Study of an Investigational Drug for the Prevention of Thrombosis-related Events Following Knee Replacement Surgery (ADVANCE-2)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT00452530
First received: March 23, 2007
Last updated: July 8, 2014
Last verified: July 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: Treatment
Conditions: Deep Vein Thrombosis
Pulmonary Embolism
Interventions: Drug: Enoxaparin
Drug: Apixaban
Drug: Enoxaparin-matching placebo
Drug: Apixaban-matching placebo

  Participant Flow
  Hide 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
Of 3221 patients enrolled, 3057 were randomized. Primary participants=those who were randomized and had an adjudicated evaluable bilateral venogram or an adjudicated venous thromboembolic event or died. Evaluable participants=those with significant protocol deviations expected to affect the primary endpoint.

Reporting Groups
  Description
Apixaban, 2.5 mg BID + 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 + Placebo Participants received enoxaparin, 40 mg QD subcutaneously, and matching apixaban-placebo tablets BID

Participant Flow:   Overall Study
    Apixaban, 2.5 mg BID + Placebo     Enoxaparin, 40 mg QD + Placebo  
STARTED     1528 [1]   1529 [1]
Received Treatment     1501     1508  
Evaluable Participants     907     921  
Primary Participants     976     997  
COMPLETED     1392     1393  
NOT COMPLETED     136     136  
Death                 1                 0  
Adverse Event                 40                 44  
Withdrawal by Subject                 68                 57  
Lost to Follow-up                 1                 0  
Poor compliance/noncompliance                 1                 2  
No longer met study criteria                 18                 22  
Not specified                 7                 11  
[1] Randomized



  Baseline Characteristics


  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Rate of Adjudicated Venous Thromboembolic Event-related and All-cause Deaths With Onset During the Intended-treatment Period   [ Time Frame: Day of randomization to later of 2 days after last dose or 14 days after first dose; 14 days after randomization for those who did not receive study drug ]

2.  Secondary:   Rate of Adjudicated Proximal Deep Vein Thrombosis (DVT), Nonfatal Pulmonary Embolism, and Venous Thromboembolic Event-related Death With Onset During the Intended Treatment Period   [ Time Frame: Day of randomization to later of 2 days after last dose or 14 days after first dose; 14 days after randomization for those who did not receive study ]

3.  Secondary:   Rate of Major Bleeding, Clinically Relevant Nonmajor Bleeding (CRNM), and Major Bleeding or CRNM   [ Time Frame: Days 1 to 12 ]

4.  Secondary:   Number of Participants With Serious Adverse Events (SAE), Bleeding Adverse Events (AEs), Discontinuations Due to AEs, and Death as Outcome   [ Time Frame: Days 1 through 12 + 2 days (nonserious AEs, bleeding AES) or 30 days (SAES, deaths) after last dose of study drug ]

5.  Other Pre-specified:   Summary of Laboratory Marked Abnormalities on Hematology and Liver and Kidney Function Test Results During the Treatment Period (Patients With Available Measurements)   [ Time Frame: Randomization to Days 2, 3, 4, and 12 (±2 days) and at Days 42 and 72 (±5 days) of follow-up ]

6.  Other Pre-specified:   Summary of Laboratory Marked Abnormalities in Electrolyte and Other Clinical Test Results During the Treatment Period (Patients With Available Measurements)   [ Time Frame: Randomization to Days 2, 3, 4, and 12 (±2 days) and at Days 42 and 72 (±5 days) of follow-up ]

7.  Other Pre-specified:   Summary of Laboratory Marked Abnormalities in Urinalysis Results During the Treatment Period-Treated Subjects With Available Measurements (Urinalysis)   [ Time Frame: Randomization to Days 2, 3, 4, and 12 (±2 days) and at Days 42 and 72 (± 5 days) of follow-up ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
  Hide 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
  Hide 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


No publications provided by Bristol-Myers Squibb

Publications automatically indexed to this study:

Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT00452530     History of Changes
Other Study ID Numbers: CV185-047, EUdraCT: 2006-006896-19
Study First Received: March 23, 2007
Results First Received: April 14, 2014
Last Updated: July 8, 2014
Health Authority: United States: Food and Drug Administration