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A Phase III Study of Apixaban in Patients With Atrial Fibrillation (AVERROES)

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ClinicalTrials.gov Identifier: NCT00496769
Recruitment Status : Completed
First Posted : July 4, 2007
Results First Posted : November 14, 2013
Last Update Posted : June 15, 2018
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
Bristol-Myers Squibb

Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Prevention
Condition: Atrial Fibrillation
Interventions: Drug: Apixaban
Drug: Acetylsalicylic acid

  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
A total 6421 patients were enrolled in the study. Of these, 5598 were randomized (2807 to apixaban and 2791 to acetylsalicylic acid). Most (435) of the patients who were not randomized (823) no longer met study criteria. Of those randomized, 5578 received treatment (2798 with apixaban, and 2780 with acetylsalicylic acid).

Reporting Groups
  Description
Apixaban, 2.5 or 5 mg Twice Daily Patients received 5 mg of apixaban twice daily. Participants who fulfilled any 2 of the following criteria at baseline received apixaban, 2.5 mg twice daily: age older than 80 years, body weight of 60 kg or less, Serum creatinine level ≥1.5 mg/dL. Participants randomized to the 2.5 mg twice daily dose of apixaban continued on this dose throughout the study even if they no longer fulfilled the previous criteria.
Acetylsalicylic Acid, 81-324 mg Once Daily Patients received 81 to 324 mg of acetylsalicylic acid once daily, with dosage based on investigator discretion Participants who completed the double-blind treatment period and met eligibility criteria had the option of enrolling in the Long Term Open Label Extension to receive open-label apixaban.
Open Label Apixaban Participants who completed the double-blind treatment period and met eligibility criteria had the option of enrolling in the Long Term Open Label Extension to receive open-label apixaban.

Participant Flow for 2 periods

Period 1:   Double Blind
    Apixaban, 2.5 or 5 mg Twice Daily   Acetylsalicylic Acid, 81-324 mg Once Daily   Open Label Apixaban
STARTED   2807 [1]   2791 [1]   0 
Received Treatment   2798   2708   0 
COMPLETED   2249   2142   0 
NOT COMPLETED   558   649   0 
>=1 reason assigned per patient                558                649                0 
[1] Randomized

Period 2:   Open Label
    Apixaban, 2.5 or 5 mg Twice Daily   Acetylsalicylic Acid, 81-324 mg Once Daily   Open Label Apixaban
STARTED   0   0   3275 
COMPLETED   0   0   2264 
NOT COMPLETED   0   0   1011 
>=1 reason assigned per patient                0                0                1011 



  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
Apixaban, 2.5 or 5 mg Twice Daily Patients received 5 mg of apixaban twice daily. Participants who fulfilled any 2 of the following criteria at baseline received apixaban, 2.5 mg twice daily: age older than 80 years, body weight of 60 kg or less, Serum creatinine level ≥1.5 mg/dL. Participants randomized to the 2.5 mg twice daily dose of apixaban continued on this dose throughout the study even if they no longer fulfilled the previous criteria.
Acetylsalicylic Acid, 81-324 mg Once Daily Patients received 81 to 324 mg of acetylsalicylic acid once daily, with dosage based on investigator discretion
Total Total of all reporting groups

Baseline Measures
   Apixaban, 2.5 or 5 mg Twice Daily   Acetylsalicylic Acid, 81-324 mg Once Daily   Total 
Overall Participants Analyzed 
[Units: Participants]
 2807   2791   5598 
Age 
[Units: Years]
Mean (Standard Deviation)
 69.7  (9.44)   70.0  (9.71)   69.9  (9.58) 
Age, Customized 
[Units: Participants]
Count of Participants
     
< 65 years      855  30.5%      865  31.0%      1720  30.7% 
>=65 but <75 years      1049  37.4%      938  33.6%      1987  35.5% 
>=75 years      903  32.2%      988  35.4%      1891  33.8% 
Sex: Female, Male 
[Units: Participants]
Count of Participants
     
Female      1147  40.9%      1174  42.1%      2321  41.5% 
Male      1660  59.1%      1617  57.9%      3277  58.5% 
Race/Ethnicity, Customized 
[Units: Participants]
Count of Participants
     
American Indian or Alaska Native      6   0.2%      6   0.2%      12   0.2% 
Asian      541  19.3%      544  19.5%      1085  19.4% 
Native Hawaiian or Other Pacific Islander      3   0.1%      1   0.0%      4   0.1% 
Black or African American      10   0.4%      26   0.9%      36   0.6% 
White      2221  79.1%      2178  78.0%      4399  78.6% 
Other      26   0.9%      36   1.3%      62   1.1% 
Number of Participants by Number of Risk Factors for Stroke 
[Units: Participants]
Count of Participants
     
1 or fewer      1085  38.7%      1077  38.6%      2162  38.6% 
2 or more      1722  61.3%      1714  61.4%      3436  61.4% 
Number of Participants With Risk Factors for Stroke [1] 
[Units: Participants]
Count of Participants
     
Age of 75 years or older   903   988   1891 
Prior stroke or transient ischemic attack   390   374   764 
Heart failure (NYHA class ≥2) or LVEF ≤35%   961   926   1887 
Diabetes mellitus   536   559   1095 
Hypertension requiring pharmacologic treatment   2408   2429   4837 
Peripheral artery disease   66   78   144 
[1] NYHA=New York Health Authority; LVEF=left ventricular ejection fraction


  Outcome Measures

1.  Primary:   Event Rate of Stroke/Systemic Embolism During the Intended-treatment Period   [ Time Frame: Randomization to efficacy cutoff date of May 28, 2010 (date revised following cessation of study for superior efficacy) ]

2.  Secondary:   Event Rate for the Composite of Stroke of Any Type, Systemic Embolism, Myocardial Infarction, or Vascular Death During the Double-blind Treatment Period   [ Time Frame: Randomization to efficacy cutoff date of May 28, 2010 (date revised following cessation of study for superior efficacy) ]

3.  Secondary:   Event Rate of All-cause Death; Net Clinical Benefit-Composite of Stroke, Systemic Embolism, Myocardial Infarction, Vascular Death, and Major Bleeding; and Vascular Death   [ Time Frame: Randomization to efficacy cutoff date of May 28, 2010 (date revised following cessation of study for superior efficacy) ]

4.  Secondary:   Event Rates for Major Bleeding, Major or Clinically Relevant Nonmajor (CNRM) Bleeding, and All Bleeding in the Double-blind Period   [ Time Frame: First dose of study drug (Day 1) to the earlier of a patient's discontinuation of double-blind study drug or the attainment of at least 226 primary efficacy events up to May 28, 2010 ]

5.  Secondary:   Rate of Unrefuted Bleeding From First Dose of Double-blind Study Drug to First Occurence of Unrefuted Bleeding During the Double-blind Treatment Period   [ Time Frame: Day 1 to first bleeding event up to efficacy cutoff date of May 28, 2010 (date revised following cessation of study for superior efficacy) ]

6.  Secondary:   Number of Participants With Serious Adverse Events (SAEs), Adverse Events (AEs), Bleeding AEs, Discontinuations Due to AEs, and Death as Outcome   [ Time Frame: First dose of study drug (Day 1) to 30 days after last dose of blinded study drug ]

7.  Secondary:   Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality   [ Time Frame: First dose of study drug (Day 1) to 30 days after last dose of blinded study drug ]

8.  Secondary:   Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality (Continued)   [ Time Frame: First dose of study drug (Day 1) to 30 days after last dose of blinded study drug ]

9.  Secondary:   Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality (Continued)   [ Time Frame: First dose of study drug (Day 1) to 30 days after last dose of blinded study drug ]


  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
On May 28, 2010, after a planned interim analysis for efficacy, the Data Monitoring Committee recommended early termination due to apixaban's superior efficacy over ASA, with an acceptable safety profile. The open-label phase is ongoing.


  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: Bristol-Myers Squibb Study Director
Organization: Bristol-Myers Squibb
e-mail: Clinical.Trials@bms.com


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


Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT00496769     History of Changes
Other Study ID Numbers: CV185-048
First Submitted: July 2, 2007
First Posted: July 4, 2007
Results First Submitted: August 1, 2013
Results First Posted: November 14, 2013
Last Update Posted: June 15, 2018