Study of an Investigational Drug for the Prevention of Thrombosis-related Events Following Hip Replacement Surgery (ADVANCE-3)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT00423319
First received: January 17, 2007
Last updated: April 14, 2014
Last verified: April 2014
Results First Received: April 14, 2014  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Investigator);   Primary Purpose: Prevention
Conditions: Deep Vein Thrombosis
Pulmonary Embolism
Interventions: Drug: Enoxaparin
Drug: Apixaban
Drug: Enoxaparin-matching placebo
Drug: Apixaban-matching 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
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
A total of 5765 subjects were enrolled, and 5407 were randomized to double-blind study drug.

Reporting Groups
  Description
Apixaban, 2.5 mg BID Plus Placebo Participants received apixaban, 2.5 mg twice daily (BID), as oral tablets, and matching enoxaparin-placebo injection once daily (QD)
Enoxaparin, 40 mg QD Plus Placebo Participants received enoxaparin, 40 mg QD subcutaneously, and matching apixaban-placebo tablets BID

Participant Flow:   Overall Study
    Apixaban, 2.5 mg BID Plus Placebo     Enoxaparin, 40 mg QD Plus Placebo  
STARTED     2708 [1]   2699 [1]
Participants Who Received Treatment     2673     2659  
COMPLETED     2484     2447  
NOT COMPLETED     224     252  
Death                 2                 0  
Adverse Event                 93                 112  
Withdrawal by Subject                 86                 99  
Lost to Follow-up                 4                 3  
Poor compliance or noncompliance                 1                 1  
No longer meets study criteria                 15                 15  
Not specified                 23                 22  
[1] Randomized



  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
Apixaban, 2.5 mg BID Plus Placebo Participants received apixaban, 2.5 mg twice daily (BID), as oral tablets, and matching enoxaparin-placebo injection once daily (QD)
Enoxaparin, 40 mg QD Plus Placebo Participants received enoxaparin, 40 mg QD subcutaneously, and matching apixaban-placebo tablets BID
Total Total of all reporting groups

Baseline Measures
    Apixaban, 2.5 mg BID Plus Placebo     Enoxaparin, 40 mg QD Plus Placebo     Total  
Number of Participants  
[units: participants]
  2708     2699     5407  
Age  
[units: Years]
Mean ± Standard Deviation
  60.9  ± 11.79     60.6  ± 11.82     60.8  ± 11.81  
Age, Customized  
[units: Participants]
     
Younger than 65 years     1608     1605     3213  
65 to younger than 75 years     770     767     1537  
75 years and older     330     327     657  
Gender  
[units: Participants]
     
Female     1430     1451     2881  
Male     1278     1248     2526  
Region of Enrollment  
[units: Participants]
     
United States     450     441     891  
Spain     32     29     61  
Ukraine     217     219     436  
Russian Federation     274     276     550  
Israel     57     56     113  
United Kingdom     77     78     155  
India     56     56     112  
France     75     74     149  
Hungary     152     150     302  
Mexico     73     74     147  
Canada     359     356     715  
Argentina     53     54     107  
Belgium     59     60     119  
Poland     184     185     369  
Romania     24     25     49  
Australia     101     99     200  
Denmark     99     99     198  
Germany     135     134     269  
Norway     47     48     95  
China     121     124     245  
Sweden     63     62     125  



  Outcome Measures
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1.  Primary:   Rate of Composite of Adjudicated Venous Thromboembolic Event (VTE)-Related (Pulmonary Embolism and Symptomatic and Asymptomatic Deep Vein Thrombosis[DVT]) and All-cause Death During the Intended Treatment Period   [ Time Frame: Day 1 (first dose of study drug) to later of 2 days after last dose or 38 days after first dose ]

2.  Secondary:   Rate of Composite of Adjudicated Proximal Deep Vein Thrombosis (DVT), Nonfatal Pulmonary Embolism, and Venous Thromboembolic Event-related Death With Onset During Intended Treatment Period   [ Time Frame: Day 1 (first dose of study drug) to later of 2 days after last dose or 38 days after first dose ]

3.  Secondary:   Rates of Adjudicated All-cause Death, VTE-related Death, Pulmonary Embolism (PE), Nonfatal PE, Deep Vein Thrombosis (DVT) (Symptomatic and Asymptomatic), Symptomatic and Asymptomatic Proximal and Distal DVT During the Intended Treatment Period   [ Time Frame: Day 1 (first dose of study drug) to later of 2 days after last dose or 38 days after first dose ]

4.  Secondary:   Rate of Major Bleeding, Clinically Relevant Nonmajor Bleeding (CRNM), Major or CRNM, and Any Bleeding During the Treatment Period   [ Time Frame: First dose of study drug (presurgery) through 2 days after the last dose of study drug ]

5.  Secondary:   Number of Participants With Serious Adverse Events (SAEs), Bleeding Adverse Events (AEs), and Death as Outcome   [ Time Frame: First dose of study drug (presurgery) through 30 days after the last dose of study drug ]

6.  Secondary:   Number of Participants With a Bleeding-related Adverse Event During the Treatment Period   [ Time Frame: First dose of study drug (presurgery) through 2 days after the last dose of study drug ]

7.  Secondary:   Number of Participants With a Bleeding-related Adverse Events During the Treatment Period (Continued)   [ Time Frame: First dose of study drug (presurgery) through 2 days after the last dose of study drug ]

8.  Secondary:   Number of Participants With a Bleeding-related Adverse Event During the Treatment Period (Continued)   [ Time Frame: First dose of study drug (presurgery) through 2 days after the last dose of study drug ]

9.  Secondary:   Number of Participants With Neurologic Adverse Events With Onset During the Treatment Period   [ Time Frame: First dose of study drug (presurgery) through 2 days after the last dose of study drug ]

10.  Secondary:   Number of Participants With Marked Abnormalities (MA) in Clinical Laboratory Test Results During the Treatment Period   [ Time Frame: First dose of study drug (presurgery) through 2 days after the last dose of study drug ]

11.  Secondary:   Number of Participants With Marked Abnormalities (MA) in Clinical Laboratory Test Results During the Treatment Period (Continued)   [ Time Frame: First dose of study drug (presurgery) through 2 days after the last dose of study drug ]

12.  Secondary:   Number of Participants With Marked Abnormalities (MA) in Clinical Laboratory Test Results During the Treatment Period (Continued)   [ Time Frame: First dose of study drug (presurgery) through 2 days after the last dose of study drug ]

13.  Secondary:   Number of Participants With Adverse Events Related to Elevations in Liver Function Test Results With Onset During the Treatment Period   [ Time Frame: First dose of study drug (presurgery) through 30 days after the last dose of study drug ]

14.  Secondary:   Rates of Adjudicated Myocardial Infarction (MI)/Stroke, MI, Stroke, and Thrombocytopenia During the Intended Treatment Period   [ Time Frame: Day 1 (first dose of study drug) to later of 2 days after last dose or 38 days after first dose ]


  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 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


No publications provided by Bristol-Myers Squibb

Publications automatically indexed to this study:

Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT00423319     History of Changes
Other Study ID Numbers: CV185-035
Study First Received: January 17, 2007
Results First Received: April 14, 2014
Last Updated: April 14, 2014
Health Authority: United States: Food and Drug Administration