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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 
Overall Participants Analyzed 
[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 
[1] Less than (<); Greater than, equal to (≥).
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 [1] 
[Units: Participants]
     
STEMI   1412   1426   2838 
non-STEMI   1582   1581   3163 
Unstable angina   693   698   1391 
[1] 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