Phase III Acute Coronary Syndrome (APPRAISE-2)

This study has been terminated.
Sponsor:
Collaborators:
Pfizer
Duke Clinical Research Institute
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT00831441
First received: January 28, 2009
Last updated: December 18, 2015
Last verified: December 2015
Results First Received: December 18, 2015  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator);   Primary Purpose: Prevention
Condition: Acute Coronary Syndrome
Interventions: Drug: Apixaban
Drug: 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
7484 participants enrolled and 7392 were randomized. Reasons for non-randomization: 2 Adverse event (AE), 18 withdrew consent, 1 lost to follow up, 3 administrative reason by sponsor, 2 deaths, 51 no longer met criteria, 15 other.

Reporting Groups
  Description
Placebo BID Placebo: Tablets, Oral, 0 mg, twice daily. The Treatment Period was planned to be completed after at least 938 participants had a primary efficacy endpoint confirmed by adjudication. After 7392 participants had been randomized into the study, an independent Data Monitoring Committee recommended that the study be terminated early due to a clinically important increase in bleeding among participants randomized to apixaban which was not offset by meaningful reductions in ischemic events. The Study terminated in Year 2.
Apixaban 5 mg BID Apixaban: Tablets, Oral, 5 mg, twice daily. The Treatment Period was planned to be completed after at least 938 participants had a primary efficacy endpoint confirmed by adjudication. After 7392 participants had been randomized into the study, an independent Data Monitoring Committee recommended that the study be terminated early due to a clinically important increase in bleeding among participants randomized to apixaban which was not offset by meaningful reductions in ischemic events. The Study terminated in Year 2.

Participant Flow for 2 periods

Period 1:   Randomized
    Placebo BID     Apixaban 5 mg BID  
STARTED     3687     3705  
Treated     3643     3672  
COMPLETED     0     0  
NOT COMPLETED     3687     3705  
Death                 82                 81  
Adverse Event                 248                 321  
Emergency procedure                 2                 2  
Elective procedure                 26                 25  
Physician Decision                 26                 35  
No longer met criteria                 13                 19  
Withdrawal by Subject                 178                 212  
Lost to Follow-up                 26                 35  
Administrative reason by sponsor                 2780                 2671  
poor/non-compliance                 30                 38  
non-specified                 276                 266  

Period 2:   Follow Up (30 Days)
    Placebo BID     Apixaban 5 mg BID  
STARTED     3508 [1]   3529 [2]
COMPLETED     3375     3355  
NOT COMPLETED     133     174  
Withdrawal by Subject                 41                 34  
Lost to Follow-up                 13                 27  
Death                 63                 86  
non-specified                 16                 26  
missing end of study status                 0                 1  
[1] 3508 participants entered the follow up period.
[2] 3529 participants entered the follow up period.



  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.
Randomized participants

Reporting Groups
  Description
Placebo Placebo: Tablets, Oral, 0 mg, twice daily.
Apixaban 5 mg BID Apixaban: Tablets, Oral, 5 mg, twice daily.
Total Total of all reporting groups

Baseline Measures
    Placebo     Apixaban 5 mg BID     Total  
Number of Participants  
[units: participants]
  3687     3705     7392  
Age  
[units: years]
Mean (Standard Deviation)
  65.4  (11.05)     65.3  (10.89)     65.4  (10.97)  
Age, Customized [1]
[units: participants]
     
< 65 years     1512     1526     3038  
≥ 65 and < 75 years     1420     1440     2860  
≥ 75 years     755     739     1494  
Gender  
[units: participants]
     
Female     1169     1209     2378  
Male     2518     2496     5014  
Region of Enrollment  
[units: participants]
     
Russian Federation     540     542     1082  
Puerto Rico     13     17     30  
Singapore     11     14     25  
United States     450     455     905  
Austria     58     56     114  
Sweden     50     55     105  
Netherlands     45     52     97  
China     36     39     75  
Poland     176     177     353  
Korea, Republic of     88     89     177  
Brazil     125     125     250  
Slovakia     30     29     59  
France     22     18     40  
Bulgaria     100     102     202  
Chile     30     26     56  
Colombia     45     43     88  
Argentina     131     125     256  
Romania     78     80     158  
Hungary     121     120     241  
Japan     91     95     186  
Ukraine     128     130     258  
United Kingdom     24     21     45  
Switzerland     18     20     38  
India     396     398     794  
Spain     81     79     160  
New Zealand     13     9     22  
Canada     126     128     254  
Czech Republic     54     54     108  
Turkey     9     11     20  
Belgium     47     50     97  
Norway     26     25     51  
Finland     4     3     7  
Denmark     37     34     71  
Italy     23     21     44  
South Africa     66     67     133  
Mexico     161     161     322  
Israel     73     66     139  
Australia     15     23     38  
Peru     66     66     132  
Germany     80     80     160  
Antiplatelet Therapy  
[units: participants]
     
Dual Antiplatelet Therapy     2965     2968     5933  
Single Antiplatelet Therapy     722     737     1459  
ACS Index Event [2]
[units: participants]
     
STEMI     1412     1426     2838  
non-STEMI     1582     1581     3163  
Unstable angina     693     698     1391  
[1] Less than (<); Greater than, equal to (≥).
[2] Participants were enrolled in the study only after experiencing an acute coronary syndrome (post-ACS) and were categorized as having ST-segment elevation myocardial infarction (STEMI), non-STEMI, or unstable angina.



  Outcome Measures
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1.  Primary:   Event Rate of Cardiovascular Death, Myocardial Infarction, or Ischemic Stroke During the Intended Treatment Period - Randomized Participants   [ Time Frame: Randomization (Day 1) to first event (CV death, MI, ischemic stroke), up to March 2011, approximately 2 years ]

2.  Primary:   Event Rate of Confirmed Major Bleeding Using Thrombolysis in Myocardial Infarction (TIMI) Criteria During the Treatment Period - Treated Participants   [ Time Frame: From first dose to first occurrence of event (TIMI major bleeding) during Treatment Period (first dose to last dose + 2 days), up to March 2011, approximately 2 years ]

3.  Secondary:   Event Rate of Unstable Angina (UA) During the Intended Treatment Period - Randomized Participants   [ Time Frame: Randomization (Day 1) to first event of UA, up to March 2011, approximately 2 years ]

4.  Secondary:   Event Rate of Stroke During the Intended Treatment Period - Randomized Participants   [ Time Frame: Randomization (Day 1) to first event (stroke), up to March 2011, approximately 2 years ]

5.  Secondary:   Event Rate of Myocardial Infarction (MI) During the Intended Treatment Period - Randomized Participants   [ Time Frame: Randomization (Day 1) to first event (MI), up to March 2011, approximately 2 years ]

6.  Secondary:   Event Rate of Stent Thrombosis During the Intended Treatment Period - Randomized Participants   [ Time Frame: Randomization (Day 1) to first event (stent thrombosis), up to March 2011, approximately 2 years ]

7.  Secondary:   Event Rate of Composite of Cardiovascular Death, Myocardial Infarction, Unstable Angina, or Ischemic Stroke During the Intended Treatment Period - Randomized Participants   [ Time Frame: Randomization (Day 1) to first event (CV death, MI, UA, Ischemic Stroke, up to March 2011, approximately 2 years ]

8.  Secondary:   Event Rate of Composite of Cardiovascular Death, Fatal Bleed, Myocardial Infarction, or Stroke During the Intended Treatment Period - Randomized Participants   [ Time Frame: Randomization (Day 1) to first event (CV death, Fatal Bleed, MI, or stroke), up to March 2011, approximately 2 years ]

9.  Secondary:   Event Rate of Composite of All-Cause Death, Myocardial Infarction, or Stroke During the Intended Treatment Period - Randomized Participants   [ Time Frame: Randomization (Day 1) to first event (All Cause Death, MI, or Stroke), up to March 2011, approximately 2 years ]

10.  Secondary:   Event Rate of Confirmed Major Bleeding Using International Society on Thrombosis and Hemostasis (ISTH) Criteria During the Treatment Period - Treated Participants   [ Time Frame: From first dose to first occurrence of event (ISTH major bleed) during Treatment Period (first dose to last dose + 2 days), up to March 2011, approximately 2 years ]

11.  Secondary:   Event Rate of Confirmed Major Bleeding or Clinically Relevant Non-Major Bleeding (CRNM) Using ISTH Criteria During the Treatment Period - Treated Participants   [ Time Frame: From first dose to first occurrence of event (ISTH major or CRNM bleed) during Treatment Period (first dose to last dose + 2 days), up to March 2011, approximately 2 years ]

12.  Secondary:   Event Rate of All Bleeding Reported by the Investigator During the Treatment Period - Treated Participants   [ Time Frame: From first dose to first occurrence of event (Bleeding) during Treatment Period (first dose to last dose + 2 days), up to March 2011, approximately 2 years ]


  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
No text entered.


  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


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


Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT00831441     History of Changes
Other Study ID Numbers: CV185-068
EUDRACT# 2008-008298-77
Study First Received: January 28, 2009
Results First Received: December 18, 2015
Last Updated: December 18, 2015
Health Authority: United States: Food and Drug Administration