
STARTED     1731     1718  
Participants Received Treatment     1718     1711  
COMPLETED     1426     1367  
NOT COMPLETED     305     351  
Adverse Event                 74                 67  
Death                 19                 22  
Lack of Efficacy                 0                 1  
Lost to Follow-up                 12                 18  
Physician Decision                 3                 6  
Protocol Violation                 16                 19  
Withdrawal by Subject                 36                 77  
Clinical endpoint reached                 28                 25  
Study terminated by sponsor                 102                 94  
Protocol driven decision point                 2                 2  
Switch to commercial drug                 0                 2  
Technical problems                 1                 1  
Participant convenience                 5                 2  
Participant did not receive treatment                 7                 13  
Site closed by investigator                 0                 2  

Period 2:   Observational Period
    Rivaroxaban (Xarelto, BAY59-7939)     Enoxaparin/VKA  
STARTED     1425 [1]   1407 [1]
COMPLETED     1380     1369  
NOT COMPLETED     45     38  
Adverse Event                 2                 2  
Death                 15                 20  
Lost to Follow-up                 12                 8  
Protocol Violation                 1                 0  
Withdrawal by Subject                 11                 8  
Physician Decision                 1                 0  
Clinical endpoint reached                 1                 0  
Participant convenience                 2                 0  
[1] All participants who took any study medication and entered the observational period.



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Rivaroxaban (Xarelto, BAY59-7939) Participants were to receive rivaroxaban 15 mg oral tablet twice daily for 3 weeks, followed by 20 mg once daily
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)
Total Total of all reporting groups

Baseline Measures
    Rivaroxaban (Xarelto, BAY59-7939)     Enoxaparin/VKA     Total  
Number of Participants  
[units: participants]
  1731     1718     3449  
Age  
[units: years]
Mean ± Standard Deviation
  55.8  ± 16.4     56.4  ± 16.3     56.1  ± 16.4  
Age, Customized  
[units: participants]
     
18 - < 40 years     314     279     593  
40 - < 60 years     642     662     1304  
60 - < 75 years     530     519     1049  
≥ 75 years     245     258     503  
Gender  
[units: participants]
     
Female     738     751     1489  
Male     993     967     1960  



  Outcome Measures
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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: 3-, 6- or 12-month study treatment period ]

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: 3-, 6- or 12-month study treatment period ]

3.  Secondary:   Percentage of Participants With an Event for Net Clinical Benefit 1 Until the Intended End of Study Treatment   [ Time Frame: 3-, 6- or 12-month study treatment period ]

4.  Secondary:   Percentage of Participants With Recurrent DVT Until the Intended End of Study Treatment   [ Time Frame: 3-, 6- or 12-month study treatment period ]

5.  Secondary:   Percentage of Participants With Clinically Relevant Bleeding, Treatment-emergent (Time Window: Until 2 Days After Last Dose)   [ Time Frame: 3-, 6- or 12-month study treatment period ]

6.  Secondary:   Percentage of Participants With All Deaths   [ Time Frame: 3-, 6- or 12-month study treatment period ]

7.  Secondary:   Percentage of Participants With Other Vascular Events, On-treatment (Time Window: Until 1 Day After Last Dose)   [ Time Frame: 3-, 6- or 12-month study treatment period ]

8.  Other Pre-specified:   Percentage of Participants With the Individual Components of Efficacy Outcomes Until the Intended End of Study Treatment   [ Time Frame: 3-, 6- or 12-month study treatment period ]

9.  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: Up to 30 days after the last intake of study medication ]

10.  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: Up to 30 days after the last intake of study medication ]

11.  Other Pre-specified:   Percentage of Participants With an Event for Net Clinical Benefit 1 During Observational Period   [ Time Frame: Up to 30 days after the last intake of study medication ]

12.  Other Pre-specified:   Percentage of Participants With Recurrent DVT During Observational Period   [ Time Frame: Up to 30 days after the last intake of study medication ]

13.  Other Pre-specified:   Percentage of Participants With the Individual Components of Efficacy Outcomes During Observational Period   [ Time Frame: Up to 30 days after the last intake of study medication ]

14.  Post-Hoc:   Percentage of Participants With an Event for Net Clinical Benefit 2 Until the Intended End of Study Treatment   [ Time Frame: 3-, 6- or 12-month study treatment period ]

15.  Post-Hoc:   Percentage of Participants With an Event for Net Clinical Benefit 2 During Observational Period   [ Time Frame: Up to 30 days after the last intake of study medication ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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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
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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.


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


Publications of Results:


Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT00440193     History of Changes
Other Study ID Numbers: 11702a, 2006-004495-13, 11702b
Study First Received: February 23, 2007
Results First Received: November 22, 2012
Last Updated: January 26, 2014
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