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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)

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ClinicalTrials.gov Identifier: NCT00781391
Recruitment Status : Completed
First Posted : October 29, 2008
Results First Posted : March 25, 2015
Last Update Posted : March 25, 2015
Sponsor:
Collaborator:
The TIMI Study Group
Information provided by (Responsible Party):
Daiichi Sankyo, Inc.

Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, 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

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

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 
Overall Participants Analyzed 
[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

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


  Other Adverse Events


  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.


  More Information

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
First Submitted: October 28, 2008
First Posted: October 29, 2008
Results First Submitted: February 5, 2015
Results First Posted: March 25, 2015
Last Update Posted: March 25, 2015