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Trial record 86 of 115 for:    centurion

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

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ClinicalTrials.gov Identifier: NCT00643201
Recruitment Status : Completed
First Posted : March 26, 2008
Results First Posted : April 10, 2014
Last Update Posted : April 21, 2014
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: Enoxaparin
Drug: warfarin
Drug: Placebo for apixaban
Drug: Placebo for enoxaparin
Drug: Placebo for warfarin
Drug: apixaban
Enrollment 5614
Recruitment Details First participant, first visit: 27 August 2008; Last participant, last visit: 12 March 2013.
Pre-assignment Details 5614 enrolled, 5395 randomized; Reasons for non-randomization: 173 did not meet inclusion/exclusion criteria; 12 withdrew consent; 5 had clinical reason to continue current treatment; 3 administrative reason by sponsor; 1 death; 1 adverse event (AE); 24 other reasons. 1 site (5 patients) excluded from analysis due to unconfirmed accuracy of data.
Arm/Group Title Apixaban Enoxaparin + Warfarin
Hide Arm/Group Description

apixaban: tablets, oral, 10 milligram (mg) tablets, twice daily, for 7 days followed by apixaban 5 mg, twice daily, 6 months.

Placebo for enoxaparin: solution, subcutaneous, 1milligram per kilogram (mg/kg) every 12 hours until sham international normalized ratio (INR) greater than, equal to ( ≥) 2.

Placebo for warfarin: tablets, oral, dosing to target sham INR range between 2.0 - 3.0, once daily, 6 months

Enoxaparin: solution, subcutaneous, 1 mg/kg Q12h until INR ≥2.

Warfarin: tablets, oral, dosing to target INR range between 2.0 - 3.0, once daily, 6 months

Placebo for apixaban: tablets, oral, 10 mg tablets, twice daily, for 7 days followed by placebo for apixaban 5 mg tablets, twice daily, 6 months

Period Title: Randomized, Completed 6 Months of Study
Started 2691 [1] 2704 [1]
Completed 2314 2291
Not Completed 377 413
Reason Not Completed
Death             20             26
Adverse Event             150             182
Withdrawal by Subject             49             49
Lost to Follow-up             14             14
Poor or non-compliance             20             23
Pregnancy             3             2
Fails to meet inclusion/exclusion             13             9
Administrative reason             1             1
not specified             107             107
[1]
15 participants were randomized to treatment but not treated.
Period Title: Completed Study Follow Up
Started 2617 2639
Completed 2547 [1] 2560 [2]
Not Completed 70 79
Reason Not Completed
Death             28             34
Withdrawal by Subject             23             29
Lost to Follow-up             18             16
non-specified             1             0
[1]
Of 70 who did not complete follow up: 7 completed treatment; 63 discontinued treatment
[2]
Of 79 who did not complete follow up: 3 completed treatment, 76 discontinued treatment
Arm/Group Title Apixaban Enoxaparin + Warfarin Total
Hide Arm/Group Description

apixaban: tablets, oral, 10 milligram (mg) tablets, twice daily, for 7 days followed by apixaban 5 mg, twice daily, 6 months.

Placebo for enoxaparin: solution, subcutaneous, 1milligram per kilogram (mg/kg) every 12 hours until sham International normalized ratio (INR) greater than, equal to ( ≥) 2.

Placebo for warfarin: tablets, oral, dosing to target sham INR range between 2.0 - 3.0, once daily, 6 months

Enoxaparin: solution, subcutaneous, 1 mg/kg Q12h until INR ≥2.

warfarin: tablets, oral, dosing to target INR range between 2.0 - 3.0, once daily, 6 months

Placebo for apixaban: tablets, oral, 10 mg tablets, twice daily, for 7 days followed by placebo for apixaban 5 mg tablets, twice daily, 6 months

Total of all reporting groups
Overall Number of Baseline Participants 2691 2704 5395
Hide Baseline Analysis Population Description
Randomized Participants
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 2691 participants 2704 participants 5395 participants
57.2  (15.98) 56.7  (16.01) 56.9  (16.00)
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 2691 participants 2704 participants 5395 participants
Less than (<) 65 1729 1762 3491
65 to < 75 560 570 1130
Greater than, equal to (>=) 75 402 372 774
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 2691 participants 2704 participants 5395 participants
Female
1122
  41.7%
1106
  40.9%
2228
  41.3%
Male
1569
  58.3%
1598
  59.1%
3167
  58.7%
Race/Ethnicity, Customized   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 2691 participants 2704 participants 5395 participants
White 2218 2243 4461
Black or African American 106 98 204
American Indian or Alaska Native 6 2 8
Asian 227 226 453
Other Race 89 85 174
Race Not Reported 45 50 95
Hispanic or Latino 20 18 38
Not Hispanic or Latino 367 380 747
Ethnicity Not Reported 2304 2306 4610
[1]
Measure Description: Ethnicity was not collected outside of the United States.
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 2691 participants 2704 participants 5395 participants
Portugal 10 9 19
United States 387 398 785
Hong Kong 2 1 3
Spain 56 51 107
Ukraine 213 211 424
Israel 162 163 325
Russian Federation 178 174 352
Italy 167 169 336
India 101 99 200
France 140 149 289
Malaysia 0 2 2
Australia 56 64 120
Denmark 69 72 141
South Africa 70 77 147
China 113 114 227
Korea, Republic of 2 2 4
Austria 40 39 79
Czech Republic 140 134 274
Hungary 145 128 273
Mexico 59 57 116
Canada 147 152 299
Argentina 17 16 33
Poland 60 59 119
Brazil 77 81 158
Singapore 5 5 10
Romania 33 41 74
Norway 40 32 72
Germany 202 205 407
Qualifying index Venous Thromboembolic Embolism   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 2691 participants 2704 participants 5395 participants
Provoked Index VTE 272 272 544
Unprovoked Index VTE 2416 2429 4845
Not Reported 3 3 6
[1]
Measure Description: Both the 2004 and 2008 American College of Chest Physicians (ACCP) recommendations for treatment of venous thromboembolic events (VTE) were used during this study and recommendations were consistent. Participants with provoked and unprovoked index events were summarized. For unprovoked events in participants with certain risk factors and medical conditions, such as cancer, an idiopathic event, presence of pro-thrombotic genotype, or presence of a marker indicative of an increased risk of recurrent thromboembolism treatment for 6 months or longer is supported by the ACCP guidelines.
Index Event Classification   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 2691 participants 2704 participants 5395 participants
Proximal DVT 1778 1814 3592
PE 913 890 1803
Adjudicated Proximal DVT 1749 1783 3532
Adjudicated PE 930 906 1836
[1]
Measure Description: Participants with events of either deep vein thrombosis (DVT) or pulmonary embolism (PE) were enrolled. If a participant had both DVT and PE, the participant was classified to PE. Each participant was counted once in a category but could be counted in more than one category. An Independent Central Adjudication Committee (ICAC) reviewed participants in a blinded manner. The ICAC included a chairman and independent reviewers who were physicians with experience in vascular medicine and thrombosis. The ICAC adjudicated all index events (proximal DVT and/or PE).
1.Primary Outcome
Title Incidence of Adjudicated Composite of Symptomatic, Recurrent Venous Thromboembolism (VTE) or VTE-Related Death During 6 Months of Treatment
Hide Description VTE: nonfatal deep vein thrombosis (DVT) or nonfatal pulmonary embolism (PE). All events were adjudicated by an ICAC 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): n/N (n=number of participants with observation; N=total number of efficacy evaluable participants). Intended treatment period: longer of the dosing period plus 2 days (completed treatment) or 355 days (discontinued early). Composite endpoint: events at any time from randomization until end of intended treatment, regardless whether drug treatment was received. All randomized participants with a non-missing primary endpoint were summarized. Missing endpoint = outcomes which could not be documented on or after study Day 154. Participants were categorized to the assigned group regardless of the treatment actually received (intent-to-treat).
Time Frame Day 1 to Week 24 + 2 Days or 355 days (Discontinued Early)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants with a non-missing primary endpoint (n/N: 59/2609; 71/2635, in apixaban, enoxaparin/warfarin, respectively). Intent-to-treat population. Confidence interval (CI) for event rate calculated based on the Wald asymptotic confidence limits.
Arm/Group Title Apixaban Enoxaparin + Warfarin
Hide Arm/Group Description:

Apixaban: tablets, oral, 10 mg tablets, twice daily, for 7 days followed by apixaban 5 mg, twice daily, 6 months

Placebo for enoxaparin: solution, subcutaneous, 1 mg/kg Q12h until sham INR ≥2.

Placebo for warfarin: tablets, oral, dosing to target sham INR range between 2.0 - 3.0, once daily, 6 months

Enoxaparin: solution, subcutaneous, 1 mg/kg Q12h until INR ≥2

warfarin: tablets, oral, dosing to target INR range between 2.0 - 3.0, once daily, 6 months

Placebo for apixaban: tablets, oral, 10 mg tablets, twice daily, for 7 days followed by placebo for apixaban 5 mg tablets, twice daily, 6 months

Overall Number of Participants Analyzed 2609 2635
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: proportion of participants
0.0226
(0.0169 to 0.0283)
0.0269
(0.0208 to 0.0331)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Apixaban, Enoxaparin + Warfarin
Comments Hypothesis that apixaban was non-inferior to enoxaparin/warfarin therapy in preventing the recurrence of VTE (nonfatal DVT or nonfatal PE)/VTE-related death.
Type of Statistical Test Non-Inferiority or Equivalence
Comments Statistical Testing: non-inferiority tested at 1-sided α=0.025 with margin of 1.8. Demonstration of non-inferiority using both relative risk (RR) (margin = 1.8) and risk difference (RD) (margin = 0.035) were required to achieve the primary objective.
Statistical Test of Hypothesis P-Value <0.0001
Comments This is the first test in a sequential testing sequence. p-value calculated based on the Yanagawa-Tango-Hiejima test stratified by index event strata for non-inferiority. Tested at 1-sided α=0.025
Method Yanagawa-Tango-Hiejima
Comments For a successful trial; rejection of the null hypotheses for both RR and RD was required.
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 0.8390
Confidence Interval (2-Sided) 95%
0.5965 to 1.1802
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Apixaban, Enoxaparin + Warfarin
Comments Hypothesis that apixaban was non-inferior to enoxaparin/warfarin therapy in preventing the recurrence of VTE (nonfatal DVT or nonfatalPE)/VTE-related death as measured by risk difference.
Type of Statistical Test Non-Inferiority or Equivalence
Comments Statistical Testing; non-inferiority tested at 1-sided α=0.025. If non-inferiority demonstrated for both RR and RD, the primary objective was achieved.
Statistical Test of Hypothesis P-Value <0.0001
Comments Yanagawa-Tango-Hiejima test statistic for risk difference (RD).
Method Yanagawa-Tango-Hiejima
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value -0.0044
Confidence Interval (2-Sided) 95%
-0.0128 to 0.0040
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Apixaban, Enoxaparin + Warfarin
Comments Hypothesis of apixaban therapy being superior to enoxaparin/warfarin therapy for the adjudicated endpoint. Inferential testing required demonstration of non-inferiority using both RR and RD plus demonstration of superiority for major bleeding.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3128
Comments Tested at 2-sided α=0.05 significance. Further inferential statistical testing halted due to failure to reject the null hypothesis of equivalence for VTE/VTE-related death.
Method Cochran-Mantel-Haenszel
Comments Relative risk, CI, and p-value were calculated based on CMH test stratified by index event strata.
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 0.8390
Confidence Interval (2-Sided) 95%
0.5965 to 1.1802
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Incidence of Adjudicated Composite of Recurrent Symptomatic Venous Thromboembolism (VTE) or All-Cause Death
Hide Description VTE included: nonfatal DVT or nonfatal PE. All events were adjudicated by an ICAC blinded to treatment. DVT was assessed by compression ultrasound and/or venography; PE was 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 participants with observation; N=total number of efficacy evaluable 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, ie intent to treat (ITT) principle. Each participant scored as having an event only if they experienced one or more of the elements of the composite. Participants with missing endpoint information excluded.
Time Frame Day 1 up to 24 Weeks + 2 Days or 355 Days (Discontinued Early)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants with non-missing secondary endpoint (n/N: 84/2609; 104/2635, in apixaban, enoxaparin/warfarin arms, respectively). Participants categorized to assigned arm, regardless of treatment actually received. Intent to Treat principle. Confidence interval (CI) for event rate calculated based on Wald asymptotic confidence limits.
Arm/Group Title Apixaban Enoxaparin + Warfarin
Hide Arm/Group Description:

Apixaban: tablets, oral, 10 mg tablets, twice daily, for 7 days followed by apixaban 5 mg, twice daily, 6 months

Placebo for enoxaparin: solution, subcutaneous, 1 mg/kg Q12h until sham INR ≥2

Placebo for warfarin: tablets, oral, dosing to target sham INR range between 2.0 - 3.0, once daily, 6 months

Enoxaparin: solution, subcutaneous, 1 mg/kg Q12h until INR ≥2

warfarin: tablets, oral, dosing to target INR range between 2.0 - 3.0, once daily, 6 months

Placebo for apixaban: tablets, oral, 10 mg tablets, twice daily, for 7 days followed by placebo for apixaban 5 mg tablets, twice daily, 6 months

Overall Number of Participants Analyzed 2609 2635
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: proportion of participants
0.0322
(0.0254 to 0.0390)
0.0395
(0.0320 to 0.0469)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Apixaban, Enoxaparin + Warfarin
Comments Exploratory hypothesis of apixaban therapy being superior to enoxaparin/warfarin therapy for the adjudicated endpoint.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1554
Comments The test was stratified by index event strata using alpha=0.05 level of significance. Analysis was performed on the secondary efficacy dataset; there was no imputation of missing data.
Method Cochran-Mantel-Haenszel
Comments Nominal p-value is reported.
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 0.8151
Confidence Interval (2-Sided) 95%
0.6146 to 1.0812
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Incidence of Adjudicated Composite of Recurrent Symptomatic VTE or Cardiovascular (CV)-Related Death
Hide Description VTE included: nonfatal DVT or nonfatal PE. All events were adjudicated by an ICAC blinded to treatment. DVT was assessed by compression ultrasound and/or venography; PE was 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 participants with observation; N=total number of efficacy evaluable participants, participants with missing endpoint information excluded). 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, ie, ITT principle. Each participant scored as having an event only if the participant experienced one or more of the elements of the composite.
Time Frame Day 1 up to 24 Weeks + 2 Days or 355 Days (Discontinued Early)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants with non-missing secondary endpoint (n/N: 61/2609; 77/2635, in apixaban, enoxaparin/warfarin arms, respectively). Participants categorized to assigned arm, regardless of treatment actually received. Intent to Treat principle. CI for event rate calculated based on Wald asymptotic confidence limits.
Arm/Group Title Apixaban Enoxaparin + Warfarin
Hide Arm/Group Description:

Apixaban: tablets, oral, 10 mg tablets, twice daily, for 7 days followed by apixaban 5 mg, twice daily, 6 months

Placebo for enoxaparin: solution, subcutaneous, 1 mg/kg Q12h until sham INR ≥2.

Placebo for warfarin: tablets, oral, dosing to target sham INR range between 2.0 - 3.0, once daily, 6 months

Enoxaparin: solution, subcutaneous, 1 mg/kg Q12h until INR ≥2

warfarin: tablets, oral, dosing to target INR range between 2.0 - 3.0, once daily, 6 months

Placebo for apixaban: tablets, oral, 10 mg tablets, twice daily, for 7 days followed by placebo for apixaban 5 mg tablets, twice daily, 6 months

Overall Number of Participants Analyzed 2609 2635
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: proportion of participants
0.0234
(0.0176 to 0.0292)
0.0292
(0.0228 to 0.0357)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Apixaban, Enoxaparin + Warfarin
Comments Exploratory hypothesis of apixaban therapy being superior to enoxaparin/warfarin therapy for the adjudicated endpoint.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1848
Comments The test was stratified by index event strata using alpha=0.05 level of significance. . Nominal p-value is reported.
Method Cochran-Mantel-Haenszel
Comments Analysis was performed on the secondary efficacy dataset; there was no imputation of missing data.
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 0.7994
Confidence Interval (2-Sided) 95%
0.5737 to 1.1137
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Incidence of Adjudicated Composite of Recurrent Symptomatic VTE or VTE-related Death or Major Bleeding
Hide Description VTE included: nonfatal DVT or nonfatal PE. All events were adjudicated by an ICAC 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. Major bleeding defined by International Society on Thrombosis and Haemostasis: acute, clinically overt bleeding associated with decrease in hemoglobin (Hgb) of 2 g/dL or more or bleeding leading to transfusion or bleeding in a critical site or bleeding that is fatal . Event rate (proportion of participants with event): n/N (n=number of participants with observation; N=Total number of participants, excluding those with missing endpoint and including those not in the efficacy evaluable population with a bleeding event that occurred during treatment period. Events included regardless of whether or not participant received treatment, ie, ITT principle
Time Frame Day 1 up to 24 Weeks + 2 Days or 355 Days (Discontinued Early)
Hide Outcome Measure Data
Hide Analysis Population Description
Total number of participants in each randomized arm, excluded those with missing endpoint and included those not in the efficacy evaluable population with bleeding event which occurred during treatment (n/N: 73/2610; 118/2635). Confidence interval (CI) for event rate calculated based on Wald asymptotic confidence limits.
Arm/Group Title Apixaban Enoxaparin + Warfarin
Hide Arm/Group Description:

Apixaban: tablets, oral, 10 mg tablets, twice daily, for 7 days followed by apixaban 5 mg, twice daily, 6 months

Placebo for enoxaparin: solution, subcutaneous, 1 mg/kg Q12h until sham INR ≥2 Placebo for warfarin: tablets, oral, dosing to target sham INR range between 2.0 - 3.0, once daily, 6 months

Enoxaparin: solution, subcutaneous, 1 mg/kg Q12h until INR ≥2

warfarin: tablets, oral, dosing to target INR range between 2.0 - 3.0, once daily, 6 months

Placebo for apixaban: tablets, oral, 10 mg tablets, twice daily, for 7 days followed by placebo for apixaban 5 mg tablets, twice daily, 6 months

Overall Number of Participants Analyzed 2610 2635
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: proportion of participants
0.0280
(0.0216 to 0.0343)
0.0448
(0.0369 to 0.0527)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Apixaban, Enoxaparin + Warfarin
Comments Exploratory hypothesis of apixaban therapy being superior to enoxaparin/warfarin therapy for the adjudicated endpoint.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0011
Comments The test was stratified by index event strata using alpha=0.05 level of significance. Nominal p-value is reported.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 0.6236
Confidence Interval (2-Sided) 95%
0.4682 to 0.8306
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Incidence of Adjudicated Composite of Recurrent Symptomatic VTE, Myocardial Infarction, Stroke, CV-related Death, Clinically Relevant Non-major (CRNM) Bleeding or Major Bleeding
Hide Description VTE=Nonfatal DVT or nonfatal PE adjudicated by ICAC blinded to treatment. DVT: compression ultrasound and/or venography; PE: spiral computed tomography scanning, pulmonary angiography, and/or ventilation/perfusion lung scan. Major Bleeding = acute, clinically overt bleeding: decrease in Hgb of 2 g/dL or more or bleeding leading to transfusion or bleeding in a critical site or fatal bleeding. CRNM = acute clinically overt bleeding: compromising hemodynamics, leading to hospitalization, hematoma, epistasis >5 minutes or repetitive, gingival bleeding, hematuria, macroscopic gastrointestinal hemorrhage, rectal blood loss, hemoptysis. n/N (n=number of participants with observation; N=Total number of participants, excluding those with missing endpoint and including those not in the efficacy evaluable population with a bleeding event that occurred during treatment period). Events included regardless of whether or not treatment was received (ITT).
Time Frame Day 1 up to 24 Weeks + 2 Days or 355 Days (Discontinued Early)
Hide Outcome Measure Data
Hide Analysis Population Description
Total number participants in each treatment group, excluded those with missing endpoint and included those not in the efficacy evaluable population with bleeding event which occurred during treatment (n/N: 183/2617; 333/2641). Events included as per ITT principle. CI for event rate calculated based on Wald asymptotic confidence limits.
Arm/Group Title Apixaban Enoxaparin + Warfarin
Hide Arm/Group Description:

Apixaban: tablets, oral, 10 mg tablets, twice daily, for 7 days followed by apixaban 5 mg, twice daily, 6 months

Placebo for enoxaparin: solution, subcutaneous, 1 mg/kg Q12h until sham INR ≥2 Placebo for warfarin: tablets, oral, dosing to target sham INR range between 2.0 - 3.0, once daily, 6 months

Enoxaparin: solution, subcutaneous, 1 mg/kg Q12h until INR ≥2

warfarin: tablets, oral, dosing to target INR range between 2.0 - 3.0, once daily, 6 months

Placebo for apixaban: tablets, oral, 10 mg tablets, twice daily, for 7 days followed by placebo for apixaban 5 mg tablets, twice daily, 6 months

Overall Number of Participants Analyzed 2617 2641
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: proportion of participants
0.0699
(0.0602 to 0.0797)
0.1261
(0.1134 to 0.1387)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Apixaban, Enoxaparin + Warfarin
Comments Exploratory hypothesis of apixaban therapy being superior to enoxaparin/warfarin therapy for the adjudicated endpoint.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments The test was stratified by index event strata using alpha=0.05 level of significance. Nominal p-value is reported.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 0.5532
Confidence Interval (2-Sided) 95%
0.4658 to 0.6569
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Incidence of Adjudicated Symptomatic Nonfatal Deep Vein Thrombosis (DVT) During the Intended Treatment Period
Hide Description DVT adjudicated by an ICAC blinded to treatment. DVT evaluated by: compression ultrasound and/or venography. Includes events that occurred during the intended treatment period, regardless of whether the participant received study medication, intent to treat principle (ITT). Event rate (proportion of participants with event): n/N (n=number of participants with observation; N=Total number of participants, excluding those with missing endpoint). Intended treatment period: longer of the dosing period plus 2 days (completed treatment) or 355 days (discontinued early).
Time Frame Day 1 up to 24 Weeks + 2 Days or 355 Days (Discontinued Early)
Hide Outcome Measure Data
Hide Analysis Population Description
Total number of participants in each randomized arm (ITT), excluding those with missing endpoint (n/N: 22/2608; 35/2633). CI for event rate calculated based on Wald asymptotic confidence limits.
Arm/Group Title Apixaban Enoxaparin + Warfarin
Hide Arm/Group Description:

Apixaban: tablets, oral, 10 mg tablets, twice daily, for 7 days followed by apixaban 5 mg, twice daily, 6 months

Placebo for enoxaparin: solution, subcutaneous, 1 mg/kg Q12h until sham INR ≥2

Placebo for warfarin: tablets, oral, dosing to target sham INR range between 2.0 - 3.0, once daily, 6 months

Enoxaparin: solution, subcutaneous, 1 mg/kg Q12h until INR ≥2

warfarin: tablets, oral, dosing to target INR range between 2.0 - 3.0, once daily, 6 months

Placebo for apixaban: tablets, oral, 10 mg tablets, twice daily, for 7 days followed by placebo for apixaban 5 mg tablets, twice daily, 6 months

Overall Number of Participants Analyzed 2608 2633
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: proportion of participants
0.0084
(0.0049 to 0.0119)
0.0133
(0.0089 to 0.0177)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Apixaban, Enoxaparin + Warfarin
Comments Exploratory hypothesis of apixaban therapy being superior to enoxaparin/warfarin therapy for the adjudicated endpoint.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 0.6347
Confidence Interval (2-Sided) 95%
0.3735 to 1.0787
Estimation Comments Relative Risk and CI was calculated based on CMH test stratified by index event strata.
7.Secondary Outcome
Title Incidence of Adjudicated Symptomatic Nonfatal Pulmonary Embolism (PE) During the Intended Treatment Period
Hide Description PE adjudicated by an ICAC blinded to treatment. PE: spiral computed tomography scanning, pulmonary angiography, and/or ventilation/perfusion lung scan. Includes events that occurred during the intended treatment period, regardless of whether the participant received study medication (ITT principle). Event rate (proportion of participants with event): n/N (n=number of participants with observation; N=Total number of participants, excluding those with missing endpoint). Intended treatment period: longer of the dosing period plus 2 days (completed treatment) or 355 days (discontinued early).
Time Frame Day 1 to Week 24 + + 2 Days or 355 Days (Discontinued Early)
Hide Outcome Measure Data
Hide Analysis Population Description
Total number of participants in each randomized arm (ITT), excluding those with missing endpoint (n/N: 27/2606; 25/2632). CI for event rate calculated based on Wald asymptotic confidence limits.
Arm/Group Title Apixaban Enoxaparin + Warfarin
Hide Arm/Group Description:

Apixaban: tablets, oral, 10 mg tablets, twice daily, for 7 days followed by apixaban 5 mg, twice daily, 6 months

Placebo for enoxaparin: solution, subcutaneous, 1 mg/kg Q12h until sham INR ≥2

Placebo for warfarin: tablets, oral, dosing to target sham INR range between 2.0 - 3.0, once daily, 6 months

Enoxaparin: solution, subcutaneous, 1 mg/kg Q12h until INR ≥2

warfarin: tablets, oral, dosing to target INR range between 2.0 - 3.0, once daily, 6 months

Placebo for apixaban: tablets, oral, 10 mg tablets, twice daily, for 7 days followed by placebo for apixaban 5 mg tablets, twice daily, 6 months

Overall Number of Participants Analyzed 2606 2632
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: proportion of participants
0.0104
(0.0065 to 0.0142)
0.0095
(0.0058 to 0.0132)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Apixaban, Enoxaparin + Warfarin
Comments Exploratory hypothesis of apixaban therapy being superior to enoxaparin/warfarin therapy for the adjudicated endpoint.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 1.0935
Confidence Interval (2-Sided) 95%
0.6363 to 1.8793
Estimation Comments Relative Risk and CI was calculated based on CMH test stratified by index event strata.
8.Secondary Outcome
Title Incidence of Adjudicated Venous Thromboembolism (VTE)-Related Death During the Intended Treatment Period
Hide Description VTE-related death included: DVT-related death or PE-related death. All events were adjudicated by an ICAC blinded to treatment. DVT was assessed by compression ultrasound and/or venography; PE was 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 participants with observation; N=total number of participants in respective treatment groups excluding participants with missing endpoint information). Intended treatment period: longer of the dosing period plus 2 days (completed treatment) or 355 days (discontinued early). Includes events that occur during the intended treatment period regardless of whether or not the participant received study medication (ITT principle).
Time Frame Day 1 to Week 24 + 2 Days or 355 Days (Discontinued Early)
Hide Outcome Measure Data
Hide Analysis Population Description
Total number of participants in respective treatment groups excluding participants with missing endpoint information. (n/N: 12/2608; 16/2630). CI for event rate calculated based on Wald asymptotic confidence limits.
Arm/Group Title Apixaban Enoxaparin + Warfarin
Hide Arm/Group Description:

Apixaban: tablets, oral, 10 mg tablets, twice daily, for 7 days followed by apixaban 5 mg, twice daily, 6 months

Placebo for enoxaparin: solution, subcutaneous, 1 mg/kg Q12h until sham INR ≥2

Placebo for warfarin: tablets, oral, dosing to target sham INR range between 2.0 - 3.0, once daily, 6 months

Enoxaparin: solution, subcutaneous, 1 mg/kg Q12h until INR ≥2

warfarin: tablets, oral, dosing to target INR range between 2.0 - 3.0, once daily, 6 months

Placebo for apixaban: tablets, oral, 10 mg tablets, twice daily, for 7 days followed by placebo for apixaban 5 mg tablets, twice daily, 6 months

Overall Number of Participants Analyzed 2608 2630
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: proportion of participants
0.0046
(0.0020 to 0.0072)
0.0061
(0.0031 to 0.0091)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Apixaban, Enoxaparin + Warfarin
Comments Exploratory hypothesis of apixaban therapy being superior to enoxaparin/warfarin therapy for the adjudicated endpoint.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 0.7521
Confidence Interval (2-Sided) 95%
0.3560 to 1.5889
Estimation Comments Relative Risk and CI was calculated based on CMH test stratified by index event strata.
9.Secondary Outcome
Title Incidence of Cardiovascular (CV)-Related Death Including VTE-related Death During the Intended Treatment Period
Hide Description VTE-related death included: DVT-related death or PE-related death. All events were adjudicated by an ICAC 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 participants with observation; N=total number of participants in respective treatment groups excluding participants with missing endpoint information). Intended treatment period: longer of the dosing period plus 2 days (completed treatment) or 355 days (discontinued early). Includes events that occur during the intended treatment period regardless of whether or not the participant received study medication (ITT principle).
Time Frame Day 1 to Week 24 + 2 Days or 355 Days (Discontinued Early)
Hide Outcome Measure Data
Hide Analysis Population Description
Total number of participants in respective groups excluding those with missing endpoint information (n/N: 15/2608; 23/2630). CI for event rate calculated based on Wald asymptotic confidence limits.
Arm/Group Title Apixaban Enoxaparin + Warfarin
Hide Arm/Group Description:

Apixaban: tablets, oral, 10 mg tablets, twice daily, for 7 days followed by apixaban 5 mg, twice daily, 6 months

Placebo for enoxaparin: solution, subcutaneous, 1 mg/kg Q12h until sham INR ≥2

Placebo for warfarin: tablets, oral, dosing to target sham INR range between 2.0 - 3.0, once daily, 6 months

Enoxaparin: solution, subcutaneous, 1 mg/kg Q12h until INR ≥2

warfarin: tablets, oral, dosing to target INR range between 2.0 - 3.0, once daily, 6 months

Placebo for apixaban: tablets, oral, 10 mg tablets, twice daily, for 7 days followed by placebo for apixaban 5 mg tablets, twice daily, 6 months

Overall Number of Participants Analyzed 2608 2630
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: proportion of participants
0.0058
(0.0028 to 0.0087)
0.0087
(0.0052 to 0.0123)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Apixaban, Enoxaparin + Warfarin
Comments Exploratory hypothesis of apixaban therapy being superior to enoxaparin/warfarin therapy for the adjudicated endpoint.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 0.6539
Confidence Interval (2-Sided) 95%
0.3419 to 1.2508
Estimation Comments Relative Risk and CI was calculated based on CMH test stratified by index event strata.
10.Secondary Outcome
Title Incidence of All-Cause Death During the Intended Treatment Period
Hide Description Intended treatment period: longer of the dosing period plus 2 days (completed treatment) or 355 days (discontinued early). Includes events that occurred during the intended treatment period, regardless of whether the participant received study medication (ITT principle). Event rate (proportion of participants with event): n/N (n=number of participants with observation; N=Total number of participants, excluding those with missing endpoint information).
Time Frame Day 1 to Week 24 + 2 Days or 355 Days (Discontinued Early)
Hide Outcome Measure Data
Hide Analysis Population Description
Total number of participants excluding those with missing endpoint (n/N: 41/2608; 52/2630). Events included regardless of whether or not participant received treatment, ie, ITT principle. CI for event rate calculated based on Wald asymptotic confidence limits.
Arm/Group Title Apixaban Enoxaparin + Warfarin
Hide Arm/Group Description:

Apixaban: tablets, oral, 10 mg tablets, twice daily, for 7 days followed by apixaban 5 mg, twice daily, 6 months

Placebo for enoxaparin: solution, subcutaneous, 1 mg/kg Q12h until sham INR ≥2

Placebo for warfarin: tablets, oral, dosing to target sham INR range between 2.0 - 3.0, once daily, 6 months

Enoxaparin: solution, subcutaneous, 1 mg/kg Q12h until INR ≥2

warfarin: tablets, oral, dosing to target INR range between 2.0 - 3.0, once daily, 6 months

Placebo for apixaban: tablets, oral, 10 mg tablets, twice daily, for 7 days followed by placebo for apixaban 5 mg tablets, twice daily, 6 months

Overall Number of Participants Analyzed 2608 2630
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: proportion of participants
0.0157
(0.0109 to 0.0205)
0.0198
(0.0145 to 0.0251)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Apixaban, Enoxaparin + Warfarin
Comments Exploratory hypothesis of apixaban therapy being superior to enoxaparin/warfarin therapy for the adjudicated endpoint.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 0.7934
Confidence Interval (2-Sided) 95%
0.5287 to 1.1906
Estimation Comments Relative Risk and CI was calculated based on CMH test stratified by index event strata.
11.Secondary Outcome
Title Incidence of Adjudicated Major Bleeding During the Treatment Period in Treated Participants
Hide Description All events were adjudicated by an ICAC blinded to treatment. Bleeding defined by International Society on Thrombosis and Haemostasis: Major Bleeding: acute, clinically overt bleeding: decrease in hemoglobin (hgb) of 2 g/dL or more or bleeding leading to transfusion or bleeding in a critical site or fatal bleeding. Event rate (proportion of participants with event): n/N (n=number of participants with observation; N=Total number of participants in respective treatment group (all participants who received at least one dose of study drug). Participants were categorized to the treatment group to which they were assigned unless incorrect study treatment was received throughout the study, in which case the participant was categorized according to the treatment received.
Time Frame Day 1 to Week 24 + 2 Days or 355 Days (Discontinued Early)
Hide Outcome Measure Data
Hide Analysis Population Description
Total number of participants receiving at least one dose of study drug n/N: 15/2676; 49/2689, in apixaban and enoxaparin/warfarin groups, respectively. CI for event rate calculated based on Wald asymptotic confidence limits. Participants were categorized according to the actual treatment received.
Arm/Group Title Apixaban Enoxaparin + Warfarin
Hide Arm/Group Description:

Apixaban: tablets, oral, 10 mg tablets, twice daily, for 7 days followed by apixaban 5 mg, twice daily, 6 months

Placebo for enoxaparin: solution, subcutaneous, 1 mg/kg Q12h until sham INR ≥2

Placebo for warfarin: tablets, oral, dosing to target sham INR range between 2.0 - 3.0, once daily, 6 months

Enoxaparin: solution, subcutaneous, 1 mg/kg Q12h until INR ≥2

warfarin: tablets, oral, dosing to target INR range between 2.0 - 3.0, once daily, 6 months

Placebo for apixaban: tablets, oral, 10 mg tablets, twice daily, for 7 days followed by placebo for apixaban 5 mg tablets, twice daily, 6 months

Overall Number of Participants Analyzed 2676 2689
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: proportion of participants
0.0056
(0.0028 to 0.0084)
0.0182
(0.0132 to 0.0233)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Apixaban, Enoxaparin + Warfarin
Comments Hypothesis: apixaban therapy being superior to enoxaparin/warfarin therapy for the adjudicated endpoint. As per the hierarchical statistical testing cascade, inferential testing for adjudicated major bleeding occurred because non-inferiority for VTE/VTE-related death (Primary efficacy endpoint) was demonstrated earlier. Rejection of the null hypothesis for equivalence for major bleeding allowed inferential testing for superiority of VTE/VTE-related death.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments p-value calculated on the CMH test stratified by index event strata.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 0.3070
Confidence Interval (2-Sided) 95%
0.1728 to 0.5452
Estimation Comments Relative risk and CI were calculated based on CMH test stratified by index event strata.
12.Secondary Outcome
Title Incidence of Adjudicated Major/CRNM Bleeding During the Treatment Period in Treated Participants
Hide Description Major Bleeding = acute, clinically overt bleeding: decrease in hemoglobin of 2 g/dL or more, or bleeding leading to transfusion, or bleeding in a critical site, or fatal bleeding. CRNM = acute clinically overt bleeding: compromising hemodynamics, leading to hospitalization, hematoma, epistasis >5 minutes or repetitive, gingival bleeding, hematuria, macroscopic gastrointestinal hemorrhage, rectal blood loss, hemoptysis. Minor =: All acute clinically overt bleeding events not meeting the criteria for either major bleeding or CRNM. All events were adjudicated by an ICAC blinded to treatment. Total bleeding = any of major, or CRNM, or minor bleeding. Event rate (proportion of participants with event): n/N (n=number of participants with observation; N=Total number of treated (received at least 1 dose of study drug).
Time Frame Day 1 to Week 24 + 2 Days or 355 Days (Discontinued Early)
Hide Outcome Measure Data
Hide Analysis Population Description
Total number of participants receiving at least one dose of study drug n/N: 115/2676; 261/2689, in apixaban and enoxaparin/warfarin groups, respectively. CI for event rate calculated based on Wald asymptotic confidence limits. Participants were categorized according to the actual treatment received.
Arm/Group Title Apixaban Enoxaparin + Warfarin
Hide Arm/Group Description:

Apixaban: tablets, oral, 10 mg tablets, twice daily, for 7 days followed by apixaban 5 mg, twice daily, 6 months

Placebo for enoxaparin: solution, subcutaneous, 1 mg/kg Q12h until sham INR ≥2

Placebo for warfarin: tablets, oral, dosing to target sham INR range between 2.0 - 3.0, once daily, 6 months

Enoxaparin: solution, subcutaneous, 1 mg/kg Q12h until INR ≥2

warfarin: tablets, oral, dosing to target INR range between 2.0 - 3.0, once daily, 6 months

Placebo for apixaban: tablets, oral, 10 mg tablets, twice daily, for 7 days followed by placebo for apixaban 5 mg tablets, twice daily, 6 months

Overall Number of Participants Analyzed 2676 2689
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: proportion of participants
0.0430
(0.0353 to 0.0507)
0.0971
(0.0859 to 0.1083)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Apixaban, Enoxaparin + Warfarin
Comments Exploratory hypothesis of apixaban therapy being superior to enoxaparin/warfarin therapy for the adjudicated endpoint. Inferential testing was not conducted because the null hypothesis pertaining to superiority for VTE/VTE-related death was not rejected.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Tested at 2-sided alpha=0.05 significance.
Method Cochran-Mantel-Haenszel
Comments Nominal p-value is reported.
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 0.4410
Confidence Interval (2-Sided) 95%
0.3566 to 0.5453
Estimation Comments Relative Risk and CI was calculated based on CMH test stratified by index event strata.
13.Secondary Outcome
Title Incidence of Adjudicated Clinically Relevant Non Major (CRNM) Bleeding During the Treatment Period in Treated Participants
Hide Description Bleeding defined by International Society on Thrombosis and Haemostasis: CRNM defined as acute clinically overt bleeding: compromising hemodynamics, leading to hospitalization, hematoma, epistasis >5 minutes or repetitive, gingival bleeding, hematuria, macroscopic gastrointestinal hemorrhage, rectal blood loss, hemoptysis. All events were adjudicated by an ICAC blinded to treatment. Event rate (proportion of participants with event): calculated as n/N (n=number of participants with observation; N=Total number of participants in respective treatment group (all participants who received at least one dose of study drug). Participants were categorized to the treatment group to which they were assigned unless incorrect study treatment was received throughout the study, in which case the participant was categorized according to the treatment received.
Time Frame Day 1 to Week 24 + 2 Days or 355 Days (Discontinued Early)
Hide Outcome Measure Data
Hide Analysis Population Description
Total number of participants receiving at least one dose of study drug n/N: 103/2676; 215/2689, in apixaban and enoxaparin/warfarin groups, respectively. CI for event rate calculated based on Wald asymptotic confidence limits. Participants were categorized according to the actual treatment received.
Arm/Group Title Apixaban Enoxaparin + Warfarin
Hide Arm/Group Description:

Apixaban: tablets, oral, 10 mg tablets, twice daily, for 7 days followed by apixaban 5 mg, twice daily, 6 months

Placebo for enoxaparin: solution, subcutaneous, 1 mg/kg Q12h until sham INR ≥2

Placebo for warfarin: tablets, oral, dosing to target sham INR range between 2.0 - 3.0, once daily, 6 months

Enoxaparin: solution, subcutaneous, 1 mg/kg Q12h until INR ≥2

warfarin: tablets, oral, dosing to target INR range between 2.0 - 3.0, once daily, 6 months

Placebo for apixaban: tablets, oral, 10 mg tablets, twice daily, for 7 days followed by placebo for apixaban 5 mg tablets, twice daily, 6 months

Overall Number of Participants Analyzed 2676 2689
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: proportion of participants
0.0385
(0.0312 to 0.0458)
0.0800
(0.0697 to 0.0902)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Apixaban, Enoxaparin + Warfarin
Comments Exploratory hypothesis of apixaban therapy being superior to enoxaparin/warfarin therapy for the adjudicated endpoint.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Tested at 2-sided alpha=0.05 significance.
Method Cochran-Mantel-Haenszel
Comments Nominal p-value is reported.
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 0.4793
Confidence Interval (2-Sided) 95%
0.3815 to 0.6022
Estimation Comments Relative Risk and CI was calculated based on CMH test stratified by index event strata.
14.Secondary Outcome
Title Incidence of Adjudicated Minor Bleeding During the Treatment Period in Treated Participants
Hide Description Bleeding defined by International Society on Thrombosis and Haemostasis: Minor bleeding: all acute clinically overt bleeding events not meeting the criteria for either major bleeding or CRNM. All events wre adjudicated by an ICAC blinded to treatment. Event rate (proportion of participants) calculated as n/N (n=number of participants with observation; N=Total number of participants in respective treatment group (all participants who received at least one dose of study drug). Participants were categorized to the treatment group to which they were assigned unless incorrect study treatment was received throughout the study, in which case the participant was categorized according to the treatment received.
Time Frame Day 1 to Week 24 + 2 Days or 355 Days (Discontinued Early)
Hide Outcome Measure Data
Hide Analysis Population Description
Total number of participants receiving at least one dose of study drug n/N: 313/2676; 505/2689, in apixaban and enoxaparin/warfarin groups, respectively. CI for event rate calculated based on Wald asymptotic confidence limits. Participants were categorized according to the actual treatment received.
Arm/Group Title Apixaban Enoxaparin + Warfarin
Hide Arm/Group Description:

Apixaban: tablets, oral, 10 mg tablets, twice daily, for 7 days followed by apixaban 5 mg, twice daily, 6 months

Placebo for enoxaparin: solution, subcutaneous, 1 mg/kg Q12h until sham INR ≥2

Placebo for warfarin: tablets, oral, dosing to target sham INR range between 2.0 - 3.0, once daily, 6 months

Enoxaparin: solution, subcutaneous, 1 mg/kg Q12h until INR ≥2

warfarin: tablets, oral, dosing to target INR range between 2.0 - 3.0, once daily, 6 months

Placebo for apixaban: tablets, oral, 10 mg tablets, twice daily, for 7 days followed by placebo for apixaban 5 mg tablets, twice daily, 6 months

Overall Number of Participants Analyzed 2676 2689
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: proportion of participants
0.1170
(0.1048 to 0.1291)
0.1878
(0.1730 to 0.2026)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Apixaban, Enoxaparin + Warfarin
Comments Exploratory hypothesis of apixaban therapy being superior to enoxaparin/warfarin therapy for the adjudicated endpoint.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Tested at 2-sided alpha=0.05 significance.
Method Cochran-Mantel-Haenszel
Comments Nominal p-value is reported.
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 0.6182
Confidence Interval (2-Sided) 95%
0.5432 to 0.7034
Estimation Comments Relative Risk and CI was calculated based on CMH test stratified by index event strata.
15.Secondary Outcome
Title Incidence of Adjudicated Total Bleeding During the Treatment Period in Treated Participants
Hide Description Bleeding defined by International Society on Thrombosis and Haemostasis: Total Bleeding defined as any of major, CRNM, or minor bleeding. All events were adjudicated by an ICAC blinded to treatment. Event rate (proportion of participants with event): n/N (n=number of participants with observation; N=Total number of participants in respective treatment group (all participants who received at least one dose of study drug). Participants were categorized to the treatment group to which they were assigned unless incorrect study treatment was received throughout the study, in which case the participant was categorized according to the treatment received.
Time Frame Day 1 to Week 24 + 2 Days or 355 Days (Discontinued Early)
Hide Outcome Measure Data
Hide Analysis Population Description
Total number of participants receiving at least one dose of study drug n/N: 402/2676; 676/2689, in apixaban and enoxaparin/warfarin groups, respectively. CI for event rate calculated based on Wald asymptotic confidence limits. Participants were categorized according to the actual treatment received.
Arm/Group Title Apixaban Enoxaparin + Warfarin
Hide Arm/Group Description:

Apixaban: tablets, oral, 10 mg tablets, twice daily, for 7 days followed by apixaban 5 mg, twice daily, 6 months

Placebo for enoxaparin: solution, subcutaneous, 1 mg/kg Q12h until sham INR ≥2

Placebo for warfarin: tablets, oral, dosing to target sham INR range between 2.0 - 3.0, once daily, 6 months

Enoxaparin: solution, subcutaneous, 1 mg/kg Q12h until INR ≥2

warfarin: tablets, oral, dosing to target INR range between 2.0 - 3.0, once daily, 6 months

Placebo for apixaban: tablets, oral, 10 mg tablets, twice daily, for 7 days followed by placebo for apixaban 5 mg tablets, twice daily, 6 months

Overall Number of Participants Analyzed 2676 2689
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: proportion of participants
0.1502
(0.1367 to 0.1638)
0.2514
(0.2350 to 0.2678)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Apixaban, Enoxaparin + Warfarin
Comments Exploratory hypothesis of apixaban therapy being superior to enoxaparin/warfarin therapy for the adjudicated endpoint.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Tested at 2-sided alpha=0.05 significance.
Method Cochran-Mantel-Haenszel
Comments Nominal p-value is reported.
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 0.5937
Confidence Interval (2-Sided) 95%
0.5318 to 0.6629
Estimation Comments Relative Risk and CI was calculated based on CMH test stratified by index event strata.
16.Secondary Outcome
Title Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Bleeding AEs, Discontinuations Due to AEs and Death During the Treatment Period in Treated Participants
Hide Description Treated Participants: all who received at least 1 dose of study drug. Participants categorized to the treatment group to which they were assigned unless incorrect study treatment was received throughout the study, in which case the participant was categorized according to treatment received. Included all SAEs and AEs with onset from first dose to last dose + 2 days (for AEs) or + 30 days (for SAEs); note; bleeding AEs and SAEs from first dose to last dose + 2 days included. Discontinuations due to AE included all AEs/SAEs from first dose until drug was discontinued. AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization.
Time Frame First dose to last dose of 24 Weeks + 2 days (AEs) or + 30 days (SAEs) or until drug discontinued
Hide Outcome Measure Data
Hide Analysis Population Description
Total number of participants receiving at least one dose of study drug. Participants were categorized according to the actual treatment received.
Arm/Group Title Apixaban Enoxaparin + Warfarin
Hide Arm/Group Description:

Apixaban: tablets, oral, 10 mg tablets, twice daily, for 7 days followed by apixaban 5 mg, twice daily, 6 months

Placebo for enoxaparin: solution, subcutaneous, 1 mg/kg Q12h until sham INR ≥2

Placebo for warfarin: tablets, oral, dosing to target sham INR range between 2.0 - 3.0, once daily, 6 months

Enoxaparin: solution, subcutaneous, 1 mg/kg Q12h until INR ≥2

warfarin: tablets, oral, dosing to target INR range between 2.0 - 3.0, once daily, 6 months

Placebo for apixaban: tablets, oral, 10 mg tablets, twice daily, for 7 days followed by placebo for apixaban 5 mg tablets, twice daily, 6 months

Overall Number of Participants Analyzed 2676 2689
Measure Type: Number
Unit of Measure: participants
AE 1795 1923
SAE 417 410
Bleeding AE or SAE 415 695
Discontinued Due to AE or SAE 162 199
Death 37 44
17.Secondary Outcome
Title Number of Treated Participants With Marked Abnormalities in Hematology Laboratory Tests
Hide Description Lower limit of normal (LLN). Upper limit of normal (ULN). Pre-therapy (PreRx). Absolute (Abs) neutrophil count, bands + neutrophils (ANC). Cells per microliter (c/µL). Grams per deciliter (g/dL). Cells per Liter (c/L). Millimeter (MM). White blood cells: < 0.75*LLN, > 1.25*ULN; Hemoglobin: <= 11.5 g/dL (males), <= 9.5 g/dL (females); Hematocrit: <= 37% (males), <= 32% (females); Erythrocytes: <0.75*10^6 c/µL*PreRx; Platelet count: < 75*10^9 c/L, > 700*10^9 c/L; ANC: < 1.00*10^3 c/µL; Abs eosinophils: > 0.750*10^3 c/µL; Abs Basophils: > 400/MM^3; Abs Monocytes> 2000/MM^3; Abs Lymphocytes: < 0.750*10*3 c/ µL, > 7.5*10^3 c/ µL.
Time Frame Day 1 to Week 24 + 2 Days or 355 Days (Discontinued Early)
Hide Outcome Measure Data
Hide Analysis Population Description
N=Treated participants who received at least one dose of study drug and had non-missing laboratory measurements.
Arm/Group Title Apixaban Enoxaparin + Warfarin
Hide Arm/Group Description:

Apixaban: tablets, oral, 10 mg tablets, twice daily, for 7 days followed by apixaban 5 mg, twice daily, 6 months

Placebo for enoxaparin: solution, subcutaneous, 1 mg/kg Q12h until sham INR ≥2

Placebo for warfarin: tablets, oral, dosing to target sham INR range between 2.0 - 3.0, once daily, 6 months

Enoxaparin: solution, subcutaneous, 1 mg/kg Q12h until INR ≥2

warfarin: tablets, oral, dosing to target INR range between 2.0 - 3.0, once daily, 6 months

Placebo for apixaban: tablets, oral, 10 mg tablets, twice daily, for 7 days followed by placebo for apixaban 5 mg tablets, twice daily, 6 months

Overall Number of Participants Analyzed 2599 2593
Measure Type: Number
Unit of Measure: participants
Erthrocytes Low (N=2599, 2593) 23 17
Hematocrit Low (N=2588, 2587) 26 20
Hemoglobin Low (N=2599, 2593) 96 101
Platelet Count Low (N=2594, 2589) 23 13
Leukocytes Low (N=2528, 2519) 41 41
Leukocytes High (N=2528, 2519) 26 15
Absolute Basophils High (N=2594,2589) 1 2
Absolute Eosinophils High (N=2594,2589) 84 79
Absolute Lyphocytes Low (N=2594,2589) 94 76
Absolute Lyphocytes High (N=2594,2589) 4 3
Absolute Monocytes High (N=2594,2589) 1 2
Absolute Neutrophils Low (N=2594,2589) 9 20
18.Secondary Outcome
Title Number of Treated Participants With Marked Abnormalities in Electrolyte Laboratory Tests
Hide Description Bicarbonate milliequivalents/Liter (mEq/L) Low/High: < 0.75*LLN or > 1.25*ULN, or if pre-dose < LLN then use < 0.75*pre-dose or > ULN if pre-dose > ULN then use > 1.25*pre-dose or < LLN; Serum Calcium mg/dL Low/High: < 0.8*LLN or > 1.2*ULN, or if pre-dose < LLN then use < 0.75*pre-dose or > ULN if pre-dose > ULN then use > 1.25*pre-dose or < LLN; Serum Chloride mEq/L: < 0.9*LLN or > 1.1*ULN, or if pre-dose < LLN then use < 0.9*pre-dose or > ULN if pre-dose > ULN then use > 1.1*pre-dose or < LLN; Serum Potassium mEq/L: < 0.9*LLN or > 1.1*ULN, or if pre-dose < LLN then use < 0.9*pre-dose or > ULN if pre-dose > ULN then use > 1.1*pre-dose or < LLN; Serum Sodium mEq/L: < 0.95*LLN or > 1.05*ULN, or if pre-dose < LLN then use < 0.95*pre-dose or > ULN if pre-dose > ULN then use > 1.05*pre-dose or < LLN.
Time Frame Day 1 to Week 24 + 2 Days or 355 Days (Discontinued Early)
Hide Outcome Measure Data
Hide Analysis Population Description
N=Treated participants who received at least one dose of study drug and had non-missing laboratory measurements.
Arm/Group Title Apixaban Enoxaparin + Warfarin
Hide Arm/Group Description:

Apixaban: tablets, oral, 10 mg tablets, twice daily, for 7 days followed by apixaban 5 mg, twice daily, 6 months

Placebo for enoxaparin: solution, subcutaneous, 1 mg/kg Q12h until sham INR ≥2

Placebo for warfarin: tablets, oral, dosing to target sham INR range between 2.0 - 3.0, once daily, 6 months

Enoxaparin: solution, subcutaneous, 1 mg/kg Q12h until INR ≥2

warfarin: tablets, oral, dosing to target INR range between 2.0 - 3.0, once daily, 6 months

Placebo for apixaban: tablets, oral, 10 mg tablets, twice daily, for 7 days followed by placebo for apixaban 5 mg tablets, twice daily, 6 months

Overall Number of Participants Analyzed 2601 2596
Measure Type: Number
Unit of Measure: participants
Bicarbonate Low (N=2600,2593) 44 31
Bicarbonate High (N=2600,2593) 17 11
Total Calcium Low (N=2601,2596) 3 10
Total Calcium High (N=2601,2596) 12 11
Chloride Low Total Calcium Low (N=2601,2596) 5 3
Chloride Low Total Calcium High (N=2601,2596) 0 1
Potassium Low (N=2601,2596) 26 22
Potassium High (N=2601,2596) 19 22
Sodium Low (N=2601,2596) 10 6
Sodium Low (N=2601,2596) 4 4
19.Secondary Outcome
Title Number of Treated Participants With Marked Abnormalities in Kidney and Liver Function Laboratory Tests
Hide Description Blood urea nitrogen (BUN), milligrams/deciliter (mg/dL), units per liter (U/L). BUN mg/dL High: > 1.5*ULN; Creatinine mg/dL: > 1.5*ULN; Alanine aminotransferase (ALT) U/L: > 3*ULN; Aspartate aminotransferase (AST) U/L: > 3*ULN; Alkaline phosphatase U/L: > 2*ULN; Bilirubin Direct mg/dL: > 1.5*ULN; Bilirubin Total mg/dL: > 2*ULN.
Time Frame Day 1 to Week 24 + 2 Days or 355 Days (Discontinued Early)
Hide Outcome Measure Data
Hide Analysis Population Description
N=Treated participants who received at least one dose of study drug and had non-missing laboratory measurements.
Arm/Group Title Apixaban Enoxaparin + Warfarin
Hide Arm/Group Description:

Apixaban: tablets, oral, 10 mg tablets, twice daily, for 7 days followed by apixaban 5 mg, twice daily, 6 months

Placebo for enoxaparin: solution, subcutaneous, 1 mg/kg Q12h until sham INR ≥2

Placebo for warfarin: tablets, oral, dosing to target sham INR range between 2.0 - 3.0, once daily, 6 months

Enoxaparin: solution, subcutaneous, 1 mg/kg Q12h until INR ≥2

warfarin: tablets, oral, dosing to target INR range between 2.0 - 3.0, once daily, 6 months

Placebo for apixaban: tablets, oral, 10 mg tablets, twice daily, for 7 days followed by placebo for apixaban 5 mg tablets, twice daily, 6 months

Overall Number of Participants Analyzed 2601 2598
Measure Type: Number
Unit of Measure: participants
BUN High (N=517, 523) 2 7
Creatinine High (N=2601, 2596) 47 37
ALT High (N=2601, 2598) 52 145
ALP High (N=2601, 2598) 35 27
AST High (N=2601, 2598) 40 40
Direct Bilirubin High (N=2601, 2593) 28 21
Total Bilirubin High (N=2601, 2597) 8 7
20.Secondary Outcome
Title Number of Treated Participants With Marked Abnormalities in Creatine Kinase, Uric Acid, and Total Protein Laboratory Tests
Hide Description Creatine kinase High: >5*ULN Units/Liter (U/L); Total Protein High/Low: < 0.9 *LLN or > 1.1*ULN, or if pre-dose < LLN then use 0.9* pre-dose or > ULN if pre-dose > ULN then use 1.1 *pre-dose or <LLN; Uric acid High: > 1.5* ULN, or if pre-dose > ULN then use > 2 *pre-dose.
Time Frame Day 1 to Week 24 + 2 Days or 355 Days (Discontinued Early)
Hide Outcome Measure Data
Hide Analysis Population Description
N=Treated participants who received at least one dose of study drug and had non-missing laboratory measurements.
Arm/Group Title Apixaban Enoxaparin + Warfarin
Hide Arm/Group Description:

Apixaban: tablets, oral, 10 mg tablets, twice daily, for 7 days followed by apixaban 5 mg, twice daily, 6 months

Placebo for enoxaparin: solution, subcutaneous, 1 mg/kg Q12h until sham INR ≥2

Placebo for warfarin: tablets, oral, dosing to target sham INR range between 2.0 - 3.0, once daily, 6 months

Enoxaparin: solution, subcutaneous, 1 mg/kg Q12h until INR ≥2

warfarin: tablets, oral, dosing to target INR range between 2.0 - 3.0, once daily, 6 months

Placebo for apixaban: tablets, oral, 10 mg tablets, twice daily, for 7 days followed by placebo for apixaban 5 mg tablets, twice daily, 6 months

Overall Number of Participants Analyzed 2601 2596
Measure Type: Number
Unit of Measure: participants
Creatine Kinase High (N=2601, 2596) 20 24
Uric Acid High (N=2601, 2596) 6 3
Total Protein Low (N=2601, 2596) 15 16
Total Protein High (N=2601, 2596) 0 0
21.Secondary Outcome
Title Number of Treated Participants With Marked Abnormalities in Urinalysis Laboratory Tests
Hide Description All tests in urine: Glucose: If missing pre-dose use ≥ 2, or if value ≥ 4, or if pre-dose = 0 or 0.5 use ≥ 2, or if pre-dose = 1 use ≥ 3, or if pre-dose = 2 or 3 use ≥ 4; Protein: If missing pre-dose use ≥ 2, or if value ≥ 4, or if pre-dose = 0 or 0.5 use ≥ 2, or if pre-dose = 1 use ≥ 3, or if pre-dose = 2 or 3 use ≥ 4; Blood: If missing pre-dose use ≥ 2, or if value ≥ 4, or if pre-dose = 0 or 0.5 use ≥ 2, or if pre-dose = 1 use ≥ 3, or if pre-dose = 2 or 3 use ≥ 4; Leukocyte esterase: If missing pre-dose use ≥ 2, or if value ≥ 4, or if pre-dose = 0 or 0.5 use ≥ 2, or if pre-dose = 1 use ≥ 3, or if pre-dose = 2 or 3 use ≥ 4;Red blood cells (RBC): If missing pre-dose use ≥ 2, or if value ≥ 4, or if pre-dose = 0 or 0.5 use ≥ 2, or if pre-dose = 1 use ≥ 3, or if pre-dose = 2 or 3 use ≥ 4; White blood cells (WBC): If missing pre-dose use ≥ 2, or if value ≥ 4, or if pre-dose = 0 or 0.5 use ≥ 2, or if pre-dose = 1 use ≥ 3, or if pre-dose = 2 or 3 use ≥ 4.
Time Frame Day 1 to Week 24 + 2 Days or 355 Days (Discontinued Early)
Hide Outcome Measure Data
Hide Analysis Population Description
N=Treated participants who received at least one dose of study drug and had non-missing laboratory measurements.
Arm/Group Title Apixaban Enoxaparin + Warfarin
Hide Arm/Group Description:

Apixaban: tablets, oral, 10 mg tablets, twice daily, for 7 days followed by apixaban 5 mg, twice daily, 6 months

Placebo for enoxaparin: solution, subcutaneous, 1 mg/kg Q12h until sham INR ≥2

Placebo for warfarin: tablets, oral, dosing to target sham INR range between 2.0 - 3.0, once daily, 6 months

Enoxaparin: solution, subcutaneous, 1 mg/kg Q12h until INR ≥2

warfarin: tablets, oral, dosing to target INR range between 2.0 - 3.0, once daily, 6 months

Placebo for apixaban: tablets, oral, 10 mg tablets, twice daily, for 7 days followed by placebo for apixaban 5 mg tablets, twice daily, 6 months

Overall Number of Participants Analyzed 1685 1719
Measure Type: Number
Unit of Measure: participants
Blood in Urine High (N=2289, 2273) 85 127
Glucose in Urine High (N=2289, 2273) 46 31
Leukocyte Esterase in Urine High (N=2289, 2273) 105 102
Protein in Urine High (N=2289, 2273) 41 50
RBC + WBC in Urine High (N=1685, 1719) 359 361
RBC in Urine High (N=1293, 1389) 111 140
WBC in Urine High (N=1354, 1361) 274 263
Time Frame Day 1 up to 24 Weeks + 2 Days or 355 Days (for those participants who discontinued early)/
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Apixaban Enoxaparin/Warfarin
Hide Arm/Group Description

Apixaban: tablets, oral, 10 mg tablets, twice daily, for 7 days followed by apixaban 5 mg, twice daily, 6 months

Placebo for enoxaparin: solution, subcutaneous, 1 mg/kg Q12h until sham INR ≥2

Placebo for warfarin: tablets, oral, dosing to target sham INR range between 2.0 - 3.0, once daily, 6 months

Enoxaparin: solution, subcutaneous, 1 mg/kg Q12h until INR ≥2

warfarin: tablets, oral, dosing to target INR range between 2.0 - 3.0, once daily, 6 months

Placebo for apixaban: tablets, oral, 10 mg tablets, twice daily, for 7 days followed by placebo for apixaban 5 mg tablets, twice daily, 6 months

All-Cause Mortality
Apixaban Enoxaparin/Warfarin
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Apixaban Enoxaparin/Warfarin
Affected / at Risk (%) Affected / at Risk (%)
Total   417/2676 (15.58%)   410/2689 (15.25%) 
Blood and lymphatic system disorders     
ANAEMIA * 1  6/2676 (0.22%)  4/2689 (0.15%) 
ANAEMIA MEGALOBLASTIC * 1  1/2676 (0.04%)  0/2689 (0.00%) 
ANAEMIA OF CHRONIC DISEASE * 1  0/2676 (0.00%)  1/2689 (0.04%) 
DISSEMINATED INTRAVASCULAR COAGULATION * 1  1/2676 (0.04%)  1/2689 (0.04%) 
HAEMORRHAGIC ANAEMIA * 1  0/2676 (0.00%)  1/2689 (0.04%) 
HILAR LYMPHADENOPATHY * 1  1/2676 (0.04%)  0/2689 (0.00%) 
IRON DEFICIENCY ANAEMIA * 1  1/2676 (0.04%)  0/2689 (0.00%) 
NEUTROPENIA * 1  1/2676 (0.04%)  0/2689 (0.00%) 
NORMOCHROMIC NORMOCYTIC ANAEMIA * 1  0/2676 (0.00%)  1/2689 (0.04%) 
SPLENIC INFARCTION * 1  1/2676 (0.04%)  0/2689 (0.00%) 
THROMBOCYTOPENIA * 1  3/2676 (0.11%)  1/2689 (0.04%) 
Cardiac disorders     
ACUTE MYOCARDIAL INFARCTION * 1  5/2676 (0.19%)  2/2689 (0.07%) 
ANGINA PECTORIS * 1  3/2676 (0.11%)  1/2689 (0.04%) 
ANGINA UNSTABLE * 1  1/2676 (0.04%)  2/2689 (0.07%) 
ATRIAL FIBRILLATION * 1  6/2676 (0.22%)  7/2689 (0.26%) 
ATRIAL FLUTTER * 1  1/2676 (0.04%)  0/2689 (0.00%) 
ATRIAL TACHYCARDIA * 1  1/2676 (0.04%)  0/2689 (0.00%) 
ATRIAL THROMBOSIS * 1  0/2676 (0.00%)  1/2689 (0.04%) 
ATRIOVENTRICULAR BLOCK * 1  0/2676 (0.00%)  1/2689 (0.04%) 
BRADYCARDIA * 1  1/2676 (0.04%)  1/2689 (0.04%) 
CARDIAC ARREST * 1  2/2676 (0.07%)  1/2689 (0.04%) 
CARDIAC FAILURE * 1  5/2676 (0.19%)  8/2689 (0.30%) 
CARDIAC FAILURE ACUTE * 1  1/2676 (0.04%)  0/2689 (0.00%) 
CARDIAC FAILURE CONGESTIVE * 1  5/2676 (0.19%)  2/2689 (0.07%) 
CARDIO-RESPIRATORY ARREST * 1  1/2676 (0.04%)  0/2689 (0.00%) 
CARDIOGENIC SHOCK * 1  0/2676 (0.00%)  2/2689 (0.07%) 
CARDIOMYOPATHY * 1  1/2676 (0.04%)  0/2689 (0.00%) 
CARDIOPULMONARY FAILURE * 1  1/2676 (0.04%)  0/2689 (0.00%) 
CORONARY ARTERY DISEASE * 1  1/2676 (0.04%)  5/2689 (0.19%) 
DILATATION VENTRICULAR * 1  0/2676 (0.00%)  1/2689 (0.04%) 
INTRACARDIAC THROMBUS * 1  1/2676 (0.04%)  1/2689 (0.04%) 
MYOCARDIAL INFARCTION * 1  2/2676 (0.07%)  3/2689 (0.11%) 
PALPITATIONS * 1  1/2676 (0.04%)  0/2689 (0.00%) 
PERICARDIAL HAEMORRHAGE * 1  1/2676 (0.04%)  0/2689 (0.00%) 
PERICARDITIS * 1  1/2676 (0.04%)  0/2689 (0.00%) 
PRINZMETAL ANGINA * 1  1/2676 (0.04%)  0/2689 (0.00%) 
RIGHT VENTRICULAR DYSFUNCTION * 1  0/2676 (0.00%)  1/2689 (0.04%) 
SUPRAVENTRICULAR TACHYCARDIA * 1  2/2676 (0.07%)  0/2689 (0.00%) 
TACHYCARDIA * 1  0/2676 (0.00%)  1/2689 (0.04%) 
VENTRICULAR EXTRASYSTOLES * 1  0/2676 (0.00%)  1/2689 (0.04%) 
VENTRICULAR FIBRILLATION * 1  1/2676 (0.04%)  0/2689 (0.00%) 
VENTRICULAR HYPOKINESIA * 1  0/2676 (0.00%)  1/2689 (0.04%) 
Congenital, familial and genetic disorders     
SICKLE CELL ANAEMIA WITH CRISIS * 1  0/2676 (0.00%)  1/2689 (0.04%) 
Ear and labyrinth disorders     
INNER EAR DISORDER * 1  1/2676 (0.04%)  0/2689 (0.00%) 
VERTIGO * 1  1/2676 (0.04%)  0/2689 (0.00%) 
Eye disorders     
CONJUNCTIVITIS * 1  0/2676 (0.00%)  1/2689 (0.04%) 
RETINAL HAEMORRHAGE * 1  0/2676 (0.00%)  1/2689 (0.04%) 
Gastrointestinal disorders     
ABDOMINAL DISTENSION * 1  1/2676 (0.04%)  0/2689 (0.00%) 
ABDOMINAL PAIN * 1  4/2676 (0.15%)  2/2689 (0.07%) 
ABDOMINAL PAIN LOWER * 1  1/2676 (0.04%)  0/2689 (0.00%) 
ABDOMINAL PAIN UPPER * 1  0/2676 (0.00%)  1/2689 (0.04%) 
ABDOMINAL WALL HAEMATOMA * 1  1/2676 (0.04%)  2/2689 (0.07%) 
ABDOMINAL WALL HAEMORRHAGE * 1  0/2676 (0.00%)  1/2689 (0.04%) 
ASCITES * 1  0/2676 (0.00%)  1/2689 (0.04%) 
COLITIS * 1  1/2676 (0.04%)  0/2689 (0.00%) 
COLONIC POLYP * 1  1/2676 (0.04%)  1/2689 (0.04%) 
CONSTIPATION * 1  1/2676 (0.04%)  0/2689 (0.00%) 
DIAPHRAGMATIC HERNIA * 1  0/2676 (0.00%)  1/2689 (0.04%) 
DIVERTICULUM * 1  0/2676 (0.00%)  1/2689 (0.04%) 
DUODENAL ULCER HAEMORRHAGE * 1  0/2676 (0.00%)  2/2689 (0.07%) 
DUODENITIS * 1  0/2676 (0.00%)  1/2689 (0.04%) 
DUODENOGASTRIC REFLUX * 1  0/2676 (0.00%)  1/2689 (0.04%) 
DYSPEPSIA * 1  1/2676 (0.04%)  1/2689 (0.04%) 
DYSPHAGIA * 1  0/2676 (0.00%)  1/2689 (0.04%) 
ENTERITIS * 1  1/2676 (0.04%)  0/2689 (0.00%) 
FLATULENCE * 1  0/2676 (0.00%)  1/2689 (0.04%) 
GASTRIC HAEMORRHAGE * 1  1/2676 (0.04%)  0/2689 (0.00%) 
GASTRIC POLYPS * 1  0/2676 (0.00%)  1/2689 (0.04%) 
GASTRIC ULCER HAEMORRHAGE * 1  1/2676 (0.04%)  0/2689 (0.00%) 
GASTRITIS * 1  0/2676 (0.00%)  2/2689 (0.07%) 
GASTRITIS EROSIVE * 1  0/2676 (0.00%)  1/2689 (0.04%) 
GASTROINTESTINAL HAEMORRHAGE * 1  8/2676 (0.30%)  14/2689 (0.52%) 
GASTROINTESTINAL HYPOMOTILITY * 1  0/2676 (0.00%)  1/2689 (0.04%) 
GASTROINTESTINAL ULCER HAEMORRHAGE * 1  0/2676 (0.00%)  1/2689 (0.04%) 
GASTROLITHIASIS * 1  1/2676 (0.04%)  0/2689 (0.00%) 
GINGIVAL BLEEDING * 1  0/2676 (0.00%)  1/2689 (0.04%) 
HAEMATEMESIS * 1  1/2676 (0.04%)  1/2689 (0.04%) 
HAEMATOCHEZIA * 1  2/2676 (0.07%)  0/2689 (0.00%) 
HAEMORRHOIDAL HAEMORRHAGE * 1  0/2676 (0.00%)  1/2689 (0.04%) 
HAEMORRHOIDS * 1  1/2676 (0.04%)  1/2689 (0.04%) 
ILEUS PARALYTIC * 1  0/2676 (0.00%)  1/2689 (0.04%) 
INTESTINAL ISCHAEMIA * 1  1/2676 (0.04%)  0/2689 (0.00%) 
INTESTINAL OBSTRUCTION * 1  1/2676 (0.04%)  2/2689 (0.07%) 
IRRITABLE BOWEL SYNDROME * 1  1/2676 (0.04%)  0/2689 (0.00%) 
LOWER GASTROINTESTINAL HAEMORRHAGE * 1  0/2676 (0.00%)  2/2689 (0.07%) 
MALLORY-WEISS SYNDROME * 1  0/2676 (0.00%)  1/2689 (0.04%) 
MELAENA * 1  1/2676 (0.04%)  1/2689 (0.04%) 
NAUSEA * 1  0/2676 (0.00%)  1/2689 (0.04%) 
NEUTROPENIC COLITIS * 1  0/2676 (0.00%)  1/2689 (0.04%) 
OESOPHAGITIS * 1  0/2676 (0.00%)  1/2689 (0.04%) 
PANCREATITIS * 1  1/2676 (0.04%)  0/2689 (0.00%) 
PANCREATITIS ACUTE * 1  1/2676 (0.04%)  0/2689 (0.00%) 
PANCREATITIS RELAPSING * 1  0/2676 (0.00%)  1/2689 (0.04%) 
PERITONEAL CYST * 1  0/2676 (0.00%)  1/2689 (0.04%) 
RECTAL HAEMORRHAGE * 1  2/2676 (0.07%)  3/2689 (0.11%) 
RETROPERITONEAL HAEMORRHAGE * 1  0/2676 (0.00%)  1/2689 (0.04%) 
SMALL INTESTINAL OBSTRUCTION * 1  1/2676 (0.04%)  0/2689 (0.00%) 
TONGUE OEDEMA * 1  1/2676 (0.04%)  0/2689 (0.00%) 
UMBILICAL HERNIA * 1  1/2676 (0.04%)  0/2689 (0.00%) 
UMBILICAL HERNIA, OBSTRUCTIVE * 1  1/2676 (0.04%)  0/2689 (0.00%) 
UPPER GASTROINTESTINAL HAEMORRHAGE * 1  0/2676 (0.00%)  1/2689 (0.04%) 
VOMITING * 1  0/2676 (0.00%)  1/2689 (0.04%) 
General disorders     
ASTHENIA * 1  1/2676 (0.04%)  2/2689 (0.07%) 
AXILLARY PAIN * 1  1/2676 (0.04%)  0/2689 (0.00%) 
CHEST PAIN * 1  3/2676 (0.11%)  4/2689 (0.15%) 
DEATH * 1  4/2676 (0.15%)  2/2689 (0.07%) 
DEVICE OCCLUSION * 1  1/2676 (0.04%)  0/2689 (0.00%) 
HERNIA OBSTRUCTIVE * 1  1/2676 (0.04%)  0/2689 (0.00%) 
MULTI-ORGAN DISORDER * 1  1/2676 (0.04%)  0/2689 (0.00%) 
MULTI-ORGAN FAILURE * 1  3/2676 (0.11%)  1/2689 (0.04%) 
NON-CARDIAC CHEST PAIN * 1  9/2676 (0.34%)  6/2689 (0.22%) 
OEDEMA PERIPHERAL * 1  3/2676 (0.11%)  3/2689 (0.11%) 
PELVIC MASS * 1  0/2676 (0.00%)  1/2689 (0.04%) 
PYREXIA * 1  4/2676 (0.15%)  1/2689 (0.04%) 
SYSTEMIC INFLAMMATORY RESPONSE SYNDROME * 1  1/2676 (0.04%)  0/2689 (0.00%) 
Hepatobiliary disorders     
CHOLECYSTITIS * 1  2/2676 (0.07%)  3/2689 (0.11%) 
CHOLECYSTITIS ACUTE * 1  2/2676 (0.07%)  0/2689 (0.00%) 
CHOLELITHIASIS * 1  2/2676 (0.07%)  2/2689 (0.07%) 
CHOLESTASIS * 1  0/2676 (0.00%)  1/2689 (0.04%) 
DRUG-INDUCED LIVER INJURY * 1  0/2676 (0.00%)  1/2689 (0.04%) 
HEPATIC CYST * 1  1/2676 (0.04%)  0/2689 (0.00%) 
HEPATIC FAILURE * 1  0/2676 (0.00%)  2/2689 (0.07%) 
HEPATIC FUNCTION ABNORMAL * 1  1/2676 (0.04%)  0/2689 (0.00%) 
HEPATITIS * 1  0/2676 (0.00%)  1/2689 (0.04%) 
JAUNDICE CHOLESTATIC * 1  1/2676 (0.04%)  0/2689 (0.00%) 
Immune system disorders     
ALLERGY TO ARTHROPOD BITE * 1  0/2676 (0.00%)  1/2689 (0.04%) 
AUTOIMMUNE DISORDER * 1  0/2676 (0.00%)  1/2689 (0.04%) 
BEHCET'S SYNDROME * 1  1/2676 (0.04%)  0/2689 (0.00%) 
DRUG HYPERSENSITIVITY * 1  0/2676 (0.00%)  1/2689 (0.04%) 
HYPERSENSITIVITY * 1  2/2676 (0.07%)  0/2689 (0.00%) 
Infections and infestations     
ABDOMINAL ABSCESS * 1  1/2676 (0.04%)  0/2689 (0.00%) 
ABDOMINAL WALL ABSCESS * 1  0/2676 (0.00%)  1/2689 (0.04%) 
ABSCESS INTESTINAL * 1  0/2676 (0.00%)  1/2689 (0.04%) 
ABSCESS LIMB * 1  1/2676 (0.04%)  0/2689 (0.00%) 
APPENDICITIS * 1  1/2676 (0.04%)  0/2689 (0.00%) 
ARTHRITIS BACTERIAL * 1  0/2676 (0.00%)  1/2689 (0.04%) 
BACTERAEMIA * 1  1/2676 (0.04%)  0/2689 (0.00%) 
BRONCHITIS * 1  4/2676 (0.15%)  2/2689 (0.07%) 
BRONCHITIS BACTERIAL * 1  1/2676 (0.04%)  0/2689 (0.00%) 
BRONCHOPNEUMONIA * 1  1/2676 (0.04%)  3/2689 (0.11%) 
CARDIAC VALVE VEGETATION * 1  1/2676 (0.04%)  0/2689 (0.00%) 
CELLULITIS * 1  6/2676 (0.22%)  3/2689 (0.11%) 
CELLULITIS ORBITAL * 1  1/2676 (0.04%)  0/2689 (0.00%) 
CLOSTRIDIAL INFECTION * 1  1/2676 (0.04%)  0/2689 (0.00%) 
CYSTITIS * 1  1/2676 (0.04%)  0/2689 (0.00%) 
CYTOMEGALOVIRUS COLITIS * 1  1/2676 (0.04%)  0/2689 (0.00%) 
DEVICE RELATED INFECTION * 1  0/2676 (0.00%)  1/2689 (0.04%) 
DIVERTICULITIS * 1  1/2676 (0.04%)  2/2689 (0.07%) 
ENTEROCOLITIS INFECTIOUS * 1  0/2676 (0.00%)  1/2689 (0.04%) 
ERYSIPELAS * 1  3/2676 (0.11%)  2/2689 (0.07%) 
GASTROENTERITIS * 1  2/2676 (0.07%)  3/2689 (0.11%) 
GENITAL HERPES * 1  1/2676 (0.04%)  0/2689 (0.00%) 
GROIN ABSCESS * 1  0/2676 (0.00%)  1/2689 (0.04%) 
HELICOBACTER GASTRITIS * 1  1/2676 (0.04%)  0/2689 (0.00%) 
HERPES ZOSTER * 1  1/2676 (0.04%)  0/2689 (0.00%) 
INFECTED SKIN ULCER * 1  1/2676 (0.04%)  1/2689 (0.04%) 
INFECTION * 1  1/2676 (0.04%)  0/2689 (0.00%) 
LOCALISED INFECTION * 1  1/2676 (0.04%)  0/2689 (0.00%) 
LUNG ABSCESS * 1  1/2676 (0.04%)  0/2689 (0.00%) 
LUNG INFECTION * 1  1/2676 (0.04%)  0/2689 (0.00%) 
MASTOIDITIS * 1  1/2676 (0.04%)  0/2689 (0.00%) 
MYCOBACTERIAL INFECTION * 1  1/2676 (0.04%)  0/2689 (0.00%) 
MYELITIS * 1  1/2676 (0.04%)  0/2689 (0.00%) 
OROPHARYNGEAL CANDIDIASIS * 1  1/2676 (0.04%)  0/2689 (0.00%) 
OSTEOMYELITIS * 1  2/2676 (0.07%)  1/2689 (0.04%) 
PERINEAL ABSCESS * 1  0/2676 (0.00%)  1/2689 (0.04%) 
PERITONITIS * 1  1/2676 (0.04%)  0/2689 (0.00%) 
PNEUMOCYSTIS JIROVECI PNEUMONIA * 1  0/2676 (0.00%)  1/2689 (0.04%) 
PNEUMONIA * 1  16/2676 (0.60%)  12/2689 (0.45%) 
PULMONARY TUBERCULOSIS * 1  0/2676 (0.00%)  1/2689 (0.04%) 
PURULENT PERICARDITIS * 1  0/2676 (0.00%)  1/2689 (0.04%) 
PYELONEPHRITIS * 1  1/2676 (0.04%)  2/2689 (0.07%) 
RESPIRATORY TRACT INFECTION * 1  2/2676 (0.07%)  1/2689 (0.04%) 
SEPSIS * 1  5/2676 (0.19%)  5/2689 (0.19%) 
SEPTIC SHOCK * 1  3/2676 (0.11%)  1/2689 (0.04%) 
STAPHYLOCOCCAL INFECTION * 1  0/2676 (0.00%)  1/2689 (0.04%) 
STAPHYLOCOCCAL SEPSIS * 1  1/2676 (0.04%)  0/2689 (0.00%) 
TONSILLITIS * 1  0/2676 (0.00%)  1/2689 (0.04%) 
TUBERCULOSIS * 1  1/2676 (0.04%)  0/2689 (0.00%) 
TULARAEMIA * 1  1/2676 (0.04%)  0/2689 (0.00%) 
URINARY TRACT INFECTION * 1  8/2676 (0.30%)  3/2689 (0.11%) 
UROSEPSIS * 1  4/2676 (0.15%)  0/2689 (0.00%) 
VIRAL INFECTION * 1  0/2676 (0.00%)  1/2689 (0.04%) 
VULVAL ABSCESS * 1  0/2676 (0.00%)  1/2689 (0.04%) 
Injury, poisoning and procedural complications     
ACCIDENTAL OVERDOSE * 1  2/2676 (0.07%)  1/2689 (0.04%) 
ANKLE FRACTURE * 1  0/2676 (0.00%)  2/2689 (0.07%) 
CERVICAL VERTEBRAL FRACTURE * 1  0/2676 (0.00%)  1/2689 (0.04%) 
CONTUSION * 1  2/2676 (0.07%)  0/2689 (0.00%) 
DRUG ADMINISTRATION ERROR * 1  1/2676 (0.04%)  0/2689 (0.00%) 
EXCORIATION * 1  0/2676 (0.00%)  1/2689 (0.04%) 
EXTRADURAL HAEMATOMA * 1  1/2676 (0.04%)  0/2689 (0.00%) 
FACE INJURY * 1  1/2676 (0.04%)  0/2689 (0.00%) 
FACIAL BONES FRACTURE * 1  0/2676 (0.00%)  1/2689 (0.04%) 
FALL * 1  1/2676 (0.04%)  0/2689 (0.00%) 
FEMUR FRACTURE * 1  0/2676 (0.00%)  2/2689 (0.07%) 
HEAD INJURY * 1  0/2676 (0.00%)  1/2689 (0.04%) 
HIP FRACTURE * 1  0/2676 (0.00%)  1/2689 (0.04%) 
HUMERUS FRACTURE * 1  1/2676 (0.04%)  1/2689 (0.04%) 
INCORRECT DOSE ADMINISTERED * 1  1/2676 (0.04%)  0/2689 (0.00%) 
JOINT DISLOCATION * 1  0/2676 (0.00%)  1/2689 (0.04%) 
LOWER LIMB FRACTURE * 1  1/2676 (0.04%)  0/2689 (0.00%) 
LUMBAR VERTEBRAL FRACTURE * 1  0/2676 (0.00%)  1/2689 (0.04%) 
MENISCUS LESION * 1  0/2676 (0.00%)  1/2689 (0.04%) 
OVERDOSE * 1  15/2676 (0.56%)  11/2689 (0.41%) 
PELVIC FRACTURE * 1  0/2676 (0.00%)  1/2689 (0.04%) 
PERIPHERAL ARTERIAL REOCCLUSION * 1  1/2676 (0.04%)  0/2689 (0.00%) 
POST PROCEDURAL HAEMORRHAGE * 1  2/2676 (0.07%)  0/2689 (0.00%) 
RADIUS FRACTURE * 1  0/2676 (0.00%)  1/2689 (0.04%) 
RENAL HAEMATOMA * 1  1/2676 (0.04%)  0/2689 (0.00%) 
SPINAL COLUMN INJURY * 1  0/2676 (0.00%)  1/2689 (0.04%) 
SPINAL COMPRESSION FRACTURE * 1  2/2676 (0.07%)  0/2689 (0.00%) 
SUBCUTANEOUS HAEMATOMA * 1  0/2676 (0.00%)  2/2689 (0.07%) 
SUBDURAL HAEMORRHAGE * 1  1/2676 (0.04%)  0/2689 (0.00%) 
TOXICITY TO VARIOUS AGENTS * 1  0/2676 (0.00%)  1/2689 (0.04%) 
TRAUMATIC HAEMATOMA * 1  0/2676 (0.00%)  1/2689 (0.04%) 
UPPER LIMB FRACTURE * 1  0/2676 (0.00%)  1/2689 (0.04%) 
VASCULAR PSEUDOANEURYSM * 1  2/2676 (0.07%)  0/2689 (0.00%) 
WRIST FRACTURE * 1  0/2676 (0.00%)  1/2689 (0.04%) 
Investigations     
ALANINE AMINOTRANSFERASE INCREASED * 1  1/2676 (0.04%)  0/2689 (0.00%) 
COAGULATION TIME PROLONGED * 1  1/2676 (0.04%)  0/2689 (0.00%) 
GAMMA-GLUTAMYLTRANSFERASE INCREASED * 1  0/2676 (0.00%)  1/2689 (0.04%) 
HEPATIC ENZYME INCREASED * 1  1/2676 (0.04%)  1/2689 (0.04%) 
INTERNATIONAL NORMALISED RATIO INCREASED * 1  3/2676 (0.11%)  7/2689 (0.26%) 
LIVER FUNCTION TEST ABNORMAL * 1  1/2676 (0.04%)  0/2689 (0.00%) 
Metabolism and nutrition disorders     
DEHYDRATION * 1  0/2676 (0.00%)  3/2689 (0.11%) 
DIABETES MELLITUS * 1  1/2676 (0.04%)  0/2689 (0.00%) 
FAILURE TO THRIVE * 1  0/2676 (0.00%)  1/2689 (0.04%) 
GOUT * 1  1/2676 (0.04%)  0/2689 (0.00%) 
HYPERGLYCAEMIA * 1  0/2676 (0.00%)  2/2689 (0.07%) 
HYPERKALAEMIA * 1  1/2676 (0.04%)  0/2689 (0.00%) 
HYPOKALAEMIA * 1  1/2676 (0.04%)  0/2689 (0.00%) 
HYPONATRAEMIA * 1  4/2676 (0.15%)  0/2689 (0.00%) 
Musculoskeletal and connective tissue disorders     
ARTHRALGIA * 1  1/2676 (0.04%)  3/2689 (0.11%) 
BACK PAIN * 1  0/2676 (0.00%)  1/2689 (0.04%) 
COSTOCHONDRITIS * 1  1/2676 (0.04%)  1/2689 (0.04%) 
FRACTURE MALUNION * 1  0/2676 (0.00%)  1/2689 (0.04%) 
GOUTY ARTHRITIS * 1  1/2676 (0.04%)  0/2689 (0.00%) 
GROIN PAIN * 1  1/2676 (0.04%)  0/2689 (0.00%) 
INTERVERTEBRAL DISC PROTRUSION * 1  0/2676 (0.00%)  1/2689 (0.04%) 
JOINT EFFUSION * 1  0/2676 (0.00%)  1/2689 (0.04%) 
LIGAMENT DISORDER * 1  0/2676 (0.00%)  1/2689 (0.04%) 
LIMB DISCOMFORT * 1  0/2676 (0.00%)  1/2689 (0.04%) 
MUSCLE HAEMORRHAGE * 1  1/2676 (0.04%)  2/2689 (0.07%) 
MUSCULOSKELETAL CHEST PAIN * 1  6/2676 (0.22%)  1/2689 (0.04%) 
MUSCULOSKELETAL PAIN * 1  0/2676 (0.00%)  2/2689 (0.07%) 
MYALGIA * 1  1/2676 (0.04%)  0/2689 (0.00%) 
OSTEOARTHRITIS * 1  1/2676 (0.04%)  0/2689 (0.00%) 
PAIN IN EXTREMITY * 1  5/2676 (0.19%)  2/2689 (0.07%) 
PATHOLOGICAL FRACTURE * 1  2/2676 (0.07%)  0/2689 (0.00%) 
POLYMYALGIA RHEUMATICA * 1  0/2676 (0.00%)  1/2689 (0.04%) 
PSEUDARTHROSIS * 1  0/2676 (0.00%)  1/2689 (0.04%) 
ROTATOR CUFF SYNDROME * 1  1/2676 (0.04%)  0/2689 (0.00%) 
SPINAL OSTEOARTHRITIS * 1  1/2676 (0.04%)  0/2689 (0.00%) 
SYNOVIAL CYST * 1  0/2676 (0.00%)  1/2689 (0.04%) 
SYSTEMIC LUPUS ERYTHEMATOSUS * 1  0/2676 (0.00%)  1/2689 (0.04%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
ADENOCARCINOMA * 1  2/2676 (0.07%)  1/2689 (0.04%) 
BASAL CELL CARCINOMA * 1  1/2676 (0.04%)  3/2689 (0.11%) 
BENIGN OVARIAN TUMOUR * 1  1/2676 (0.04%)  0/2689 (0.00%) 
BILE DUCT CANCER * 1  3/2676 (0.11%)  0/2689 (0.00%) 
BLADDER CANCER * 1  2/2676 (0.07%)  0/2689 (0.00%) 
BLADDER PAPILLOMA * 1  1/2676 (0.04%)  0/2689 (0.00%) 
BLADDER TRANSITIONAL CELL CARCINOMA * 1  0/2676 (0.00%)  1/2689 (0.04%) 
BONE NEOPLASM * 1  0/2676 (0.00%)  1/2689 (0.04%) 
BRAIN CANCER METASTATIC * 1  1/2676 (0.04%)  0/2689 (0.00%) 
BREAST CANCER * 1  3/2676 (0.11%)  2/2689 (0.07%) 
BREAST CANCER RECURRENT * 1  0/2676 (0.00%)  1/2689 (0.04%) 
BRONCHIAL CARCINOMA * 1  2/2676 (0.07%)  0/2689 (0.00%) 
CERVIX CARCINOMA * 1  0/2676 (0.00%)  1/2689 (0.04%) 
CERVIX NEOPLASM * 1  0/2676 (0.00%)  1/2689 (0.04%) 
CHOLESTEATOMA * 1  0/2676 (0.00%)  1/2689 (0.04%) 
COLON CANCER * 1  2/2676 (0.07%)  2/2689 (0.07%) 
COLON CANCER METASTATIC * 1  2/2676 (0.07%)  3/2689 (0.11%) 
COLON NEOPLASM * 1  0/2676 (0.00%)  1/2689 (0.04%) 
COLORECTAL CANCER * 1  1/2676 (0.04%)  1/2689 (0.04%) 
ENDOCRINE NEOPLASM MALIGNANT * 1  1/2676 (0.04%)  0/2689 (0.00%) 
ESSENTIAL THROMBOCYTHAEMIA * 1  0/2676 (0.00%)  1/2689 (0.04%) 
GALLBLADDER CANCER * 1  1/2676 (0.04%)  0/2689 (0.00%) 
GASTRIC CANCER * 1  1/2676 (0.04%)  0/2689 (0.00%) 
GASTRIC CANCER RECURRENT * 1  0/2676 (0.00%)  1/2689 (0.04%) 
GASTROINTESTINAL CANCER METASTATIC * 1  0/2676 (0.00%)  1/2689 (0.04%) 
GASTROINTESTINAL CARCINOMA * 1  1/2676 (0.04%)  0/2689 (0.00%) 
GASTROINTESTINAL STROMAL TUMOUR * 1  1/2676 (0.04%)  0/2689 (0.00%) 
GASTROINTESTINAL TRACT ADENOMA * 1  1/2676 (0.04%)  0/2689 (0.00%) 
GLIOBLASTOMA MULTIFORME * 1  1/2676 (0.04%)  0/2689 (0.00%) 
HEPATIC CANCER METASTATIC * 1  1/2676 (0.04%)  0/2689 (0.00%) 
INTESTINAL ADENOCARCINOMA * 1  0/2676 (0.00%)  1/2689 (0.04%) 
LEIOMYOMA * 1  1/2676 (0.04%)  0/2689 (0.00%) 
LUNG ADENOCARCINOMA * 1  1/2676 (0.04%)  0/2689 (0.00%) 
LUNG CANCER METASTATIC * 1  0/2676 (0.00%)  2/2689 (0.07%) 
LUNG NEOPLASM MALIGNANT * 1  2/2676 (0.07%)  6/2689 (0.22%) 
LUNG SQUAMOUS CELL CARCINOMA STAGE UNSPECIFIED * 1  0/2676 (0.00%)  1/2689 (0.04%) 
LYMPHOMA * 1  1/2676 (0.04%)  0/2689 (0.00%) 
MALIGNANT NEOPLASM PROGRESSION * 1  1/2676 (0.04%)  2/2689 (0.07%) 
MALIGNANT PERITONEAL NEOPLASM * 1  1/2676 (0.04%)  0/2689 (0.00%) 
METASTASES TO ABDOMINAL CAVITY * 1  0/2676 (0.00%)  1/2689 (0.04%) 
METASTASES TO BONE * 1  1/2676 (0.04%)  0/2689 (0.00%) 
METASTASES TO CENTRAL NERVOUS SYSTEM * 1  0/2676 (0.00%)  1/2689 (0.04%) 
METASTASES TO LIVER * 1  1/2676 (0.04%)  0/2689 (0.00%) 
METASTASES TO LUNG * 1  2/2676 (0.07%)  0/2689 (0.00%) 
METASTASES TO PERITONEUM * 1  0/2676 (0.00%)  1/2689 (0.04%) 
METASTASIS * 1  1/2676 (0.04%)  0/2689 (0.00%) 
METASTATIC CARCINOMA OF THE BLADDER * 1  0/2676 (0.00%)  1/2689 (0.04%) 
METASTATIC NEOPLASM * 1  2/2676 (0.07%)  3/2689 (0.11%) 
METASTATIC RENAL CELL CARCINOMA * 1  1/2676 (0.04%)  0/2689 (0.00%) 
MYELODYSPLASTIC SYNDROME * 1  1/2676 (0.04%)  0/2689 (0.00%) 
NEOPLASM * 1  1/2676 (0.04%)  0/2689 (0.00%) 
NEOPLASM MALIGNANT * 1  2/2676 (0.07%)  1/2689 (0.04%) 
NEUROENDOCRINE TUMOUR * 1  0/2676 (0.00%)  1/2689 (0.04%) 
NON-HODGKIN'S LYMPHOMA * 1  0/2676 (0.00%)  1/2689 (0.04%) 
OESOPHAGEAL CANCER METASTATIC * 1  0/2676 (0.00%)  1/2689 (0.04%) 
ONCOCYTOMA * 1  0/2676 (0.00%)  1/2689 (0.04%) 
OVARIAN CANCER * 1  1/2676 (0.04%)  1/2689 (0.04%) 
OVARIAN CANCER METASTATIC * 1  0/2676 (0.00%)  1/2689 (0.04%) 
PANCREATIC CARCINOMA * 1  1/2676 (0.04%)  4/2689 (0.15%) 
PANCREATIC CARCINOMA METASTATIC * 1  0/2676 (0.00%)  3/2689 (0.11%) 
PANCREATIC CARCINOMA RECURRENT * 1  0/2676 (0.00%)  1/2689 (0.04%) 
PANCREATIC CARCINOMA STAGE IV * 1  0/2676 (0.00%)  1/2689 (0.04%) 
PANCREATIC NEUROENDOCRINE TUMOUR * 1  0/2676 (0.00%)  1/2689 (0.04%) 
PARAPROTEINAEMIA * 1  0/2676 (0.00%)  1/2689 (0.04%) 
PELVIC NEOPLASM * 1  1/2676 (0.04%)  1/2689 (0.04%) 
POLYCYTHAEMIA VERA * 1  0/2676 (0.00%)  1/2689 (0.04%) 
PROSTATE CANCER * 1  3/2676 (0.11%)  3/2689 (0.11%) 
PROSTATE CANCER RECURRENT * 1  0/2676 (0.00%)  1/2689 (0.04%) 
RECTAL CANCER * 1  0/2676 (0.00%)  1/2689 (0.04%) 
RECTOSIGMOID CANCER * 1  1/2676 (0.04%)  0/2689 (0.00%) 
RENAL CANCER * 1  0/2676 (0.00%)  2/2689 (0.07%) 
RENAL CELL CARCINOMA * 1  2/2676 (0.07%)  1/2689 (0.04%) 
SALIVARY GLAND CANCER * 1  0/2676 (0.00%)  1/2689 (0.04%) 
SMALL CELL LUNG CANCER METASTATIC * 1  0/2676 (0.00%)  1/2689 (0.04%) 
SQUAMOUS CELL CARCINOMA * 1  2/2676 (0.07%)  2/2689 (0.07%) 
TESTIS CANCER * 1  1/2676 (0.04%)  0/2689 (0.00%) 
THYROID CANCER METASTATIC * 1  1/2676 (0.04%)  0/2689 (0.00%) 
THYROID NEOPLASM * 1  1/2676 (0.04%)  0/2689 (0.00%) 
TONGUE NEOPLASM MALIGNANT STAGE UNSPECIFIED * 1  1/2676 (0.04%)  0/2689 (0.00%) 
TRANSITIONAL CELL CARCINOMA * 1  2/2676 (0.07%)  0/2689 (0.00%) 
TUMOUR ULCERATION * 1  0/2676 (0.00%)  1/2689 (0.04%) 
UTERINE CANCER * 1  1/2676 (0.04%)  0/2689 (0.00%) 
UTERINE LEIOMYOMA * 1  0/2676 (0.00%)  1/2689 (0.04%) 
Nervous system disorders     
CAROTID ARTERY STENOSIS * 1  0/2676 (0.00%)  1/2689 (0.04%) 
CEREBRAL HAEMORRHAGE * 1  2/2676 (0.07%)  1/2689 (0.04%) 
CEREBRAL INFARCTION * 1  2/2676 (0.07%)  0/2689 (0.00%) 
CEREBROVASCULAR ACCIDENT * 1  2/2676 (0.07%)  2/2689 (0.07%) 
CERVICOBRACHIAL SYNDROME * 1  0/2676 (0.00%)  1/2689 (0.04%) 
COMA * 1  1/2676 (0.04%)  0/2689 (0.00%) 
COMPLEX REGIONAL PAIN SYNDROME * 1  0/2676 (0.00%)  1/2689 (0.04%) 
CONVULSION * 1  1/2676 (0.04%)  2/2689 (0.07%) 
ENCEPHALOPATHY * 1  0/2676 (0.00%)  1/2689 (0.04%) 
GRAND MAL CONVULSION * 1  1/2676 (0.04%)  0/2689 (0.00%) 
HAEMORRHAGE INTRACRANIAL * 1  0/2676 (0.00%)  1/2689 (0.04%) 
HAEMORRHAGIC STROKE * 1  2/2676 (0.07%)  1/2689 (0.04%) 
HEADACHE * 1  0/2676 (0.00%)  2/2689 (0.07%) 
ISCHAEMIC STROKE * 1  5/2676 (0.19%)  5/2689 (0.19%) 
LACUNAR INFARCTION * 1  1/2676 (0.04%)  0/2689 (0.00%) 
MIGRAINE * 1  1/2676 (0.04%)  0/2689 (0.00%) 
MULTIPLE SCLEROSIS * 1  2/2676 (0.07%)  0/2689 (0.00%) 
NERVOUS SYSTEM DISORDER * 1  1/2676 (0.04%)  1/2689 (0.04%) 
NEURALGIA * 1  1/2676 (0.04%)  0/2689 (0.00%) 
NEURITIS * 1  1/2676 (0.04%)  0/2689 (0.00%) 
NEUROPATHY PERIPHERAL * 1  2/2676 (0.07%)  0/2689 (0.00%) 
PARAESTHESIA * 1  1/2676 (0.04%)  0/2689 (0.00%) 
PARAPLEGIA * 1  1/2676 (0.04%)  0/2689 (0.00%) 
PERONEAL NERVE PALSY * 1  1/2676 (0.04%)  0/2689 (0.00%) 
POLYNEUROPATHY * 1  1/2676 (0.04%)  0/2689 (0.00%) 
PRESYNCOPE * 1  0/2676 (0.00%)  1/2689 (0.04%) 
SCIATICA * 1  2/2676 (0.07%)  3/2689 (0.11%) 
SPINAL CORD COMPRESSION * 1  1/2676 (0.04%)  0/2689 (0.00%) 
SUBARACHNOID HAEMORRHAGE * 1  0/2676 (0.00%)  2/2689 (0.07%) 
SYNCOPE * 1  3/2676 (0.11%)  3/2689 (0.11%) 
THALAMIC INFARCTION * 1  1/2676 (0.04%)  0/2689 (0.00%) 
TOXIC ENCEPHALOPATHY * 1  1/2676 (0.04%)  0/2689 (0.00%) 
TRANSIENT ISCHAEMIC ATTACK * 1  2/2676 (0.07%)  3/2689 (0.11%) 
Pregnancy, puerperium and perinatal conditions     
ABORTION SPONTANEOUS * 1  1/2676 (0.04%)  0/2689 (0.00%) 
PREGNANCY * 1  5/2676 (0.19%)  2/2689 (0.07%) 
Psychiatric disorders     
ADJUSTMENT DISORDER * 1  0/2676 (0.00%)  1/2689 (0.04%) 
ALCOHOL ABUSE * 1  0/2676 (0.00%)  1/2689 (0.04%) 
ALCOHOLISM * 1  0/2676 (0.00%)  1/2689 (0.04%) 
ANXIETY * 1  3/2676 (0.11%)  2/2689 (0.07%) 
APATHY * 1  1/2676 (0.04%)  0/2689 (0.00%) 
BIPOLAR DISORDER * 1  1/2676 (0.04%)  0/2689 (0.00%) 
CONFUSIONAL STATE * 1  1/2676 (0.04%)  1/2689 (0.04%) 
DEPRESSION * 1  2/2676 (0.07%)  3/2689 (0.11%) 
DEPRESSION SUICIDAL * 1  1/2676 (0.04%)  0/2689 (0.00%) 
MENTAL DISORDER * 1  1/2676 (0.04%)  0/2689 (0.00%) 
PANIC ATTACK * 1  0/2676 (0.00%)  2/2689 (0.07%) 
SUICIDAL IDEATION * 1  1/2676 (0.04%)  0/2689 (0.00%) 
TIC * 1  1/2676 (0.04%)  0/2689 (0.00%) 
Renal and urinary disorders     
GLOMERULONEPHRITIS CHRONIC * 1  0/2676 (0.00%)  1/2689 (0.04%) 
GLOMERULONEPHRITIS MEMBRANOPROLIFERATIVE * 1  0/2676 (0.00%)  1/2689 (0.04%) 
HAEMATURIA * 1  5/2676 (0.19%)  13/2689 (0.48%) 
HAEMORRHAGE URINARY TRACT * 1  0/2676 (0.00%)  1/2689 (0.04%) 
HYDRONEPHROSIS * 1  0/2676 (0.00%)  2/2689 (0.07%) 
NEPHROLITHIASIS * 1  3/2676 (0.11%)  1/2689 (0.04%) 
OLIGURIA * 1  1/2676 (0.04%)  0/2689 (0.00%) 
RENAL COLIC * 1  0/2676 (0.00%)  1/2689 (0.04%) 
RENAL CYST HAEMORRHAGE * 1  0/2676 (0.00%)  1/2689 (0.04%) 
RENAL FAILURE * 1  3/2676 (0.11%)  2/2689 (0.07%) 
RENAL FAILURE ACUTE * 1  3/2676 (0.11%)  3/2689 (0.11%) 
RENAL FAILURE CHRONIC * 1  1/2676 (0.04%)  0/2689 (0.00%) 
RENAL IMPAIRMENT * 1  1/2676 (0.04%)  0/2689 (0.00%) 
URINARY BLADDER HAEMORRHAGE * 1  0/2676 (0.00%)  1/2689 (0.04%) 
URINARY RETENTION * 1  1/2676 (0.04%)  0/2689 (0.00%) 
URINARY TRACT OBSTRUCTION * 1  0/2676 (0.00%)  1/2689 (0.04%) 
Reproductive system and breast disorders     
ENDOMETRIAL HYPERTROPHY * 1  0/2676 (0.00%)  1/2689 (0.04%) 
MENORRHAGIA * 1  1/2676 (0.04%)  0/2689 (0.00%) 
METRORRHAGIA * 1  2/2676 (0.07%)  1/2689 (0.04%) 
OVARIAN CYST * 1  0/2676 (0.00%)  1/2689 (0.04%) 
UTERINE HAEMORRHAGE * 1  2/2676 (0.07%)  2/2689 (0.07%) 
UTERINE POLYP * 1  1/2676 (0.04%)  0/2689 (0.00%) 
VAGINAL HAEMORRHAGE * 1  1/2676 (0.04%)  1/2689 (0.04%) 
Respiratory, thoracic and mediastinal disorders     
ACUTE RESPIRATORY FAILURE * 1  2/2676 (0.07%)  0/2689 (0.00%) 
ADENOIDAL HYPERTROPHY * 1  0/2676 (0.00%)  1/2689 (0.04%) 
ALLERGIC GRANULOMATOUS ANGIITIS * 1  0/2676 (0.00%)  1/2689 (0.04%) 
ASTHMA * 1  6/2676 (0.22%)  0/2689 (0.00%) 
ASTHMATIC CRISIS * 1  1/2676 (0.04%)  0/2689 (0.00%) 
ATELECTASIS * 1  1/2676 (0.04%)  0/2689 (0.00%) 
BRONCHOSTENOSIS * 1  1/2676 (0.04%)  0/2689 (0.00%) 
CHRONIC OBSTRUCTIVE PULMONARY DISEASE * 1  9/2676 (0.34%)  6/2689 (0.22%) 
DYSPNOEA * 1  9/2676 (0.34%)  5/2689 (0.19%) 
EPISTAXIS * 1  1/2676 (0.04%)  2/2689 (0.07%) 
HAEMOPTYSIS * 1  1/2676 (0.04%)  1/2689 (0.04%) 
INTERSTITIAL LUNG DISEASE * 1  1/2676 (0.04%)  1/2689 (0.04%) 
LUNG CONSOLIDATION * 1  1/2676 (0.04%)  0/2689 (0.00%) 
PLEURAL EFFUSION * 1  3/2676 (0.11%)  7/2689 (0.26%) 
PLEURISY * 1  0/2676 (0.00%)  1/2689 (0.04%) 
PLEURITIC PAIN * 1  5/2676 (0.19%)  2/2689 (0.07%) 
PNEUMONIA ASPIRATION * 1  1/2676 (0.04%)  0/2689 (0.00%) 
PNEUMONITIS * 1  0/2676 (0.00%)  1/2689 (0.04%) 
PNEUMOTHORAX * 1  0/2676 (0.00%)  3/2689 (0.11%) 
PULMONARY ALVEOLAR HAEMORRHAGE * 1  1/2676 (0.04%)  0/2689 (0.00%) 
PULMONARY AMYLOIDOSIS * 1  0/2676 (0.00%)  1/2689 (0.04%) 
PULMONARY ARTERIAL HYPERTENSION * 1  1/2676 (0.04%)  0/2689 (0.00%) 
PULMONARY EMBOLISM * 1  24/2676 (0.90%)  38/2689 (1.41%) 
PULMONARY HYPERTENSION * 1  1/2676 (0.04%)  1/2689 (0.04%) 
PULMONARY INFARCTION * 1  0/2676 (0.00%)  3/2689 (0.11%) 
PULMONARY MASS * 1  1/2676 (0.04%)  0/2689 (0.00%) 
PULMONARY OEDEMA * 1  0/2676 (0.00%)  1/2689 (0.04%) 
RESPIRATORY DISTRESS * 1  1/2676 (0.04%)  0/2689 (0.00%) 
RESPIRATORY FAILURE * 1  2/2676 (0.07%)  0/2689 (0.00%) 
SLEEP APNOEA SYNDROME * 1  0/2676 (0.00%)  1/2689 (0.04%) 
Skin and subcutaneous tissue disorders     
CAPILLARITIS * 1  1/2676 (0.04%)  0/2689 (0.00%) 
CUTANEOUS VASCULITIS * 1  1/2676 (0.04%)  0/2689 (0.00%) 
DERMATITIS ALLERGIC * 1  0/2676 (0.00%)  1/2689 (0.04%) 
DIABETIC FOOT * 1  1/2676 (0.04%)  0/2689 (0.00%) 
DRUG ERUPTION * 1  1/2676 (0.04%)  0/2689 (0.00%) 
ECCHYMOSIS * 1  0/2676 (0.00%)  1/2689 (0.04%) 
ECZEMA * 1  0/2676 (0.00%)  2/2689 (0.07%) 
HAEMORRHAGE SUBCUTANEOUS * 1  0/2676 (0.00%)  1/2689 (0.04%) 
PURPURA * 1  1/2676 (0.04%)  0/2689 (0.00%) 
RASH * 1  1/2676 (0.04%)  1/2689 (0.04%) 
SKIN LESION * 1  0/2676 (0.00%)  2/2689 (0.07%) 
SKIN NECROSIS * 1  0/2676 (0.00%)  1/2689 (0.04%) 
SKIN ULCER * 1  1/2676 (0.04%)  0/2689 (0.00%) 
STASIS DERMATITIS * 1  1/2676 (0.04%)  0/2689 (0.00%) 
URTICARIA * 1  0/2676 (0.00%)  1/2689 (0.04%) 
Social circumstances     
PREGNANCY OF PARTNER * 1  1/2676 (0.04%)  0/2689 (0.00%) 
Vascular disorders     
ANGIODYSPLASIA * 1  0/2676 (0.00%)  1/2689 (0.04%) 
AORTIC ANEURYSM * 1  0/2676 (0.00%)  1/2689 (0.04%) 
AORTIC RUPTURE * 1  0/2676 (0.00%)  1/2689 (0.04%) 
ARTERIAL THROMBOSIS * 1  1/2676 (0.04%)  0/2689 (0.00%) 
ARTERIOSCLEROSIS * 1  0/2676 (0.00%)  2/2689 (0.07%) 
DEEP VEIN THROMBOSIS * 1  20/2676 (0.75%)  33/2689 (1.23%) 
EMBOLISM VENOUS * 1  2/2676 (0.07%)  0/2689 (0.00%) 
FEMORAL ARTERY ANEURYSM * 1  0/2676 (0.00%)  1/2689 (0.04%) 
HAEMATOMA * 1  1/2676 (0.04%)  4/2689 (0.15%) 
HYPERTENSION * 1  1/2676 (0.04%)  1/2689 (0.04%) 
HYPERTENSIVE CRISIS * 1  2/2676 (0.07%)  0/2689 (0.00%) 
HYPOTENSION * 1  0/2676 (0.00%)  1/2689 (0.04%) 
INTRA-ABDOMINAL HAEMATOMA * 1  0/2676 (0.00%)  1/2689 (0.04%) 
JUGULAR VEIN THROMBOSIS * 1  0/2676 (0.00%)  1/2689 (0.04%) 
ORTHOSTATIC HYPOTENSION * 1  1/2676 (0.04%)  0/2689 (0.00%) 
PERIPHERAL ARTERIAL OCCLUSIVE DISEASE * 1  1/2676 (0.04%)  0/2689 (0.00%) 
PERIPHERAL ARTERY ANEURYSM * 1  1/2676 (0.04%)  0/2689 (0.00%) 
PERIPHERAL ARTERY STENOSIS * 1  0/2676 (0.00%)  1/2689 (0.04%) 
PERIPHERAL ISCHAEMIA * 1  2/2676 (0.07%)  1/2689 (0.04%) 
PERIPHERAL VASCULAR DISORDER * 1  0/2676 (0.00%)  1/2689 (0.04%) 
SHOCK HAEMORRHAGIC * 1  1/2676 (0.04%)  1/2689 (0.04%) 
TEMPORAL ARTERITIS * 1  1/2676 (0.04%)  0/2689 (0.00%) 
THROMBOPHLEBITIS * 1  0/2676 (0.00%)  3/2689 (0.11%) 
THROMBOPHLEBITIS SUPERFICIAL * 1  1/2676 (0.04%)  0/2689 (0.00%) 
THROMBOSIS * 1  0/2676 (0.00%)  2/2689 (0.07%) 
VENA CAVA THROMBOSIS * 1  0/2676 (0.00%)  1/2689 (0.04%) 
VENOUS STENOSIS * 1  1/2676 (0.04%)  0/2689 (0.00%) 
VENOUS THROMBOSIS * 1  6/2676 (0.22%)  0/2689 (0.00%) 
VENOUS THROMBOSIS LIMB * 1  1/2676 (0.04%)  0/2689 (0.00%) 
*
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 Enoxaparin/Warfarin
Affected / at Risk (%) Affected / at Risk (%)
Total   1014/2676 (37.89%)   1207/2689 (44.89%) 
Gastrointestinal disorders     
CONSTIPATION * 1  73/2676 (2.73%)  87/2689 (3.24%) 
DIARRHOEA * 1  100/2676 (3.74%)  106/2689 (3.94%) 
NAUSEA * 1  81/2676 (3.03%)  106/2689 (3.94%) 
VOMITING * 1  50/2676 (1.87%)  69/2689 (2.57%) 
General disorders     
FATIGUE * 1  58/2676 (2.17%)  50/2689 (1.86%) 
OEDEMA PERIPHERAL * 1  93/2676 (3.48%)  111/2689 (4.13%) 
PYREXIA * 1  54/2676 (2.02%)  56/2689 (2.08%) 
Infections and infestations     
BRONCHITIS * 1  51/2676 (1.91%)  56/2689 (2.08%) 
NASOPHARYNGITIS * 1  104/2676 (3.89%)  98/2689 (3.64%) 
URINARY TRACT INFECTION * 1  92/2676 (3.44%)  82/2689 (3.05%) 
Injury, poisoning and procedural complications     
CONTUSION * 1  48/2676 (1.79%)  97/2689 (3.61%) 
Investigations     
ALANINE AMINOTRANSFERASE INCREASED * 1  30/2676 (1.12%)  105/2689 (3.90%) 
BLOOD CREATINE PHOSPHOKINASE INCREASED * 1  33/2676 (1.23%)  78/2689 (2.90%) 
GAMMA-GLUTAMYLTRANSFERASE INCREASED * 1  38/2676 (1.42%)  56/2689 (2.08%) 
Metabolism and nutrition disorders     
HYPERCHOLESTEROLAEMIA * 1  28/2676 (1.05%)  55/2689 (2.05%) 
Musculoskeletal and connective tissue disorders     
ARTHRALGIA * 1  74/2676 (2.77%)  84/2689 (3.12%) 
BACK PAIN * 1  80/2676 (2.99%)  87/2689 (3.24%) 
PAIN IN EXTREMITY * 1  119/2676 (4.45%)  130/2689 (4.83%) 
Nervous system disorders     
DIZZINESS * 1  66/2676 (2.47%)  69/2689 (2.57%) 
HEADACHE * 1  169/2676 (6.32%)  167/2689 (6.21%) 
Renal and urinary disorders     
HAEMATURIA * 1  41/2676 (1.53%)  91/2689 (3.38%) 
Respiratory, thoracic and mediastinal disorders     
COUGH * 1  61/2676 (2.28%)  58/2689 (2.16%) 
DYSPNOEA * 1  64/2676 (2.39%)  73/2689 (2.71%) 
EPISTAXIS * 1  77/2676 (2.88%)  144/2689 (5.36%) 
Vascular disorders     
HAEMATOMA * 1  34/2676 (1.27%)  72/2689 (2.68%) 
HYPERTENSION * 1  70/2676 (2.62%)  68/2689 (2.53%) 
*
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: NCT00643201     History of Changes
Other Study ID Numbers: CV185-056
EUDRACT: 2007-007867-25
First Submitted: March 20, 2008
First Posted: March 26, 2008
Results First Submitted: March 4, 2014
Results First Posted: April 10, 2014
Last Update Posted: April 21, 2014