ClinicalTrials.gov
ClinicalTrials.gov Menu

A Study to Evaluate the Safety of Apixaban in Acute Coronary Syndrome (ACS) Japanese Patients

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00852397
Recruitment Status : Terminated (See termination reason in detailed description.)
First Posted : February 27, 2009
Results First Posted : August 29, 2013
Last Update Posted : August 29, 2013
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
Pfizer

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Acute Coronary Syndrome
Interventions Drug: Apixaban
Other: Placebo
Enrollment 151
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Placebo Apixaban 2.5 mg BID Apixaban 5.0 mg BID
Hide Arm/Group Description Placebo was administered twice a day in addition to the standard therapy (aspirin with or without clopidogrel or ticlopidine) for 24 weeks. Apixaban 2.5 mg was administered twice a day in addition to the standard therapy (aspirin with or without clopidogrel or ticlopidine) for 24 weeks. Apixaban 5.0 mg was administered twice a day in addition to the standard therapy (aspirin with or without clopidogrel or ticlopidine) for 24 weeks.
Period Title: Overall Study
Started 52 49 50
Treated Participants 51 49 49
Completed 41 41 36
Not Completed 11 8 14
Reason Not Completed
Adverse Event             4             6             4
Death             0             0             1
Withdrawal by Subject             4             1             2
Study terminated by sponsor             2             1             6
Difficulty in study site visit             1             0             0
Protocol Violation             0             0             1
Arm/Group Title Placebo Apixaban 2.5 mg BID Apixaban 5.0 mg BID Total
Hide Arm/Group Description

Placebo was administered twice a day in addition to the standard therapy (aspirin with or without clopidogrel or ticlopidine) for 24 weeks.

Number of participants in baseline characteristics means randomized participants.

2.5 mg was administered twice a day in addition to the standard therapy (aspirin with or without clopidogrel or ticlopidine) for 24 weeks.

Number of participants in baseline characteristics means randomized participants.

Apixaban 5.0 mg was administered twice a day in addition to the standard therapy (aspirin with or without clopidogrel or ticlopidine) for 24 weeks.

Number of participants in baseline characteristics means randomized participants.

Total of all reporting groups
Overall Number of Baseline Participants 52 49 50 151
Hide Baseline Analysis Population Description
[Not Specified]
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 52 participants 49 participants 50 participants 151 participants
63.9  (10.1) 66.0  (9.0) 64.0  (9.2) 64.6  (9.5)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 52 participants 49 participants 50 participants 151 participants
Female
10
  19.2%
6
  12.2%
4
   8.0%
20
  13.2%
Male
42
  80.8%
43
  87.8%
46
  92.0%
131
  86.8%
1.Primary Outcome
Title Percentage of Participants Who Had Composite of International Society on Thrombosis and Haemostasis (ISTH)-Defined Major and Clinically-relevant Non-major (CRNM) Bleeding Events Occurring During the Treatment Period.
Hide Description Major bleeding event was acute clinically overt bleeding accompanied by decrease in hemoglobin of 2 g/dL or more over a 24-hour period, transfusion of 2 or more units of packed red blood cells, or bleeding that occurs in critical site (e.g., intracranial). Fatal bleeding was also major bleeding event. CRNM bleeding was acute or sub-acute clinically overt bleeding that did not satisfy the criteria for major bleeding and that led to either hospital admission for bleeding, physician guided medical or surgical treatment for bleeding or a change in antithrombotic therapy.
Time Frame Week 0 to Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Bleeding endpoint was included in safety evaluations. The safety analysis set was defined as all treated participants (randomized participants who received at least one dose of study drug).
Arm/Group Title Placebo Apixaban 2.5 mg BID Apixaban 5.0 mg BID
Hide Arm/Group Description:
Placebo was administered twice a day in addition to the standard therapy (aspirin with or without clopidogrel or ticlopidine) for 24 weeks.
Apixaban 2.5 mg was administered twice a day in addition to the standard therapy (aspirin with or without clopidogrel or ticlopidine) for 24 weeks.
Apixaban 5.0 mg was administered twice a day in addition to the standard therapy (aspirin with or without clopidogrel or ticlopidine) for 24 weeks.
Overall Number of Participants Analyzed 51 49 49
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
2.0
(0.10 to 9.82)
4.1
(0.73 to 13.34)
4.1
(0.73 to 13.34)
2.Secondary Outcome
Title Percentage of Participants Who Had One or More All Bleeding Occurring During the Treatment Period.
Hide Description All bleeding included major bleeding (including fatal bleeding), clinically-relevant non-major (CRNM) bleeding, and minor bleeding per international society on thrombosis and haemostasis (ISTH) definitions.
Time Frame Week 0 to Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Bleeding endpoint was included in safety evaluations. The safety analysis set was defined as all treated participants (randomized participants who received at least one dose of study drug).
Arm/Group Title Placebo Apixaban 2.5 mg BID Apixaban 5.0 mg BID
Hide Arm/Group Description:
Placebo was administered twice a day in addition to the standard therapy (aspirin with or without clopidogrel or ticlopidine) for 24 weeks.
Apixaban 2.5 mg was administered twice a day in addition to the standard therapy (aspirin with or without clopidogrel or ticlopidine) for 24 weeks.
Apixaban 5.0 mg was administered twice a day in addition to the standard therapy (aspirin with or without clopidogrel or ticlopidine) for 24 weeks.
Overall Number of Participants Analyzed 51 49 49
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
33.3
(20.76 to 47.23)
38.8
(26.01 to 53.76)
44.9
(30.83 to 59.77)
3.Secondary Outcome
Title Percentage of Participants Who Had Major Bleeding Occurring During the Treatment Period Per International Society on Thrombosis and Haemostasis (ISTH) Definitions.
Hide Description Major bleeding event was defined as an acute clinically overt bleeding accompanied by decrease in hemoglobin of 2 g/dL or more over a 24-hour period, transfusion of 2 or more units of packed red blood cells, or bleeding that occured in critical site (e.g., intracranial). Fatal bleeding was also major bleeding event.
Time Frame Week 0 to Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Bleeding endpoint was included in safety evaluations. The safety analysis set was defined as all treated participants (randomized participants who received at least one dose of study drug).
Arm/Group Title Placebo Apixaban 2.5 mg BID Apixaban 5.0 mg BID
Hide Arm/Group Description:
Placebo was administered twice a day in addition to the standard therapy (aspirin with or without clopidogrel or ticlopidine) for 24 weeks.
Apixaban 2.5 mg was administered twice a day in addition to the standard therapy (aspirin with or without clopidogrel or ticlopidine) for 24 weeks.
Apixaban 5.0 mg was administered twice a day in addition to the standard therapy (aspirin with or without clopidogrel or ticlopidine) for 24 weeks.
Overall Number of Participants Analyzed 51 49 49
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
0
(0.00 to 6.31)
2.0
(0.10 to 10.24)
4.1
(0.73 to 13.34)
4.Secondary Outcome
Title Percentage of Participants Who Had Thrombolysis in Myocardial Infarction (TIMI)-Defined Major Bleeding Occurring During the Treatment Period.
Hide Description TIMI major bleeding event was difined as an intracranial bleeding or clinically overt bleeding (including bleeding evident on imaging studies) associated with a >= 5 gm/dL fall in hemoglobin or a 15% fall in hematocrit from baseline, accounting for the effect of transfusions (1 unit packed red blood cells = 1 gm/dL hemoglobin = 3% hematocrit).
Time Frame Week 0 to Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Bleeding endpoint was included in safety evaluations. The safety analysis set was defined as all treated participants (randomized participants who received at least one dose of study drug).
Arm/Group Title Placebo Apixaban 2.5 mg BID Apixaban 5.0 mg BID
Hide Arm/Group Description:
Placebo was administered twice a day in addition to the standard therapy (aspirin with or without clopidogrel or ticlopidine) for 24 weeks.
Apixaban 2.5 mg was administered twice a day in addition to the standard therapy (aspirin with or without clopidogrel or ticlopidine) for 24 weeks.
Apixaban 5.0 mg was administered twice a day in addition to the standard therapy (aspirin with or without clopidogrel or ticlopidine) for 24 weeks.
Overall Number of Participants Analyzed 51 49 49
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
0
(0.00 to 6.31)
2.0
(0.10 to 10.24)
2.0
(0.10 to 10.24)
5.Secondary Outcome
Title Percentage of Participants Who Had Composite of All-cause Death, Non-fatal Myocardial Infarction, Unstable Angina and Stroke During 30 Days After Discontinuation of Therapy.
Hide Description [Not Specified]
Time Frame For 30 days after Week 24 or the discontinuation of study drug
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Bleeding endpoint was included in safety evaluations. The safety analysis set was defined as all treated participants (randomized participants who received at least one dose of study drug).
Arm/Group Title Placebo Apixaban 2.5 mg BID Apixaban 5.0 mg BID
Hide Arm/Group Description:
Placebo was administered twice a day in addition to the standard therapy (aspirin with or without clopidogrel or ticlopidine) for 24 weeks.
Apixaban 2.5 mg was administered twice a day in addition to the standard therapy (aspirin with or without clopidogrel or ticlopidine) for 24 weeks.
Apixaban 5.0 mg was administered twice a day in addition to the standard therapy (aspirin with or without clopidogrel or ticlopidine) for 24 weeks.
Overall Number of Participants Analyzed 51 49 49
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
0
(0.00 to 6.31)
0
(0.00 to 6.53)
2
(0.10 to 10.24)
6.Secondary Outcome
Title Percentage of Participants Who Had Composite of All-cause Death, Non-fatal Myocardial Infarction (MI), Unstable Angina, and Non-hemorrhagic Stroke Occurring During the Intended Treatment Period.
Hide Description Intended treatment period for efficacy endpoints was defined as a period starting on the day of randomization and ending at the later date of either 2-days after the last dose of study drug or Day 168/Week 24 after randomization day (or the study termination date [19 November 2010, Japan time]).
Time Frame From the day of randomization to the later date of either 2-days after the last dose of study drug or Day 168/Week 24 after randomization day (or the study termination date [19 November 2010, Japan time])
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The efficacy analysis set was all randomized participants.
Arm/Group Title Placebo Apixaban 2.5 mg BID Apixaban 5.0 mg BID
Hide Arm/Group Description:
Placebo was administered twice a day in addition to the standard therapy (aspirin with or without clopidogrel or ticlopidine) for 24 weeks.
Apixaban 2.5 mg was administered twice a day in addition to the standard therapy (aspirin with or without clopidogrel or ticlopidine) for 24 weeks.
Apixaban 5.0 mg was administered twice a day in addition to the standard therapy (aspirin with or without clopidogrel or ticlopidine) for 24 weeks.
Overall Number of Participants Analyzed 52 49 50
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
1.9
(0.10 to 9.63)
0
(0.00 to 6.53)
2.0
(0.10 to 10.03)
7.Other Pre-specified Outcome
Title Percentage of Participants Who Had International Society on Thrombosis and Haemostasis (ISTH)-Defined Individual Bleeding Endpoints (Clinically-relevant Non-major [CRNM] or Minor Bleeding) During the Treatment Period.
Hide Description

ISTH-defined CRNM bleeding was defined as an acute or sub-acute clinically overt bleeding that did not satisfy the criteria for major bleeding and that led to either hospital admission for bleeding, physician guided medical or surgical treatment for bleeding or a change in antithrombotic therapy.

ISTH defined minor bleeding event was defined as all acute clinically overt bleeding events not meeting the criteria for either major bleeding or CRNM bleeding were classified as minor bleeding.

Time Frame Week 0 to Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Bleeding endpoint was included in safety evaluations. The safety analysis set was defined as all treated participants (randomized participants who received at least one dose of study drug).
Arm/Group Title Placebo Apixaban 2.5 mg BID Apixaban 5.0 mg BID
Hide Arm/Group Description:
Placebo was administered twice a day in addition to the standard therapy (aspirin with or without clopidogrel or ticlopidine) for 24 weeks.
Apixaban 2.5 mg was administered twice a day in addition to the standard therapy (aspirin with or without clopidogrel or ticlopidine) for 24 weeks.
Apixaban 5.0 mg was administered twice a day in addition to the standard therapy (aspirin with or without clopidogrel or ticlopidine) for 24 weeks.
Overall Number of Participants Analyzed 51 49 49
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
ISTH defined CRNM
2.0
(0.10 to 9.82)
2.0
(0.10 to 10.24)
0
(0.00 to 6.53)
ISTH defined minor bleeding
31.4
(19.63 to 45.07)
36.7
(23.64 to 51.64)
40.8
(27.00 to 55.79)
8.Other Pre-specified Outcome
Title Percentage of Participants Who Had Thrombolysis in Myocardial Infarction (TIMI) Defined-individual Bleeding Endpoints (Minor or Minimal Bleeding) During the Treatment Period.
Hide Description

TIMI minor bleeding event was defined as a clinically overt bleeding (including bleeding evident on imaging studies) associated with a >= 3 gm/dL fall in hemoglobin or a 9% fall in hematocrit from baseline, accounting for the effect of transfusions (1 unit packed red blood cells = 1 gm/dL hemoglobin = 3% hematocrit).

TIMI minimal bleeding event was defined as a clinically overt bleeding (including bleeding evident on imaging studies) not meeting criteria for TIMI minor bleeding.

Time Frame Week 0 to Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Bleeding endpoint was included in safety evaluations. The safety analysis set was defined as all treated participants (randomized participants who received at least one dose of study drug).
Arm/Group Title Placebo Apixaban 2.5 mg BID Apixaban 5.0 mg BID
Hide Arm/Group Description:
Placebo was administered twice a day in addition to the standard therapy (aspirin with or without clopidogrel or ticlopidine) for 24 weeks.
Apixaban 2.5 mg was administered twice a day in addition to the standard therapy (aspirin with or without clopidogrel or ticlopidine) for 24 weeks.
Apixaban 5.0 mg was administered twice a day in addition to the standard therapy (aspirin with or without clopidogrel or ticlopidine) for 24 weeks.
Overall Number of Participants Analyzed 51 49 49
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
TIMI defined minor bleeding
0
(0.00 to 6.31)
2.0
(0.00 to 6.53)
2.0
(0.10 to 10.24)
TIMI defined minimal bleeding
33.3
(20.76 to 47.23)
38.8
(26.01 to 53.76)
40.8
(27.00 to 55.79)
Time Frame [Not Specified]
Adverse Event Reporting Description The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
 
Arm/Group Title Placebo Apixaban 2.5 mg BID Apixaban 5.0 mg BID
Hide Arm/Group Description Placebo was administered twice a day in addition to the standard therapy (aspirin with or without clopidogrel or ticlopidine) for 24 weeks. Apixaban 2.5 mg was administered twice a day in addition to the standard therapy (aspirin with or without clopidogrel or ticlopidine) for 24 weeks. Apixaban 5.0 mg was administered twice a day in addition to the standard therapy (aspirin with or without clopidogrel or ticlopidine) for 24 weeks.
All-Cause Mortality
Placebo Apixaban 2.5 mg BID Apixaban 5.0 mg BID
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Placebo Apixaban 2.5 mg BID Apixaban 5.0 mg BID
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   8/51 (15.69%)   11/49 (22.45%)   7/49 (14.29%) 
Cardiac disorders       
Angina pectoris  1  1/51 (1.96%)  0/49 (0.00%)  1/49 (2.04%) 
Angina unstable  1  1/51 (1.96%)  1/49 (2.04%)  1/49 (2.04%) 
Arteriospasm coronary  1  0/51 (0.00%)  0/49 (0.00%)  1/49 (2.04%) 
Cardiac failure  1  1/51 (1.96%)  0/49 (0.00%)  0/49 (0.00%) 
Coronary artery occlusion  1  0/51 (0.00%)  1/49 (2.04%)  0/49 (0.00%) 
Eye disorders       
Cataract  1  0/51 (0.00%)  1/49 (2.04%)  0/49 (0.00%) 
Pterygium  1  0/51 (0.00%)  0/49 (0.00%)  1/49 (2.04%) 
Gastrointestinal disorders       
Diverticulum intestinal haemorrhagic  1  0/51 (0.00%)  0/49 (0.00%)  1/49 (2.04%) 
Lower gastrointestinal haemorrhage  1  0/51 (0.00%)  1/49 (2.04%)  0/49 (0.00%) 
Oesophageal ulcer  1  0/51 (0.00%)  0/49 (0.00%)  1/49 (2.04%) 
Upper gastrointestinal haemorrhage  1  0/51 (0.00%)  0/49 (0.00%)  1/49 (2.04%) 
General disorders       
Chest pain  1  0/51 (0.00%)  1/49 (2.04%)  0/49 (0.00%) 
Feeling abnormal  1  0/51 (0.00%)  0/49 (0.00%)  1/49 (2.04%) 
Sudden cardiac death  1  0/51 (0.00%)  0/49 (0.00%)  1/49 (2.04%) 
Infections and infestations       
Diverticulitis  1  1/51 (1.96%)  0/49 (0.00%)  0/49 (0.00%) 
Lung abscess  1  1/51 (1.96%)  0/49 (0.00%)  0/49 (0.00%) 
Injury, poisoning and procedural complications       
Arterial restenosis  1  0/51 (0.00%)  1/49 (2.04%)  0/49 (0.00%) 
Coronary artery restenosis  1  1/51 (1.96%)  2/49 (4.08%)  1/49 (2.04%) 
Overdose  1  0/51 (0.00%)  1/49 (2.04%)  0/49 (0.00%) 
Road traffic accident  1  0/51 (0.00%)  1/49 (2.04%)  0/49 (0.00%) 
Musculoskeletal and connective tissue disorders       
Muscular weakness  1  0/51 (0.00%)  0/49 (0.00%)  1/49 (2.04%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Colon cancer  1  0/51 (0.00%)  1/49 (2.04%)  0/49 (0.00%) 
Rectal cancer  1  0/51 (0.00%)  1/49 (2.04%)  0/49 (0.00%) 
Nervous system disorders       
Cerebral infarction  1  1/51 (1.96%)  0/49 (0.00%)  0/49 (0.00%) 
Respiratory, thoracic and mediastinal disorders       
Interstitial lung disease  1  0/51 (0.00%)  1/49 (2.04%)  0/49 (0.00%) 
Skin and subcutaneous tissue disorders       
Urticaria  1  1/51 (1.96%)  0/49 (0.00%)  0/49 (0.00%) 
Vascular disorders       
Arteriosclerosis obliterans  1  1/51 (1.96%)  0/49 (0.00%)  0/49 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 13.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo Apixaban 2.5 mg BID Apixaban 5.0 mg BID
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   22/51 (43.14%)   28/49 (57.14%)   22/49 (44.90%) 
Gastrointestinal disorders       
Diarrhoea  1  1/51 (1.96%)  0/49 (0.00%)  3/49 (6.12%) 
Gingival bleeding  1  0/51 (0.00%)  2/49 (4.08%)  3/49 (6.12%) 
General disorders       
Chest discomfort  1  4/51 (7.84%)  1/49 (2.04%)  4/49 (8.16%) 
Infections and infestations       
Nasopharyngitis  1  4/51 (7.84%)  4/49 (8.16%)  8/49 (16.33%) 
Injury, poisoning and procedural complications       
Fall  1  0/51 (0.00%)  3/49 (6.12%)  2/49 (4.08%) 
Post procedural haemorrhage  1  6/51 (11.76%)  6/49 (12.24%)  4/49 (8.16%) 
Investigations       
Blood urine present  1  0/51 (0.00%)  2/49 (4.08%)  4/49 (8.16%) 
Musculoskeletal and connective tissue disorders       
Back pain  1  3/51 (5.88%)  2/49 (4.08%)  0/49 (0.00%) 
Nervous system disorders       
Dizziness  1  2/51 (3.92%)  3/49 (6.12%)  2/49 (4.08%) 
Headache  1  4/51 (7.84%)  3/49 (6.12%)  1/49 (2.04%) 
Respiratory, thoracic and mediastinal disorders       
Cough  1  1/51 (1.96%)  4/49 (8.16%)  1/49 (2.04%) 
Epistaxis  1  3/51 (5.88%)  2/49 (4.08%)  2/49 (4.08%) 
Skin and subcutaneous tissue disorders       
Haemorrhage subcutaneous  1  4/51 (7.84%)  5/49 (10.20%)  6/49 (12.24%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 13.1
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.
Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
Results Point of Contact
Name/Title: Pfizer ClinicalTrials.gov Call Center
Organization: Pfizer, Inc.
Phone: 1-800-718-1021
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT00852397     History of Changes
Other Study ID Numbers: B0661004
First Submitted: February 26, 2009
First Posted: February 27, 2009
Results First Submitted: June 4, 2013
Results First Posted: August 29, 2013
Last Update Posted: August 29, 2013