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Trial record 77 of 114 for:    centurion

Phase III Acute Coronary Syndrome (APPRAISE-2)

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: NCT00831441
Recruitment Status : Terminated
First Posted : January 29, 2009
Results First Posted : January 27, 2016
Last Update Posted : January 27, 2016
Sponsor:
Collaborators:
Pfizer
Duke Clinical Research Institute
Information provided by (Responsible Party):
Bristol-Myers Squibb

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Prevention
Condition Acute Coronary Syndrome
Interventions Drug: Apixaban
Drug: Placebo
Enrollment 7484
Recruitment Details  
Pre-assignment Details 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.
Arm/Group Title Placebo BID Apixaban 5 mg BID
Hide Arm/Group Description 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: 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.
Period Title: Randomized
Started 3687 3705
Treated 3643 3672
Completed 0 0
Not Completed 3687 3705
Reason Not Completed
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 Title: Follow Up (30 Days)
Started 3508 [1] 3529 [2]
Completed 3375 3355
Not Completed 133 174
Reason Not Completed
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.
Arm/Group Title Placebo Apixaban 5 mg BID Total
Hide Arm/Group Description Placebo: Tablets, Oral, 0 mg, twice daily. Apixaban: Tablets, Oral, 5 mg, twice daily. Total of all reporting groups
Overall Number of Baseline Participants 3687 3705 7392
Hide Baseline Analysis Population Description
Randomized participants
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 3687 participants 3705 participants 7392 participants
65.4  (11.05) 65.3  (10.89) 65.4  (10.97)
Age, Customized   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 3687 participants 3705 participants 7392 participants
< 65 years 1512 1526 3038
≥ 65 and < 75 years 1420 1440 2860
≥ 75 years 755 739 1494
[1]
Measure Description: Less than (<); Greater than, equal to (≥).
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3687 participants 3705 participants 7392 participants
Female
1169
  31.7%
1209
  32.6%
2378
  32.2%
Male
2518
  68.3%
2496
  67.4%
5014
  67.8%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 3687 participants 3705 participants 7392 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  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 3687 participants 3705 participants 7392 participants
Dual Antiplatelet Therapy 2965 2968 5933
Single Antiplatelet Therapy 722 737 1459
ACS Index Event   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 3687 participants 3705 participants 7392 participants
STEMI 1412 1426 2838
non-STEMI 1582 1581 3163
Unstable angina 693 698 1391
[1]
Measure Description: 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.
1.Primary Outcome
Title Event Rate of Cardiovascular Death, Myocardial Infarction, or Ischemic Stroke During the Intended Treatment Period - Randomized Participants
Hide Description Event rate was percent of participants with an event of cardiovascular (CV) death, myocardial infarction (MI), or ischemic stroke (number of participants with event/number randomized) per 100 patient (100-pt) years. Study was terminated early and last patient, last visit was in Year 2. Only events confirmed by the adjudication committee were included in the analyses. CV death included deaths due to CV causes (eg, cardiogenic shock, heart failure, arrhythmia/sudden death, cardiac rupture, ischemic stroke, pulmonary embolism, venous/arterial thrombotic events) and other sudden deaths for which an alternative cause was not identified. Intended Treatment Period: the period that started on the day of randomization and ended at the efficacy cut-off date (cut-off date: the date all sites were informed that study drug should be discontinued for all participants, 18 November 2010).
Time Frame Randomization (Day 1) to first event (CV death, MI, ischemic stroke), up to March 2011, approximately 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants were analyzed.
Arm/Group Title Placebo Apixaban 5 mg BID
Hide Arm/Group Description:
Placebo: Tablets, Oral, 0 mg, twice daily.
Apixaban: Tablets, Oral, 5 mg, twice daily. Study was terminated in Year 2.
Overall Number of Participants Analyzed 3687 3705
Measure Type: Number
Unit of Measure: percentage of participants/100-pt years
13.96 13.20
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Apixaban 5 mg BID
Comments A test of superiority at the one-sided α = 0.025 significance level for the primary efficacy outcome was performed.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5094
Comments [Not Specified]
Method Cox proportional hazard models
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.95
Confidence Interval (2-Sided) 95%
0.80 to 1.11
Estimation Comments [Not Specified]
2.Primary Outcome
Title Event Rate of Confirmed Major Bleeding Using Thrombolysis in Myocardial Infarction (TIMI) Criteria During the Treatment Period - Treated Participants
Hide Description TIMI Major Bleed Criteria: Fatal bleeding, intracranial hemorrhage, and clinically overt bleeding with a hemoglobin (Hgb) drop of ≥ 5 grams per deciliter (g/dL), or ≥15% absolute decrease in hematocrit. To account for transfusions, Hgb measurements were adjusted for transfusions. A transfusion of 1 unit of blood was assumed to result in an increase by 1 g/dL in Hgb or 3% in hematocrit. Event rate was percent of participants with an event of Major Bleed as per TIMI (number of participants with event/number randomized) per 100 patient (100-pt) years. Only events confirmed by the adjudication committee were included in the analyses. Treatment Period=events with onset from first dose to last dose plus 2 days.
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
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least one dose of blinded study drug and signed informed consent were analyzed.
Arm/Group Title Placebo Apixaban 5 mg BID
Hide Arm/Group Description:
Placebo: Tablets, Oral, 0 mg, twice daily.
Apixaban: Tablets, Oral, 5 mg, twice daily. Study was terminated at Year 2.
Overall Number of Participants Analyzed 3643 3672
Measure Type: Number
Unit of Measure: percentage of participants/100-pt years
0.91 2.40
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Apixaban 5 mg BID
Comments A point estimate and two-sided 95% confidence interval (CI) for relative risk, as measured by the hazard ratio and a p-value for the test of equality of rates (HR = 1) was calculated.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0006
Comments [Not Specified]
Method Cox Proportional Hazard model
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 2.59
Confidence Interval (2-Sided) 95%
1.50 to 4.46
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Event Rate of Unstable Angina (UA) During the Intended Treatment Period - Randomized Participants
Hide Description Unstable Angina (UA) defined as worsening or recurrent severe or repetitive angina symptoms at rest lasting at least 10 minutes with at least 2 of the following: New and dynamic electrocardiogram (ECG) changes; angina symptoms leading to inpatient hospitalization; angina symptoms leading to an unplanned or urgent cardiac catheterization, with or without revascularization, that showed evidence of hemodynamically and clinically significant stenosis. Event rate was percent of participants with an event of unstable angina (number of participants with event/number randomized) per 100 patient (100-pt) years. Only events confirmed by the adjudication committee were included in the analyses. Intended Treatment Period: the period that started on the day of randomization and ended at the efficacy cut-off date (cut-off date: the date all sites were informed that study drug should be discontinued for all participants, 18 November 2010).
Time Frame Randomization (Day 1) to first event of UA, up to March 2011, approximately 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants were analyzed.
Arm/Group Title Placebo Apixaban 5 mg BID
Hide Arm/Group Description:
Placebo: Tablets, Oral, 0 mg, twice daily.
Apixaban: Tablets, Oral, 5 mg, twice daily. Study was terminated at Year 2.
Overall Number of Participants Analyzed 3687 3705
Measure Type: Number
Unit of Measure: percentage of participants/100-pt years
4.21 3.95
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Apixaban 5 mg BID
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6702
Comments [Not Specified]
Method Cox proportional hazard models
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.94
Confidence Interval (2-Sided) 95%
0.70 to 1.26
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Event Rate of Stroke During the Intended Treatment Period - Randomized Participants
Hide Description Event rate was percent of participants with an event of stroke (number of participants with event/number randomized) per 100 patient (100-pt) years. Only events confirmed by the adjudication committee were included in the analyses. Diagnosis of stroke required a new, non-traumatic, focal neurological deficit of sudden onset, lasting at least 24 hours that was not due to a readily identifiable non-vascular cause (ie, brain tumor). All strokes were classified as hemorrhagic (documentation on imaging (eg computed tomography scan or magnetic resonance imaging) of hemorrhage in the cerebral parenchyma, or a subdural or subarachnoid hemorrhage), non-hemorrhagic/ischemic stroke, ischemic stroke with hemorrhagic conversion, or type unknown. Intended Treatment Period: the period that started on the day of randomization (Day 1) and ended at the efficacy cut-off date (notification of study termination).
Time Frame Randomization (Day 1) to first event (stroke), up to March 2011, approximately 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants were analyzed.
Arm/Group Title Placebo Apixaban 5 mg BID
Hide Arm/Group Description:
Placebo: Tablets, Oral, 0 mg, twice daily.
Apixaban: Tablets, Oral, 5 mg, twice daily. Study was terminated at Year 2.
Overall Number of Participants Analyzed 3687 3705
Measure Type: Number
Unit of Measure: percentage of participants/100-pt years
1.85 1.65
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Apixaban 5 mg BID
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6311
Comments [Not Specified]
Method Cox proportional hazard models
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.90
Confidence Interval (2-Sided) 95%
0.57 to 1.40
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Event Rate of Myocardial Infarction (MI) During the Intended Treatment Period - Randomized Participants
Hide Description MI took into account whether the participant had a recent percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) surgery. Selected key criteria: Elevation of cardiac biomarkers (eg, Creatine Kinase MB fraction (CKMB), Troponin T, Troponin I) above the upper reference limit (URL) plus ischemic symptoms, ECG changes, or imaging evidence of new loss of viable myocardium or new regional wall motion abnormality; Death of CV etiology with new ST-segment elevation or left bundle branch block (LBBB) or fresh intracoronary thrombus by angiography or at autopsy occurring before biomarkers could be obtained or before their appearance in the blood; Following a PCI, elevation of cardiac biomarkers more than 3*URL; Following CABG surgery, elevation of cardiac biomarkers more than 5*URL; New, significant (≥0.04 s) Q waves in ≥2 contiguous leads; Pathologic findings of acute MI. Intended Treatment Period: Day of randomization (Day 1) to efficacy cut-off notice.
Time Frame Randomization (Day 1) to first event (MI), up to March 2011, approximately 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants were analyzed.
Arm/Group Title Placebo Apixaban 5 mg BID
Hide Arm/Group Description:
Placebo: Tablets, Oral, 0 mg, twice daily.
Apixaban: Tablets, Oral, 5 mg, twice daily. Study was terminated at Year 2.
Overall Number of Participants Analyzed 3687 3705
Measure Type: Number
Unit of Measure: percentage of participants/100-pt years
9.20 8.59
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Apixaban 5 mg BID
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5086
Comments [Not Specified]
Method Cox proportional hazard models
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.93
Confidence Interval (2-Sided) 95%
0.76 to 1.14
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Event Rate of Stent Thrombosis During the Intended Treatment Period - Randomized Participants
Hide Description Stent thrombosis: Definite stent thrombosis considered to have occurred by either angiographic or pathological confirmation; Probable stent thrombosis considered to have occurred in the following cases: any unexplained death within the first 30 days after stent implantation; irrespective of the time after the procedure, any MI that was related to documented acute ischemia in the territory of the implanted stent without angiographic confirmation of stent thrombosis and in the absence of any other obvious cause; Possible stent thrombosis considered to have occurred with any unexplained death from 30 days after intracoronary stenting until end of study (in Year 2). Event rate was percent of participants with an event of stent thrombosis (number with event/number randomized) per 100-pt years. Only events confirmed by the adjudication committee were included in the analyses. Intended Treatment Period: Day of randomization (Day 1) to efficacy cut-off notice of study termination.
Time Frame Randomization (Day 1) to first event (stent thrombosis), up to March 2011, approximately 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants were analyzed.
Arm/Group Title Placebo Apixaban 5 mg BID
Hide Arm/Group Description:
Placebo: Tablets, Oral, 0 mg, twice daily.
Apixaban: Tablets, Oral, 5 mg, twice daily. Study was terminated at Year 2.
Overall Number of Participants Analyzed 3687 3705
Measure Type: Number
Unit of Measure: percentage of participants/100-pt years
2.21 1.61
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Apixaban 5 mg BID
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1502
Comments [Not Specified]
Method Cox proportional hazard models
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.73
Confidence Interval (2-Sided) 95%
0.47 to 1.12
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Event Rate of Composite of Cardiovascular Death, Myocardial Infarction, Unstable Angina, or Ischemic Stroke During the Intended Treatment Period - Randomized Participants
Hide Description Event rate was percent of participants with an event of CV death, MI, unstable angina (UA), or ischemic stroke (number of participants with event/number randomized) per 100-pt years. Only events confirmed by the adjudication committee were included in the analyses. Each type of event was counted once per participant, but participants could have been counted in multiple categories. Intended Treatment Period: Day of randomization (Day 1) to efficacy cut-off date (notification of study termination).
Time Frame Randomization (Day 1) to first event (CV death, MI, UA, Ischemic Stroke, up to March 2011, approximately 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants were analyzed.
Arm/Group Title Placebo Apixaban 5 mg BID
Hide Arm/Group Description:
Placebo: Tablets, Oral, 0 mg, twice daily.
Apixaban: Tablets, Oral, 5 mg, twice daily. Study was terminated at Year 2.
Overall Number of Participants Analyzed 3687 3705
Measure Type: Number
Unit of Measure: percentage of participants/100-pt years
17.95 16.92
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Apixaban 5 mg BID
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4317
Comments [Not Specified]
Method Cox proportional hazard models
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.94
Confidence Interval (2-Sided) 95%
0.82 to 1.09
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Event Rate of Composite of Cardiovascular Death, Fatal Bleed, Myocardial Infarction, or Stroke During the Intended Treatment Period - Randomized Participants
Hide Description Event rate was percent of participants with an event of CV death, fatal bleed, MI, or stroke (number of participants with event/number randomized) per 100 patient (100-pt) years. Only events confirmed by the adjudication committee were included in the analyses. CV death included deaths due to CV causes; Diagnosis of stroke required a new, non-traumatic, focal neurological deficit of sudden onset, lasting at least 24 hours that was not due to a readily identifiable non-vascular cause; Fatal bleeding defined as bleeding that Adjudication Committee determined was the primary cause of death or contributed directly to death; MI took into account whether the participant had a recent PCI or CABG surgery. Intended Treatment Period: Day of randomization (Day 1) to efficacy cut-off date (notification of study termination).
Time Frame Randomization (Day 1) to first event (CV death, Fatal Bleed, MI, or stroke), up to March 2011, approximately 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants were analyzed.
Arm/Group Title Placebo Apixaban 5 mg BID
Hide Arm/Group Description:
Placebo: Tablets, Oral, 0 mg, twice daily.
Apixaban: Tablets, Oral, 5 mg, twice daily. Study was terminated at Year 2.
Overall Number of Participants Analyzed 3687 3705
Measure Type: Number
Unit of Measure: percentage of participants/100-pt years
14.27 13.97
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Apixaban 5 mg BID
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8015
Comments [Not Specified]
Method Cox proportional hazard models
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.98
Confidence Interval (2-Sided) 95%
0.83 to 1.15
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Event Rate of Composite of All-Cause Death, Myocardial Infarction, or Stroke During the Intended Treatment Period - Randomized Participants
Hide Description

Cause of death was determined by the principal condition that caused the death, not the immediate mode of death.

CV death: included deaths due to CV causes. Non-CV death: included non-CV deaths caused primarily by a malignancy, infection, bleeding, trauma, non-CV system organ failure, or non-CV surgery. Unknown: included deaths that were not attributable to one of the above categories of CV death or to a non-CV cause. MI accounted whether the participant had a recent PCI or CABG surgery. Diagnosis of stroke required a new, non-traumatic, focal neurological deficit of sudden onset, lasting at least 24 hours that was not due to a readily identifiable non-vascular cause. Only events confirmed by the adjudication committee were included in analyses. Intended Treatment Period: Day of randomization (Day 1) to efficacy cut-off date (notification of study termination).

Time Frame Randomization (Day 1) to first event (All Cause Death, MI, or Stroke), up to March 2011, approximately 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants were analyzed.
Arm/Group Title Placebo Apixaban 5 mg BID
Hide Arm/Group Description:
Placebo: Tablets, Oral, 0 mg, twice daily.
Apixaban: Tablets, Oral, 5 mg, twice daily. Study was terminated at Year 2.
Overall Number of Participants Analyzed 3687 3705
Measure Type: Number
Unit of Measure: percentage of participants/100-pt years
15.65 15.48
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Apixaban 5 mg BID
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8948
Comments [Not Specified]
Method Cox proportional hazard models
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.99
Confidence Interval (2-Sided) 95%
0.85 to 1.15
Estimation Comments [Not Specified]
10.Secondary Outcome
Title Event Rate of Confirmed Major Bleeding Using International Society on Thrombosis and Hemostasis (ISTH) Criteria During the Treatment Period - Treated Participants
Hide Description ISTH Criteria: Acute clinically overt bleeding defined as new onset, visible bleeding or signs or symptoms suggestive of bleeding confirmed by imaging techniques, which can detect the presence of blood (eg, ultrasound, CT, MRI). Major bleeding: acute clinically overt bleeding accompanied by one or more of the following: A decrease in Hgb of 2 g/dL or more over 24 hours; A transfusion of 2 or more units of packed red blood cells (RBCs); Bleeding that occurs in at least one of the following sites: intracranial, intraspinal, intraocular (within the corpus of the eye; thus, a conjunctival bleed is not an intraocular bleed), pericardial, intra-articular, intramuscular with compartment syndrome, retroperitoneal; Bleeding that was fatal. Bleeding events were adjudicated by the Adjudication Committee. Event rate was percent of participants with an event (number with event/number randomized) per 100-pt years. Treatment Period=events with onset from first dose to last dose plus 2 days.
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
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least one dose of blinded study drug and signed informed consent were analyzed.
Arm/Group Title Placebo Apixaban 5 mg BID
Hide Arm/Group Description:
Placebo: Tablets, Oral, 0 mg, twice daily.
Apixaban: Tablets, Oral, 5 mg, twice daily. Study was terminated at Year 2.
Overall Number of Participants Analyzed 3643 3672
Measure Type: Number
Unit of Measure: percentage of participants/100-pt years
2.04 5.13
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Apixaban 5 mg BID
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Cox Proportional Hazard model
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 2.48
Confidence Interval (2-Sided) 95%
1.72 to 3.58
Estimation Comments [Not Specified]
11.Secondary Outcome
Title Event Rate of Confirmed Major Bleeding or Clinically Relevant Non-Major Bleeding (CRNM) Using ISTH Criteria During the Treatment Period - Treated Participants
Hide Description ISTH Major bleed: acute clinically overt bleeding accompanied by one or more of the following: A decrease in Hgb of 2 g/dL or more over 24 hours; A transfusion of 2 or more units of packed RBCs; Bleeding that occurs in at least one of the following critical sites: intracranial, intraspinal, intraocular (within the corpus of the eye), pericardial, intra-articular, intramuscular with compartment syndrome, retroperitoneal; Bleeding that was fatal. CRNM: acute clinically overt bleeding that did not satisfy additional criteria required for the bleeding event to be defined as a major bleeding event and meets at least one of the following: Hospital admission for bleeding; Physician guided medical or surgical treatment for bleeding; Change in anti-thrombotic treatment (anticoagulant or antiplatelet) therapy. Bleeding events were adjudicated by the Adjudication Committee. Treatment Period=events with onset from first dose to last dose plus 2 days.
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
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least one dose of blinded study drug and signed informed consent were analyzed.
Arm/Group Title Placebo Apixaban 5 mg BID
Hide Arm/Group Description:
Placebo: Tablets, Oral, 0 mg, twice daily.
Apixaban: Tablets, Oral, 5 mg, twice daily. Study was terminated at Year 2.
Overall Number of Participants Analyzed 3643 3672
Measure Type: Number
Unit of Measure: percentage of participants/100-pt years
2.29 6.15
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Apixaban 5 mg BID
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Cox Proportional Hazard model
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 2.64
Confidence Interval (2-Sided) 95%
1.87 to 3.72
Estimation Comments [Not Specified]
12.Secondary Outcome
Title Event Rate of All Bleeding Reported by the Investigator During the Treatment Period - Treated Participants
Hide Description Bleeding events were adjudicated by the Adjudication Committee and classified according to Thrombolysis in Myocardial Infarction (TIMI) major, minor, minimal, and International Society on Thrombosis and Hemostasis (ISTH) major and clinically relevant non-major bleeding (CRNM) criteria. The adjudicated results based on TIMI and ISTH classifications, and programmatically identified events (not adjudicated) according to Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) classification were used in the analyses of bleeding endpoints. GUSTO Bleed Criteria included Severe or life-threatening: Intracranial hemorrhage, or bleeding that causes hemodynamic compromise requiring intervention; Moderate: Bleeding that requires a blood transfusion, but does not result in hemodynamic compromise; Mild: Bleeding that does not meet criteria for either severe or moderate bleeding. Treatment Period=events with onset from first dose to last dose plus 2 days.
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
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least one dose of blinded study drug and signed informed consent were analyzed.
Arm/Group Title Placebo Apixaban 5 mg BID
Hide Arm/Group Description:
Placebo: Tablets, Oral, 0 mg, twice daily.
Apixaban: Tablets, Oral, 5 mg, twice daily. Study was terminated at Year 2.
Overall Number of Participants Analyzed 3643 3672
Measure Type: Number
Unit of Measure: percentage of participants/100-pt years
16.33 39.98
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Apixaban 5 mg BID
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Cox Proportional Hazard model
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 2.36
Confidence Interval (2-Sided) 95%
2.06 to 2.70
Estimation Comments [Not Specified]
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Apixaban 5 mg BID Placebo BID
Hide Arm/Group Description 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. 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.
All-Cause Mortality
Apixaban 5 mg BID Placebo BID
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Apixaban 5 mg BID Placebo BID
Affected / at Risk (%) Affected / at Risk (%)
Total   894/3672 (24.35%)   884/3643 (24.27%) 
Blood and lymphatic system disorders     
Iron deficiency anaemia  1  0/3672 (0.00%)  2/3643 (0.05%) 
Thrombocytopenia  1  1/3672 (0.03%)  1/3643 (0.03%) 
Eosinophilia  1  1/3672 (0.03%)  0/3643 (0.00%) 
Leukocytosis  1  0/3672 (0.00%)  1/3643 (0.03%) 
Haemorrhagic anaemia  1  0/3672 (0.00%)  1/3643 (0.03%) 
Anaemia  1  16/3672 (0.44%)  8/3643 (0.22%) 
Nephrogenic anaemia  1  0/3672 (0.00%)  2/3643 (0.05%) 
Lymphadenopathy  1  1/3672 (0.03%)  0/3643 (0.00%) 
Cardiac disorders     
Arteriospasm coronary  1  1/3672 (0.03%)  0/3643 (0.00%) 
Atrial flutter  1  2/3672 (0.05%)  2/3643 (0.05%) 
Cardiac failure acute  1  6/3672 (0.16%)  3/3643 (0.08%) 
Cardiac failure congestive  1  16/3672 (0.44%)  17/3643 (0.47%) 
Cardiomyopathy  1  2/3672 (0.05%)  1/3643 (0.03%) 
Interventricular septum rupture  1  1/3672 (0.03%)  0/3643 (0.00%) 
Supraventricular extrasystoles  1  1/3672 (0.03%)  0/3643 (0.00%) 
Angina pectoris  1  37/3672 (1.01%)  41/3643 (1.13%) 
Atrioventricular block  1  1/3672 (0.03%)  1/3643 (0.03%) 
Bundle branch block left  1  0/3672 (0.00%)  1/3643 (0.03%) 
Cardiac arrest  1  4/3672 (0.11%)  4/3643 (0.11%) 
Cardiac failure chronic  1  1/3672 (0.03%)  3/3643 (0.08%) 
Ventricular asystole  1  0/3672 (0.00%)  1/3643 (0.03%) 
Ventricular tachycardia  1  8/3672 (0.22%)  11/3643 (0.30%) 
Acute coronary syndrome  1  1/3672 (0.03%)  1/3643 (0.03%) 
Cardiopulmonary failure  1  1/3672 (0.03%)  0/3643 (0.00%) 
Coronary artery insufficiency  1  1/3672 (0.03%)  1/3643 (0.03%) 
Coronary artery occlusion  1  3/3672 (0.08%)  4/3643 (0.11%) 
Coronary artery stenosis  1  20/3672 (0.54%)  16/3643 (0.44%) 
Ischaemic cardiomyopathy  1  1/3672 (0.03%)  3/3643 (0.08%) 
Left ventricular failure  1  1/3672 (0.03%)  3/3643 (0.08%) 
Atrioventricular block second degree  1  0/3672 (0.00%)  1/3643 (0.03%) 
Cardiac failure  1  94/3672 (2.56%)  82/3643 (2.25%) 
Cardio-respiratory arrest  1  1/3672 (0.03%)  3/3643 (0.08%) 
Dressler's syndrome  1  1/3672 (0.03%)  0/3643 (0.00%) 
Myocardial ischaemia  1  1/3672 (0.03%)  4/3643 (0.11%) 
Sick sinus syndrome  1  0/3672 (0.00%)  3/3643 (0.08%) 
Sinus bradycardia  1  0/3672 (0.00%)  1/3643 (0.03%) 
Aortic valve incompetence  1  2/3672 (0.05%)  0/3643 (0.00%) 
Arrhythmia  1  4/3672 (0.11%)  1/3643 (0.03%) 
Atrioventricular block complete  1  0/3672 (0.00%)  5/3643 (0.14%) 
Cardiogenic shock  1  2/3672 (0.05%)  7/3643 (0.19%) 
Prinzmetal angina  1  1/3672 (0.03%)  0/3643 (0.00%) 
Tachycardia  1  0/3672 (0.00%)  1/3643 (0.03%) 
Ventricular fibrillation  1  8/3672 (0.22%)  5/3643 (0.14%) 
Acute left ventricular failure  1  1/3672 (0.03%)  1/3643 (0.03%) 
Atrial fibrillation  1  26/3672 (0.71%)  29/3643 (0.80%) 
Cardiac disorder  1  1/3672 (0.03%)  0/3643 (0.00%) 
Cardiac perforation  1  0/3672 (0.00%)  1/3643 (0.03%) 
Cardiac tamponade  1  1/3672 (0.03%)  0/3643 (0.00%) 
Congestive cardiomyopathy  1  1/3672 (0.03%)  0/3643 (0.00%) 
Mitral valve incompetence  1  0/3672 (0.00%)  1/3643 (0.03%) 
Myocardial infarction  1  150/3672 (4.08%)  158/3643 (4.34%) 
Parasystole  1  1/3672 (0.03%)  0/3643 (0.00%) 
Pericarditis  1  0/3672 (0.00%)  1/3643 (0.03%) 
Sinus tachycardia  1  1/3672 (0.03%)  0/3643 (0.00%) 
Ventricle rupture  1  1/3672 (0.03%)  0/3643 (0.00%) 
Angina unstable  1  157/3672 (4.28%)  157/3643 (4.31%) 
Coronary artery dissection  1  0/3672 (0.00%)  1/3643 (0.03%) 
Pericardial effusion  1  4/3672 (0.11%)  0/3643 (0.00%) 
Pericardial haemorrhage  1  3/3672 (0.08%)  4/3643 (0.11%) 
Ventricular arrhythmia  1  2/3672 (0.05%)  1/3643 (0.03%) 
Arteriosclerosis coronary artery  1  6/3672 (0.16%)  3/3643 (0.08%) 
Bradycardia  1  9/3672 (0.25%)  3/3643 (0.08%) 
Cardiovascular insufficiency  1  0/3672 (0.00%)  1/3643 (0.03%) 
Coronary artery disease  1  22/3672 (0.60%)  18/3643 (0.49%) 
Intracardiac thrombus  1  0/3672 (0.00%)  2/3643 (0.05%) 
Left ventricular dysfunction  1  2/3672 (0.05%)  1/3643 (0.03%) 
Myocardial rupture  1  1/3672 (0.03%)  1/3643 (0.03%) 
Sinus arrhythmia  1  0/3672 (0.00%)  1/3643 (0.03%) 
Ventricular extrasystoles  1  1/3672 (0.03%)  0/3643 (0.00%) 
Ear and labyrinth disorders     
Vertigo  1  2/3672 (0.05%)  4/3643 (0.11%) 
Vertigo positional  1  1/3672 (0.03%)  0/3643 (0.00%) 
Endocrine disorders     
Hyperthyroidism  1  2/3672 (0.05%)  0/3643 (0.00%) 
Eye disorders     
Cataract  1  1/3672 (0.03%)  4/3643 (0.11%) 
Eye haemorrhage  1  2/3672 (0.05%)  0/3643 (0.00%) 
Maculopathy  1  0/3672 (0.00%)  1/3643 (0.03%) 
Retinal detachment  1  1/3672 (0.03%)  1/3643 (0.03%) 
Gastrointestinal disorders     
Oesophageal ulcer  1  0/3672 (0.00%)  1/3643 (0.03%) 
Oesophagitis  1  1/3672 (0.03%)  0/3643 (0.00%) 
Thrombosis mesenteric vessel  1  0/3672 (0.00%)  1/3643 (0.03%) 
Duodenal ulcer  1  2/3672 (0.05%)  0/3643 (0.00%) 
Impaired gastric emptying  1  1/3672 (0.03%)  0/3643 (0.00%) 
Irritable bowel syndrome  1  0/3672 (0.00%)  1/3643 (0.03%) 
Pancreatitis acute  1  1/3672 (0.03%)  1/3643 (0.03%) 
Pancreatitis chronic  1  1/3672 (0.03%)  1/3643 (0.03%) 
Periproctitis  1  1/3672 (0.03%)  0/3643 (0.00%) 
Subileus  1  0/3672 (0.00%)  1/3643 (0.03%) 
Gastroduodenitis  1  0/3672 (0.00%)  1/3643 (0.03%) 
Gastrointestinal haemorrhage  1  69/3672 (1.88%)  23/3643 (0.63%) 
Ischaemic gastritis  1  0/3672 (0.00%)  1/3643 (0.03%) 
Pharyngoesophageal diverticulum  1  1/3672 (0.03%)  0/3643 (0.00%) 
Ascites  1  0/3672 (0.00%)  1/3643 (0.03%) 
Diabetic gastroparesis  1  1/3672 (0.03%)  0/3643 (0.00%) 
Duodenitis  1  1/3672 (0.03%)  0/3643 (0.00%) 
Gastric ulcer  1  4/3672 (0.11%)  2/3643 (0.05%) 
Gastritis erosive  1  1/3672 (0.03%)  1/3643 (0.03%) 
Gastroduodenal ulcer  1  0/3672 (0.00%)  1/3643 (0.03%) 
Haematochezia  1  1/3672 (0.03%)  2/3643 (0.05%) 
Haemorrhoids  1  1/3672 (0.03%)  0/3643 (0.00%) 
Mouth haemorrhage  1  3/3672 (0.08%)  0/3643 (0.00%) 
Pancreatitis  1  2/3672 (0.05%)  1/3643 (0.03%) 
Retroperitoneal haemorrhage  1  2/3672 (0.05%)  2/3643 (0.05%) 
Abdominal pain  1  5/3672 (0.14%)  2/3643 (0.05%) 
Colonic polyp  1  1/3672 (0.03%)  0/3643 (0.00%) 
Faeces discoloured  1  0/3672 (0.00%)  1/3643 (0.03%) 
Gastritis  1  12/3672 (0.33%)  6/3643 (0.16%) 
Haematemesis  1  5/3672 (0.14%)  4/3643 (0.11%) 
Intestinal haemorrhage  1  0/3672 (0.00%)  1/3643 (0.03%) 
Nausea  1  0/3672 (0.00%)  2/3643 (0.05%) 
Rectal fissure  1  1/3672 (0.03%)  0/3643 (0.00%) 
Diverticulum  1  2/3672 (0.05%)  1/3643 (0.03%) 
Gastric polyps  1  0/3672 (0.00%)  1/3643 (0.03%) 
Intestinal obstruction  1  1/3672 (0.03%)  1/3643 (0.03%) 
Abdominal hernia  1  1/3672 (0.03%)  1/3643 (0.03%) 
Constipation  1  1/3672 (0.03%)  1/3643 (0.03%) 
Diarrhoea  1  1/3672 (0.03%)  1/3643 (0.03%) 
Dysphagia  1  0/3672 (0.00%)  1/3643 (0.03%) 
Gastrooesophageal reflux disease  1  2/3672 (0.05%)  1/3643 (0.03%) 
Mechanical ileus  1  0/3672 (0.00%)  1/3643 (0.03%) 
Melaena  1  4/3672 (0.11%)  1/3643 (0.03%) 
Periodontitis  1  1/3672 (0.03%)  0/3643 (0.00%) 
Vomiting  1  0/3672 (0.00%)  2/3643 (0.05%) 
Abdominal pain upper  1  2/3672 (0.05%)  0/3643 (0.00%) 
Colitis  1  1/3672 (0.03%)  0/3643 (0.00%) 
Duodenal ulcer perforation  1  0/3672 (0.00%)  1/3643 (0.03%) 
Gastric varices haemorrhage  1  1/3672 (0.03%)  0/3643 (0.00%) 
Ileus  1  2/3672 (0.05%)  0/3643 (0.00%) 
Inguinal hernia  1  1/3672 (0.03%)  0/3643 (0.00%) 
Intestinal ischaemia  1  2/3672 (0.05%)  0/3643 (0.00%) 
Reflux oesophagitis  1  0/3672 (0.00%)  1/3643 (0.03%) 
General disorders     
General physical health deterioration  1  0/3672 (0.00%)  1/3643 (0.03%) 
Influenza like illness  1  0/3672 (0.00%)  1/3643 (0.03%) 
Sudden death  1  19/3672 (0.52%)  13/3643 (0.36%) 
Cardiac death  1  1/3672 (0.03%)  1/3643 (0.03%) 
Discomfort  1  1/3672 (0.03%)  0/3643 (0.00%) 
Generalised oedema  1  0/3672 (0.00%)  1/3643 (0.03%) 
Oedema peripheral  1  1/3672 (0.03%)  0/3643 (0.00%) 
Drug withdrawal syndrome  1  1/3672 (0.03%)  1/3643 (0.03%) 
Ischaemic ulcer  1  1/3672 (0.03%)  0/3643 (0.00%) 
Non-cardiac chest pain  1  38/3672 (1.03%)  46/3643 (1.26%) 
Fatigue  1  0/3672 (0.00%)  1/3643 (0.03%) 
Vessel puncture site haemorrhage  1  0/3672 (0.00%)  1/3643 (0.03%) 
Asthenia  1  0/3672 (0.00%)  6/3643 (0.16%) 
Death  1  11/3672 (0.30%)  8/3643 (0.22%) 
Device dislocation  1  1/3672 (0.03%)  3/3643 (0.08%) 
Chest pain  1  11/3672 (0.30%)  7/3643 (0.19%) 
Pain  1  1/3672 (0.03%)  0/3643 (0.00%) 
Pyrexia  1  3/3672 (0.08%)  1/3643 (0.03%) 
Sudden cardiac death  1  10/3672 (0.27%)  11/3643 (0.30%) 
Multi-organ failure  1  4/3672 (0.11%)  1/3643 (0.03%) 
Hepatobiliary disorders     
Hepatic steatosis  1  1/3672 (0.03%)  0/3643 (0.00%) 
Cholangitis acute  1  1/3672 (0.03%)  0/3643 (0.00%) 
Cholecystitis acute  1  5/3672 (0.14%)  1/3643 (0.03%) 
Cholelithiasis  1  3/3672 (0.08%)  3/3643 (0.08%) 
Bile duct stone  1  1/3672 (0.03%)  1/3643 (0.03%) 
Biliary colic  1  0/3672 (0.00%)  1/3643 (0.03%) 
Hepatic failure  1  0/3672 (0.00%)  1/3643 (0.03%) 
Hepatic function abnormal  1  1/3672 (0.03%)  0/3643 (0.00%) 
Hepatitis acute  1  0/3672 (0.00%)  1/3643 (0.03%) 
Cholecystitis  1  6/3672 (0.16%)  3/3643 (0.08%) 
Cholestasis  1  0/3672 (0.00%)  1/3643 (0.03%) 
Immune system disorders     
Sarcoidosis  1  2/3672 (0.05%)  0/3643 (0.00%) 
Anaphylactic shock  1  1/3672 (0.03%)  0/3643 (0.00%) 
Contrast media allergy  1  1/3672 (0.03%)  0/3643 (0.00%) 
Drug hypersensitivity  1  0/3672 (0.00%)  1/3643 (0.03%) 
Infections and infestations     
Bacterial tracheitis  1  1/3672 (0.03%)  0/3643 (0.00%) 
Erysipelas  1  0/3672 (0.00%)  1/3643 (0.03%) 
Gastroenteritis viral  1  1/3672 (0.03%)  1/3643 (0.03%) 
Mediastinitis  1  2/3672 (0.05%)  0/3643 (0.00%) 
Pneumonia  1  35/3672 (0.95%)  35/3643 (0.96%) 
Pneumonia bacterial  1  0/3672 (0.00%)  1/3643 (0.03%) 
Post procedural infection  1  0/3672 (0.00%)  1/3643 (0.03%) 
Upper respiratory tract infection  1  1/3672 (0.03%)  1/3643 (0.03%) 
Viral infection  1  0/3672 (0.00%)  1/3643 (0.03%) 
Arthritis infective  1  1/3672 (0.03%)  0/3643 (0.00%) 
Cellulitis  1  4/3672 (0.11%)  6/3643 (0.16%) 
Gangrene  1  1/3672 (0.03%)  4/3643 (0.11%) 
Herpes zoster  1  0/3672 (0.00%)  1/3643 (0.03%) 
Postoperative wound infection  1  2/3672 (0.05%)  5/3643 (0.14%) 
Respiratory tract infection  1  1/3672 (0.03%)  0/3643 (0.00%) 
Urinary tract infection  1  8/3672 (0.22%)  9/3643 (0.25%) 
Bacteraemia  1  1/3672 (0.03%)  1/3643 (0.03%) 
Cholecystitis infective  1  1/3672 (0.03%)  0/3643 (0.00%) 
Diverticulitis  1  0/3672 (0.00%)  1/3643 (0.03%) 
Respiratory tract infection viral  1  1/3672 (0.03%)  0/3643 (0.00%) 
Sepsis  1  5/3672 (0.14%)  7/3643 (0.19%) 
Staphylococcal infection  1  1/3672 (0.03%)  0/3643 (0.00%) 
Chronic sinusitis  1  0/3672 (0.00%)  1/3643 (0.03%) 
Endocarditis  1  1/3672 (0.03%)  2/3643 (0.05%) 
Infective exacerbation of chronic obstructive airways disease  1  1/3672 (0.03%)  0/3643 (0.00%) 
Intervertebral discitis  1  0/3672 (0.00%)  1/3643 (0.03%) 
Osteomyelitis  1  1/3672 (0.03%)  0/3643 (0.00%) 
Appendicitis  1  4/3672 (0.11%)  0/3643 (0.00%) 
Epiglottitis  1  0/3672 (0.00%)  1/3643 (0.03%) 
Lower respiratory tract infection  1  1/3672 (0.03%)  0/3643 (0.00%) 
Pulmonary tuberculosis  1  0/3672 (0.00%)  1/3643 (0.03%) 
Septic shock  1  4/3672 (0.11%)  2/3643 (0.05%) 
Wound infection  1  1/3672 (0.03%)  0/3643 (0.00%) 
Abscess limb  1  1/3672 (0.03%)  0/3643 (0.00%) 
Device related sepsis  1  0/3672 (0.00%)  1/3643 (0.03%) 
Encephalitis herpes  1  1/3672 (0.03%)  0/3643 (0.00%) 
Gastroenteritis  1  3/3672 (0.08%)  5/3643 (0.14%) 
Gastrointestinal infection  1  2/3672 (0.05%)  0/3643 (0.00%) 
Injection site infection  1  0/3672 (0.00%)  1/3643 (0.03%) 
Laryngitis  1  0/3672 (0.00%)  2/3643 (0.05%) 
Skin infection  1  0/3672 (0.00%)  1/3643 (0.03%) 
Bronchitis  1  6/3672 (0.16%)  1/3643 (0.03%) 
Bronchopneumonia  1  0/3672 (0.00%)  2/3643 (0.05%) 
Gallbladder empyema  1  1/3672 (0.03%)  0/3643 (0.00%) 
Lobar pneumonia  1  1/3672 (0.03%)  0/3643 (0.00%) 
Localised infection  1  0/3672 (0.00%)  3/3643 (0.08%) 
Necrotising fasciitis  1  0/3672 (0.00%)  1/3643 (0.03%) 
Pyelonephritis  1  2/3672 (0.05%)  1/3643 (0.03%) 
Rectal abscess  1  0/3672 (0.00%)  1/3643 (0.03%) 
Soft tissue infection  1  0/3672 (0.00%)  1/3643 (0.03%) 
Staphylococcal bacteraemia  1  2/3672 (0.05%)  0/3643 (0.00%) 
Tracheobronchitis  1  1/3672 (0.03%)  1/3643 (0.03%) 
Urosepsis  1  3/3672 (0.08%)  0/3643 (0.00%) 
Bacterial sepsis  1  1/3672 (0.03%)  0/3643 (0.00%) 
Fungal skin infection  1  1/3672 (0.03%)  0/3643 (0.00%) 
Infected bites  1  0/3672 (0.00%)  1/3643 (0.03%) 
Sinusitis  1  0/3672 (0.00%)  1/3643 (0.03%) 
Subcutaneous abscess  1  1/3672 (0.03%)  0/3643 (0.00%) 
Injury, poisoning and procedural complications     
Fall  1  5/3672 (0.14%)  4/3643 (0.11%) 
Hip fracture  1  3/3672 (0.08%)  3/3643 (0.08%) 
Incision site haemorrhage  1  1/3672 (0.03%)  0/3643 (0.00%) 
Joint dislocation  1  1/3672 (0.03%)  0/3643 (0.00%) 
Lumbar vertebral fracture  1  0/3672 (0.00%)  1/3643 (0.03%) 
Overdose  1  2/3672 (0.05%)  0/3643 (0.00%) 
Road traffic accident  1  0/3672 (0.00%)  1/3643 (0.03%) 
Skull fractured base  1  1/3672 (0.03%)  0/3643 (0.00%) 
Clavicle fracture  1  0/3672 (0.00%)  1/3643 (0.03%) 
Procedural pain  1  1/3672 (0.03%)  0/3643 (0.00%) 
Pubis fracture  1  1/3672 (0.03%)  0/3643 (0.00%) 
Skin injury  1  1/3672 (0.03%)  0/3643 (0.00%) 
Subdural haematoma  1  3/3672 (0.08%)  2/3643 (0.05%) 
Tibia fracture  1  1/3672 (0.03%)  0/3643 (0.00%) 
Ankle fracture  1  3/3672 (0.08%)  0/3643 (0.00%) 
Postoperative thoracic procedure complication  1  1/3672 (0.03%)  0/3643 (0.00%) 
Silicosis  1  0/3672 (0.00%)  1/3643 (0.03%) 
Therapeutic agent toxicity  1  1/3672 (0.03%)  1/3643 (0.03%) 
Incisional hernia, obstructive  1  2/3672 (0.05%)  0/3643 (0.00%) 
Rib fracture  1  0/3672 (0.00%)  4/3643 (0.11%) 
Animal bite  1  1/3672 (0.03%)  0/3643 (0.00%) 
Coronary artery restenosis  1  2/3672 (0.05%)  1/3643 (0.03%) 
Extradural haematoma  1  0/3672 (0.00%)  1/3643 (0.03%) 
Fat embolism  1  1/3672 (0.03%)  0/3643 (0.00%) 
Multiple fractures  1  0/3672 (0.00%)  1/3643 (0.03%) 
Post procedural haemorrhage  1  2/3672 (0.05%)  0/3643 (0.00%) 
Wound secretion  1  0/3672 (0.00%)  1/3643 (0.03%) 
Brain contusion  1  0/3672 (0.00%)  1/3643 (0.03%) 
Femoral neck fracture  1  0/3672 (0.00%)  2/3643 (0.05%) 
Femur fracture  1  2/3672 (0.05%)  2/3643 (0.05%) 
Foot fracture  1  1/3672 (0.03%)  0/3643 (0.00%) 
Head injury  1  0/3672 (0.00%)  2/3643 (0.05%) 
Incisional hernia  1  0/3672 (0.00%)  1/3643 (0.03%) 
Joint injury  1  1/3672 (0.03%)  0/3643 (0.00%) 
Soft tissue injury  1  0/3672 (0.00%)  1/3643 (0.03%) 
Accidental overdose  1  5/3672 (0.14%)  2/3643 (0.05%) 
Chest injury  1  1/3672 (0.03%)  0/3643 (0.00%) 
Contusion  1  6/3672 (0.16%)  3/3643 (0.08%) 
Drug toxicity  1  0/3672 (0.00%)  2/3643 (0.05%) 
Facial bones fracture  1  0/3672 (0.00%)  1/3643 (0.03%) 
Operative haemorrhage  1  1/3672 (0.03%)  1/3643 (0.03%) 
Radius fracture  1  0/3672 (0.00%)  1/3643 (0.03%) 
Vascular pseudoaneurysm  1  3/3672 (0.08%)  1/3643 (0.03%) 
Wound  1  1/3672 (0.03%)  1/3643 (0.03%) 
Arterial injury  1  1/3672 (0.03%)  0/3643 (0.00%) 
In-stent coronary artery restenosis  1  7/3672 (0.19%)  7/3643 (0.19%) 
Patella fracture  1  1/3672 (0.03%)  0/3643 (0.00%) 
Investigations     
Electrocardiogram QRS complex prolonged  1  1/3672 (0.03%)  0/3643 (0.00%) 
Hepatic enzyme increased  1  2/3672 (0.05%)  2/3643 (0.05%) 
Aspartate aminotransferase increased  1  0/3672 (0.00%)  2/3643 (0.05%) 
Weight decreased  1  0/3672 (0.00%)  1/3643 (0.03%) 
Clostridium test positive  1  0/3672 (0.00%)  1/3643 (0.03%) 
Haemoglobin decreased  1  4/3672 (0.11%)  0/3643 (0.00%) 
Occult blood positive  1  2/3672 (0.05%)  0/3643 (0.00%) 
Alanine aminotransferase increased  1  0/3672 (0.00%)  2/3643 (0.05%) 
Haematocrit decreased  1  1/3672 (0.03%)  0/3643 (0.00%) 
Liver function test abnormal  1  1/3672 (0.03%)  1/3643 (0.03%) 
Blood creatinine increased  1  0/3672 (0.00%)  1/3643 (0.03%) 
Drug screen positive  1  1/3672 (0.03%)  0/3643 (0.00%) 
Electrocardiogram QT prolonged  1  1/3672 (0.03%)  0/3643 (0.00%) 
Metabolism and nutrition disorders     
Diabetes mellitus  1  1/3672 (0.03%)  5/3643 (0.14%) 
Gout  1  0/3672 (0.00%)  1/3643 (0.03%) 
Metabolic acidosis  1  1/3672 (0.03%)  1/3643 (0.03%) 
Vitamin B12 deficiency  1  1/3672 (0.03%)  1/3643 (0.03%) 
Hyperglycaemia  1  3/3672 (0.08%)  3/3643 (0.08%) 
Failure to thrive  1  1/3672 (0.03%)  0/3643 (0.00%) 
Hypoglycaemia  1  5/3672 (0.14%)  8/3643 (0.22%) 
Hyperkalaemia  1  2/3672 (0.05%)  4/3643 (0.11%) 
Decreased appetite  1  1/3672 (0.03%)  0/3643 (0.00%) 
Diabetic foot  1  2/3672 (0.05%)  0/3643 (0.00%) 
Hypervolaemia  1  1/3672 (0.03%)  0/3643 (0.00%) 
Hypokalaemia  1  3/3672 (0.08%)  0/3643 (0.00%) 
Diabetic ketoacidosis  1  4/3672 (0.11%)  2/3643 (0.05%) 
Electrolyte imbalance  1  0/3672 (0.00%)  1/3643 (0.03%) 
Hyperglycaemic hyperosmolar nonketotic syndrome  1  0/3672 (0.00%)  1/3643 (0.03%) 
Hyponatraemia  1  2/3672 (0.05%)  3/3643 (0.08%) 
Iron deficiency  1  1/3672 (0.03%)  0/3643 (0.00%) 
Fluid retention  1  1/3672 (0.03%)  0/3643 (0.00%) 
Acidosis  1  0/3672 (0.00%)  1/3643 (0.03%) 
Dehydration  1  4/3672 (0.11%)  4/3643 (0.11%) 
Diabetes mellitus inadequate control  1  1/3672 (0.03%)  2/3643 (0.05%) 
Musculoskeletal and connective tissue disorders     
Intervertebral disc protrusion  1  1/3672 (0.03%)  0/3643 (0.00%) 
Rhabdomyolysis  1  1/3672 (0.03%)  1/3643 (0.03%) 
Arthralgia  1  1/3672 (0.03%)  0/3643 (0.00%) 
Arthritis  1  0/3672 (0.00%)  2/3643 (0.05%) 
Costochondritis  1  1/3672 (0.03%)  0/3643 (0.00%) 
Muscle haemorrhage  1  3/3672 (0.08%)  0/3643 (0.00%) 
Rotator cuff syndrome  1  1/3672 (0.03%)  1/3643 (0.03%) 
Connective tissue disorder  1  1/3672 (0.03%)  0/3643 (0.00%) 
Haemarthrosis  1  2/3672 (0.05%)  0/3643 (0.00%) 
Musculoskeletal chest pain  1  6/3672 (0.16%)  4/3643 (0.11%) 
Tenosynovitis  1  0/3672 (0.00%)  1/3643 (0.03%) 
Muscular weakness  1  1/3672 (0.03%)  0/3643 (0.00%) 
Neck pain  1  0/3672 (0.00%)  2/3643 (0.05%) 
Periarthritis  1  1/3672 (0.03%)  1/3643 (0.03%) 
Rheumatoid arthritis  1  1/3672 (0.03%)  0/3643 (0.00%) 
Arthropathy  1  1/3672 (0.03%)  0/3643 (0.00%) 
Back pain  1  2/3672 (0.05%)  7/3643 (0.19%) 
Bursitis  1  1/3672 (0.03%)  0/3643 (0.00%) 
Pain in extremity  1  3/3672 (0.08%)  0/3643 (0.00%) 
Spinal osteoarthritis  1  1/3672 (0.03%)  0/3643 (0.00%) 
Lumbar spinal stenosis  1  0/3672 (0.00%)  1/3643 (0.03%) 
Musculoskeletal pain  1  1/3672 (0.03%)  4/3643 (0.11%) 
Osteoarthritis  1  0/3672 (0.00%)  3/3643 (0.08%) 
Spinal column stenosis  1  1/3672 (0.03%)  0/3643 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Basal cell carcinoma  1  1/3672 (0.03%)  2/3643 (0.05%) 
Bile duct cancer  1  1/3672 (0.03%)  0/3643 (0.00%) 
Breast cancer  1  1/3672 (0.03%)  0/3643 (0.00%) 
Gastric cancer  1  5/3672 (0.14%)  2/3643 (0.05%) 
Ovarian cancer  1  1/3672 (0.03%)  0/3643 (0.00%) 
Rectal cancer  1  1/3672 (0.03%)  1/3643 (0.03%) 
Thyroid neoplasm  1  0/3672 (0.00%)  1/3643 (0.03%) 
Bladder neoplasm  1  1/3672 (0.03%)  0/3643 (0.00%) 
Neoplasm  1  1/3672 (0.03%)  0/3643 (0.00%) 
Neoplasm prostate  1  1/3672 (0.03%)  0/3643 (0.00%) 
Non-small cell lung cancer stage IV  1  1/3672 (0.03%)  0/3643 (0.00%) 
Tumour haemorrhage  1  1/3672 (0.03%)  0/3643 (0.00%) 
Anal cancer stage IV  1  0/3672 (0.00%)  1/3643 (0.03%) 
Pituitary tumour benign  1  1/3672 (0.03%)  0/3643 (0.00%) 
Gastrointestinal carcinoma  1  1/3672 (0.03%)  0/3643 (0.00%) 
Metastases to liver  1  1/3672 (0.03%)  0/3643 (0.00%) 
Oesophageal adenocarcinoma  1  1/3672 (0.03%)  0/3643 (0.00%) 
Pancreatic carcinoma  1  1/3672 (0.03%)  0/3643 (0.00%) 
Prostate cancer  1  1/3672 (0.03%)  2/3643 (0.05%) 
Lip neoplasm malignant stage unspecified  1  0/3672 (0.00%)  1/3643 (0.03%) 
Small cell lung cancer stage unspecified  1  1/3672 (0.03%)  0/3643 (0.00%) 
Glioblastoma  1  1/3672 (0.03%)  1/3643 (0.03%) 
Renal cell carcinoma  1  1/3672 (0.03%)  0/3643 (0.00%) 
Testis cancer recurrent  1  1/3672 (0.03%)  0/3643 (0.00%) 
Bladder cancer  1  2/3672 (0.05%)  0/3643 (0.00%) 
Bowen's disease  1  0/3672 (0.00%)  1/3643 (0.03%) 
Endometrial cancer  1  1/3672 (0.03%)  0/3643 (0.00%) 
Non-small cell lung cancer stage I  1  0/3672 (0.00%)  1/3643 (0.03%) 
Adenocarcinoma pancreas  1  0/3672 (0.00%)  1/3643 (0.03%) 
Bladder cancer stage II  1  1/3672 (0.03%)  0/3643 (0.00%) 
Colon cancer  1  3/3672 (0.08%)  4/3643 (0.11%) 
Lung neoplasm malignant  1  5/3672 (0.14%)  1/3643 (0.03%) 
Lymphoma  1  0/3672 (0.00%)  1/3643 (0.03%) 
Neoplasm malignant  1  0/3672 (0.00%)  1/3643 (0.03%) 
Pancreatic carcinoma metastatic  1  2/3672 (0.05%)  0/3643 (0.00%) 
Spinal meningioma benign  1  0/3672 (0.00%)  1/3643 (0.03%) 
Squamous cell carcinoma of skin  1  1/3672 (0.03%)  1/3643 (0.03%) 
Nervous system disorders     
Cerebrovascular accident  1  20/3672 (0.54%)  39/3643 (1.07%) 
Post herpetic neuralgia  1  0/3672 (0.00%)  1/3643 (0.03%) 
Transient ischaemic attack  1  5/3672 (0.14%)  6/3643 (0.16%) 
Carotid artery disease  1  1/3672 (0.03%)  0/3643 (0.00%) 
Epilepsy  1  0/3672 (0.00%)  1/3643 (0.03%) 
Headache  1  2/3672 (0.05%)  0/3643 (0.00%) 
Hemiparesis  1  1/3672 (0.03%)  0/3643 (0.00%) 
Metabolic encephalopathy  1  2/3672 (0.05%)  0/3643 (0.00%) 
Polyneuropathy  1  1/3672 (0.03%)  0/3643 (0.00%) 
Tremor  1  1/3672 (0.03%)  1/3643 (0.03%) 
Basilar migraine  1  0/3672 (0.00%)  1/3643 (0.03%) 
Spinal cord haemorrhage  1  1/3672 (0.03%)  0/3643 (0.00%) 
Encephalopathy  1  2/3672 (0.05%)  0/3643 (0.00%) 
Guillain-Barre syndrome  1  0/3672 (0.00%)  1/3643 (0.03%) 
Spinal cord ischaemia  1  0/3672 (0.00%)  1/3643 (0.03%) 
VIIth nerve paralysis  1  2/3672 (0.05%)  0/3643 (0.00%) 
Carotid artery stenosis  1  5/3672 (0.14%)  2/3643 (0.05%) 
Dizziness  1  4/3672 (0.11%)  6/3643 (0.16%) 
Presyncope  1  2/3672 (0.05%)  3/3643 (0.08%) 
Carotid artery occlusion  1  0/3672 (0.00%)  1/3643 (0.03%) 
Haemorrhage intracranial  1  8/3672 (0.22%)  1/3643 (0.03%) 
Syncope  1  13/3672 (0.35%)  14/3643 (0.38%) 
Altered state of consciousness  1  2/3672 (0.05%)  0/3643 (0.00%) 
Carotid arteriosclerosis  1  0/3672 (0.00%)  1/3643 (0.03%) 
Convulsion  1  2/3672 (0.05%)  0/3643 (0.00%) 
Dementia  1  1/3672 (0.03%)  0/3643 (0.00%) 
Diabetic neuropathy  1  0/3672 (0.00%)  1/3643 (0.03%) 
Intercostal neuralgia  1  1/3672 (0.03%)  0/3643 (0.00%) 
Intraventricular haemorrhage  1  5/3672 (0.14%)  0/3643 (0.00%) 
Mental retardation  1  0/3672 (0.00%)  1/3643 (0.03%) 
Paraplegia  1  1/3672 (0.03%)  0/3643 (0.00%) 
Sciatica  1  2/3672 (0.05%)  0/3643 (0.00%) 
Subarachnoid haemorrhage  1  2/3672 (0.05%)  2/3643 (0.05%) 
Psychiatric disorders     
Bipolar I disorder  1  1/3672 (0.03%)  0/3643 (0.00%) 
Anxiety  1  0/3672 (0.00%)  2/3643 (0.05%) 
Psychotic disorder  1  0/3672 (0.00%)  1/3643 (0.03%) 
Mental status changes  1  0/3672 (0.00%)  1/3643 (0.03%) 
Suicide attempt  1  1/3672 (0.03%)  0/3643 (0.00%) 
Major depression  1  0/3672 (0.00%)  1/3643 (0.03%) 
Alcohol withdrawal syndrome  1  0/3672 (0.00%)  1/3643 (0.03%) 
Confusional state  1  0/3672 (0.00%)  2/3643 (0.05%) 
Completed suicide  1  0/3672 (0.00%)  1/3643 (0.03%) 
Depression  1  0/3672 (0.00%)  4/3643 (0.11%) 
Panic disorder  1  1/3672 (0.03%)  0/3643 (0.00%) 
Renal and urinary disorders     
Renal failure acute  1  17/3672 (0.46%)  10/3643 (0.27%) 
Nephrolithiasis  1  2/3672 (0.05%)  1/3643 (0.03%) 
Bladder diverticulum  1  0/3672 (0.00%)  1/3643 (0.03%) 
Dysuria  1  2/3672 (0.05%)  0/3643 (0.00%) 
Renal injury  1  0/3672 (0.00%)  1/3643 (0.03%) 
Calculus bladder  1  1/3672 (0.03%)  0/3643 (0.00%) 
Renal failure  1  8/3672 (0.22%)  5/3643 (0.14%) 
Renal infarct  1  1/3672 (0.03%)  0/3643 (0.00%) 
Haematuria  1  13/3672 (0.35%)  5/3643 (0.14%) 
Acute prerenal failure  1  2/3672 (0.05%)  0/3643 (0.00%) 
Renal impairment  1  5/3672 (0.14%)  6/3643 (0.16%) 
Hydronephrosis  1  1/3672 (0.03%)  0/3643 (0.00%) 
Nephropathy  1  0/3672 (0.00%)  1/3643 (0.03%) 
Nephropathy toxic  1  3/3672 (0.08%)  0/3643 (0.00%) 
Renal colic  1  0/3672 (0.00%)  1/3643 (0.03%) 
Renal failure chronic  1  3/3672 (0.08%)  2/3643 (0.05%) 
Urethral stenosis  1  0/3672 (0.00%)  1/3643 (0.03%) 
Reproductive system and breast disorders     
Benign prostatic hyperplasia  1  0/3672 (0.00%)  1/3643 (0.03%) 
Vaginal haemorrhage  1  1/3672 (0.03%)  0/3643 (0.00%) 
Prostatomegaly  1  1/3672 (0.03%)  0/3643 (0.00%) 
Balanoposthitis  1  1/3672 (0.03%)  0/3643 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Acute respiratory failure  1  1/3672 (0.03%)  2/3643 (0.05%) 
Bronchitis chronic  1  0/3672 (0.00%)  1/3643 (0.03%) 
Pulmonary hypertension  1  0/3672 (0.00%)  1/3643 (0.03%) 
Acute pulmonary oedema  1  5/3672 (0.14%)  7/3643 (0.19%) 
Dyspnoea  1  4/3672 (0.11%)  4/3643 (0.11%) 
Hypercapnia  1  0/3672 (0.00%)  1/3643 (0.03%) 
Pulmonary embolism  1  3/3672 (0.08%)  6/3643 (0.16%) 
Dyspnoea exertional  1  0/3672 (0.00%)  1/3643 (0.03%) 
Haemothorax  1  3/3672 (0.08%)  0/3643 (0.00%) 
Respiratory distress  1  1/3672 (0.03%)  0/3643 (0.00%) 
Respiratory failure  1  2/3672 (0.05%)  3/3643 (0.08%) 
Lung disorder  1  0/3672 (0.00%)  1/3643 (0.03%) 
Pleural effusion  1  4/3672 (0.11%)  6/3643 (0.16%) 
Pneumomediastinum  1  0/3672 (0.00%)  1/3643 (0.03%) 
Asthma  1  1/3672 (0.03%)  2/3643 (0.05%) 
Bronchospasm  1  0/3672 (0.00%)  1/3643 (0.03%) 
Interstitial lung disease  1  0/3672 (0.00%)  1/3643 (0.03%) 
Laryngeal hypertrophy  1  0/3672 (0.00%)  1/3643 (0.03%) 
Pulmonary congestion  1  0/3672 (0.00%)  1/3643 (0.03%) 
Pulmonary oedema  1  9/3672 (0.25%)  3/3643 (0.08%) 
Chronic obstructive pulmonary disease  1  14/3672 (0.38%)  8/3643 (0.22%) 
Cough  1  0/3672 (0.00%)  1/3643 (0.03%) 
Haemoptysis  1  2/3672 (0.05%)  2/3643 (0.05%) 
Hypoxia  1  0/3672 (0.00%)  1/3643 (0.03%) 
Pulmonary artery thrombosis  1  1/3672 (0.03%)  0/3643 (0.00%) 
Bronchial disorder  1  0/3672 (0.00%)  1/3643 (0.03%) 
Epistaxis  1  5/3672 (0.14%)  5/3643 (0.14%) 
Pleuritic pain  1  1/3672 (0.03%)  0/3643 (0.00%) 
Skin and subcutaneous tissue disorders     
Actinic keratosis  1  0/3672 (0.00%)  1/3643 (0.03%) 
Rash papular  1  0/3672 (0.00%)  1/3643 (0.03%) 
Rash pruritic  1  1/3672 (0.03%)  0/3643 (0.00%) 
Toxic skin eruption  1  0/3672 (0.00%)  1/3643 (0.03%) 
Skin necrosis  1  0/3672 (0.00%)  1/3643 (0.03%) 
Urticaria  1  0/3672 (0.00%)  1/3643 (0.03%) 
Dermatitis  1  0/3672 (0.00%)  1/3643 (0.03%) 
Skin ulcer  1  2/3672 (0.05%)  0/3643 (0.00%) 
Dermatomyositis  1  0/3672 (0.00%)  1/3643 (0.03%) 
Vascular disorders     
Embolism arterial  1  0/3672 (0.00%)  2/3643 (0.05%) 
Extravasation blood  1  1/3672 (0.03%)  0/3643 (0.00%) 
Hypertension  1  16/3672 (0.44%)  13/3643 (0.36%) 
Peripheral ischaemia  1  3/3672 (0.08%)  1/3643 (0.03%) 
Vasospasm  1  1/3672 (0.03%)  0/3643 (0.00%) 
Aortic dissection  1  1/3672 (0.03%)  0/3643 (0.00%) 
Aortic stenosis  1  1/3672 (0.03%)  1/3643 (0.03%) 
Arteriosclerosis obliterans  1  0/3672 (0.00%)  1/3643 (0.03%) 
Jugular vein thrombosis  1  0/3672 (0.00%)  1/3643 (0.03%) 
Orthostatic hypotension  1  2/3672 (0.05%)  0/3643 (0.00%) 
Thrombosis  1  0/3672 (0.00%)  1/3643 (0.03%) 
Accelerated hypertension  1  0/3672 (0.00%)  2/3643 (0.05%) 
Hypertensive crisis  1  5/3672 (0.14%)  4/3643 (0.11%) 
Hypotension  1  5/3672 (0.14%)  3/3643 (0.08%) 
Leriche syndrome  1  0/3672 (0.00%)  1/3643 (0.03%) 
Thrombophlebitis  1  0/3672 (0.00%)  1/3643 (0.03%) 
Arterial thrombosis  1  1/3672 (0.03%)  0/3643 (0.00%) 
Arteriosclerosis  1  2/3672 (0.05%)  0/3643 (0.00%) 
Artery dissection  1  1/3672 (0.03%)  0/3643 (0.00%) 
Femoral arterial stenosis  1  0/3672 (0.00%)  1/3643 (0.03%) 
Peripheral vascular disorder  1  1/3672 (0.03%)  9/3643 (0.25%) 
Aortic aneurysm  1  0/3672 (0.00%)  1/3643 (0.03%) 
Arterial stenosis  1  1/3672 (0.03%)  0/3643 (0.00%) 
Femoral artery occlusion  1  2/3672 (0.05%)  0/3643 (0.00%) 
Intermittent claudication  1  1/3672 (0.03%)  3/3643 (0.08%) 
Peripheral embolism  1  0/3672 (0.00%)  2/3643 (0.05%) 
Ischaemia  1  1/3672 (0.03%)  0/3643 (0.00%) 
Peripheral artery aneurysm  1  1/3672 (0.03%)  0/3643 (0.00%) 
Deep vein thrombosis  1  3/3672 (0.08%)  1/3643 (0.03%) 
Femoral artery aneurysm  1  1/3672 (0.03%)  0/3643 (0.00%) 
Haematoma  1  14/3672 (0.38%)  5/3643 (0.14%) 
Haemorrhage  1  1/3672 (0.03%)  0/3643 (0.00%) 
Arterial thrombosis limb  1  1/3672 (0.03%)  1/3643 (0.03%) 
Circulatory collapse  1  0/3672 (0.00%)  1/3643 (0.03%) 
Hypertensive emergency  1  1/3672 (0.03%)  0/3643 (0.00%) 
Peripheral arterial occlusive disease  1  4/3672 (0.11%)  4/3643 (0.11%) 
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%
Apixaban 5 mg BID Placebo BID
Affected / at Risk (%) Affected / at Risk (%)
Total   357/3672 (9.72%)   231/3643 (6.34%) 
General disorders     
Chest pain  1  186/3672 (5.07%)  173/3643 (4.75%) 
Respiratory, thoracic and mediastinal disorders     
Epistaxis  1  186/3672 (5.07%)  63/3643 (1.73%) 
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.
Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Bristol-Myers Squibb Study Director
Organization: Bristol-Myers Squibb
EMail: Clinical.Trials@bms.com
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT00831441     History of Changes
Other Study ID Numbers: CV185-068
EUDRACT# 2008-008298-77
First Submitted: January 28, 2009
First Posted: January 29, 2009
Results First Submitted: December 18, 2015
Results First Posted: January 27, 2016
Last Update Posted: January 27, 2016