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Efficacy and Safety Study of Apixaban for Extended Treatment of Deep Vein Thrombosis or Pulmonary Embolism

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ClinicalTrials.gov Identifier: NCT00633893
Recruitment Status : Completed
First Posted : March 12, 2008
Results First Posted : October 25, 2013
Last Update Posted : November 25, 2013
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
Bristol-Myers Squibb

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Venous Thrombosis
Interventions Drug: Apixaban
Drug: Placebo
Enrollment 2711
Recruitment Details First participant, first visit: 16 May 2008; Last participant, last visit: 24 August 2012.
Pre-assignment Details 2711 enrolled/2482 randomized: 133 did not meet inclusion, exclusion criteria; 48 withdrew consent; 8 non-compliance; 3 each administrative and clinical reasons; 2 lost to follow up; 1 death; 1 adverse event (AE), 30 other. Data from 4 participants in site 0650 not analyzed/included in randomized population because source for data not confirmed.
Arm/Group Title Apixaban 2.5 mg Apixaban 5 mg Placebo
Hide Arm/Group Description Participants received 2.5 mg oral tablet apixaban twice a day (BID) Participants received 5 mg oral tablet apixaban BID. Participants received matching placebo oral tablet BID.
Period Title: Overall Study
Started 840 813 [1] 829 [2]
Completed 726 684 641
Not Completed 114 129 188
Reason Not Completed
Death             1             3             9
Adverse Event             65             58             126
Withdrawal by Subject             7             12             6
Lost to Follow-up             2             4             8
Poor/non-compliance             5             12             3
Pregnancy             2             1             1
Not meet/no longer meets criteria             4             6             4
not specified             28             33             31
[1]
2 participants were randomized to 5 mg study drug but not treated.
[2]
3 participants were randomized to placebo but not treated.
Arm/Group Title Apixaban 2.5 mg Apixaban 5 mg Placebo Total
Hide Arm/Group Description Participants received 2.5 mg oral tablet apixaban BID. Participants received 5 mg oral tablet apixaban BID. Participants received matching placebo oral tablet BID. Total of all reporting groups
Overall Number of Baseline Participants 840 813 829 2482
Hide Baseline Analysis Population Description
All randomized participants regardless of whether treatment was actually received were included; intent to treat (ITT) principle.
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 840 participants 813 participants 829 participants 2482 participants
56.6  (15.3) 56.4  (15.6) 57.1  (15.2) 56.7  (15.4)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 840 participants 813 participants 829 participants 2482 participants
Female
353
  42.0%
344
  42.3%
361
  43.5%
1058
  42.6%
Male
487
  58.0%
469
  57.7%
468
  56.5%
1424
  57.4%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 840 participants 813 participants 829 participants 2482 participants
Portugal 1 1 0 2
United States 88 75 96 259
Philippines 5 3 3 11
Hong Kong 4 3 4 11
Spain 27 25 26 78
Ukraine 87 77 88 252
Chile 2 1 2 5
Russian Federation 45 49 46 140
Israel 34 34 34 102
Italy 67 65 61 193
India 24 23 24 71
France 60 55 50 165
Australia 30 28 31 89
Denmark 47 58 42 147
South Africa 34 42 30 106
Korea, Republic of 4 3 2 9
Austria 12 8 11 31
United Kingdom 33 29 30 92
Czech Republic 43 49 48 140
Mexico 22 18 22 62
Canada 22 17 15 54
Argentina 7 9 6 22
Poland 45 44 48 137
Brazil 19 24 30 73
Singapore 1 2 3 6
Romania 6 7 7 20
Norway 9 9 10 28
Germany 62 55 60 177
Index Event Classification   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 840 participants 813 participants 829 participants 2482 participants
Proximal DVT 544 527 551 1622
PE 296 286 278 860
[1]
Measure Description: Number of participants with Proximal DVT (defined at the site) and number with PE (defined at the site). In the event a participant had both proximal DVT and PE, the participant was classified to PE.
1.Primary Outcome
Title Adjudicated Composite of Symptomatic, Recurrent Venous Thromboembolism (VTE) or All-Cause Death During the Intended Treatment Period - Randomized Population With Imputation
Hide Description VTE included: nonfatal deep vein thrombosis (DVT) or nonfatal pulmonary embolism (PE). All index events, DVT and/or PE were adjudicated/confirmed by a central independent adjudication committee blinded to treatment. DVT assessed by compression ultrasound and/or venography; PE assessed by spiral computed tomography scanning, pulmonary angiography, and/or ventilation/perfusion lung scan. Event rate (proportion of participants with event) calculated as n/N (n=number of events; N=number of participants). Intended treatment period: longer of the dosing period plus 2 days (completed treatment) or 355 days (discontinued early). Composite endpoint included events at any time from randomization until end of the intended treatment period, regardless whether drug treatment was received. For missing endpoint data, participants were imputed as having had a primary efficacy outcome event.
Time Frame Day 1 up to 12 Months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent to treat: all randomized participants with consent. Analyzed per randomized treatment assigned. (n) number of events=32, 34, 96 in apixaban 2.5 mg, 5 mg, and placebo arms, respectively; number of events imputed=13, 20, 19, respectively. Confidence interval (CI) for event rate was calculated based on the Wald asymptotic confidence limits.
Arm/Group Title Apixaban 2.5 mg Apixaban 5 mg Placebo
Hide Arm/Group Description:
Participants received 2.5 mg oral tablet apixaban BID.
Participants received 5 mg oral tablet apixaban BID.
Participants received matching placebo oral tablet BID.
Overall Number of Participants Analyzed 840 813 829
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Proportion of participants
0.0381
(0.0252 to 0.0510)
0.0418
(0.0281 to 0.0556)
0.1158
(0.0940 to 0.1376)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Apixaban 2.5 mg, Placebo
Comments Null hypothesis is relative risk proportion of apixaban participants with VTE/all cause mortality to proportion of placebo participants with VTE/all cause mortality equal to 1.0. Participants with missing data were assumed to have experienced VTE/all cause mortality. Events occurring anytime during the intended treatment period (12 months) were included regardless of whether the participant was on treatment or not or whether the participant ever took drug, ie, Intent to treat (ITT) principle.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Hochberg adjusted p-value for superiority based on 2 hypotheses tests for apixaban 2.5mg group comparing with placebo group and for apixaban 5mg group comparing with placebo group.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 0.3283
Confidence Interval (2-Sided) 95%
0.2225 to 0.4844
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Apixaban 5 mg, Placebo
Comments Null hypothesis is relative risk proportion of apixaban participants with VTE/all cause mortality to proportion of placebo participants with VTE/all cause mortality equal to 1.0. Participants with missing data were assumed to have experienced VTE/all cause mortality. Events occurring anytime during the intended treatment period (12 months) were included regardless of whether the participant was on treatment or not or whether the participant ever took drug, ie, Intent to treat principle.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Hochberg adjusted p-value for superiority based on 2 hypotheses tests for apixaban 2.5mg group comparing with placebo group and for apixaban 5mg group comparing with placebo group.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 0.3615
Confidence Interval (2-Sided) 95%
0.2475 to 0.5281
Estimation Comments [Not Specified]
2.Primary Outcome
Title Adjudicated Composite of Symptomatic, Recurrent Venous Thromboembolism (VTE) or All-Cause Death During the Intended Treatment Period - Randomized Population Without Imputation
Hide Description VTE included: nonfatal DVT or nonfatal PE. Event rate (proportion of participants with event) calculated as n/N (n=number of events; N=number of participants). Intended treatment period: longer of the dosing period plus 2 days (completed treatment) or 355 days (discontinued early). Composite endpoint included events at any time from randomization until end of the intended treatment period, regardless whether drug treatment was received. No imputation was done for these endpoints; participants who had an event during the intended treatment period were counted. Confidence interval (CI) for single event rate was calculated based on the Wald asymptotic confidence limits.
Time Frame Day 1 up to 12 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent to treat: all randomized participants with valid consent. Analyzed per randomized treatment assigned.(n)number of events = 19, 14, 77 in apixaban 2.5 mg, 5 mg, and placebo arms, respectively. All events were counted; no events were imputed.
Arm/Group Title Apixaban 2.5 mg Apixaban 5 mg Placebo
Hide Arm/Group Description:
Participants received 2.5 mg oral tablet apixaban BID.
Participants received 5 mg oral tablet apixaban BID.
Participants received matching placebo oral tablet BID.
Overall Number of Participants Analyzed 840 813 829
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Proportion of participants
0.0226
(0.0126 to 0.0327)
0.0172
(0.0083 to 0.0262)
0.0929
(0.0731 to 0.1126)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Apixaban 2.5 mg, Placebo
Comments Null hypothesis is relative risk proportion of apixaban participants with VTE/all cause mortality to proportion of placebo participants with VTE/all cause mortality equal to 1.0. Events occurring anytime during the intended treatment period (12 months) were included regardless of whether the participant was on treatment or not or whether the participant ever took drug, ie, Intent to treat (ITT) principle.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Hochberg adjusted p-value for superiority based on 2 hypotheses tests for apixaban 2.5mg group comparing with placebo group and for apixaban 5mg group comparing with placebo group.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 0.2422
Confidence Interval (2-Sided) 95%
0.1476 to 0.3975
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Apixaban 5 mg, Placebo
Comments Null hypothesis is relative risk proportion of apixaban participants with VTE/all cause mortality to proportion of placebo participants with VTE/all cause mortality equal to 1.0. Events occurring anytime during the intended treatment period (12 months) were included regardless of whether the participant was on treatment or not or whether the participant ever took drug, ie, Intent to treat (ITT) principle.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Hochberg adjusted p-value for superiority based on 2 hypotheses tests for apixaban 2.5mg group comparing with placebo group and for apixaban 5mg group comparing with placebo group.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 0.1861
Confidence Interval (2-Sided) 95%
0.1062 to 0.3261
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Adjudicated Composite of Recurrent, Symptomatic Venous Thromboembolism (VTE) or VTE-related Death During the Intended Treatment Period - Randomized Population With Imputation
Hide Description VTE includes nonfatal DVT or nonfatal PE. All index events, DVT and/or PE were adjudicated/confirmed by a central independent adjudication committee blinded to treatment. DVT assessed by compression ultrasound and/or venography; PE assessed by spiral computed tomography scanning, pulmonary angiography, and/or ventilation/perfusion lung scan. Event rate (proportion of participants with event) calculated as n/N (n=number of events; N=number of participants). Intended treatment period: longer of the dosing period plus 2 days (completed treatment) or 355 days (discontinued early). Composite endpoint included events at any time from randomization until end of the intended treatment period, regardless whether drug treatment was received. For missing endpoint data, participants were imputed as having had a primary efficacy outcome event.
Time Frame Day 1 up to 12 Months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT: all randomized participants with consent. Analyzed per randomized treatment assigned. (n) number of events=27, 34, 92 in apixaban 2.5 mg, 5 mg, placebo arms, respectively. Number of imputed events=13, 20, 19 in apixaban 2.5 mg, 5 mg, placebo arms, respectively. CI for single event rate was calculated based on Wald asymptotic confidence limits.
Arm/Group Title Apixaban 2.5 mg Apixaban 5 mg Placebo
Hide Arm/Group Description:
Participants received 2.5 mg oral tablet apixaban BID.
Participants received 5 mg oral tablet apixaban BID.
Participants received matching placebo oral tablet BID.
Overall Number of Participants Analyzed 840 813 829
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Proportion of participants
0.0321
(0.0202 to 0.0441)
0.0418
(0.0281 to 0.0556)
0.1110
(0.0896 to 0.1324)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Apixaban 2.5 mg, Placebo
Comments Null hypothesis is relative risk proportion of apixaban participants with VTE/VTE-related death to proportion of placebo participants with VTE/ VTE-related death equal to 1.0. Participants with missing data were assumed to have experienced VTE/ VTE-related death. Events occurring anytime during the intended treatment period (12 months) were included regardless of whether the participant was on treatment or not or whether the participant ever took drug, ie, ITT principle.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Hochberg adjusted p-value for superiority based on 2 hypotheses tests for apixaban 2.5mg group comparing with placebo group and for apixaban 5mg group comparing with placebo group.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 0.2891
Confidence Interval (2-Sided) 95%
0.1902 to 0.4395
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Apixaban 5 mg, Placebo
Comments Null hypothesis is relative risk proportion of apixaban participants with VTE/VTE-related death to proportion of placebo participants with VTE/ VTE-related death equal to 1.0. Participants with missing data were assumed to have experienced VTE/ VTE-related death. Events occurring anytime during the intended treatment period (12 months) were included regardless of whether the participant was on treatment or not or whether the participant ever took drug, ie, ITT principle.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Hochberg adjusted p-value for superiority based on 2 hypotheses tests for apixaban 2.5mg group comparing with placebo group and for apixaban 5mg group comparing with placebo group.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 0.3774
Confidence Interval (2-Sided) 95%
0.2577 to 0.5525
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Adjudicated Composite of Recurrent, Symptomatic Venous Thromboembolism (VTE) or Cardio Vascular (CV) -Related Death During the Intended Treatment Period - Randomized Population With Imputation
Hide Description VTE includes nonfatal DVT or nonfatal PE. All index events, DVT and/or PE were adjudicated/confirmed by a central independent adjudication committee blinded to treatment. DVT assessed by compression ultrasound and/or venography; PE assessed by spiral computed tomography scanning, pulmonary angiography, and/or ventilation/perfusion lung scan. Event rate is proportion of participants with event; calculated as n/N (n=number of events; N=number of participants). Composite endpoint included events that occurred any time from randomization until end of the intended treatment period, regardless of whether the participants were receiving drug treatment. Intended treatment period was defined as the longer of the dosing period plus 2 days or 355 days. If there were missing endpoint data, participants were imputed as having had an efficacy outcome event.
Time Frame Day 1 up to 12 Months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent to treat: all randomized participants with consent.(n)number of events=27, 34, 95 in apixaban 2.5 mg, 5 mg, placebo arms, respectively. The (n)number of imputed events were = 13, 20, 19 in apixaban 2.5 mg, 5 mg, placebo arms, respectively. CI for single event rate was calculated based on the Wald asymptotic confidence limits
Arm/Group Title Apixaban 2.5 mg Apixaban 5 mg Placebo
Hide Arm/Group Description:
Participants received 2.5 mg oral tablet apixaban BID.
Participants received 5 mg oral tablet apixaban BID.
Participants received matching placebo oral tablet BID.
Overall Number of Participants Analyzed 840 813 829
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: proportion of participants
0.0321
(0.0202 to 0.0441)
0.0418
(0.0281 to 0.0556)
0.1146
(0.0929 to 0.1363)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Apixaban 2.5 mg, Placebo
Comments Null hypothesis is relative risk proportion of apixaban participants with VTE/CV-related death to proportion of placebo participants with VTE/CV-related death equal to 1.0. Participants with missing data were assumed to have experienced VTE/CV-related death. Events occurring anytime during the intended treatment period (12 months) were included regardless of whether the participant was on treatment or not or whether the participant ever took drug, ie, ITT principle.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Hochberg adjusted p-value for superiority based on 2 hypotheses tests for apixaban 2.5mg group comparing with placebo group and for apixaban 5mg group comparing with placebo group.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 0.2799
Confidence Interval (2-Sided) 95%
0.1844 to 0.4247
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Apixaban 5 mg, Placebo
Comments Null hypothesis is relative risk proportion of apixaban participants with VTE/CV-related death to proportion of placebo participants with VTE/CV-related death equal to 1.0. Participants with missing data were assumed to have experienced VTE/CV-related death. Events occurring anytime during the intended treatment period (12 months) were included regardless of whether the participant was on treatment or not or whether the participant ever took drug, ie, ITT principle.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Hochberg adjusted p-value for superiority based on 2 hypotheses tests for apixaban 2.5mg group comparing with placebo group and for apixaban 5mg group comparing with placebo group.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 0.3653
Confidence Interval (2-Sided) 95%
0.2500 to 0.5338
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Adjudicated Nonfatal Deep Vein Thrombosis (DVT) During the Intended Treatment Period - Randomized Population With Imputation
Hide Description DVT was adjudicated/confirmed by a central independent adjudication committee blinded to treatment and assessed by compression ultrasound and/or venography. Event rate is proportion of participants with event; calculated as n/N (n=number of events; N=number of participants). Intended treatment period: longer of the dosing period plus 2 days (completed treatment) or 355 days (discontinued early). Endpoint included events at any time from randomization until end of the intended treatment period, regardless whether drug treatment was received. Participants with missing endpoint information were classified as having had the efficacy event (imputation). Confidence interval (CI) for single event rate was calculated based on the Wald asymptotic confidence limits.
Time Frame Day 1 up to 12 Months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent to treat: all randomized participants with valid consent. Analyzed per randomized treatment assigned. (n) number of events = 19, 28, 72 in apixaban 2.5 mg, 5 mg, placebo arms, respectively.
Arm/Group Title Apixaban 2.5 mg Apixaban 5 mg Placebo
Hide Arm/Group Description:
Participants received 2.5 mg oral tablet apixaban BID.
Participants received 5 mg oral tablet apixaban BID.
Participants received matching placebo oral tablet BID.
Overall Number of Participants Analyzed 840 813 829
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Proportion of participants
0.0226
(0.0126 to 0.0327)
0.0344
(0.0219 to 0.0470)
0.0869
(0.0677 to 0.1060)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Apixaban 2.5 mg, Placebo
Comments Null hypothesis is relative risk proportion of apixaban participants with nonfatal DVT to proportion of placebo participants with nonfatal DVT equal to 1.0. Participants with missing data were assumed to have experienced nonfatal DVT. Events occurring anytime during the intended treatment period (12 months) were included regardless of whether the participant was on treatment or not or whether the participant ever took drug, ie, Intent to treat (ITT) principle.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Hochberg adjusted p-value for superiority based on 2 hypotheses tests for apixaban 2.5mg group comparing with placebo group and for apixaban 5mg group comparing with placebo group.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 0.2615
Confidence Interval (2-Sided) 95%
0.1593 to 0.4292
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Apixaban 5 mg, Placebo
Comments Null hypothesis is relative risk proportion of apixaban participants with nonfatal DVT to proportion of placebo participants with nonfatal DVT equal to 1.0. Participants with missing data were assumed to have experienced nonfatal DVT. Events occurring anytime during the intended treatment period (12 months) were included regardless of whether the participant was on treatment or not or whether the participant ever took drug, ie, ITT principle.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Hochberg adjusted p-value for superiority based on 2 hypotheses tests for apixaban 2.5mg group comparing with placebo group and for apixaban 5mg group comparing with placebo group.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 0.3972
Confidence Interval (2-Sided) 95%
0.2595 to 0.6079
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Adjudicated Nonfatal Pulmonary Embolism (PE) During the Intended Treatment Period - Randomized Population With Imputation
Hide Description PE was adjudicated/confirmed by a central independent adjudication committee blinded to treatment and was assessed by spiral computed tomography scanning, pulmonary angiography, and/or ventilation/perfusion lung scan. Event rate is proportion of participants with event; calculated as n/N (n=number of events; N=number of participants). Intended treatment period was defined as the longer of the dosing period plus 2 days or 355 days. Endpoint included events at any time from randomization until end of the intended treatment period, regardless whether drug treatment was received. Participants with missing endpoint information were classified as having had the efficacy event (imputation). CI for single event rate was calculated based on the Wald asymptotic confidence limits.
Time Frame Day 1 up to 12 Months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent to treat: all randomized participants with valid consent. Analyzed per randomized treatment assigned. (n) number of events = 23, 25, 37 in apixaban 2.5 mg, 5 mg, placebo arms, respectively.
Arm/Group Title Apixaban 2.5 mg Apixaban 5 mg Placebo
Hide Arm/Group Description:
Participants received 2.5 mg oral tablet apixaban BID.
Participants received 5 mg oral tablet apixaban BID.
Participants received matching placebo oral tablet BID.
Overall Number of Participants Analyzed 840 813 829
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Proportion of participants
0.0274
(0.0163 to 0.0384)
0.0308
(0.0189 to 0.0426)
0.0446
(0.0306 to 0.0587)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Apixaban 2.5 mg, Placebo
Comments Null hypothesis is relative risk proportion of apixaban participants with nonfatal PE to proportion of placebo participants with nonfatal PE equal to 1.0. Participants with missing data were assumed to have experienced nonfatal PE. Events occurring anytime during the intended treatment period (12 months) were included regardless of whether the participant was on treatment or not or whether the participant ever took drug, ie, ITT principle.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1084
Comments Hochberg adjusted p-value for superiority based on 2 hypotheses tests for apixaban 2.5mg group comparing with placebo group and for apixaban 5mg group comparing with placebo group.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 0.6087
Confidence Interval (2-Sided) 95%
0.3653 to 1.0145
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Apixaban 5 mg, Placebo
Comments Null hypothesis is relative risk proportion of apixaban participants with nonfatal PE to proportion of placebo participants with nonfatal PE equal to 1.0. Participants with missing data were assumed to have experienced nonfatal PE. Events occurring anytime during the intended treatment period (12 months) were included regardless of whether the participant was on treatment or not or whether the participant ever took drug, ie, ITT principle.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1329
Comments Hochberg adjusted p-value for superiority based on 2 hypotheses tests for apixaban 2.5mg group comparing with placebo group and for apixaban 5mg group comparing with placebo group.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 0.6846
Confidence Interval (2-Sided) 95%
0.4164 to 1.1257
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Adjudicated Venous Thromboembolism (VTE) - Related Death During the Intended Treatment Period - Randomized Population With Imputation
Hide Description VTE-related death defined as: PE (based on objective diagnostic testing, autopsy), unexplained death (and VTE cannot be ruled out), sudden death (and VTE cannot be ruled out). DVT and/or PE were adjudicated/confirmed by a central independent adjudication committee blinded to treatment: DVT assessed by compression ultrasound and/or venography; PE assessed by spiral computed tomography scanning, pulmonary angiography, and/or ventilation/perfusion lung scan. New/recurrent VTE, death, venous/arterial thromboembolic events, bleeding, thrombocytopenia, acute myocardial infarction and stroke were also adjudicated. Event rate is proportion of participants with event; calculated as n/N (n=number of events; N=number of participants). Intended treatment period was defined as the longer of the dosing period plus 2 days or 355 days. Participants with missing endpoint information were classified as having had the efficacy event (imputation).
Time Frame Day 1 up to 12 Months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent to treat: all randomized participants with valid consent. Analyzed per randomized treatment assigned. (n) number of events = 17, 24, 26 in apixaban 2.5 mg, 5 mg, placebo arms, respectively. CI for single event rate was calculated based on the Wald asymptotic confidence limits.
Arm/Group Title Apixaban 2.5 mg Apixaban 5 mg Placebo
Hide Arm/Group Description:
Participants received 2.5 mg oral tablet apixaban BID.
Participants received 5 mg oral tablet apixaban BID.
Participants received matching placebo oral tablet BID.
Overall Number of Participants Analyzed 840 813 829
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Proportion of participants
0.0202
(0.0107 to 0.0298)
0.0295
(0.0179 to 0.0412)
0.0314
(0.0195 to 0.0432)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Apixaban 2.5 mg, Placebo
Comments Null hypothesis is relative risk proportion of apixaban participants with VTE-related death to proportion of placebo participants with VTE-related death equal to 1.0. Participants with missing data were assumed to have experienced VTE-related death. Events occurring anytime during the intended treatment period (12 months) were included regardless of whether the participant was on treatment or not or whether the participant ever took drug, ie, ITT principle.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3059
Comments Hochberg adjusted p-value for superiority based on 2 hypotheses tests for apixaban 2.5mg group comparing with placebo group and for apixaban 5mg group comparing with placebo group.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 0.6470
Confidence Interval (2-Sided) 95%
0.3543 to 1.1813
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Apixaban 5 mg, Placebo
Comments Null hypothesis is relative risk proportion of apixaban participants with VTE-related death to proportion of placebo participants with VTE-related death equal to 1.0. Participants with missing data were assumed to have experienced VTE-related death. Events occurring anytime during the intended treatment period (12 months) were included regardless of whether the participant was on treatment or not or whether the participant ever took drug, ie, ITT principle.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8288
Comments Hochberg adjusted p-value for superiority based on 2 hypotheses tests for apixaban 2.5mg group comparing with placebo group and for apixaban 5mg group comparing with placebo group.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 0.9416
Confidence Interval (2-Sided) 95%
0.5458 to 1.6245
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Adjudicated Cardiovascular (CV)-Related Death During the Intended Treatment Period - Randomized Population With Imputation
Hide Description CV-related death was defined as myocardial infarction, stroke, or other specified cardiovascular event and were adjudicated/confirmed by a central independent adjudication committee blinded to treatment. Event rate is proportion of participants with event; calculated as n/N (n=number of events; N=number of participants). Intended treatment period was defined as the longer of the dosing period plus 2 days or 355 days. Endpoint included events at any time from randomization until end of the intended treatment period, regardless whether drug treatment was received. Participants with missing endpoint information were classified as having had the efficacy event (imputation). CI for single event rate was calculated based on the Wald asymptotic confidence limits.
Time Frame Day 1 up to 12 Months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent to treat: all randomized participants with valid consent. Analyzed per randomized treatment assigned. number of events (n)= 17, 24, 29 in the apixaban 2.5 mg, 5 mg, placebo arms, respectively.
Arm/Group Title Apixaban 2.5 mg Apixaban 5 mg Placebo
Hide Arm/Group Description:
Participants received 2.5 mg oral tablet apixaban BID.
Participants received 5 mg oral tablet apixaban BID.
Participants received matching placebo oral tablet BID.
Overall Number of Participants Analyzed 840 813 829
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Proportion of Participants
0.0202
(0.0107 to 0.0298)
0.0295
(0.0179 to 0.0412)
0.0350
(0.0225 to 0.0475)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Apixaban 2.5 mg, Placebo
Comments Null hypothesis is relative risk proportion of apixaban participants with CV-related death to proportion of placebo participants with CV-related death equal to 1.0. Participants with missing data were assumed to have experienced CV-related death. Events occurring anytime during the intended treatment period (12 months) were included regardless of whether the participant was on treatment or not or whether the participant ever took drug, ie, ITT principle.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1316
Comments Hochberg adjusted p-value for superiority based on 2 hypotheses tests for apixaban 2.5mg group comparing with placebo group and for apixaban 5mg group comparing with placebo group.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 0.5794
Confidence Interval (2-Sided) 95%
0.3215 to 1.0443
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Apixaban 5 mg, Placebo
Comments Null hypothesis is relative risk proportion of apixaban participants with CV-related death to proportion of placebo participants with CV-related death equal to 1.0. Participants with missing data were assumed to have experienced CV-related death. Events occurring anytime during the intended treatment period (12 months) were included regardless of whether the participant was on treatment or not or whether the participant ever took drug, ie, ITT principle.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5288
Comments Hochberg adjusted p-value for superiority based on 2 hypotheses tests for apixaban 2.5mg group comparing with placebo group and for apixaban 5mg group comparing with placebo group.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 0.8433
Confidence Interval (2-Sided) 95%
0.4959 to 1.4341
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Adjudicated All-Cause Death During the Intended Treatment Period - Randomized Population With Imputation
Hide Description DVT and/or PE were adjudicated/confirmed by a central independent adjudication committee blinded to treatment: DVT assessed by compression ultrasound and/or venography; PE assessed by spiral computed tomography scanning, pulmonary angiography, and/or ventilation/perfusion lung scan. New/recurrent VTE, death, venous/arterial thromboembolic events, bleeding, thrombocytopenia, acute myocardial infarction and stroke were also adjudicated. Event rate is proportion of participants with event; calculated as n/N (n=number of events; N=number of participants). Intended treatment period was defined as the longer of the dosing period plus 2 days or 355 days. Participants with missing endpoint information were classified as having had the efficacy event (imputation). CI for single event rate was calculated based on the Wald asymptotic confidence limits.
Time Frame Day 1 up to 12 Months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent to treat: all randomized participants with valid consent. (n) number of events = 22, 25, 33 in apixaban 2.5 mg, apixaban 5 mg, and placebo arms, respectively.
Arm/Group Title Apixaban 2.5 mg Apixaban 5 mg Placebo
Hide Arm/Group Description:
Participants received 2.5 mg oral tablet apixaban BID.
Participants received 5 mg oral tablet apixaban BID.
Participants received matching placebo oral tablet BID.
Overall Number of Participants Analyzed 840 813 829
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Proportion of participants
0.0262
(0.0154 to 0.0370)
0.0308
(0.0189 to 0.0426)
0.0398
(0.0265 to 0.0531)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Apixaban 2.5 mg, Placebo
Comments Null hypothesis is relative risk proportion of apixaban participants with all cause mortality to proportion of placebo participants with all cause mortality equal to 1.0. Participants with missing data were assumed to have experienced all cause mortality. Events occurring anytime during the intended treatment period (12 months) were included regardless of whether the participant was on treatment or not or whether the participant ever took drug, ie, ITT principle.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2361
Comments Hochberg adjusted p-value for superiority based on 2 hypotheses tests for apixaban 2.5mg group comparing with placebo group and for apixaban 5mg group comparing with placebo group.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 0.6577
Confidence Interval (2-Sided) 95%
0.3874 to 1.1169
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Apixaban 5 mg, Placebo
Comments Null hypothesis is relative risk proportion of apixaban participants with all cause mortality to proportion of placebo participants with all cause mortality equal to 1.0. Participants with missing data were assumed to have experienced all cause mortality. Events occurring anytime during the intended treatment period (12 months) were included regardless of whether the participant was on treatment or not or whether the participant ever took drug, ie, ITT principle.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3155
Comments Hochberg adjusted p-value for superiority based on 2 hypotheses tests for apixaban 2.5mg group comparing with placebo group and for apixaban 5mg group comparing with placebo group.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 0.7708
Confidence Interval (2-Sided) 95%
0.4631 to 1.2832
Estimation Comments [Not Specified]
10.Secondary Outcome
Title Number of Participants With an Adjudicated Symptomatic Nonfatal Venous Thromboembolism (VTE) Recurrence or Death (All Cause) During the Intended Treatment Period - Randomized Participants Without Imputation
Hide Description All index events, DVT and/or PE were adjudicated/confirmed by a central independent adjudication committee blinded to treatment. DVT assessed by compression ultrasound and/or venography; PE assessed by spiral computed tomography scanning, pulmonary angiography, and/or ventilation/perfusion lung scan. Intended treatment period was defined as the longer of the dosing period plus 2 days or 355 days. Endpoint included events at any time from randomization until end of the intended treatment period, regardless whether drug treatment was received. First event category was the first primary event for each participant and each participant was counted once. CV-related death was presented excluding VTE-related death. In participants with event category, each participant was counted once in each event category but could have been counted in multiple categories. No imputation was done for these endpoints; participants who had an event during the intended treatment period were counted.
Time Frame Day 1 up to 12 Months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent to treat: all randomized participants with valid consent. Analyzed per randomized treatment assigned. In first event (first primary event) each participant counted once. In event category, each participant was counted only once in each event category but could have been counted in multiple categories.
Arm/Group Title Apixaban 2.5 mg Apixaban 5 mg Placebo
Hide Arm/Group Description:
Participants received 2.5 mg oral tablet apixaban BID.
Participants received 5 mg oral tablet apixaban BID.
Participants received matching placebo oral tablet BID.
Overall Number of Participants Analyzed 840 813 829
Measure Type: Number
Unit of Measure: participants
First event: Participants with nonfatal DVT 6 7 53
First event: Participants with nonfatal PE 7 4 13
First event: All-Cause Death 6 3 11
CV-related Death (included in all-cause total) 0 0 3
VTE-related Death (included in all-cause total) 2 3 7
Participants with event: nonfatal DVT 6 8 53
Participants with event: nonfatal PE 8 4 15
Participants with event: All cause death 7 4 14
11.Secondary Outcome
Title Adjudicated Major Bleeding During the Treatment Period - Treated Population
Hide Description Major bleeding was adjudicated/confirmed by a central independent adjudication committee blinded to treatment and was defined as acute clinically overt bleeding: associated with a fall in hemoglobin of 2 grams per deciliter (g/dL) or more, or leading to a transfusion of 2 or more units of packed red blood cells or 1000 milliliters (mL) or more of whole blood, or in a critical site: intracranial, intraspinal, intraocular, pericardial, intra-articular, intramuscular with compartment syndrome, retroperitoneal, or another critical organ; or is fatal. Event rate is proportion of participants with event; calculated as n/N (n=number of events; N=number of participants). Confidence interval (CI) for event rate was calculated based on the Wald asymptotic confidence limits. Treated population includes randomized participants who received at least one dose of study drug.
Time Frame Day 1 up to 12 Months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Treated population includes randomized participants who received at least one dose of study drug. (n) number of events = 2, 1, 4 in apixaban 2.5 mg, and 5 mg, and placebo arms, respectively.
Arm/Group Title Apixaban 2.5 mg Apixaban 5 mg Placebo
Hide Arm/Group Description:
Participants received 2.5 mg oral tablet apixaban BID.
Participants received 5 mg oral tablet apixaban BID.
Participants received matching placebo oral tablet BID.
Overall Number of Participants Analyzed 840 811 826
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Proportion of participants
0.0024
(0.0000 to 0.0057)
0.0012
(0.0000 to 0.0036)
0.0048
(0.0001 to 0.0096)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Apixaban 2.5 mg, Placebo
Comments Null hypothesis is relative risk proportion of apixaban participants with major bleeding to proportion of placebo participants with major bleeding equal to 1.0. Treated participants with at least one dose of study drug were included.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3925
Comments Hochberg adjusted p-value for superiority based on 2 hypotheses tests for apixaban 2.5mg group comparing with placebo group and for apixaban 5mg group comparing with placebo group.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 0.4850
Confidence Interval (2-Sided) 95%
0.0891 to 2.6391
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Apixaban 5 mg, Placebo
Comments Null hypothesis is relative risk proportion of apixaban participants with major bleeding to proportion of placebo participants with major bleeding equal to 1.0. Participants treated with at least one dose of study drug were included.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3551
Comments Hochberg adjusted p-value for superiority based on 2 hypotheses tests for apixaban 2.5mg group comparing with placebo group and for apixaban 5mg group comparing with placebo group.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 0.2457
Confidence Interval (2-Sided) 95%
0.0269 to 2.2437
Estimation Comments [Not Specified]
12.Secondary Outcome
Title Adjudicated Composite of Major/Clinically Relevant Non-major Bleeding During the Treatment Period - Treated Participants
Hide Description Major bleeding and clinically relevant non-major bleeding were adjudicated/confirmed by a central independent adjudication committee blinded to treatment. Major bleeding was defined as acute clinically overt bleeding: associated with a fall in hemoglobin of 2 g/dL or more, or leading to a transfusion of 2 or more units of packed red blood cells or 1000 mL or more of whole blood, or in a critical site: intracranial, intraspinal, intraocular, pericardial, intra-articular, intramuscular with compartment syndrome, retroperitoneal, or another critical organ or is fatal. Event rate is proportion of participants with event; calculated as n/N (n=number of events; N=number of participants). CI for single event rate was calculated based on the Wald asymptotic confidence limits. Treated population includes randomized participants who received at least one dose of study drug.
Time Frame Day 1 up to 12 Months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Treated participants were those who received at least 1 dose of study drug. (n)number of events = 27, 35, 22 in apixaban 2.5 mg, 5 mg, and placebo arms, respectively.
Arm/Group Title Apixaban 2.5 mg Apixaban 5 mg Placebo
Hide Arm/Group Description:
Participants received 2.5 mg oral tablet apixaban BID.
Participants received 5 mg oral tablet apixaban BID.
Participants received matching placebo oral tablet BID.
Overall Number of Participants Analyzed 840 811 826
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: proportion of participants
0.0321
(0.0202 to 0.0441)
0.0432
(0.0292 to 0.0571)
0.0266
(0.0157 to 0.0376)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Apixaban 2.5 mg
Comments Null hypothesis is relative risk proportion of apixaban participants with major/clinically relevant non-major bleeding to proportion of placebo participants with major/clinically relevant non-major bleeding equal to 1.0.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5148
Comments Hochberg adjusted p-value for superiority based on 2 hypotheses tests for apixaban 2.5mg group comparing with placebo group and for apixaban 5mg group comparing with placebo group.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 1.2027
Confidence Interval (2-Sided) 95%
0.6897 to 2.0975
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Apixaban 5 mg, Placebo
Comments Null hypothesis is relative risk proportion of apixaban participants with major/clinically relevant non-major bleeding to proportion of placebo participants with major/clinically relevant non-major bleeding equal to 1.0.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1412
Comments Hochberg adjusted p-value for superiority based on 2 hypotheses tests for apixaban 2.5mg group comparing with placebo group and for apixaban 5mg group comparing with placebo group.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 1.6160
Confidence Interval (2-Sided) 95%
0.9554 to 2.7336
Estimation Comments [Not Specified]
13.Secondary Outcome
Title Adjudicated Clinically Relevant Non-major Bleeding During the Treatment Period - Treated Participants
Hide Description Non-major clinically relevant bleeding was adjudicated/confirmed by a central independent adjudication committee blinded to treatment and defined as: acute clinically overt bleeding compromising hemodynamics; leading to hospitalization; traumatic subcutaneous hematoma; intramuscular hematoma; epistaxis that lasted for more than 5 minutes, was repetitive or led to an intervention; spontaneous gingival bleeding (or lasting more than 5 minutes); spontaneous hematuria (macroscopic or lasted more than 24 hours after instrumentation of the urogenital tract); macroscopic gastrointestinal hemorrhage (including at least 1 episode of melena or hematemesis (if clinically apparent with positive results on a fecal occult-blood test); rectal blood loss. Event rate is proportion of participants with event; calculated as n/N (n=number of events; N=number of participants). CI for single event rate was calculated based on the Wald asymptotic confidence limits.
Time Frame Day 1 up to 12 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Treated population includes randomized participants who received at least one dose of study drug. (n)number of events = 25, 34, 19 in apixaban 2.5 mg, 5 mg, and placebo arms, respectively.
Arm/Group Title Apixaban 2.5 mg Apixaban 5 mg Placebo
Hide Arm/Group Description:
Participants received 2.5 mg oral tablet apixaban BID.
Participants received 5 mg oral tablet apixaban BID.
Participants received matching placebo oral tablet BID.
Overall Number of Participants Analyzed 840 811 826
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Proportion of participants
0.0298
(0.0183 to 0.0413)
0.0419
(0.0281 to 0.0557)
0.0230
(0.0128 to 0.0332)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Apixaban 2.5 mg, Placebo
Comments Null hypothesis is relative risk proportion of apixaban participants with clinically relevant non-major bleeding to proportion of placebo participants with clinically relevant non-major bleeding equal to 1.0.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3932
Comments Hochberg adjusted p-value for superiority based on 2 hypotheses tests for apixaban 2.5mg group comparing with placebo group and for apixaban 5mg group comparing with placebo group.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 1.2928
Confidence Interval (2-Sided) 95%
0.7158 to 2.3348
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Apixaban 5 mg, Placebo
Comments Null hypothesis is relative risk proportion of apixaban participants with clinically relevant non-major bleeding to proportion of placebo participants with clinically relevant non-major bleeding equal to 1.0.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0621
Comments Hochberg adjusted p-value for superiority based on 2 hypotheses tests for apixaban 2.5mg group comparing with placebo group and for apixaban 5mg group comparing with placebo group.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 1.8235
Confidence Interval 95%
1.0470 to 3.1760
Estimation Comments [Not Specified]
14.Secondary Outcome
Title Adjudicated Clinically Relevant Minor Bleeding During the Treatment Period - Treated Participants
Hide Description All bleeding events were reviewed by the central independent adjudication committee blinded to treatment and classified as major bleeding, clinically relevant non-major bleeding, minor bleeding or no bleeding. If event was not major or clinically relevant non-major, it was judged to be minor. Event rate is proportion of participants with event; calculated as n/N (n=number of events; N=number of participants). Confidence interval (CI) for single event rate was calculated based on the Wald asymptotic confidence limits. Treated population includes randomized participants who received at least one dose of study drug.
Time Frame Day 1 up to 12 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Treated population includes randomized participants who received at least one dose of study drug. (n)number of events = 75, 98, 58 in apixaban 2.5 mg, 5 mg, and placebo arms, respectively.
Arm/Group Title Apixaban 2.5 mg Apixaban 5 mg Placebo
Hide Arm/Group Description:
Participants received 2.5 mg oral tablet apixaban BID.
Participants received 5 mg oral tablet apixaban BID.
Participants received matching placebo oral tablet BID.
Overall Number of Participants Analyzed 840 811 826
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Proportion of participants
0.0893
(0.0700 to 0.1086)
0.1208
(0.0984 to 0.1433)
0.0702
(0.0528 to 0.0876)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Apixaban 2.5 mg, Placebo
Comments Null hypothesis is relative risk proportion of apixaban participants with minor bleeding to proportion of placebo participants with minor bleeding equal to 1.0.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1691
Comments Hochberg adjusted p-value for superiority based on 2 hypotheses tests for apixaban 2.5mg group comparing with placebo group and for apixaban 5mg group comparing with placebo group.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 1.2579
Confidence Interval (2-Sided) 95%
0.9064 to 1.7457
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Apixaban 5 mg, Placebo
Comments Null hypothesis is relative risk proportion of apixaban participants with minor bleeding to proportion of placebo participants with minor bleeding equal to 1.0.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0013
Comments Hochberg adjusted p-value for superiority based on 2 hypotheses tests for apixaban 2.5mg group comparing with placebo group and for apixaban 5mg group comparing with placebo group.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 1.6971
Confidence Interval (2-Sided) 95%
1.2468 to 2.3102
Estimation Comments [Not Specified]
15.Secondary Outcome
Title Adjudicated Total Bleeding During the Treatment Period - Treated Participants
Hide Description All bleeding events were adjudicated/confirmed by a central independent adjudication committee blinded to treatment. Total bleeding was defined as any major, clinically relevant non-major, or minor bleeding. Event rate is proportion of participants with event; calculated as n/N (n=number of events; N=number of participants). CI for single event rate was calculated based on the Wald asymptotic confidence limits. Treated population includes randomized participants who received at least one dose of study drug.
Time Frame Day 1 up to 12 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Treated population includes randomized participants who received at least one dose of study drug. (n) number of events = 94, 121, 74 in apixaban 2.5 mg, 5 mg, and placebo arms, respectively.
Arm/Group Title Apixaban 2.5 mg Apixaban 5 mg Placebo
Hide Arm/Group Description:
Participants received 2.5 mg oral tablet apixaban BID.
Participants received 5 mg oral tablet apixaban BID.
Participants received matching placebo oral tablet BID.
Overall Number of Participants Analyzed 840 811 826
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Proportion of participants
0.1119
(0.0906 to 0.1332)
0.1492
(0.1247 to 0.1737)
0.0896
(0.0701 to 0.1091)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Apixaban 2.5 mg, Placebo
Comments Null hypothesis is relative risk proportion of apixaban participants with total bleeding to proportion of placebo participants with total bleeding equal to 1.0. Total bleeding was defined as any major, clinically relevant non-major, or minor bleeding.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1466
Comments Hochberg adjusted p-value for superiority based on 2 hypotheses tests for apixaban 2.5mg group comparing with placebo group and for apixaban 5mg group comparing with placebo group.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 1.2374
Confidence Interval (2-Sided) 95%
0.9276 to 1.6507
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Apixaban 5 mg, Placebo
Comments Null hypothesis is relative risk proportion of apixaban participants with total bleeding to proportion of placebo participants with total bleeding equal to 1.0. Total bleeding is any major, clinically relevant non-major, or minor bleeding.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0005
Comments Hochberg adjusted p-value for superiority based on 2 hypotheses tests for apixaban 2.5mg group comparing with placebo group and for apixaban 5mg group comparing with placebo group.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 1.6468
Confidence Interval (2-Sided) 95%
1.2552 to 2.1606
Estimation Comments [Not Specified]
16.Secondary Outcome
Title Adjudicated Composite of Recurrent, Symptomatic Venous Thromboembolism (VTE) or Venous Thromboembolism-related Death During the Intended Treatment Period - Randomized Population Without Imputation
Hide Description VTE related death defined as PE (based on objective diagnostic testing, autopsy), unexplained death (and VTE cannot be ruled out), sudden death (and VTE cannot be ruled out). DVT and/or PE were adjudicated/confirmed by a central independent adjudication committee blinded to treatment: DVT assessed by compression ultrasound and/or venography; PE assessed by spiral computed tomography scanning, pulmonary angiography, and/or ventilation/perfusion lung scan. New/recurrent VTE and death, were also adjudicated. Event rate is proportion of participants with event; calculated as n/N (n=number of events; N=number of participants). Intended treatment period was defined as the longer of the dosing period plus 2 days or 355 days. Endpoint included events at any time from randomization until end of the intended treatment period, regardless whether drug treatment was received. No imputation was done for these endpoints.
Time Frame Day 1 up to 12 Months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent to treat: all randomized participants with valid consent. Participants analyzed per randomized treatment assigned. (n) number of events = 14, 14, 73 in apixaban 2.5 mg, 5 mg, and placebo arms, respectively. CI for single event rate was calculated based on the Wald asymptotic confidence limits.
Arm/Group Title Apixaban 2.5 mg Apixaban 5 mg Placebo
Hide Arm/Group Description:
Participants received 2.5 mg oral tablet apixaban BID.
Participants received 5 mg oral tablet apixaban BID.
Participants received matching placebo oral tablet BID.
Overall Number of Participants Analyzed 840 813 829
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: proportion of participants
0.0167
(0.0080 to 0.0253)
0.0172
(0.0083 to 0.0262)
0.0881
(0.0688 to 0.1073)
17.Secondary Outcome
Title Adjudicated Composite of Recurrent, Symptomatic Venous Thromboembolism (VTE) or Cardio Vascular (CV) - Related Death During the Intended Treatment Period - Randomized Population Without Imputation
Hide Description CV-related death was defined as myocardial infarction, stroke, or other specified cardiovascular event. Index events of DVT and/or PE, along with myocardial infarction and stroke were adjudicated/confirmed by a central independent adjudication committee blinded to treatment: DVT assessed by compression ultrasound and/or venography; PE assessed by spiral computed tomography scanning, pulmonary angiography, and/or ventilation/perfusion lung scan. Event rate is proportion of participants with event; calculated as n/N (n=number of events; N=number of participants). Intended treatment period was defined as the longer of the dosing period plus 2 days or 355 days. Composite endpoint included events at any time from randomization until end of the intended treatment period, regardless whether drug treatment was received. No imputation was done for these endpoints; participants who had an event during the intended treatment period were counted.
Time Frame Day 1 up to 12 Months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent to treat: all randomized participants with valid consent. Participants analyzed per randomized treatment assigned. (n) number of events = 14, 14, 76 in apixaban 2.5 mg, 5 mg, and placebo arms, respectively. CI for single event rate was calculated based on the Wald asymptotic confidence limits.
Arm/Group Title Apixaban 2.5 mg Apixaban 5 mg Placebo
Hide Arm/Group Description:
Participants received 2.5 mg oral tablet apixaban BID.
Participants received 5 mg oral tablet apixaban BID.
Participants received matching placebo oral tablet BID.
Overall Number of Participants Analyzed 840 813 829
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: proportion of participants
0.0167
(0.0080 to 0.0253)
0.0172
(0.0083 to 0.0262)
0.0917
(0.0720 to 0.1113)
18.Secondary Outcome
Title Adjudicated Nonfatal Deep Vein Thrombosis (DVT) During the Intended Treatment Period - Randomized Population Without Imputation
Hide Description DVT was adjudicated/confirmed by a central independent adjudication committee blinded to treatment: DVT assessed by compression ultrasound and/or venography. Event rate is proportion of participants with event; calculated as n/N (n=number of events; N=number of participants). Intended treatment period was defined as the longer of the dosing period plus 2 days or 355 days. Endpoint included events at any time from randomization until end of the intended treatment period, regardless whether drug treatment was received. No imputation was done for this endpoint; participants who had an event during the intended treatment period were counted.
Time Frame Day 1 up to 12 Months
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Hide Analysis Population Description
Intent to treat: all randomized participants with valid consent. Participants analyzed per randomized treatment assigned. (n) number of events = 6, 8, 53 in apixaban 2.5 mg, 5 mg, and placebo arms, respectively. CI for single event rate was calculated based on the Wald asymptotic confidence limits.
Arm/Group Title Apixaban 2.5 mg Apixaban 5 mg Placebo
Hide Arm/Group Description:
Participants received 2.5 mg oral tablet apixaban BID.
Participants received 5 mg oral tablet apixaban BID.
Participants received matching placebo oral tablet BID.
Overall Number of Participants Analyzed 840 813 829
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: proportion of participants
0.0071
(0.0014 to 0.0128)
0.0098
(0.0031 to 0.0166)
0.0639
(0.0473 to 0.0806)
19.Secondary Outcome
Title Adjudicated Nonfatal Pulmonary Embolism (PE) During the Intended Treatment Period - Randomized Population Without Imputation
Hide Description PE was adjudicated/confirmed by a central independent adjudication committee blinded to treatment: PE assessed by spiral computed tomography scanning, pulmonary angiography, and/or ventilation/perfusion lung scan. Event rate is proportion of participants with event; calculated as n/N (n=number of events; N=number of participants). Intended treatment period was defined as the longer of the dosing period plus 2 days or 355 days. Endpoint included events at any time from randomization until end of the intended treatment period, regardless whether drug treatment was received. No imputation was done for this endpoint; participants who had an event during the intended treatment period were counted.
Time Frame Day 1 up to 12 Months
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Hide Analysis Population Description
Intent to treat: all randomized participants with valid consent. Participants analyzed per randomized treatment assigned. (n) number of events = 8, 4, 15 in apixaban 2.5 mg, 5 mg, and placebo arms, respectively. CI for single event rate was calculated based on the Wald asymptotic confidence limits.
Arm/Group Title Apixaban 2.5 mg Apixaban 5 mg Placebo
Hide Arm/Group Description:
Participants received 2.5 mg oral tablet apixaban BID.
Participants received 5 mg oral tablet apixaban BID.
Participants received matching placebo oral tablet BID.
Overall Number of Participants Analyzed 840 813 829
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Proportion of participants
0.0095
(0.0030 to 0.0161)
0.0049
(0.0001 to 0.0097)
0.0181
(0.0090 to 0.0272)
20.Secondary Outcome
Title Adjudicated Venous Thromboembolism (VTE)- Related Death During the Intended Treatment Period - Randomized Population Without Imputation
Hide Description VTE related death defined as PE (based on objective diagnostic testing, autopsy), unexplained death (and VTE cannot be ruled out), sudden death (and VTE cannot be ruled out). DVT and/or PE were adjudicated/confirmed by a central independent adjudication committee blinded to treatment: DVT assessed by compression ultrasound and/or venography; PE assessed by spiral computed tomography scanning, pulmonary angiography, and/or ventilation/perfusion lung scan. New/recurrent VTE, and death, were also adjudicated. Event rate is proportion of participants with event; calculated as n/N (n=number of events; N=number of participants). Intended treatment period was defined as the longer of the dosing period plus 2 days or 355 days. Endpoint included events at any time from randomization until end of the intended treatment period, regardless whether drug treatment was received. No imputation was done for this endpoint.
Time Frame Day 1 up to 12 Months
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Hide Analysis Population Description
Intent to treat: all randomized participants with valid consent. Participants analyzed per randomized treatment assigned. (n) number of events = 2, 3, 7 in apixaban 2.5 mg, 5 mg, and placebo arms, respectively. CI for single event rate was calculated based on the Wald asymptotic confidence limits.
Arm/Group Title Apixaban 2.5 mg Apixaban 5 mg Placebo
Hide Arm/Group Description:
Participants received 2.5 mg oral tablet apixaban BID.
Participants received 5 mg oral tablet apixaban BID.
Participants received matching placebo oral tablet BID.
Overall Number of Participants Analyzed 840 813 829
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Proportion of participants
0.0024
(0.0000 to 0.0057)
0.0037
(0.0000 to 0.0079)
0.0084
(0.0022 to 0.0147)
21.Secondary Outcome
Title Adjudicated Cardio Vascular (CV)-Related Death During the Intended Treatment Period - Randomized Population Without Imputation
Hide Description CV-related death was defined as myocardial infarction, stroke, or other specified cardiovascular event and these were adjudicated/confirmed by a central independent adjudication committee blinded to treatment. Event rate is proportion of participants with event; calculated as n/N (n=number of events; N=number of participants). Intended treatment period was defined as the longer of the dosing period plus 2 days or 355 days. Endpoint included events at any time from randomization until end of the intended treatment period, regardless whether drug treatment was received. No imputation was done for this endpoint; participants who had an event during the intended treatment period were counted.
Time Frame Day 1 up to 12 Months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent to treat: all randomized participants with valid consent. Participants analyzed per randomized treatment assigned. (n) number of events = 2, 3, 10 in apixaban 2.5 mg, 5 mg, and placebo arms, respectively. CI for single event rate was calculated based on the Wald asymptotic confidence limits.
Arm/Group Title Apixaban 2.5 mg Apixaban 5 mg Placebo
Hide Arm/Group Description:
Participants received 2.5 mg oral tablet apixaban BID.
Participants received 5 mg oral tablet apixaban BID.
Participants received matching placebo oral tablet BID.
Overall Number of Participants Analyzed 840 813 829
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Proportion of participants
0.0024
(0.0000 to 0.0057)
0.0037
(0.0000 to 0.0079)
0.0121
(0.0046 to 0.0195)
22.Secondary Outcome
Title Adjudicated All-Cause Death During the Intended Treatment Period - Randomized Population Without Imputation
Hide Description DVT and/or PE were adjudicated/confirmed by a central independent adjudication committee blinded to treatment: DVT assessed by compression ultrasound and/or venography; PE assessed by spiral computed tomography scanning, pulmonary angiography, and/or ventilation/perfusion lung scan. New/recurrent VTE, death, venous/arterial thromboembolic events, bleeding, thrombocytopenia, acute myocardial infarction and stroke were also adjudicated. Event rate is proportion of participants with event; calculated as n/N (n=number of events; N=number of participants). Intended treatment period was defined as the longer of the dosing period plus 2 days or 355 days. Endpoint included events at any time from randomization until end of the intended treatment period, regardless whether drug treatment was received. No imputation was done for this endpoint; participants who had an event during the intended treatment period were counted.
Time Frame Day 1 up to 12 Months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent to treat: all randomized participants with valid consent. Participants analyzed per randomized treatment assigned. (n) number of events = 7, 4, 14 in apixaban 2.5 mg, 5 mg, and placebo arms, respectively. CI for single event rate was calculated based on the Wald asymptotic confidence limits.
Arm/Group Title Apixaban 2.5 mg Apixaban 5 mg Placebo
Hide Arm/Group Description:
Participants received 2.5 mg oral tablet apixaban BID.
Participants received 5 mg oral tablet apixaban BID.
Participants received matching placebo oral tablet BID.
Overall Number of Participants Analyzed 840 813 829
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Proportion of participants
0.0083
(0.0022 to 0.0145)
0.0049
(0.0001 to 0.0097)
0.0169
(0.0081 to 0.0257)
Time Frame Day 1 up to 12 months
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Apixaban 2.5mg Apixaban 5mg Placebo
Hide Arm/Group Description Participants received 2.5 mg oral tablet apixaban BID Participants received 5 mg oral tablet apixaban BID Participants received oral tablet of placebo BID
All-Cause Mortality
Apixaban 2.5mg Apixaban 5mg Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Apixaban 2.5mg Apixaban 5mg Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   112/840 (13.33%)   107/811 (13.19%)   158/826 (19.13%) 
Blood and lymphatic system disorders       
ANAEMIA * 1  0/840 (0.00%)  3/811 (0.37%)  2/826 (0.24%) 
IRON DEFICIENCY ANAEMIA * 1  0/840 (0.00%)  1/811 (0.12%)  0/826 (0.00%) 
Cardiac disorders       
ACUTE CORONARY SYNDROME * 1  0/840 (0.00%)  1/811 (0.12%)  0/826 (0.00%) 
ACUTE MYOCARDIAL INFARCTION * 1  1/840 (0.12%)  2/811 (0.25%)  0/826 (0.00%) 
ANGINA PECTORIS * 1  3/840 (0.36%)  0/811 (0.00%)  0/826 (0.00%) 
ANGINA UNSTABLE * 1  1/840 (0.12%)  1/811 (0.12%)  1/826 (0.12%) 
ARTERIOSCLEROSIS CORONARY ARTERY * 1  1/840 (0.12%)  0/811 (0.00%)  0/826 (0.00%) 
ATRIAL FIBRILLATION * 1  2/840 (0.24%)  1/811 (0.12%)  4/826 (0.48%) 
BRADYCARDIA * 1  0/840 (0.00%)  1/811 (0.12%)  1/826 (0.12%) 
CARDIAC ARREST * 1  1/840 (0.12%)  0/811 (0.00%)  1/826 (0.12%) 
CARDIAC FAILURE * 1  0/840 (0.00%)  0/811 (0.00%)  1/826 (0.12%) 
CARDIAC FAILURE CONGESTIVE * 1  2/840 (0.24%)  0/811 (0.00%)  1/826 (0.12%) 
CARDIO-RESPIRATORY ARREST * 1  0/840 (0.00%)  1/811 (0.12%)  0/826 (0.00%) 
CONGESTIVE CARDIOMYOPATHY * 1  0/840 (0.00%)  0/811 (0.00%)  1/826 (0.12%) 
CORONARY ARTERY DISEASE * 1  2/840 (0.24%)  0/811 (0.00%)  1/826 (0.12%) 
EXTRASYSTOLES * 1  1/840 (0.12%)  0/811 (0.00%)  0/826 (0.00%) 
MITRAL VALVE INCOMPETENCE * 1  0/840 (0.00%)  0/811 (0.00%)  1/826 (0.12%) 
MYOCARDIAL INFARCTION * 1  1/840 (0.12%)  3/811 (0.37%)  2/826 (0.24%) 
MYOCARDIAL ISCHAEMIA * 1  0/840 (0.00%)  1/811 (0.12%)  3/826 (0.36%) 
SICK SINUS SYNDROME * 1  0/840 (0.00%)  0/811 (0.00%)  1/826 (0.12%) 
TACHYCARDIA * 1  1/840 (0.12%)  0/811 (0.00%)  0/826 (0.00%) 
VENTRICULAR FIBRILLATION * 1  0/840 (0.00%)  1/811 (0.12%)  0/826 (0.00%) 
Congenital, familial and genetic disorders       
HIP DYSPLASIA * 1  1/840 (0.12%)  0/811 (0.00%)  0/826 (0.00%) 
Ear and labyrinth disorders       
OTOSCLEROSIS * 1  1/840 (0.12%)  0/811 (0.00%)  0/826 (0.00%) 
VERTIGO * 1  0/840 (0.00%)  0/811 (0.00%)  2/826 (0.24%) 
Endocrine disorders       
THYROIDITIS * 1  0/840 (0.00%)  0/811 (0.00%)  1/826 (0.12%) 
Eye disorders       
CATARACT * 1  1/840 (0.12%)  0/811 (0.00%)  0/826 (0.00%) 
EYE HAEMORRHAGE * 1  0/840 (0.00%)  0/811 (0.00%)  2/826 (0.24%) 
MACULAR OEDEMA * 1  1/840 (0.12%)  0/811 (0.00%)  0/826 (0.00%) 
RETINAL HAEMORRHAGE * 1  1/840 (0.12%)  0/811 (0.00%)  0/826 (0.00%) 
RETINAL VEIN OCCLUSION * 1  1/840 (0.12%)  0/811 (0.00%)  0/826 (0.00%) 
RETINAL VEIN THROMBOSIS * 1  0/840 (0.00%)  1/811 (0.12%)  0/826 (0.00%) 
Gastrointestinal disorders       
ABDOMINAL PAIN * 1  0/840 (0.00%)  1/811 (0.12%)  0/826 (0.00%) 
ABDOMINAL PAIN LOWER * 1  1/840 (0.12%)  0/811 (0.00%)  0/826 (0.00%) 
ABDOMINAL STRANGULATED HERNIA * 1  1/840 (0.12%)  0/811 (0.00%)  0/826 (0.00%) 
ANAL FISSURE * 1  0/840 (0.00%)  1/811 (0.12%)  0/826 (0.00%) 
GASTRIC ULCER HAEMORRHAGE * 1  0/840 (0.00%)  1/811 (0.12%)  0/826 (0.00%) 
GASTRITIS * 1  0/840 (0.00%)  1/811 (0.12%)  0/826 (0.00%) 
GASTROINTESTINAL HAEMORRHAGE * 1  0/840 (0.00%)  0/811 (0.00%)  1/826 (0.12%) 
GASTROOESOPHAGEAL REFLUX DISEASE * 1  2/840 (0.24%)  0/811 (0.00%)  0/826 (0.00%) 
HAEMATEMESIS * 1  2/840 (0.24%)  0/811 (0.00%)  0/826 (0.00%) 
HAEMORRHOIDAL HAEMORRHAGE * 1  0/840 (0.00%)  2/811 (0.25%)  0/826 (0.00%) 
HIATUS HERNIA * 1  0/840 (0.00%)  1/811 (0.12%)  0/826 (0.00%) 
ILEUS * 1  0/840 (0.00%)  0/811 (0.00%)  1/826 (0.12%) 
INGUINAL HERNIA * 1  0/840 (0.00%)  1/811 (0.12%)  0/826 (0.00%) 
INTESTINAL ISCHAEMIA * 1  0/840 (0.00%)  0/811 (0.00%)  1/826 (0.12%) 
PANCREATITIS * 1  1/840 (0.12%)  0/811 (0.00%)  0/826 (0.00%) 
PANCREATITIS ACUTE * 1  1/840 (0.12%)  0/811 (0.00%)  0/826 (0.00%) 
POLYP COLORECTAL * 1  0/840 (0.00%)  0/811 (0.00%)  1/826 (0.12%) 
RECTAL HAEMORRHAGE * 1  0/840 (0.00%)  1/811 (0.12%)  0/826 (0.00%) 
SMALL INTESTINAL OBSTRUCTION * 1  0/840 (0.00%)  1/811 (0.12%)  0/826 (0.00%) 
UPPER GASTROINTESTINAL HAEMORRHAGE * 1  0/840 (0.00%)  0/811 (0.00%)  1/826 (0.12%) 
VOMITING * 1  1/840 (0.12%)  0/811 (0.00%)  0/826 (0.00%) 
General disorders       
ASTHENIA * 1  1/840 (0.12%)  0/811 (0.00%)  0/826 (0.00%) 
CHEST PAIN * 1  0/840 (0.00%)  0/811 (0.00%)  1/826 (0.12%) 
DEATH * 1  0/840 (0.00%)  0/811 (0.00%)  2/826 (0.24%) 
FATIGUE * 1  0/840 (0.00%)  0/811 (0.00%)  1/826 (0.12%) 
GENERAL PHYSICAL HEALTH DETERIORATION * 1  1/840 (0.12%)  0/811 (0.00%)  0/826 (0.00%) 
MULTI-ORGAN FAILURE * 1  0/840 (0.00%)  1/811 (0.12%)  0/826 (0.00%) 
NON-CARDIAC CHEST PAIN * 1  1/840 (0.12%)  0/811 (0.00%)  2/826 (0.24%) 
OEDEMA PERIPHERAL * 1  0/840 (0.00%)  0/811 (0.00%)  1/826 (0.12%) 
PYREXIA * 1  0/840 (0.00%)  1/811 (0.12%)  0/826 (0.00%) 
SUDDEN DEATH * 1  0/840 (0.00%)  1/811 (0.12%)  3/826 (0.36%) 
Hepatobiliary disorders       
BILE DUCT STONE * 1  0/840 (0.00%)  0/811 (0.00%)  1/826 (0.12%) 
CHOLANGITIS ACUTE * 1  1/840 (0.12%)  0/811 (0.00%)  0/826 (0.00%) 
CHOLECYSTITIS * 1  0/840 (0.00%)  2/811 (0.25%)  0/826 (0.00%) 
CHOLECYSTITIS ACUTE * 1  3/840 (0.36%)  0/811 (0.00%)  0/826 (0.00%) 
CHOLECYSTITIS CHRONIC * 1  1/840 (0.12%)  0/811 (0.00%)  0/826 (0.00%) 
CHOLELITHIASIS * 1  1/840 (0.12%)  0/811 (0.00%)  0/826 (0.00%) 
DRUG-INDUCED LIVER INJURY * 1  0/840 (0.00%)  2/811 (0.25%)  0/826 (0.00%) 
HEPATITIS * 1  0/840 (0.00%)  0/811 (0.00%)  1/826 (0.12%) 
Immune system disorders       
AMYLOIDOSIS * 1  1/840 (0.12%)  0/811 (0.00%)  0/826 (0.00%) 
ANTIPHOSPHOLIPID SYNDROME * 1  0/840 (0.00%)  0/811 (0.00%)  1/826 (0.12%) 
Infections and infestations       
ACUTE SINUSITIS * 1  0/840 (0.00%)  1/811 (0.12%)  0/826 (0.00%) 
BRONCHITIS * 1  1/840 (0.12%)  2/811 (0.25%)  1/826 (0.12%) 
BRONCHOPNEUMONIA * 1  1/840 (0.12%)  0/811 (0.00%)  0/826 (0.00%) 
CELLULITIS * 1  2/840 (0.24%)  0/811 (0.00%)  2/826 (0.24%) 
DIVERTICULITIS * 1  1/840 (0.12%)  1/811 (0.12%)  0/826 (0.00%) 
EMPYEMA * 1  0/840 (0.00%)  1/811 (0.12%)  0/826 (0.00%) 
ENCEPHALITIS MENINGOCOCCAL * 1  0/840 (0.00%)  1/811 (0.12%)  0/826 (0.00%) 
ERYSIPELAS * 1  1/840 (0.12%)  0/811 (0.00%)  1/826 (0.12%) 
ESCHERICHIA SEPSIS * 1  0/840 (0.00%)  1/811 (0.12%)  0/826 (0.00%) 
GASTROENTERITIS * 1  2/840 (0.24%)  0/811 (0.00%)  0/826 (0.00%) 
HAEMATOMA INFECTION * 1  1/840 (0.12%)  0/811 (0.00%)  0/826 (0.00%) 
HERPES ZOSTER * 1  0/840 (0.00%)  0/811 (0.00%)  2/826 (0.24%) 
LOBAR PNEUMONIA * 1  0/840 (0.00%)  1/811 (0.12%)  0/826 (0.00%) 
LOWER RESPIRATORY TRACT INFECTION * 1  1/840 (0.12%)  0/811 (0.00%)  0/826 (0.00%) 
ORCHITIS * 1  0/840 (0.00%)  1/811 (0.12%)  0/826 (0.00%) 
OSTEOMYELITIS * 1  0/840 (0.00%)  0/811 (0.00%)  1/826 (0.12%) 
PERIRECTAL ABSCESS * 1  1/840 (0.12%)  0/811 (0.00%)  0/826 (0.00%) 
PNEUMONIA * 1  5/840 (0.60%)  3/811 (0.37%)  1/826 (0.12%) 
PYELONEPHRITIS * 1  0/840 (0.00%)  2/811 (0.25%)  1/826 (0.12%) 
RESPIRATORY TRACT INFECTION * 1  0/840 (0.00%)  3/811 (0.37%)  1/826 (0.12%) 
SALPINGITIS * 1  1/840 (0.12%)  0/811 (0.00%)  1/826 (0.12%) 
SEPSIS * 1  0/840 (0.00%)  2/811 (0.25%)  0/826 (0.00%) 
SINUSITIS * 1  0/840 (0.00%)  0/811 (0.00%)  1/826 (0.12%) 
TONSILLITIS * 1  0/840 (0.00%)  0/811 (0.00%)  1/826 (0.12%) 
URINARY TRACT INFECTION * 1  1/840 (0.12%)  2/811 (0.25%)  1/826 (0.12%) 
VIRAL INFECTION * 1  0/840 (0.00%)  0/811 (0.00%)  1/826 (0.12%) 
VIRAL SINUSITIS * 1  1/840 (0.12%)  0/811 (0.00%)  0/826 (0.00%) 
Injury, poisoning and procedural complications       
ACCIDENTAL EXPOSURE * 1  0/840 (0.00%)  1/811 (0.12%)  0/826 (0.00%) 
ANKLE FRACTURE * 1  0/840 (0.00%)  0/811 (0.00%)  1/826 (0.12%) 
CONCUSSION * 1  0/840 (0.00%)  0/811 (0.00%)  1/826 (0.12%) 
FEMUR FRACTURE * 1  0/840 (0.00%)  1/811 (0.12%)  0/826 (0.00%) 
FOREIGN BODY * 1  0/840 (0.00%)  1/811 (0.12%)  0/826 (0.00%) 
FRACTURED SACRUM * 1  0/840 (0.00%)  1/811 (0.12%)  0/826 (0.00%) 
HAND FRACTURE * 1  0/840 (0.00%)  1/811 (0.12%)  0/826 (0.00%) 
HEAT EXHAUSTION * 1  1/840 (0.12%)  0/811 (0.00%)  0/826 (0.00%) 
HIP FRACTURE * 1  2/840 (0.24%)  0/811 (0.00%)  0/826 (0.00%) 
HUMERUS FRACTURE * 1  0/840 (0.00%)  0/811 (0.00%)  1/826 (0.12%) 
INCISIONAL HERNIA * 1  0/840 (0.00%)  1/811 (0.12%)  0/826 (0.00%) 
JOINT INJURY * 1  0/840 (0.00%)  1/811 (0.12%)  0/826 (0.00%) 
LACERATION * 1  0/840 (0.00%)  1/811 (0.12%)  0/826 (0.00%) 
LIGAMENT RUPTURE * 1  1/840 (0.12%)  0/811 (0.00%)  1/826 (0.12%) 
LIMB INJURY * 1  1/840 (0.12%)  0/811 (0.00%)  0/826 (0.00%) 
LOWER LIMB FRACTURE * 1  0/840 (0.00%)  1/811 (0.12%)  0/826 (0.00%) 
LUMBAR VERTEBRAL FRACTURE * 1  0/840 (0.00%)  1/811 (0.12%)  0/826 (0.00%) 
MENISCUS LESION * 1  1/840 (0.12%)  0/811 (0.00%)  1/826 (0.12%) 
OVERDOSE * 1  1/840 (0.12%)  1/811 (0.12%)  0/826 (0.00%) 
POST PROCEDURAL HAEMATOMA * 1  1/840 (0.12%)  0/811 (0.00%)  0/826 (0.00%) 
POST PROCEDURAL HAEMORRHAGE * 1  1/840 (0.12%)  0/811 (0.00%)  0/826 (0.00%) 
RADIUS FRACTURE * 1  0/840 (0.00%)  1/811 (0.12%)  0/826 (0.00%) 
SPINAL COMPRESSION FRACTURE * 1  0/840 (0.00%)  1/811 (0.12%)  0/826 (0.00%) 
SPINAL FRACTURE * 1  1/840 (0.12%)  0/811 (0.00%)  0/826 (0.00%) 
THERMAL BURN * 1  0/840 (0.00%)  1/811 (0.12%)  0/826 (0.00%) 
TOXICITY TO VARIOUS AGENTS * 1  0/840 (0.00%)  0/811 (0.00%)  1/826 (0.12%) 
WOUND HAEMORRHAGE * 1  1/840 (0.12%)  0/811 (0.00%)  0/826 (0.00%) 
WRIST FRACTURE * 1  1/840 (0.12%)  0/811 (0.00%)  1/826 (0.12%) 
Investigations       
BIOPSY BONE * 1  0/840 (0.00%)  0/811 (0.00%)  1/826 (0.12%) 
COAGULATION TIME PROLONGED * 1  0/840 (0.00%)  1/811 (0.12%)  0/826 (0.00%) 
PLATELET COUNT DECREASED * 1  1/840 (0.12%)  0/811 (0.00%)  0/826 (0.00%) 
Metabolism and nutrition disorders       
DEHYDRATION * 1  0/840 (0.00%)  1/811 (0.12%)  0/826 (0.00%) 
DIABETES MELLITUS * 1  0/840 (0.00%)  0/811 (0.00%)  1/826 (0.12%) 
ELECTROLYTE IMBALANCE * 1  0/840 (0.00%)  1/811 (0.12%)  0/826 (0.00%) 
HYPERGLYCAEMIA * 1  0/840 (0.00%)  1/811 (0.12%)  0/826 (0.00%) 
HYPONATRAEMIA * 1  0/840 (0.00%)  2/811 (0.25%)  0/826 (0.00%) 
Musculoskeletal and connective tissue disorders       
ARTHRALGIA * 1  0/840 (0.00%)  1/811 (0.12%)  1/826 (0.12%) 
ARTHRITIS * 1  1/840 (0.12%)  0/811 (0.00%)  0/826 (0.00%) 
INTERVERTEBRAL DISC DEGENERATION * 1  0/840 (0.00%)  1/811 (0.12%)  0/826 (0.00%) 
INTERVERTEBRAL DISC PROTRUSION * 1  1/840 (0.12%)  1/811 (0.12%)  0/826 (0.00%) 
JOINT ANKYLOSIS * 1  0/840 (0.00%)  1/811 (0.12%)  0/826 (0.00%) 
LIGAMENT DISORDER * 1  0/840 (0.00%)  1/811 (0.12%)  0/826 (0.00%) 
LUMBAR SPINAL STENOSIS * 1  1/840 (0.12%)  0/811 (0.00%)  0/826 (0.00%) 
MUSCULOSKELETAL CHEST PAIN * 1  1/840 (0.12%)  0/811 (0.00%)  0/826 (0.00%) 
MUSCULOSKELETAL PAIN * 1  0/840 (0.00%)  1/811 (0.12%)  1/826 (0.12%) 
OSTEOARTHRITIS * 1  3/840 (0.36%)  0/811 (0.00%)  3/826 (0.36%) 
PSORIATIC ARTHROPATHY * 1  0/840 (0.00%)  1/811 (0.12%)  0/826 (0.00%) 
RHEUMATOID ARTHRITIS * 1  0/840 (0.00%)  0/811 (0.00%)  1/826 (0.12%) 
ROTATOR CUFF SYNDROME * 1  1/840 (0.12%)  1/811 (0.12%)  0/826 (0.00%) 
SCOLIOSIS * 1  0/840 (0.00%)  0/811 (0.00%)  1/826 (0.12%) 
TENDONITIS * 1  1/840 (0.12%)  0/811 (0.00%)  0/826 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
BASAL CELL CARCINOMA * 1  2/840 (0.24%)  0/811 (0.00%)  1/826 (0.12%) 
BENIGN PANCREATIC NEOPLASM * 1  0/840 (0.00%)  1/811 (0.12%)  0/826 (0.00%) 
BREAST CANCER * 1  1/840 (0.12%)  2/811 (0.25%)  3/826 (0.36%) 
CARCINOID TUMOUR * 1  0/840 (0.00%)  1/811 (0.12%)  0/826 (0.00%) 
CERVIX CARCINOMA * 1  0/840 (0.00%)  1/811 (0.12%)  1/826 (0.12%) 
COLON ADENOMA * 1  0/840 (0.00%)  1/811 (0.12%)  0/826 (0.00%) 
COLON CANCER * 1  1/840 (0.12%)  0/811 (0.00%)  1/826 (0.12%) 
COLON CANCER METASTATIC * 1  0/840 (0.00%)  0/811 (0.00%)  1/826 (0.12%) 
ENDOMETRIAL CANCER * 1  1/840 (0.12%)  1/811 (0.12%)  0/826 (0.00%) 
GASTROINTESTINAL CARCINOMA * 1  0/840 (0.00%)  1/811 (0.12%)  0/826 (0.00%) 
GASTROINTESTINAL STROMAL TUMOUR * 1  0/840 (0.00%)  0/811 (0.00%)  1/826 (0.12%) 
LIP AND/OR ORAL CAVITY CANCER * 1  0/840 (0.00%)  1/811 (0.12%)  0/826 (0.00%) 
LIPOMA * 1  1/840 (0.12%)  0/811 (0.00%)  0/826 (0.00%) 
LUNG ADENOCARCINOMA * 1  0/840 (0.00%)  1/811 (0.12%)  0/826 (0.00%) 
LUNG NEOPLASM MALIGNANT * 1  2/840 (0.24%)  0/811 (0.00%)  0/826 (0.00%) 
MALIGNANT MELANOMA * 1  0/840 (0.00%)  1/811 (0.12%)  0/826 (0.00%) 
METASTASES TO BONE * 1  0/840 (0.00%)  0/811 (0.00%)  1/826 (0.12%) 
METASTATIC BRONCHIAL CARCINOMA * 1  0/840 (0.00%)  1/811 (0.12%)  0/826 (0.00%) 
METASTATIC NEOPLASM * 1  3/840 (0.36%)  0/811 (0.00%)  0/826 (0.00%) 
MULTIPLE MYELOMA * 1  1/840 (0.12%)  1/811 (0.12%)  0/826 (0.00%) 
MYELODYSPLASTIC SYNDROME * 1  0/840 (0.00%)  1/811 (0.12%)  0/826 (0.00%) 
NON-HODGKIN'S LYMPHOMA RECURRENT * 1  0/840 (0.00%)  0/811 (0.00%)  1/826 (0.12%) 
OVARIAN ADENOMA * 1  0/840 (0.00%)  0/811 (0.00%)  1/826 (0.12%) 
OVARIAN NEOPLASM * 1  0/840 (0.00%)  0/811 (0.00%)  1/826 (0.12%) 
PANCREATIC NEOPLASM * 1  0/840 (0.00%)  0/811 (0.00%)  1/826 (0.12%) 
PROSTATE CANCER * 1  2/840 (0.24%)  1/811 (0.12%)  0/826 (0.00%) 
RECTAL CANCER RECURRENT * 1  0/840 (0.00%)  0/811 (0.00%)  1/826 (0.12%) 
RENAL CANCER * 1  0/840 (0.00%)  0/811 (0.00%)  1/826 (0.12%) 
SKIN CANCER * 1  0/840 (0.00%)  1/811 (0.12%)  0/826 (0.00%) 
SQUAMOUS CELL CARCINOMA OF SKIN * 1  1/840 (0.12%)  0/811 (0.00%)  1/826 (0.12%) 
THYROID CANCER * 1  0/840 (0.00%)  0/811 (0.00%)  1/826 (0.12%) 
UTERINE LEIOMYOMA * 1  1/840 (0.12%)  0/811 (0.00%)  1/826 (0.12%) 
VOCAL CORD NEOPLASM * 1  1/840 (0.12%)  0/811 (0.00%)  0/826 (0.00%) 
Nervous system disorders       
CEREBRAL HAEMORRHAGE * 1  0/840 (0.00%)  0/811 (0.00%)  1/826 (0.12%) 
CEREBROVASCULAR ACCIDENT * 1  1/840 (0.12%)  1/811 (0.12%)  3/826 (0.36%) 
CONVULSION * 1  1/840 (0.12%)  1/811 (0.12%)  0/826 (0.00%) 
DEMYELINATING POLYNEUROPATHY * 1  0/840 (0.00%)  0/811 (0.00%)  1/826 (0.12%) 
EPILEPSY * 1  0/840 (0.00%)  0/811 (0.00%)  1/826 (0.12%) 
EXTRAPYRAMIDAL DISORDER * 1  1/840 (0.12%)  0/811 (0.00%)  0/826 (0.00%) 
FEBRILE CONVULSION * 1  1/840 (0.12%)  0/811 (0.00%)  0/826 (0.00%) 
HEADACHE * 1  0/840 (0.00%)  2/811 (0.25%)  0/826 (0.00%) 
HEMIANOPIA HOMONYMOUS * 1  1/840 (0.12%)  0/811 (0.00%)  0/826 (0.00%) 
ISCHAEMIC STROKE * 1  1/840 (0.12%)  1/811 (0.12%)  2/826 (0.24%) 
MIGRAINE * 1  1/840 (0.12%)  0/811 (0.00%)  0/826 (0.00%) 
MULTIPLE SCLEROSIS * 1  0/840 (0.00%)  0/811 (0.00%)  1/826 (0.12%) 
OPTIC NEURITIS * 1  0/840 (0.00%)  1/811 (0.12%)  0/826 (0.00%) 
PRESYNCOPE * 1  0/840 (0.00%)  1/811 (0.12%)  0/826 (0.00%) 
SCIATICA * 1  2/840 (0.24%)  0/811 (0.00%)  0/826 (0.00%) 
SYNCOPE * 1  1/840 (0.12%)  1/811 (0.12%)  1/826 (0.12%) 
TRANSIENT ISCHAEMIC ATTACK * 1  0/840 (0.00%)  0/811 (0.00%)  2/826 (0.24%) 
Pregnancy, puerperium and perinatal conditions       
ABORTION SPONTANEOUS * 1  0/840 (0.00%)  1/811 (0.12%)  0/826 (0.00%) 
PREGNANCY * 1  3/840 (0.36%)  4/811 (0.49%)  1/826 (0.12%) 
Psychiatric disorders       
ALCOHOLISM * 1  1/840 (0.12%)  0/811 (0.00%)  0/826 (0.00%) 
DELIRIUM * 1  1/840 (0.12%)  0/811 (0.00%)  0/826 (0.00%) 
DEPRESSION * 1  0/840 (0.00%)  1/811 (0.12%)  1/826 (0.12%) 
DRUG DEPENDENCE * 1  0/840 (0.00%)  0/811 (0.00%)  1/826 (0.12%) 
PANIC ATTACK * 1  0/840 (0.00%)  0/811 (0.00%)  1/826 (0.12%) 
SUICIDAL IDEATION * 1  1/840 (0.12%)  0/811 (0.00%)  0/826 (0.00%) 
Renal and urinary disorders       
CALCULUS URINARY * 1  1/840 (0.12%)  0/811 (0.00%)  1/826 (0.12%) 
HAEMATURIA * 1  0/840 (0.00%)  2/811 (0.25%)  2/826 (0.24%) 
HYDRONEPHROSIS * 1  0/840 (0.00%)  1/811 (0.12%)  1/826 (0.12%) 
NEPHROLITHIASIS * 1  2/840 (0.24%)  0/811 (0.00%)  1/826 (0.12%) 
RENAL COLIC * 1  0/840 (0.00%)  1/811 (0.12%)  3/826 (0.36%) 
RENAL FAILURE ACUTE * 1  2/840 (0.24%)  0/811 (0.00%)  2/826 (0.24%) 
RENAL IMPAIRMENT * 1  1/840 (0.12%)  0/811 (0.00%)  0/826 (0.00%) 
URETERIC STENOSIS * 1  0/840 (0.00%)  0/811 (0.00%)  2/826 (0.24%) 
URINARY RETENTION * 1  0/840 (0.00%)  1/811 (0.12%)  0/826 (0.00%) 
Reproductive system and breast disorders       
METRORRHAGIA * 1  1/840 (0.12%)  0/811 (0.00%)  0/826 (0.00%) 
OVARIAN CYST * 1  0/840 (0.00%)  0/811 (0.00%)  1/826 (0.12%) 
Respiratory, thoracic and mediastinal disorders       
ACUTE PULMONARY OEDEMA * 1  0/840 (0.00%)  1/811 (0.12%)  0/826 (0.00%) 
ALLERGIC GRANULOMATOUS ANGIITIS * 1  0/840 (0.00%)  0/811 (0.00%)  1/826 (0.12%) 
ASTHMA * 1  0/840 (0.00%)  1/811 (0.12%)  1/826 (0.12%) 
ASTHMATIC CRISIS * 1  0/840 (0.00%)  0/811 (0.00%)  1/826 (0.12%) 
BRONCHITIS CHRONIC * 1  1/840 (0.12%)  0/811 (0.00%)  0/826 (0.00%) 
CHRONIC OBSTRUCTIVE PULMONARY DISEASE * 1  3/840 (0.36%)  3/811 (0.37%)  2/826 (0.24%) 
DYSPNOEA EXERTIONAL * 1  0/840 (0.00%)  1/811 (0.12%)  0/826 (0.00%) 
EPISTAXIS * 1  0/840 (0.00%)  2/811 (0.25%)  1/826 (0.12%) 
HAEMOPTYSIS * 1  1/840 (0.12%)  0/811 (0.00%)  0/826 (0.00%) 
LARYNGEAL OEDEMA * 1  0/840 (0.00%)  0/811 (0.00%)  1/826 (0.12%) 
PLEURAL EFFUSION * 1  0/840 (0.00%)  0/811 (0.00%)  2/826 (0.24%) 
PLEURISY * 1  0/840 (0.00%)  0/811 (0.00%)  1/826 (0.12%) 
PLEURITIC PAIN * 1  1/840 (0.12%)  0/811 (0.00%)  1/826 (0.12%) 
PULMONARY EMBOLISM * 1  5/840 (0.60%)  3/811 (0.37%)  20/826 (2.42%) 
RESPIRATORY DISORDER * 1  0/840 (0.00%)  1/811 (0.12%)  0/826 (0.00%) 
SLEEP APNOEA SYNDROME * 1  0/840 (0.00%)  1/811 (0.12%)  0/826 (0.00%) 
Skin and subcutaneous tissue disorders       
DECUBITUS ULCER * 1  0/840 (0.00%)  1/811 (0.12%)  0/826 (0.00%) 
DIABETIC FOOT * 1  1/840 (0.12%)  0/811 (0.00%)  0/826 (0.00%) 
Social circumstances       
MISCARRIAGE OF PARTNER * 1  0/840 (0.00%)  0/811 (0.00%)  1/826 (0.12%) 
PREGNANCY OF PARTNER * 1  0/840 (0.00%)  1/811 (0.12%)  1/826 (0.12%) 
Surgical and medical procedures       
ABORTION INDUCED * 1  0/840 (0.00%)  0/811 (0.00%)  1/826 (0.12%) 
HOSPITALISATION * 1  0/840 (0.00%)  2/811 (0.25%)  1/826 (0.12%) 
Vascular disorders       
ANEURYSM * 1  0/840 (0.00%)  0/811 (0.00%)  1/826 (0.12%) 
ARTERIAL DISORDER * 1  1/840 (0.12%)  0/811 (0.00%)  0/826 (0.00%) 
DEEP VEIN THROMBOSIS * 1  3/840 (0.36%)  9/811 (1.11%)  40/826 (4.84%) 
EMBOLISM VENOUS * 1  0/840 (0.00%)  0/811 (0.00%)  1/826 (0.12%) 
FEMORAL ARTERY EMBOLISM * 1  1/840 (0.12%)  1/811 (0.12%)  0/826 (0.00%) 
HAEMATOMA * 1  0/840 (0.00%)  0/811 (0.00%)  1/826 (0.12%) 
HYPERTENSIVE CRISIS * 1  1/840 (0.12%)  0/811 (0.00%)  0/826 (0.00%) 
HYPOTENSION * 1  0/840 (0.00%)  1/811 (0.12%)  1/826 (0.12%) 
MALIGNANT HYPERTENSION * 1  1/840 (0.12%)  0/811 (0.00%)  0/826 (0.00%) 
ORTHOSTATIC HYPOTENSION * 1  1/840 (0.12%)  0/811 (0.00%)  0/826 (0.00%) 
PERIPHERAL VASCULAR DISORDER * 1  0/840 (0.00%)  1/811 (0.12%)  0/826 (0.00%) 
THROMBOPHLEBITIS SUPERFICIAL * 1  0/840 (0.00%)  0/811 (0.00%)  1/826 (0.12%) 
THROMBOSIS * 1  1/840 (0.12%)  0/811 (0.00%)  0/826 (0.00%) 
VARICOPHLEBITIS * 1  0/840 (0.00%)  1/811 (0.12%)  0/826 (0.00%) 
VENOUS INSUFFICIENCY * 1  0/840 (0.00%)  0/811 (0.00%)  1/826 (0.12%) 
VENOUS THROMBOSIS * 1  0/840 (0.00%)  0/811 (0.00%)  3/826 (0.36%) 
VENOUS THROMBOSIS LIMB * 1  0/840 (0.00%)  0/811 (0.00%)  1/826 (0.12%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, 15.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 2%
Apixaban 2.5mg Apixaban 5mg Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   341/840 (40.60%)   305/811 (37.61%)   318/826 (38.50%) 
Gastrointestinal disorders       
CONSTIPATION * 1  18/840 (2.14%)  12/811 (1.48%)  14/826 (1.69%) 
DIARRHOEA * 1  37/840 (4.40%)  24/811 (2.96%)  24/826 (2.91%) 
NAUSEA * 1  20/840 (2.38%)  18/811 (2.22%)  20/826 (2.42%) 
General disorders       
FATIGUE * 1  17/840 (2.02%)  14/811 (1.73%)  10/826 (1.21%) 
OEDEMA PERIPHERAL * 1  28/840 (3.33%)  25/811 (3.08%)  33/826 (4.00%) 
Infections and infestations       
BRONCHITIS * 1  24/840 (2.86%)  30/811 (3.70%)  13/826 (1.57%) 
INFLUENZA * 1  18/840 (2.14%)  20/811 (2.47%)  20/826 (2.42%) 
NASOPHARYNGITIS * 1  41/840 (4.88%)  31/811 (3.82%)  40/826 (4.84%) 
UPPER RESPIRATORY TRACT INFECTION * 1  18/840 (2.14%)  18/811 (2.22%)  18/826 (2.18%) 
URINARY TRACT INFECTION * 1  28/840 (3.33%)  30/811 (3.70%)  34/826 (4.12%) 
Investigations       
BLOOD CREATINE PHOSPHOKINASE INCREASED * 1  26/840 (3.10%)  20/811 (2.47%)  21/826 (2.54%) 
Musculoskeletal and connective tissue disorders       
ARTHRALGIA * 1  32/840 (3.81%)  21/811 (2.59%)  22/826 (2.66%) 
BACK PAIN * 1  27/840 (3.21%)  45/811 (5.55%)  24/826 (2.91%) 
MUSCLE SPASMS * 1  21/840 (2.50%)  16/811 (1.97%)  13/826 (1.57%) 
PAIN IN EXTREMITY * 1  44/840 (5.24%)  52/811 (6.41%)  54/826 (6.54%) 
Nervous system disorders       
DIZZINESS * 1  20/840 (2.38%)  18/811 (2.22%)  15/826 (1.82%) 
HEADACHE * 1  44/840 (5.24%)  41/811 (5.06%)  42/826 (5.08%) 
Respiratory, thoracic and mediastinal disorders       
COUGH * 1  21/840 (2.50%)  21/811 (2.59%)  18/826 (2.18%) 
DYSPNOEA * 1  18/840 (2.14%)  15/811 (1.85%)  19/826 (2.30%) 
EPISTAXIS * 1  13/840 (1.55%)  27/811 (3.33%)  8/826 (0.97%) 
Skin and subcutaneous tissue disorders       
RASH * 1  18/840 (2.14%)  8/811 (0.99%)  12/826 (1.45%) 
Vascular disorders       
DEEP VEIN THROMBOSIS * 1  12/840 (1.43%)  8/811 (0.99%)  23/826 (2.78%) 
HYPERTENSION * 1  34/840 (4.05%)  19/811 (2.34%)  14/826 (1.69%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, 15.0
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
Name/Title: Bristol-Myers Squibb Study Director
Organization: Bristol-Myers Squibb
Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT00633893     History of Changes
Other Study ID Numbers: CV185-057
EUDRACT: 2007-004953-27
First Submitted: March 5, 2008
First Posted: March 12, 2008
Results First Submitted: August 19, 2013
Results First Posted: October 25, 2013
Last Update Posted: November 25, 2013