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Global Study to Assess the Safety and Effectiveness of Edoxaban (DU-176b) vs Standard Practice of Dosing With Warfarin in Patients With Atrial Fibrillation (EngageAFTIMI48)

This study has been completed.
Sponsor:
Collaborator:
The TIMI Study Group
Information provided by (Responsible Party):
Daiichi Sankyo Inc.
ClinicalTrials.gov Identifier:
NCT00781391
First received: October 28, 2008
Last updated: March 12, 2015
Last verified: March 2015
History of Changes
Results First Received: February 5, 2015  
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
Conditions: Stroke
Atrial Fibrillation
Embolism
Interventions: Drug: warfarin tablets
Drug: Edoxaban tablets (high dose regimen-60mg)
Drug: Edoxaban tablets (low dose regimen-30mg)
Drug: placebo warfarin
Drug: placebo edoxaban

  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
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Warfarin/Placebo Edoxaban

Warfarin tablets plus placebo Edoxaban tablets

warfarin tablets: Warfarin tablets plus Edoxaban placebo tablets each taken once daily for 24 months

placebo edoxaban: placebo edoxaban
High Dose Edoxaban/Placebo Warfarin

Edoxaban tablets plus warfarin placebo tablets

60mg Edoxaban tablets (high dose regimen): Edoxaban tablets plus warfarin placebo tablets each taken once daily for 24 months

placebo warfarin: placebo warfarin
Low Dose Edoxaban/Placebo Warfarin

Edoxaban tablets plus warfarin placebo tablets

30mg Edoxaban tablets (low dose regimen): Edoxaban tablets plus warfarin placebo tablets each taken once daily for 24 months

placebo warfarin: placebo warfarin

Participant Flow:   Overall Study
    Warfarin/Placebo Edoxaban     High Dose Edoxaban/Placebo Warfarin     Low Dose Edoxaban/Placebo Warfarin  
STARTED     7036     7035     7034  
Safety Analysis Set (Received Drug)     7012     7012     7002  
mITT Analysis Set (Received Drug)     7012     7012     7002  
Per Protocol Analysis Set     6993     6995     6982  
COMPLETED     6157     6228     6250  
NOT COMPLETED     879     807     784  
never received study drug                 24                 23                 32  
Protocol Violation                 19                 17                 20  
Death                 789                 730                 706  
Withdrawal by Subject                 47                 37                 25  
Lost to Follow-up                 0                 0                 1  



  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
Warfarin/Placebo Edoxaban

Warfarin tablets plus placebo Edoxaban tablets

warfarin tablets: Warfarin tablets plus Edoxaban placebo tablets each taken once daily for 24 months

placebo edoxaban: placebo edoxaban
High Dose Edoxaban/Placebo Warfarin

Edoxaban tablets plus warfarin placebo tablets

60mg Edoxaban tablets (high dose regimen): Edoxaban tablets plus warfarin placebo tablets each taken once daily for 24 months

placebo warfarin: placebo warfarin
Low Dose Edoxaban/Placebo Warfarin

Edoxaban tablets plus warfarin placebo tablets

30mg Edoxaban tablets (low dose regimen): Edoxaban tablets plus warfarin placebo tablets each taken once daily for 24 months

placebo warfarin: placebo warfarin
Total Total of all reporting groups

Baseline Measures
    Warfarin/Placebo Edoxaban     High Dose Edoxaban/Placebo Warfarin     Low Dose Edoxaban/Placebo Warfarin     Total  
Number of Participants  
[units: participants]
 		  7012     7012     7002     21026  
Age  
[units: participants]
 		       
<=18 years     0     0     0     0  
Between 18 and 65 years     1869     1830     1784     5483  
>=65 years     5143     5182     5218     15543  
Age  
[units: years]
Mean (Standard Deviation) 		  70.5  (9.44)     70.6  (9.51)     70.6  (9.31)     70.6  (9.42)  
Gender  
[units: participants]
 		       
Female     2629     2659     2718     8006  
Male     4383     4353     4284     13020  
Race (NIH/OMB)  
[units: participants]
 		       
American Indian or Alaska Native     0     0     0     0  
Asian     963     956     975     2894  
Native Hawaiian or Other Pacific Islander     0     0     0     0  
Black or African American     88     96     94     278  
White     5679     5679     5650     17008  
More than one race     0     0     0     0  
Unknown or Not Reported     282     281     283     846  
Region of Enrollment  
[units: participants]
 		       
Portugal     46     71     61     178  
United States     1297     1288     1308     3893  
Serbia     95     107     74     276  
Philippines     43     36     45     124  
Estonia     76     55     60     191  
Taiwan     77     72     85     234  
Slovakia     143     133     129     405  
Greece     14     27     9     50  
Spain     44     65     54     163  
Thailand     40     40     33     113  
Ukraine     360     386     402     1148  
Israel     104     88     88     280  
Chile     74     91     88     253  
Russian Federation     375     406     369     1150  
Colombia     51     42     48     141  
Switzerland     0     1     4     5  
Italy     60     55     54     169  
India     232     220     234     686  
France     40     38     32     110  
Peru     64     46     60     170  
Denmark     68     80     70     218  
Australia     30     40     32     102  
South Africa     97     92     90     279  
Netherlands     64     49     40     153  
China     163     150     152     465  
Korea, Republic of     64     84     78     226  
Finland     9     18     15     42  
Guatemala     48     48     39     135  
Turkey     40     39     31     110  
United Kingdom     132     121     145     398  
Hungary     151     143     167     461  
Czech Republic     410     369     386     1165  
Mexico     60     70     60     190  
Canada     259     271     242     772  
Argentina     352     345     362     1059  
Brazil     236     242     225     703  
Belgium     41     44     64     149  
Poland     395     424     454     1273  
Croatia     53     33     39     125  
Romania     141     144     124     409  
Bulgaria     179     174     165     518  
Norway     11     8     15     34  
Germany     308     293     307     908  
Japan     337     336     337     1010  
New Zealand     40     50     40     130  
Sweden     89     78     86     253  



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Compare Edoxaban to Warfarin for Composite of Stroke and Systemic Embolic Events (SEE).   [ Time Frame: on-treatment period 2.5 years of median study drug exposure and 2.8 year of median follow-up ]
  Show Outcome Measure 1

2.  Primary:   Compare Edoxaban to Warfarin for Composite of Stroke and Systemic Embolic Events (SEE).   [ Time Frame: overall study period 2.5 years of median study drug exposure and 2.8 year of median follow-up ]
  Show Outcome Measure 2

3.  Primary:   Compare Edoxaban to Warfarin for Composite of Stroke and Systemic Embolic Events (SEE).   [ Time Frame: on-treatment period 2.5 years of median study drug exposure and 2.8 year of median follow-up ]
  Show Outcome Measure 3

4.  Primary:   Compare Edoxaban to Warfarin for Composite of Stroke and Systemic Embolic Events (SEE).   [ Time Frame: overall study period 2.5 years of median study drug exposure and 2.8 year of median follow-up ]
  Show Outcome Measure 4

5.  Primary:   Compare Edoxaban to Warfarin for Superiority for Composite of Stroke and Systemic Embolic Events (SEE).   [ Time Frame: overall study period 2.5 years of median study drug exposure and 2.8 year of median follow-up ]
  Show Outcome Measure 5

6.  Secondary:   Compare Edoxaban to Warfarin for Composite of Stroke, Systemic Embolic Event (SEE), and Cardiovascular (CV) Mortality   [ Time Frame: overall study period 2.5 years of median study drug exposure and 2.8 year of median follow-up ]
  Show Outcome Measure 6

7.  Secondary:   Compare Edoxaban to Warfarin for Major Adverse Cardiac Event (MACE): a Composite of Non-fatal MI, Non-fatal Stroke, Non-fatal SEE, and Death Due to CV Cause or Bleeding   [ Time Frame: overall study period 2.5 years of median study drug exposure and 2.8 year of median follow-up ]
  Show Outcome Measure 7

8.  Secondary:   Compare Edoxaban to Warfarin for Composite of Stroke, SEE, and All-cause Mortality   [ Time Frame: overall study period 2.5 years of median study drug exposure and 2.8 year of median follow-up ]
  Show Outcome Measure 8

9.  Secondary:   Adjudicated Bleeding Events   [ Time Frame: on-treatment period 2.5 years of median study drug exposure and 2.8 year of median follow-up ]
  Show Outcome Measure 9


  Serious Adverse Events
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  Other Adverse Events
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  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 less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
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.


Results Point of Contact:  
Name/Title: James Hanyok, Sr. Director
Organization: Daiichi Sankyo, Inc.
phone: 732-590-5000
e-mail: jhanyok@dsi.com


Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):


Responsible Party: Daiichi Sankyo Inc.
ClinicalTrials.gov Identifier: NCT00781391     History of Changes
Other Study ID Numbers: DU176b-C-U301
Study First Received: October 28, 2008
Results First Received: February 5, 2015
Last Updated: March 12, 2015
Health Authority: United States: Food and Drug Administration