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Oral Direct Factor Xa Inhibitor Rivaroxaban in Patients With Acute Symptomatic Pulmonary Embolism - The EINSTEIN PE Study

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00439777
Recruitment Status : Completed
First Posted : February 26, 2007
Results First Posted : January 24, 2013
Last Update Posted : February 27, 2014
Sponsor:
Collaborator:
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Information provided by (Responsible Party):
Bayer

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Pulmonary Embolism
Interventions Drug: Rivaroxaban (Xarelto, BAY59-7939)
Drug: Enoxaparin overlapping with and followed by VKA
Enrollment 4833
Recruitment Details Participants with confirmed acute symptomatic pulmonary embolism (PE) with or without symptomatic deep vein thrombosis (DVT) were recruited at specialized study sites.
Pre-assignment Details Out of 4843 participants screened, 10 failed screening (6 due to protocol violations, 2 due to investigator decision and another 2 subjects due to technical problems [interactive voice response system did not work properly]). 4833 participants were randomized (2420 to rivaroxaban and 2413 to enoxaparin/VKA).
Arm/Group Title Rivaroxaban (Xarelto, BAY59-7939) Enoxaparin/VKA
Hide Arm/Group Description Participants received 15 mg rivaroxaban (oral) twice daily (b.i.d.) for 3 weeks, followed by 20 mg once daily (o.d.) Participants received enoxaparin (subcutaneous) 1.0 mg/kg b.i.d. for minimal 5 days, plus vitamin K antagonist (VKA) at individually titrated doses to achieve a target international normalized ratio (INR) of 2.5 (range: 2.0 - 3.0)
Period Title: Treatment Period
Started 2420 2413
Participants Received Treatment 2412 2405
Completed 2001 1954
Not Completed 419 459
Reason Not Completed
Death             29             21
Study terminated by sponsor             125             132
Site closed by investigator             0             1
Did not take study treatment             7             8
Adverse Event             111             92
Protocol Violation             23             30
Withdrawal by Subject             66             118
Lack of Efficacy             1             4
Lost to Follow-up             8             10
Protocol driven decision point             1             3
Physician Decision             7             18
Clinical endpoint reached             26             13
Technical problems             3             1
Participant convenience             12             8
Period Title: Observational Period
Started 2206 [1] 2197 [1]
Completed 2165 2156
Not Completed 41 41
Reason Not Completed
Protocol Violation             0             2
Withdrawal by Subject             9             5
Lost to Follow-up             1             11
Death             27             20
Study terminated by sponsor             3             1
Protocol driven decision point             0             1
Lack of Efficacy             1             0
Technical problems             0             1
[1]
All participants who took any study medication and entered the observational period.
Arm/Group Title Rivaroxaban (Xarelto, BAY59-7939) Enoxaparin/VKA Total
Hide Arm/Group Description Participants received 15 mg rivaroxaban (oral) twice daily (b.i.d.) for 3 weeks, followed by 20 mg once daily (o.d.) Participants received enoxaparin (subcutaneous) 1.0 mg/kg b.i.d. for minimal 5 days, plus vitamin K antagonist (VKA) at individually titrated doses to achieve a target international normalized ratio (INR) of 2.5 (range: 2.0 - 3.0) Total of all reporting groups
Overall Number of Baseline Participants 2419 2413 4832
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous   [1] 
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 2419 participants 2413 participants 4832 participants
57.9  (17.3) 57.5  (17.2) 57.7  (17.3)
[1]
Measure Description: Intention-to-treat (ITT) population
Age, Customized   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 2419 participants 2413 participants 4832 participants
18 - < 40 years 410 432 842
40 - < 60 years 794 779 1573
60 - < 75 years 740 754 1494
≥ 75 years 475 448 923
[1]
Measure Description: Intention-to-treat (ITT) population
Sex: Female, Male   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 2419 participants 2413 participants 4832 participants
Female
1309
  54.1%
1247
  51.7%
2556
  52.9%
Male
1110
  45.9%
1166
  48.3%
2276
  47.1%
[1]
Measure Description: Intention-to-treat (ITT) population
1.Primary Outcome
Title Percentage of Participants With Symptomatic Recurrent Venous Thromboembolism [VTE] (i.e. the Composite of Recurrent Deep Vein Thrombosis [DVT] or Fatal or Non-fatal Pulmonary Embolism [PE]) Until the Intended End of Study Treatment
Hide Description All events were adjudicated and confirmed by a central independent adjudication committee blinded to treatment. Events were assessed based on either compression ultrasound (for DVT), venography (for DVT), spiral computed tomography (CT) scanning (for PE), pulmonary angiography (for PE), ventilation/perfusion lung scan (for PE), lung scintigraphy (for PE), autopsy (for fatal PE) or unexplained death for which DVT/PE could not be ruled out (for fatal PE), and/or case summaries.
Time Frame 3-, 6-, or 12-month study treatment period
Hide Outcome Measure Data
Hide Analysis Population Description
The intention-to-treat (ITT) population consisted of all randomized participants with valid informed consent. Participants were analyzed according to the treatment assigned at randomization.
Arm/Group Title Rivaroxaban (Xarelto, BAY59-7939) Enoxaparin/VKA
Hide Arm/Group Description:
Participants received 15 mg rivaroxaban (oral) twice daily (b.i.d.) for 3 weeks, followed by 20 mg once daily (o.d.)
Participants received enoxaparin (subcutaneous) 1.0 mg/kg b.i.d. for minimal 5 days, plus vitamin K antagonist (VKA) at individually titrated doses to achieve a target international normalized ratio (INR) of 2.5 (range: 2.0 - 3.0)
Overall Number of Participants Analyzed 2419 2413
Measure Type: Number
Unit of Measure: Percentage of participants
2.1 1.8
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rivaroxaban (Xarelto, BAY59-7939), Enoxaparin/VKA
Comments The rivaroxaban to comparator hazard ratio was computed with a 95% CI (confidence interval) (two-sided testing). Based on this model, rivaroxaban would be considered at least as effective as the comparator if the upper limit of the CI was less than 2.0.
Type of Statistical Test Non-Inferiority or Equivalence
Comments Assuming equal efficacy, a total of 88 events will give a power of 90% to demonstrate that rivaroxaban is at least as effective as the comparator, considering a relative non-inferiority upper CI margin for the hazard ratio of 2.0 (two-sided alpha=0.05). The mean overall incidence for the primary efficacy outcome of 3% was expected and therefore 1465 patients per group would be needed. This number was to be adjusted based on the observed overall incidence of symptomatic recurrent VTE.
Statistical Test of Hypothesis P-Value 0.0026
Comments [Not Specified]
Method Regression, Cox
Comments Stratified by intend treatment duration, adjusted for presence of active malignancy at baseline
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.12
Confidence Interval (2-Sided) 95%
0.75 to 1.68
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.2067
Estimation Comments The standard error of the log hazard ratio was estimated.
2.Secondary Outcome
Title Percentage of Participants With the Composite Variable Comprising Recurrent DVT, Non-fatal PE and All Cause Mortality Until the Intended End of Study Treatment
Hide Description All events were adjudicated and confirmed by a central independent adjudication committee blinded to treatment. Events were assessed based on either compression ultrasound (for DVT), venography (for DVT), spiral computed tomography (CT) scanning (for PE), pulmonary angiography (for PE), ventilation/perfusion lung scan (for PE), lung scintigraphy (for PE), autopsy (for deaths), results/films/images of confirmatory testing, and/or case summaries.
Time Frame 3-, 6-, or 12-month study treatment period
Hide Outcome Measure Data
Hide Analysis Population Description
The intention-to-treat (ITT) population consisted of all randomized participants with valid informed consent. Participants were analyzed according to the treatment assigned at randomization.
Arm/Group Title Rivaroxaban (Xarelto, BAY59-7939) Enoxaparin/VKA
Hide Arm/Group Description:
Participants received 15 mg rivaroxaban (oral) twice daily (b.i.d.) for 3 weeks, followed by 20 mg once daily (o.d.)
Participants received enoxaparin (subcutaneous) 1.0 mg/kg b.i.d. for minimal 5 days, plus vitamin K antagonist (VKA) at individually titrated doses to achieve a target international normalized ratio (INR) of 2.5 (range: 2.0 - 3.0)
Overall Number of Participants Analyzed 2419 2413
Measure Type: Number
Unit of Measure: Percentage of participants
4.0 3.4
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rivaroxaban (Xarelto, BAY59-7939), Enoxaparin/VKA
Comments Stratified by intend treatment duration, adjusted for presence of active malignancy at baseline.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.33
Comments Nominal p-value
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.16
Confidence Interval (2-Sided) 95%
0.86 to 1.56
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.1500
Estimation Comments The standard error of the log hazard ratio was estimated.
3.Secondary Outcome
Title Percentage of Participants With an Event for Net Clinical Benefit 1 Until the Intended End of Study Treatment
Hide Description Net clinical benefit 1: composite of recurrent DVT or non-fatal or fatal PE, and major bleeding. Major bleeding was overt bleeding associated with 2 g/dL or greater fall in hemoglobin, leading to a transfusion of ≥2 units, occurring in a critical site or contributing to death. Net clinical benefit was considered greater in those participants with fewer composite events. All events were adjudicated and confirmed by a central independent adjudication committee blinded to treatment, based on either compression ultrasound, venography, spiral computed tomography scanning, pulmonary angiography, ventilation/perfusion lung scan, lung scintigraphy, autopsy or unexplained death for which DVT/PE could not be ruled out, results/films/images of confirmatory testing, and/or case summaries.
Time Frame 3-, 6-, or 12-month study treatment period
Hide Outcome Measure Data
Hide Analysis Population Description
The intention-to-treat (ITT) population consisted of all randomized participants with valid informed consent. Participants were analyzed according to the treatment assigned at randomization.
Arm/Group Title Rivaroxaban (Xarelto, BAY59-7939) Enoxaparin/VKA
Hide Arm/Group Description:
Participants received 15 mg rivaroxaban (oral) twice daily (b.i.d.) for 3 weeks, followed by 20 mg once daily (o.d.)
Participants received enoxaparin (subcutaneous) 1.0 mg/kg b.i.d. for minimal 5 days, plus vitamin K antagonist (VKA) at individually titrated doses to achieve a target international normalized ratio (INR) of 2.5 (range: 2.0 - 3.0)
Overall Number of Participants Analyzed 2419 2413
Measure Type: Number
Unit of Measure: Percentage of participants
3.4 4.0
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rivaroxaban (Xarelto, BAY59-7939), Enoxaparin/VKA
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.275
Comments Nominal p-value
Method Regression, Cox
Comments Stratified by intend treatment duration, adjusted for presence of active malignancy at baseline
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.85
Confidence Interval (2-Sided) 95%
0.63 to 1.14
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.1499
Estimation Comments The standard error of the log hazard ratio was estimated.
4.Secondary Outcome
Title Percentage of Participants With Recurrent PE Until the Intended End of Study Treatment
Hide Description All events were adjudicated and confirmed by a central independent adjudication committee blinded to treatment. Events were assessed based on spiral computed tomography scanning, pulmonary angiography, ventilation/perfusion lung scan, lung scintigraphy, autopsy or unexplained death for which DVT/PE could not be ruled out, results/films/images of confirmatory testing, and/or case summaries.
Time Frame 3-, 6- or 12-month study treatment period
Hide Outcome Measure Data
Hide Analysis Population Description
The intention-to-treat (ITT) population consisted of all randomized participants with valid informed consent. Participants were analyzed according to the treatment assigned at randomization.
Arm/Group Title Rivaroxaban (Xarelto, BAY59-7939) Enoxaparin/VKA
Hide Arm/Group Description:
Participants received 15 mg rivaroxaban (oral) twice daily (b.i.d.) for 3 weeks, followed by 20 mg once daily (o.d.)
Participants received enoxaparin (subcutaneous) 1.0 mg/kg b.i.d. for minimal 5 days, plus vitamin K antagonist (VKA) at individually titrated doses to achieve a target international normalized ratio (INR) of 2.5 (range: 2.0 - 3.0)
Overall Number of Participants Analyzed 2419 2413
Measure Type: Number
Unit of Measure: Percentage of participants
1.4 1.2
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rivaroxaban (Xarelto, BAY59-7939), Enoxaparin/VKA
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.55
Comments nominal p-value
Method Regression, Cox
Comments Stratified by intend treatment duration, adjusted for presence of active malignancy at baseline.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.16
Confidence Interval (2-Sided) 95%
0.70 to 1.93
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.2570
Estimation Comments The standard error of the log hazard ratio was estimated.
5.Secondary Outcome
Title Percentage of Participants With Recurrent DVT Until the Intended End of Study Treatment
Hide Description All events were adjudicated and confirmed by a central independent adjudication committee blinded to treatment. Events were assessed based on either compression ultrasound, venography, results/films/images of confirmatory testing, and/or case summaries.
Time Frame 3-, 6- or 12-month study treatment period
Hide Outcome Measure Data
Hide Analysis Population Description
The intention-to-treat (ITT) population consisted of all randomized participants with valid informed consent. Participants were analyzed according to the treatment assigned at randomization.
Arm/Group Title Rivaroxaban (Xarelto, BAY59-7939) Enoxaparin/VKA
Hide Arm/Group Description:
Participants received 15 mg rivaroxaban (oral) twice daily (b.i.d.) for 3 weeks, followed by 20 mg once daily (o.d.)
Participants received enoxaparin (subcutaneous) 1.0 mg/kg b.i.d. for minimal 5 days, plus vitamin K antagonist (VKA) at individually titrated doses to achieve a target international normalized ratio (INR) of 2.5 (range: 2.0 - 3.0)
Overall Number of Participants Analyzed 2419 2413
Measure Type: Number
Unit of Measure: Percentage of participants
0.7 0.8
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rivaroxaban (Xarelto, BAY59-7939), Enoxaparin/VKA
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.85
Comments Nominal p-value
Method Regression, Cox
Comments Stratified by intend treatment duration, adjusted for presence of active malignancy at baseline.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.94
Confidence Interval (2-Sided) 95%
0.49 to 1.79
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.3289
Estimation Comments The standard error of the log hazard ratio was estimated.
6.Secondary Outcome
Title Percentage of Participants With Clinically Relevant Bleeding, Treatment-emergent (Time Window: Until 2 Days After Last Dose)
Hide Description All events were adjudicated and confirmed by a central independent adjudication committee blinded to treatment. Clinically relevant bleeding included major bleeding (overt bleeding associated with 2 g/dL or greater fall in hemoglobin, leading to a transfusion of 2 or more units of packed red blood cells or whole blood, occurring in a critical site or contributing to death) and non-major bleeding associated with medical intervention, unscheduled physician contact, (temporary) cessation of study treatment, discomfort for the participants such as pain, or impairment of activities of daily life.
Time Frame 3-, 6- or 12-month study treatment period
Hide Outcome Measure Data
Hide Analysis Population Description
The valid-for-safety analysis population consisted of all participants who were randomized with valid informed consent and received at least one dose of anticoagulant study treatment after randomization (i.e. enoxaparin, warfarin, acenocoumarol, rivaroxaban). Participants were analyzed according to the treatment they actually received.
Arm/Group Title Rivaroxaban (Xarelto, BAY59-7939) Enoxaparin/VKA
Hide Arm/Group Description:
Participants received 15 mg rivaroxaban (oral) twice daily (b.i.d.) for 3 weeks, followed by 20 mg once daily (o.d.)
Participants received enoxaparin (subcutaneous) 1.0 mg/kg b.i.d. for minimal 5 days, plus vitamin K antagonist (VKA) at individually titrated doses to achieve a target international normalized ratio (INR) of 2.5 (range: 2.0 - 3.0)
Overall Number of Participants Analyzed 2412 2405
Measure Type: Number
Unit of Measure: Percentage of participants
10.3 11.4
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rivaroxaban (Xarelto, BAY59-7939), Enoxaparin/VKA
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.23
Comments If the primary efficacy analysis shows that rivaroxaban is non-inferior to the comparator, the principal safety outcome was to be compared between treatment groups to maintain the overall type I error of 0.05 (2-sided) (a closed testing procedure).
Method Regression, Cox
Comments Stratified by intend treatment duration, adjusted for presence of active malignancy at baseline.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.90
Confidence Interval (2-Sided) 95%
0.76 to 1.07
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.08756
Estimation Comments The standard error of the log hazard ratio was estimated.
7.Secondary Outcome
Title Percentage of Participants With All Deaths
Hide Description All events were adjudicated and confirmed by a central independent adjudication committee blinded to treatment. Events were assessed based on either autopsy, results/films/images of confirmatory testing, and/or case summaries.
Time Frame 3-, 6- or 12-month study treatment period
Hide Outcome Measure Data
Hide Analysis Population Description
The valid-for-safety analysis population consisted of all participants who were randomized with valid informed consent and received at least one dose of anticoagulant study treatment after randomization (i.e. enoxaparin, warfarin, acenocoumarol, rivaroxaban). Participants were analyzed according to the treatment they actually received.
Arm/Group Title Rivaroxaban (Xarelto, BAY59-7939) Enoxaparin/VKA
Hide Arm/Group Description:
Participants received 15 mg rivaroxaban (oral) twice daily (b.i.d.) for 3 weeks, followed by 20 mg once daily (o.d.)
Participants received enoxaparin (subcutaneous) 1.0 mg/kg b.i.d. for minimal 5 days, plus vitamin K antagonist (VKA) at individually titrated doses to achieve a target international normalized ratio (INR) of 2.5 (range: 2.0 - 3.0)
Overall Number of Participants Analyzed 2412 2405
Measure Type: Number
Unit of Measure: Percentage of participants
All post-randomization 2.6 2.1
Treatment-emergent (time window: 2 days) 1.2 0.8
Treatment-emergent (time window: 7 days) 1.5 1.1
8.Secondary Outcome
Title Percentage of Participants With Other Vascular Events, On-treatment (Time Window: Until 1 Day After Last Dose)
Hide Description All pre-defined vascular events (ST segment elevation myocardial infarction, non ST segment elevation myocardial infarction, unstable angina, ischemic stroke, transient ischemic attack, non-central nervous system systemic embolism or vascular death) were adjudicated and confirmed by a central independent adjudication committee blinded to treatment. Events were assessed based results/films/images of confirmatory testing, and/or case summaries.
Time Frame 3-, 6- or 12-month study treatment period
Hide Outcome Measure Data
Hide Analysis Population Description
The valid-for-safety analysis population consisted of all participants who were randomized with valid informed consent and received at least one dose of anticoagulant study treatment after randomization (i.e. enoxaparin, warfarin, acenocoumarol, rivaroxaban). Participants were analyzed according to the treatment they actually received.
Arm/Group Title Rivaroxaban (Xarelto, BAY59-7939) Enoxaparin/VKA
Hide Arm/Group Description:
Participants received 15 mg rivaroxaban (oral) twice daily (b.i.d.) for 3 weeks, followed by 20 mg once daily (o.d.)
Participants received enoxaparin (subcutaneous) 1.0 mg/kg b.i.d. for minimal 5 days, plus vitamin K antagonist (VKA) at individually titrated doses to achieve a target international normalized ratio (INR) of 2.5 (range: 2.0 - 3.0)
Overall Number of Participants Analyzed 2412 2405
Measure Type: Number
Unit of Measure: Percentage of participants
1.5 1.5
9.Other Pre-specified Outcome
Title Percentage of Participants With the Individual Components of Efficacy Outcomes Until the Intended End of Study Treatment
Hide Description All events were adjudicated and confirmed by a central independent adjudication committee blinded to treatment, based on either compression ultrasound, venography, spiral computed tomography scanning, pulmonary angiography, ventilation/perfusion lung scan, lung scintigraphy, autopsy or unexplained death for which DVT/PE could not be ruled out, results/films/images of confirmatory testing, and/or case summaries. Major bleeding was overt bleeding associated with 2 g/dL or greater fall in hemoglobin, leading to a transfusion of ≥2 units, occurring in a critical site or contributing to death.
Time Frame 3-, 6- or 12-month study treatment period
Hide Outcome Measure Data
Hide Analysis Population Description
The intention-to-treat (ITT) population consisted of all randomized participants with valid informed consent. Participants were analyzed according to the treatment assigned at randomization.
Arm/Group Title Rivaroxaban (Xarelto, BAY59-7939) Enoxaparin/VKA
Hide Arm/Group Description:
Participants received 15 mg rivaroxaban (oral) twice daily (b.i.d.) for 3 weeks, followed by 20 mg once daily (o.d.)
Participants received enoxaparin (subcutaneous) 1.0 mg/kg b.i.d. for minimal 5 days, plus vitamin K antagonist (VKA) at individually titrated doses to achieve a target international normalized ratio (INR) of 2.5 (range: 2.0 - 3.0)
Overall Number of Participants Analyzed 2419 2413
Measure Type: Number
Unit of Measure: Percentage of participants
Death (PE) 0.1 0.04
Death (PE cannot be excluded) 0.3 0.2
Symptomatic PE and DVT 0.0 0.1
Symptomatic recurrent PE only 1.0 0.8
Symptomatic recurrent DVT only 0.7 0.7
Death (bleeding) 0.2 0.2
Death (cardiovascular) 0.4 0.1
Death (other) 1.3 1.5
Major bleeding 1.4 2.4
10.Other Pre-specified Outcome
Title Percentage of Participants With Symptomatic Recurrent VTE (i.e. the Composite of Recurrent DVT or Fatal or Non-fatal PE) During Observational Period
Hide Description All events were adjudicated and confirmed by a central independent adjudication committee blinded to treatment. Events were assessed based on either compression ultrasound (for DVT), venography (for DVT), spiral computed tomography (CT) scanning (for PE), pulmonary angiography (for PE), ventilation/perfusion lung scan (for PE), lung scintigraphy (for PE), autopsy (for fatal PE) or unexplained death for which DVT/PE could not be ruled out (for fatal PE), and/or case summaries.
Time Frame Up to 30 days after the last intake of study medication
Hide Outcome Measure Data
Hide Analysis Population Description
Participants entering the observational period were participants for whom the investigator indicated on the eCRF (electronic case report form) that the participant entered the observational period or had a confirmed event more than one day and up to 30 days after the last dose as a component of the respective composite outcome.
Arm/Group Title Rivaroxaban (Xarelto, BAY59-7939) Enoxaparin/VKA
Hide Arm/Group Description:
Participants received 15 mg rivaroxaban (oral) twice daily (b.i.d.) for 3 weeks, followed by 20 mg once daily (o.d.)
Participants received enoxaparin (subcutaneous) 1.0 mg/kg b.i.d. for minimal 5 days, plus vitamin K antagonist (VKA) at individually titrated doses to achieve a target international normalized ratio (INR) of 2.5 (range: 2.0 - 3.0)
Overall Number of Participants Analyzed 2211 2201
Measure Type: Number
Unit of Measure: Percentage of participants
0.9 0.7
11.Other Pre-specified Outcome
Title Percentage of Participants With the Composite Variable Comprising Recurrent DVT, Non-fatal PE and All Cause Mortality During Observational Period
Hide Description All events were adjudicated and confirmed by a central independent adjudication committee blinded to treatment. Events were assessed based on either compression ultrasound (for DVT), venography (for DVT), spiral computed tomography (CT) scanning (for PE), pulmonary angiography (for PE), ventilation/perfusion lung scan (for PE), lung scintigraphy (for PE), autopsy (for deaths), results/films/images of confirmatory testing, and/or case summaries.
Time Frame Up to 30 days after the last intake of study medication
Hide Outcome Measure Data
Hide Analysis Population Description
Participants entering the observational period were participants for whom the investigator indicated on the eCRF that the participant entered the observational period or had a confirmed event more than one day and up to 30 days after the last dose as a component of the respective composite outcome.
Arm/Group Title Rivaroxaban (Xarelto, BAY59-7939) Enoxaparin/VKA
Hide Arm/Group Description:
Participants received 15 mg rivaroxaban (oral) twice daily (b.i.d.) for 3 weeks, followed by 20 mg once daily (o.d.)
Participants received enoxaparin (subcutaneous) 1.0 mg/kg b.i.d. for minimal 5 days, plus vitamin K antagonist (VKA) at individually titrated doses to achieve a target international normalized ratio (INR) of 2.5 (range: 2.0 - 3.0)
Overall Number of Participants Analyzed 2213 2203
Measure Type: Number
Unit of Measure: Percentage of participants
2.1 1.5
12.Other Pre-specified Outcome
Title Percentage of Participants With an Event for Net Clinical Benefit 1 During Observational Period
Hide Description Net clinical benefit 1: composite of recurrent DVT or non-fatal or fatal PE, and major bleeding. Major bleeding was overt bleeding associated with 2 g/dL or greater fall in hemoglobin, leading to a transfusion of ≥2 units, occurring in a critical site or contributing to death. Net clinical benefit was considered greater in those participants with fewer composite events. All events were adjudicated and confirmed by a central independent adjudication committee blinded to treatment, based on either compression ultrasound, venography, spiral computed tomography scanning, pulmonary angiography, ventilation/perfusion lung scan, lung scintigraphy, autopsy or unexplained death for which DVT/PE could not be ruled out, results/films/images of confirmatory testing, and/or case summaries.
Time Frame Up to 30 days after the last intake of study medication
Hide Outcome Measure Data
Hide Analysis Population Description
Participants entering the observational period were participants for whom the investigator indicated on the eCRF that the participant entered the observational period or had a confirmed event more than one day and up to 30 days after the last dose as a component of the respective composite outcome.
Arm/Group Title Rivaroxaban (Xarelto, BAY59-7939) Enoxaparin/VKA
Hide Arm/Group Description:
Participants received 15 mg rivaroxaban (oral) twice daily (b.i.d.) for 3 weeks, followed by 20 mg once daily (o.d.)
Participants received enoxaparin (subcutaneous) 1.0 mg/kg b.i.d. for minimal 5 days, plus vitamin K antagonist (VKA) at individually titrated doses to achieve a target international normalized ratio (INR) of 2.5 (range: 2.0 - 3.0)
Overall Number of Participants Analyzed 2212 2201
Measure Type: Number
Unit of Measure: Percentage of participants
1.2 1.2
13.Other Pre-specified Outcome
Title Percentage of Participants With Recurrent DVT During Observational Period
Hide Description All events were adjudicated and confirmed by a central independent adjudication committee blinded to treatment. Events were assessed based on either compression ultrasound, venography, results/films/images of confirmatory testing, and/or case summaries.
Time Frame Up to 30 days after the last intake of study medication
Hide Outcome Measure Data
Hide Analysis Population Description
Participants entering the observational period were participants for whom the investigator indicated on the eCRF that the participant entered the observational period or had a confirmed event more than one day and up to 30 days after the last dose as a component of the respective composite outcome.
Arm/Group Title Rivaroxaban (Xarelto, BAY59-7939) Enoxaparin/VKA
Hide Arm/Group Description:
Participants received 15 mg rivaroxaban (oral) twice daily (b.i.d.) for 3 weeks, followed by 20 mg once daily (o.d.)
Participants received enoxaparin (subcutaneous) 1.0 mg/kg b.i.d. for minimal 5 days, plus vitamin K antagonist (VKA) at individually titrated doses to achieve a target international normalized ratio (INR) of 2.5 (range: 2.0 - 3.0)
Overall Number of Participants Analyzed 2210 2201
Measure Type: Number
Unit of Measure: Percentage of participants
0.3 0.1
14.Other Pre-specified Outcome
Title Percentage of Participants With the Individual Components of Efficacy Outcomes During Observational Period
Hide Description All events were adjudicated and confirmed by a central independent adjudication committee blinded to treatment, based on either compression ultrasound, venography, spiral computed tomography scanning, pulmonary angiography, ventilation/perfusion lung scan, lung scintigraphy, autopsy or unexplained death for which DVT/PE could not be ruled out, results/films/images of confirmatory testing, and/or case summaries. Major bleeding was overt bleeding associated with 2 g/dL or greater fall in hemoglobin, leading to a transfusion of ≥2 units, occurring in a critical site or contributing to death.
Time Frame Up to 30 days after the last intake of study medication
Hide Outcome Measure Data
Hide Analysis Population Description
Participants entering the observational period were participants for whom the investigator indicated on the eCRF that the participant entered the observational period or had a confirmed event more than one day and up to 30 days after the last dose as a component of the respective composite outcome.
Arm/Group Title Rivaroxaban (Xarelto, BAY59-7939) Enoxaparin/VKA
Hide Arm/Group Description:
Participants received 15 mg rivaroxaban (oral) twice daily (b.i.d.) for 3 weeks, followed by 20 mg once daily (o.d.)
Participants received enoxaparin (subcutaneous) 1.0 mg/kg b.i.d. for minimal 5 days, plus vitamin K antagonist (VKA) at individually titrated doses to achieve a target international normalized ratio (INR) of 2.5 (range: 2.0 - 3.0)
Overall Number of Participants Analyzed 2213 2203
Measure Type: Number
Unit of Measure: Percentage of participants
Death (PE) 0.09 0
Death (PE cannot be excluded) 0 0.05
Symptomatic PE and DVT 0.09 0
Symptomatic recurrent PE only 0.5 0.5
Symptomatic recurrent DVT only 0.2 0.1
Death (bleeding) 0.09 0.09
Death (cardiovascular) 0.3 0.05
Death (other) 0.8 0.7
Major bleeding 0.3 0.5
15.Post-Hoc Outcome
Title Percentage of Participants With an Event for Net Clinical Benefit 2 Until the Intended End of Study Treatment
Hide Description Net clinical benefit 2: composite of recurrent DVT or non-fatal or fatal PE, major bleeding (associated with 2 g/dL or greater fall in hemoglobin, leading to transfusion of ≥2 units, occurring in a critical site or contributing to death), cardiovascular death, myocardial infarction, stroke, and non CNS (central nervous system) systemic embolism. Net clinical benefit was considered greater in those participants with fewer composite events. All events were adjudicated and confirmed by a central independent adjudication committee blinded to treatment, based on either compression ultrasound (DVT), venography (DVT), spiral CT scanning (PE), pulmonary angiography (PE), ventilation/perfusion lung scan (PE), lung scintigraphy (PE), autopsy or unexplained death for which DVT/PE could not be ruled out, results/films/images of confirmatory testing, and/or case summaries.
Time Frame 3-, 6- or 12-month study treatment period
Hide Outcome Measure Data
Hide Analysis Population Description
The intention-to-treat (ITT) population consisted of all randomized participants with valid informed consent. Participants were analyzed according to the treatment assigned at randomization.
Arm/Group Title Rivaroxaban (Xarelto, BAY59-7939) Enoxaparin/VKA
Hide Arm/Group Description:
Participants received 15 mg rivaroxaban (oral) twice daily (b.i.d.) for 3 weeks, followed by 20 mg once daily (o.d.)
Participants received enoxaparin (subcutaneous) 1.0 mg/kg b.i.d. for minimal 5 days, plus vitamin K antagonist (VKA) at individually titrated doses to achieve a target international normalized ratio (INR) of 2.5 (range: 2.0 - 3.0)
Overall Number of Participants Analyzed 2419 2413
Measure Type: Number
Unit of Measure: Percentage of participants
4.5 4.8
16.Post-Hoc Outcome
Title Percentage of Participants With an Event for Net Clinical Benefit 2 During Observational Period
Hide Description Net clinical benefit 2: composite of recurrent DVT or non-fatal or fatal PE, major bleeding (associated with 2 g/dL or greater fall in hemoglobin, leading to transfusion of ≥2 units, occurring in a critical site or contributing to death), cardiovascular death, myocardial infarction, stroke, and non CNS (central nervous system) systemic embolism. Net clinical benefit was considered greater in those participants with fewer composite events. All events were adjudicated and confirmed by a central independent adjudication committee blinded to treatment, based on either compression ultrasound (DVT), venography (DVT), spiral CT scanning (PE), pulmonary angiography (PE), ventilation/perfusion lung scan (PE), lung scintigraphy (PE), autopsy or unexplained death for which DVT/PE could not be ruled out, results/films/images of confirmatory testing, and/or case summaries.
Time Frame Up to 30 days after the last intake of study medication
Hide Outcome Measure Data
Hide Analysis Population Description
Participants entering the observational period were participants for whom the investigator indicated on the eCRF that the participant entered the observational period or had a confirmed event more than one day and up to 30 days after the last dose as a component of the respective composite outcome.
Arm/Group Title Rivaroxaban (Xarelto, BAY59-7939) Enoxaparin/VKA
Hide Arm/Group Description:
Participants received 15 mg rivaroxaban (oral) twice daily (b.i.d.) for 3 weeks, followed by 20 mg once daily (o.d.)
Participants received enoxaparin (subcutaneous) 1.0 mg/kg b.i.d. for minimal 5 days, plus vitamin K antagonist (VKA) at individually titrated doses to achieve a target international normalized ratio (INR) of 2.5 (range: 2.0 - 3.0)
Overall Number of Participants Analyzed 2213 2201
Measure Type: Number
Unit of Measure: Percentage of participants
1.5 1.4
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Rivaroxaban (Xarelto, BAY59-7939) Enoxaparin/VKA
Hide Arm/Group Description Participants received 15 mg rivaroxaban (oral) twice daily (b.i.d.) for 3 weeks, followed by 20 mg once daily (o.d.) Participants received enoxaparin (subcutaneous) 1.0 mg/kg b.i.d. for minimal 5 days, plus vitamin K antagonist (VKA) at individually titrated doses to achieve a target international normalized ratio (INR) of 2.5 (range: 2.0 - 3.0)
All-Cause Mortality
Rivaroxaban (Xarelto, BAY59-7939) Enoxaparin/VKA
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Hide Serious Adverse Events
Rivaroxaban (Xarelto, BAY59-7939) Enoxaparin/VKA
Affected / at Risk (%) Affected / at Risk (%)
Total   504/2412 (20.90%)   495/2405 (20.58%) 
Blood and lymphatic system disorders     
Anaemia * 1  14/2412 (0.58%)  6/2405 (0.25%) 
Anaemia folate deficiency * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Coagulopathy * 1  0/2412 (0.00%)  2/2405 (0.08%) 
Disseminated intravascular coagulation * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Eosinophilia * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Febrile neutropenia * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Haemolytic anaemia * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Hypercoagulation * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Idiopathic thrombocytopenic purpura * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Leukopenia * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Lymphadenopathy * 1  1/2412 (0.04%)  1/2405 (0.04%) 
Neutropenia * 1  0/2412 (0.00%)  2/2405 (0.08%) 
Pancytopenia * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Pernicious anaemia * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Splenic haemorrhage * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Splenic infarction * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Thrombocytopenia * 1  2/2412 (0.08%)  0/2405 (0.00%) 
Haemorrhagic anaemia * 1  1/2412 (0.04%)  2/2405 (0.08%) 
Cardiac disorders     
Acute myocardial infarction * 1  6/2412 (0.25%)  10/2405 (0.42%) 
Angina pectoris * 1  3/2412 (0.12%)  4/2405 (0.17%) 
Angina unstable * 1  7/2412 (0.29%)  2/2405 (0.08%) 
Arrhythmia * 1  2/2412 (0.08%)  1/2405 (0.04%) 
Atrial fibrillation * 1  8/2412 (0.33%)  11/2405 (0.46%) 
Atrial flutter * 1  1/2412 (0.04%)  1/2405 (0.04%) 
Atrioventricular block * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Cardiac arrest * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Cardiac failure * 1  9/2412 (0.37%)  7/2405 (0.29%) 
Cardiac failure acute * 1  4/2412 (0.17%)  2/2405 (0.08%) 
Cardiac failure congestive * 1  4/2412 (0.17%)  5/2405 (0.21%) 
Cardio-respiratory arrest * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Cardiogenic shock * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Cardiomyopathy * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Cor pulmonale * 1  3/2412 (0.12%)  1/2405 (0.04%) 
Cor pulmonale acute * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Cor pulmonale chronic * 1  1/2412 (0.04%)  1/2405 (0.04%) 
Coronary artery disease * 1  1/2412 (0.04%)  8/2405 (0.33%) 
Coronary artery stenosis * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Left ventricular failure * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Mitral valve incompetence * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Myocardial infarction * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Myocardial ischaemia * 1  0/2412 (0.00%)  2/2405 (0.08%) 
Myocarditis * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Palpitations * 1  2/2412 (0.08%)  2/2405 (0.08%) 
Pericardial effusion * 1  1/2412 (0.04%)  1/2405 (0.04%) 
Pericardial haemorrhage * 1  1/2412 (0.04%)  2/2405 (0.08%) 
Pericarditis * 1  2/2412 (0.08%)  0/2405 (0.00%) 
Right ventricular failure * 1  3/2412 (0.12%)  0/2405 (0.00%) 
Sick sinus syndrome * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Sinus tachycardia * 1  0/2412 (0.00%)  2/2405 (0.08%) 
Supraventricular tachycardia * 1  1/2412 (0.04%)  4/2405 (0.17%) 
Tachycardia * 1  1/2412 (0.04%)  2/2405 (0.08%) 
Ventricular fibrillation * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Ventricular tachycardia * 1  3/2412 (0.12%)  1/2405 (0.04%) 
Coronary artery dissection * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Acute coronary syndrome * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Congestive cardiomyopathy * 1  2/2412 (0.08%)  0/2405 (0.00%) 
Acute left ventricular failure * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Congenital, familial and genetic disorders     
Atrial septal defect * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Hydrocele * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Phimosis * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Ear and labyrinth disorders     
Vertigo * 1  3/2412 (0.12%)  4/2405 (0.17%) 
Vertigo positional * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Deafness unilateral * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Sudden hearing loss * 1  1/2412 (0.04%)  1/2405 (0.04%) 
Endocrine disorders     
Addison's disease * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Adrenal haemorrhage * 1  1/2412 (0.04%)  1/2405 (0.04%) 
Diabetes insipidus * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Goitre * 1  0/2412 (0.00%)  2/2405 (0.08%) 
Hyperparathyroidism primary * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Hyperthyroidism * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Eye disorders     
Amaurosis * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Cataract * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Diplopia * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Eye haemorrhage * 1  0/2412 (0.00%)  3/2405 (0.12%) 
Eye pain * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Optic ischaemic neuropathy * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Retinal degeneration * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Retinal haemorrhage * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Vision blurred * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Age-related macular degeneration * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Gastrointestinal disorders     
Abdominal pain * 1  1/2412 (0.04%)  4/2405 (0.17%) 
Abdominal pain upper * 1  1/2412 (0.04%)  4/2405 (0.17%) 
Acute abdomen * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Anorectal disorder * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Ascites * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Colitis * 1  1/2412 (0.04%)  1/2405 (0.04%) 
Colitis ischaemic * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Colonic polyp * 1  2/2412 (0.08%)  0/2405 (0.00%) 
Colonic stenosis * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Dental caries * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Diarrhoea * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Diarrhoea haemorrhagic * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Diverticulum * 1  1/2412 (0.04%)  1/2405 (0.04%) 
Diverticulum intestinal * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Diverticulum oesophageal * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Duodenal ulcer * 1  2/2412 (0.08%)  0/2405 (0.00%) 
Dyspepsia * 1  2/2412 (0.08%)  0/2405 (0.00%) 
Dysphagia * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Gastric haemorrhage * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Gastric perforation * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Gastric ulcer * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Gastric ulcer haemorrhage * 1  1/2412 (0.04%)  1/2405 (0.04%) 
Gastritis * 1  1/2412 (0.04%)  2/2405 (0.08%) 
Gastritis haemorrhagic * 1  1/2412 (0.04%)  1/2405 (0.04%) 
Gastrooesophageal reflux disease * 1  1/2412 (0.04%)  1/2405 (0.04%) 
Gastrointestinal haemorrhage * 1  7/2412 (0.29%)  5/2405 (0.21%) 
Haematemesis * 1  4/2412 (0.17%)  2/2405 (0.08%) 
Haematochezia * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Haemorrhoids * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Hiatus hernia * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Ileus * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Inguinal hernia * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Intestinal fistula * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Intestinal infarction * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Intestinal obstruction * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Large intestine perforation * 1  1/2412 (0.04%)  2/2405 (0.08%) 
Melaena * 1  2/2412 (0.08%)  7/2405 (0.29%) 
Nausea * 1  2/2412 (0.08%)  0/2405 (0.00%) 
Oesophageal ulcer * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Oesophageal ulcer haemorrhage * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Pancreatitis * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Pancreatitis acute * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Rectal haemorrhage * 1  6/2412 (0.25%)  6/2405 (0.25%) 
Retroperitoneal haemorrhage * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Small intestinal obstruction * 1  1/2412 (0.04%)  1/2405 (0.04%) 
Small intestinal perforation * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Tooth loss * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Umbilical hernia * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Upper gastrointestinal haemorrhage * 1  2/2412 (0.08%)  2/2405 (0.08%) 
Vomiting * 1  3/2412 (0.12%)  3/2405 (0.12%) 
Intestinal polyp * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Gastrointestinal dysplasia * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Subileus * 1  1/2412 (0.04%)  1/2405 (0.04%) 
Lower gastrointestinal haemorrhage * 1  2/2412 (0.08%)  3/2405 (0.12%) 
Haemorrhoidal haemorrhage * 1  1/2412 (0.04%)  2/2405 (0.08%) 
Retroperitoneal haematoma * 1  0/2412 (0.00%)  2/2405 (0.08%) 
Intestinal haemorrhage * 1  1/2412 (0.04%)  3/2405 (0.12%) 
Abdominal hernia * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Large intestinal obstruction * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Abdominal wall haematoma * 1  0/2412 (0.00%)  2/2405 (0.08%) 
General disorders     
Asthenia * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Chest discomfort * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Chest pain * 1  21/2412 (0.87%)  27/2405 (1.12%) 
Cyst * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Death * 1  4/2412 (0.17%)  2/2405 (0.08%) 
Fatigue * 1  2/2412 (0.08%)  0/2405 (0.00%) 
Gait disturbance * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Granuloma * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Impaired healing * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Malaise * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Multi-organ failure * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Oedema peripheral * 1  1/2412 (0.04%)  2/2405 (0.08%) 
Pyrexia * 1  4/2412 (0.17%)  2/2405 (0.08%) 
Sudden death * 1  3/2412 (0.12%)  1/2405 (0.04%) 
General physical health deterioration * 1  3/2412 (0.12%)  2/2405 (0.08%) 
Adverse drug reaction * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Drug intolerance * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Non-cardiac chest pain * 1  6/2412 (0.25%)  3/2405 (0.12%) 
Implant site thrombosis * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Device deposit issue * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Hepatobiliary disorders     
Bile duct stone * 1  1/2412 (0.04%)  1/2405 (0.04%) 
Biliary colic * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Cholangitis * 1  1/2412 (0.04%)  1/2405 (0.04%) 
Cholecystitis * 1  2/2412 (0.08%)  1/2405 (0.04%) 
Cholecystitis acute * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Cholelithiasis * 1  4/2412 (0.17%)  5/2405 (0.21%) 
Hepatic failure * 1  1/2412 (0.04%)  2/2405 (0.08%) 
Hepatic function abnormal * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Hepatic pain * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Hepatic steatosis * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Hepatitis * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Hepatitis acute * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Hepatitis chronic active * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Ischaemic hepatitis * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Jaundice * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Cytolytic hepatitis * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Immune system disorders     
Antiphospholipid syndrome * 1  1/2412 (0.04%)  1/2405 (0.04%) 
Drug hypersensitivity * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Hypersensitivity * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Sarcoidosis * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Infections and infestations     
Appendicitis * 1  0/2412 (0.00%)  2/2405 (0.08%) 
Bacteraemia * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Bronchitis * 1  5/2412 (0.21%)  8/2405 (0.33%) 
Bronchopneumonia * 1  4/2412 (0.17%)  4/2405 (0.17%) 
Bronchopulmonary aspergillosis * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Cellulitis * 1  4/2412 (0.17%)  5/2405 (0.21%) 
Cystitis * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Diverticulitis * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Endocarditis * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Endocarditis bacterial * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Gastroenteritis * 1  3/2412 (0.12%)  0/2405 (0.00%) 
Gastroenteritis salmonella * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Hepatitis A * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Herpes simplex * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Herpes zoster * 1  0/2412 (0.00%)  2/2405 (0.08%) 
Lobar pneumonia * 1  4/2412 (0.17%)  1/2405 (0.04%) 
Localised infection * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Lower respiratory tract infection * 1  3/2412 (0.12%)  4/2405 (0.17%) 
Lung abscess * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Mastitis * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Osteomyelitis * 1  0/2412 (0.00%)  2/2405 (0.08%) 
Pneumonia * 1  22/2412 (0.91%)  21/2405 (0.87%) 
Pneumonia mycoplasmal * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Pneumonia primary atypical * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Postoperative wound infection * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Pyelonephritis * 1  3/2412 (0.12%)  2/2405 (0.08%) 
Pyelonephritis acute * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Sepsis * 1  13/2412 (0.54%)  2/2405 (0.08%) 
Sinusitis * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Skin infection * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Tracheobronchitis * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Tuberculosis * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Urinary tract infection * 1  7/2412 (0.29%)  4/2405 (0.17%) 
Viral rash * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Wound infection * 1  2/2412 (0.08%)  0/2405 (0.00%) 
Urosepsis * 1  2/2412 (0.08%)  2/2405 (0.08%) 
Anal abscess * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Neutropenic sepsis * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Appendiceal abscess * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Groin abscess * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Abscess limb * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Abscess soft tissue * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Prostate infection * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Skin bacterial infection * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Abscess neck * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Pneumonia necrotising * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Subdiaphragmatic abscess * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Infective exacerbation of chronic obstructive airways disease * 1  1/2412 (0.04%)  2/2405 (0.08%) 
Biliary sepsis * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Joint abscess * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Wound infection staphylococcal * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Intervertebral discitis * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Lung infection * 1  3/2412 (0.12%)  4/2405 (0.17%) 
Respiratory tract infection * 1  1/2412 (0.04%)  2/2405 (0.08%) 
Cholecystitis infective * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Device related infection * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Infectious peritonitis * 1  4/2412 (0.17%)  0/2405 (0.00%) 
Injury, poisoning and procedural complications     
Alcohol poisoning * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Ankle fracture * 1  3/2412 (0.12%)  0/2405 (0.00%) 
Cerebral haemorrhage traumatic * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Concussion * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Facial bones fracture * 1  2/2412 (0.08%)  0/2405 (0.00%) 
Fall * 1  4/2412 (0.17%)  1/2405 (0.04%) 
Femoral neck fracture * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Femur fracture * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Fibula fracture * 1  1/2412 (0.04%)  1/2405 (0.04%) 
Foot fracture * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Hip fracture * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Humerus fracture * 1  0/2412 (0.00%)  2/2405 (0.08%) 
Joint dislocation * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Kidney rupture * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Multiple injuries * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Operative haemorrhage * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Overdose * 1  2/2412 (0.08%)  2/2405 (0.08%) 
Rib fracture * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Road traffic accident * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Soft tissue injury * 1  0/2412 (0.00%)  2/2405 (0.08%) 
Spinal compression fracture * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Splenic haematoma * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Sternal fracture * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Subcutaneous haematoma * 1  1/2412 (0.04%)  3/2405 (0.12%) 
Subdural haematoma * 1  1/2412 (0.04%)  3/2405 (0.12%) 
Subdural haemorrhage * 1  0/2412 (0.00%)  3/2405 (0.12%) 
Tendon rupture * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Tibia fracture * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Traumatic haematoma * 1  0/2412 (0.00%)  2/2405 (0.08%) 
Anaemia postoperative * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Vascular pseudoaneurysm * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Perirenal haematoma * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Traumatic fracture * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Cervical vertebral fracture * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Lumbar vertebral fracture * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Thoracic vertebral fracture * 1  0/2412 (0.00%)  2/2405 (0.08%) 
Contusion * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Post procedural haemorrhage * 1  2/2412 (0.08%)  3/2405 (0.12%) 
Incision site haemorrhage * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Brain contusion * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Cardiac valve replacement complication * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Postoperative ileus * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Procedural complication * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Joint injury * 1  2/2412 (0.08%)  0/2405 (0.00%) 
Limb injury * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Chest injury * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Upper limb fracture * 1  1/2412 (0.04%)  1/2405 (0.04%) 
Toxicity to various agents * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Craniocerebral injury * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Investigations     
Activated partial thromboplastin time prolonged * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Alanine aminotransferase increased * 1  6/2412 (0.25%)  9/2405 (0.37%) 
Aspartate aminotransferase increased * 1  1/2412 (0.04%)  1/2405 (0.04%) 
Blood amylase increased * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Blood potassium increased * 1  1/2412 (0.04%)  0/2405 (0.00%) 
C-reactive protein increased * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Coagulation time prolonged * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Coagulation time shortened * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Gamma-glutamyltransferase increased * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Haemoglobin decreased * 1  1/2412 (0.04%)  0/2405 (0.00%) 
International normalised ratio abnormal * 1  0/2412 (0.00%)  1/2405 (0.04%) 
International normalised ratio increased * 1  1/2412 (0.04%)  4/2405 (0.17%) 
Liver function test abnormal * 1  4/2412 (0.17%)  9/2405 (0.37%) 
Prostatic specific antigen increased * 1  1/2412 (0.04%)  1/2405 (0.04%) 
Ultrasound liver abnormal * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Ejection fraction decreased * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Medical observation * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Transaminases increased * 1  2/2412 (0.08%)  2/2405 (0.08%) 
Hepatic enzyme increased * 1  3/2412 (0.12%)  1/2405 (0.04%) 
Metabolism and nutrition disorders     
Acidosis * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Dehydration * 1  1/2412 (0.04%)  2/2405 (0.08%) 
Diabetes mellitus * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Failure to thrive * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Gout * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Hypercalcaemia * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Hyperglycaemia * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Hyperkalaemia * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Hypoalbuminaemia * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Hypocalcaemia * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Hypoglycaemia * 1  2/2412 (0.08%)  0/2405 (0.00%) 
Hypokalaemia * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Hyponatraemia * 1  1/2412 (0.04%)  2/2405 (0.08%) 
Hypovolaemia * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Shock hypoglycaemic * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Metabolic disorder * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Malnutrition * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Decreased appetite * 1  1/2412 (0.04%)  1/2405 (0.04%) 
Type 2 diabetes mellitus * 1  2/2412 (0.08%)  0/2405 (0.00%) 
Musculoskeletal and connective tissue disorders     
Arthralgia * 1  2/2412 (0.08%)  2/2405 (0.08%) 
Back pain * 1  5/2412 (0.21%)  6/2405 (0.25%) 
Bone pain * 1  0/2412 (0.00%)  3/2405 (0.12%) 
Cervical spinal stenosis * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Groin pain * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Haemarthrosis * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Joint stiffness * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Muscle haemorrhage * 1  1/2412 (0.04%)  9/2405 (0.37%) 
Muscle twitching * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Muscular weakness * 1  4/2412 (0.17%)  3/2405 (0.12%) 
Musculoskeletal pain * 1  3/2412 (0.12%)  1/2405 (0.04%) 
Myalgia * 1  2/2412 (0.08%)  0/2405 (0.00%) 
Osteoarthritis * 1  4/2412 (0.17%)  6/2405 (0.25%) 
Osteolysis * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Osteonecrosis * 1  1/2412 (0.04%)  1/2405 (0.04%) 
Pain in extremity * 1  4/2412 (0.17%)  1/2405 (0.04%) 
Rheumatoid arthritis * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Rotator cuff syndrome * 1  2/2412 (0.08%)  0/2405 (0.00%) 
Scoliosis * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Spinal column stenosis * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Spinal osteoarthritis * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Systemic lupus erythematosus * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Temporomandibular joint syndrome * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Pseudarthrosis * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Musculoskeletal chest pain * 1  3/2412 (0.12%)  1/2405 (0.04%) 
Intervertebral disc compression * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Intervertebral disc degeneration * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Spinal disorder * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Intervertebral disc disorder * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Acute lymphocytic leukaemia * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Acute promyelocytic leukaemia * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Adenocarcinoma * 1  1/2412 (0.04%)  0/2405 (0.00%) 
B-cell lymphoma * 1  1/2412 (0.04%)  1/2405 (0.04%) 
Basal cell carcinoma * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Benign oesophageal neoplasm * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Bile duct cancer non-resectable * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Bladder cancer * 1  1/2412 (0.04%)  2/2405 (0.08%) 
Bladder neoplasm * 1  0/2412 (0.00%)  2/2405 (0.08%) 
Breast cancer * 1  1/2412 (0.04%)  1/2405 (0.04%) 
Breast cancer recurrent * 1  1/2412 (0.04%)  1/2405 (0.04%) 
Breast neoplasm * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Bronchial carcinoma * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Cervix carcinoma * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Colon cancer * 1  8/2412 (0.33%)  1/2405 (0.04%) 
Fibroadenoma of breast * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Gallbladder cancer * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Gastric cancer * 1  3/2412 (0.12%)  0/2405 (0.00%) 
Glioblastoma multiforme * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Lung adenocarcinoma * 1  3/2412 (0.12%)  4/2405 (0.17%) 
Lung carcinoma cell type unspecified recurrent * 1  1/2412 (0.04%)  1/2405 (0.04%) 
Lung squamous cell carcinoma stage unspecified * 1  1/2412 (0.04%)  1/2405 (0.04%) 
Lymphoma * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Malignant ascites * 1  1/2412 (0.04%)  1/2405 (0.04%) 
Malignant melanoma * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Malignant pleural effusion * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Meningioma * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Mesothelioma malignant * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Metastases to liver * 1  2/2412 (0.08%)  4/2405 (0.17%) 
Metastases to lung * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Metastases to lymph nodes * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Metastases to pleura * 1  0/2412 (0.00%)  2/2405 (0.08%) 
Metastases to spine * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Multiple myeloma * 1  1/2412 (0.04%)  1/2405 (0.04%) 
Myelodysplastic syndrome * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Myelofibrosis * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Neoplasm malignant * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Neoplasm prostate * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Ovarian cancer * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Ovarian germ cell teratoma benign * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Pancreatic carcinoma * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Pancreatic carcinoma metastatic * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Parathyroid tumour benign * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Polycythaemia vera * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Prostate cancer recurrent * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Prostatic adenoma * 1  2/2412 (0.08%)  2/2405 (0.08%) 
Rectal cancer * 1  2/2412 (0.08%)  1/2405 (0.04%) 
Renal cancer * 1  1/2412 (0.04%)  3/2405 (0.12%) 
Small cell lung cancer stage unspecified * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Squamous cell carcinoma of skin * 1  0/2412 (0.00%)  1/2405 (0.04%) 
T-cell lymphoma * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Uterine leiomyoma * 1  4/2412 (0.17%)  2/2405 (0.08%) 
Histiocytosis haematophagic * 1  1/2412 (0.04%)  1/2405 (0.04%) 
Tumour haemorrhage * 1  1/2412 (0.04%)  1/2405 (0.04%) 
Lung cancer metastatic * 1  1/2412 (0.04%)  2/2405 (0.08%) 
Gastrointestinal stromal tumour * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Metastases to peritoneum * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Rectal cancer metastatic * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Breast cancer metastatic * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Colon cancer metastatic * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Lung neoplasm malignant * 1  5/2412 (0.21%)  4/2405 (0.17%) 
Metastases to central nervous system * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Prostate cancer * 1  3/2412 (0.12%)  7/2405 (0.29%) 
Brain neoplasm * 1  2/2412 (0.08%)  0/2405 (0.00%) 
Colon neoplasm * 1  2/2412 (0.08%)  0/2405 (0.00%) 
Mantle cell lymphoma * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Metastatic neoplasm * 1  0/2412 (0.00%)  2/2405 (0.08%) 
Ovarian epithelial cancer * 1  2/2412 (0.08%)  0/2405 (0.00%) 
Pelvic neoplasm * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Colorectal cancer * 1  2/2412 (0.08%)  0/2405 (0.00%) 
Renal neoplasm * 1  1/2412 (0.04%)  1/2405 (0.04%) 
Adrenal neoplasm * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Extranodal marginal zone B-cell lymphoma (MALT type) * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Non-small cell lung cancer * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Gastric neoplasm * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Lung neoplasm * 1  0/2412 (0.00%)  2/2405 (0.08%) 
Rectal neoplasm * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Metastasis * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Metastatic gastric cancer * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Thyroid cancer * 1  0/2412 (0.00%)  2/2405 (0.08%) 
Renal cell carcinoma * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Inflammatory pseudotumour * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Nervous system disorders     
Altered state of consciousness * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Amyotrophic lateral sclerosis * 1  1/2412 (0.04%)  1/2405 (0.04%) 
Ataxia * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Carotid artery stenosis * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Cauda equina syndrome * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Cerebellar haemorrhage * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Cerebral haemorrhage * 1  0/2412 (0.00%)  4/2405 (0.17%) 
Cerebral infarction * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Cerebrovascular accident * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Clumsiness * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Coma * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Convulsion * 1  2/2412 (0.08%)  3/2405 (0.12%) 
Dementia Alzheimer's type * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Depressed level of consciousness * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Dizziness * 1  3/2412 (0.12%)  3/2405 (0.12%) 
Encephalopathy * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Epilepsy * 1  2/2412 (0.08%)  1/2405 (0.04%) 
Guillain-Barre syndrome * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Haemorrhage intracranial * 1  0/2412 (0.00%)  2/2405 (0.08%) 
Headache * 1  3/2412 (0.12%)  4/2405 (0.17%) 
Hepatic encephalopathy * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Leukoencephalopathy * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Loss of consciousness * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Migraine * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Nervous system disorder * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Neuropathy peripheral * 1  2/2412 (0.08%)  0/2405 (0.00%) 
Parkinsonism * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Presyncope * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Sciatica * 1  2/2412 (0.08%)  1/2405 (0.04%) 
Spinal cord compression * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Subarachnoid haemorrhage * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Syncope * 1  8/2412 (0.33%)  6/2405 (0.25%) 
Tension headache * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Transient ischaemic attack * 1  3/2412 (0.12%)  3/2405 (0.12%) 
Balance disorder * 1  1/2412 (0.04%)  0/2405 (0.00%) 
VIIth nerve paralysis * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Lacunar infarction * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Haemorrhagic transformation stroke * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Cerebrovascular insufficiency * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Radicular pain * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Ischaemic stroke * 1  13/2412 (0.54%)  5/2405 (0.21%) 
Parkinson's disease * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Complex regional pain syndrome * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Pregnancy, puerperium and perinatal conditions     
Post abortion haemorrhage * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Pregnancy * 1  0/2412 (0.00%)  2/2405 (0.08%) 
Psychiatric disorders     
Alcohol abuse * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Alcoholism * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Anxiety * 1  5/2412 (0.21%)  3/2405 (0.12%) 
Bipolar I disorder * 1  1/2412 (0.04%)  1/2405 (0.04%) 
Confusional state * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Delusion * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Depression * 1  4/2412 (0.17%)  3/2405 (0.12%) 
Mania * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Panic attack * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Suicide attempt * 1  1/2412 (0.04%)  1/2405 (0.04%) 
Mental status changes * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Somatoform disorder * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Mental disorder * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Mental disorder due to a general medical condition * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Renal and urinary disorders     
Acute prerenal failure * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Anuria * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Bladder dilatation * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Dysuria * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Glomerulonephritis membranous * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Haematuria * 1  8/2412 (0.33%)  11/2405 (0.46%) 
Nephritis * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Nephrolithiasis * 1  0/2412 (0.00%)  3/2405 (0.12%) 
Nephropathy toxic * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Nephrotic syndrome * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Renal colic * 1  0/2412 (0.00%)  3/2405 (0.12%) 
Renal cyst * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Renal failure acute * 1  2/2412 (0.08%)  4/2405 (0.17%) 
Urinary retention * 1  2/2412 (0.08%)  0/2405 (0.00%) 
Urinary tract disorder * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Urinary bladder polyp * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Renal mass * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Renal impairment * 1  1/2412 (0.04%)  1/2405 (0.04%) 
Urethral stenosis * 1  0/2412 (0.00%)  2/2405 (0.08%) 
Reproductive system and breast disorders     
Benign prostatic hyperplasia * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Cervical dysplasia * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Cervical polyp * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Dysfunctional uterine bleeding * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Menorrhagia * 1  9/2412 (0.37%)  2/2405 (0.08%) 
Metrorrhagia * 1  4/2412 (0.17%)  2/2405 (0.08%) 
Ovarian cyst * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Priapism * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Prostatitis * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Uterine polyp * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Uterine prolapse * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Vaginal haemorrhage * 1  4/2412 (0.17%)  0/2405 (0.00%) 
Vulval disorder * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Genital haemorrhage * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Prostatic mass * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Respiratory, thoracic and mediastinal disorders     
Acute pulmonary oedema * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Acute respiratory distress syndrome * 1  2/2412 (0.08%)  1/2405 (0.04%) 
Acute respiratory failure * 1  1/2412 (0.04%)  4/2405 (0.17%) 
Asthma * 1  4/2412 (0.17%)  2/2405 (0.08%) 
Bronchial obstruction * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Bronchiectasis * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Bronchospasm * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Chronic obstructive pulmonary disease * 1  9/2412 (0.37%)  5/2405 (0.21%) 
Cough * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Dyspnoea * 1  17/2412 (0.70%)  13/2405 (0.54%) 
Emphysema * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Epistaxis * 1  3/2412 (0.12%)  2/2405 (0.08%) 
Haemoptysis * 1  6/2412 (0.25%)  8/2405 (0.33%) 
Haemothorax * 1  1/2412 (0.04%)  2/2405 (0.08%) 
Hyperventilation * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Interstitial lung disease * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Lung disorder * 1  3/2412 (0.12%)  2/2405 (0.08%) 
Pharyngeal cyst * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Pleural effusion * 1  9/2412 (0.37%)  11/2405 (0.46%) 
Pleurisy * 1  0/2412 (0.00%)  4/2405 (0.17%) 
Pleuritic pain * 1  4/2412 (0.17%)  8/2405 (0.33%) 
Pneumothorax * 1  1/2412 (0.04%)  3/2405 (0.12%) 
Pulmonary congestion * 1  1/2412 (0.04%)  1/2405 (0.04%) 
Pulmonary embolism * 1  6/2412 (0.25%)  1/2405 (0.04%) 
Pulmonary fibrosis * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Pulmonary haemorrhage * 1  2/2412 (0.08%)  0/2405 (0.00%) 
Pulmonary hypertension * 1  4/2412 (0.17%)  1/2405 (0.04%) 
Pulmonary infarction * 1  3/2412 (0.12%)  2/2405 (0.08%) 
Pulmonary oedema * 1  1/2412 (0.04%)  1/2405 (0.04%) 
Pulmonary venous thrombosis * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Respiratory arrest * 1  1/2412 (0.04%)  1/2405 (0.04%) 
Respiratory failure * 1  3/2412 (0.12%)  5/2405 (0.21%) 
Sleep apnoea syndrome * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Mediastinal haemorrhage * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Pulmonary arterial hypertension * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Skin and subcutaneous tissue disorders     
Angioedema * 1  1/2412 (0.04%)  1/2405 (0.04%) 
Dermatitis * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Dermatitis exfoliative * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Dermatomyositis * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Drug eruption * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Haemorrhage subcutaneous * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Hyperkeratosis * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Lichen planus * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Purpura * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Rash morbilliform * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Skin lesion * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Skin necrosis * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Skin ulcer * 1  1/2412 (0.04%)  1/2405 (0.04%) 
Urticaria * 1  2/2412 (0.08%)  0/2405 (0.00%) 
Social circumstances     
Miscarriage of partner * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Surgical and medical procedures     
Abortion induced * 1  2/2412 (0.08%)  3/2405 (0.12%) 
Vascular disorders     
Aortic aneurysm * 1  1/2412 (0.04%)  2/2405 (0.08%) 
Aortic aneurysm rupture * 1  0/2412 (0.00%)  2/2405 (0.08%) 
Aortic dissection * 1  2/2412 (0.08%)  0/2405 (0.00%) 
Aortic thrombosis * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Circulatory collapse * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Embolism arterial * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Haematoma * 1  4/2412 (0.17%)  4/2405 (0.17%) 
Hypertension * 1  1/2412 (0.04%)  3/2405 (0.12%) 
Hypertensive crisis * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Hypotension * 1  3/2412 (0.12%)  1/2405 (0.04%) 
Hypovolaemic shock * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Iliac artery thrombosis * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Orthostatic hypotension * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Peripheral ischaemia * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Temporal arteritis * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Thrombophlebitis superficial * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Vena cava thrombosis * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Lymphocele * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Intra-abdominal haematoma * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Varicophlebitis * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Arterial haemorrhage * 1  0/2412 (0.00%)  1/2405 (0.04%) 
Intra-abdominal haemorrhage * 1  1/2412 (0.04%)  2/2405 (0.08%) 
Paradoxical embolism * 1  1/2412 (0.04%)  0/2405 (0.00%) 
Distributive shock * 1  0/2412 (0.00%)  1/2405 (0.04%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 14.1
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Rivaroxaban (Xarelto, BAY59-7939) Enoxaparin/VKA
Affected / at Risk (%) Affected / at Risk (%)
Total   1053/2412 (43.66%)   1065/2405 (44.28%) 
Gastrointestinal disorders     
Constipation * 1  146/2412 (6.05%)  141/2405 (5.86%) 
Diarrhoea * 1  128/2412 (5.31%)  132/2405 (5.49%) 
Nausea * 1  113/2412 (4.68%)  131/2405 (5.45%) 
General disorders     
Chest pain * 1  179/2412 (7.42%)  181/2405 (7.53%) 
Infections and infestations     
Nasopharyngitis * 1  188/2412 (7.79%)  195/2405 (8.11%) 
Injury, poisoning and procedural complications     
Contusion * 1  95/2412 (3.94%)  133/2405 (5.53%) 
Musculoskeletal and connective tissue disorders     
Back pain * 1  87/2412 (3.61%)  134/2405 (5.57%) 
Pain in extremity * 1  172/2412 (7.13%)  162/2405 (6.74%) 
Nervous system disorders     
Headache * 1  196/2412 (8.13%)  177/2405 (7.36%) 
Respiratory, thoracic and mediastinal disorders     
Cough * 1  160/2412 (6.63%)  179/2405 (7.44%) 
Dyspnoea * 1  156/2412 (6.47%)  147/2405 (6.11%) 
Epistaxis * 1  229/2412 (9.49%)  205/2405 (8.52%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 14.1
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Therapeutic Area Head
Organization: BAYER
EMail: clinical-trials-contact@bayerhealthcare.com
Publications of Results:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT00439777    
Other Study ID Numbers: 11702b
2006-004495-13 ( EudraCT Number )
First Submitted: February 23, 2007
First Posted: February 26, 2007
Results First Submitted: November 22, 2012
Results First Posted: January 24, 2013
Last Update Posted: February 27, 2014