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Oral Direct Factor Xa Inhibitor Rivaroxaban in Patients With Acute Symptomatic Deep Vein Thrombosis - The EINSTEIN DVT Study

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ClinicalTrials.gov Identifier: NCT00440193
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 Venous Thrombosis
Interventions Drug: Rivaroxaban (Xarelto, BAY59-7939)
Drug: Enoxaparin followed by VKA
Enrollment 3449

Recruitment Details Participants with confirmed acute proximal symptomatic deep vein thrombosis (DVT) without symptomatic pulmonary embolism (PE) were recruited at specialized study sites.
Pre-assignment Details Out of 3459 participants screened, 10 failed screening due to protocol violations, and 3449 participants were randomized (1731 to rivaroxaban and 1718 to enoxaparin/VKA).
Arm/Group Title Rivaroxaban (Xarelto, BAY59-7939) Enoxaparin/VKA
Hide Arm/Group Description Participants were to receive rivaroxaban 15 mg oral tablet twice daily for 3 weeks, followed by 20 mg once daily Participants were to receive 1.0 mg/kg enoxaparin twice daily (subcutaneous) for at least 5 days, plus vitamin K antagonist (VKA) (oral) at individually titrated doses to achieve a target international normalized ratio (INR) of 2.5 (range: 2.0 to 3.0)
Period Title: Treatment Period
Started 1731 1718
Participants Received Treatment 1718 1711
Completed 1426 1367
Not Completed 305 351
Reason Not Completed
Adverse Event             74             67
Death             19             22
Lack of Efficacy             0             1
Lost to Follow-up             12             18
Physician Decision             3             6
Protocol Violation             16             19
Withdrawal by Subject             36             77
Clinical endpoint reached             28             25
Study terminated by sponsor             102             94
Protocol driven decision point             2             2
Switch to commercial drug             0             2
Technical problems             1             1
Participant convenience             5             2
Participant did not receive treatment             7             13
Site closed by investigator             0             2
Period Title: Observational Period
Started 1425 [1] 1407 [1]
Completed 1380 1369
Not Completed 45 38
Reason Not Completed
Adverse Event             2             2
Death             15             20
Lost to Follow-up             12             8
Protocol Violation             1             0
Withdrawal by Subject             11             8
Physician Decision             1             0
Clinical endpoint reached             1             0
Participant convenience             2             0
[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 were to receive rivaroxaban 15 mg oral tablet twice daily for 3 weeks, followed by 20 mg once daily Participants were to receive 1.0 mg/kg enoxaparin twice daily (subcutaneous) for at least 5 days, plus vitamin K antagonist (VKA) (oral) at individually titrated doses to achieve a target international normalized ratio (INR) of 2.5 (range: 2.0 to 3.0) Total of all reporting groups
Overall Number of Baseline Participants 1731 1718 3449
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 1731 participants 1718 participants 3449 participants
55.8  (16.4) 56.4  (16.3) 56.1  (16.4)
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 1731 participants 1718 participants 3449 participants
18 - < 40 years 314 279 593
40 - < 60 years 642 662 1304
60 - < 75 years 530 519 1049
≥ 75 years 245 258 503
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 1731 participants 1718 participants 3449 participants
Female
738
  42.6%
751
  43.7%
1489
  43.2%
Male
993
  57.4%
967
  56.3%
1960
  56.8%
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
Show Outcome Measure DataHide 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 were to receive rivaroxaban 15 mg oral tablet twice daily for 3 weeks, followed by 20 mg once daily
Participants were to receive 1.0 mg/kg enoxaparin twice daily (subcutaneous) for at least 5 days, plus vitamin K antagonist (VKA) (oral) at individually titrated doses to achieve a target international normalized ratio (INR) of 2.5 (range: 2.0 to 3.0)
Overall Number of Participants Analyzed 1731 1718
Measure Type: Number
Unit of Measure: Percentage of participants
2.1 3.0
Show Statistical Analysis 1 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 was calculated to give a power of 90% to prove that rivaroxaban is at least as effective as the comparator, considering a non-inferiority upper CI margin for the hazard ratio of 2.0 (two-sided α=0.05). A mean incidence for the primary efficacy outcome of 3% was expected and at least 1465 participants per group were determined to be necessary. This number was to be adjusted based on the observed overall incidence of symptomatic recurrent VTE.
Statistical Test of Hypothesis P-Value < 0.0001
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 0.68
Confidence Interval 95%
0.44 to 1.04
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.2179
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
Show Outcome Measure DataHide 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 were to receive rivaroxaban 15 mg oral tablet twice daily for 3 weeks, followed by 20 mg once daily
Participants were to receive 1.0 mg/kg enoxaparin twice daily (subcutaneous) for at least 5 days, plus vitamin K antagonist (VKA) (oral) at individually titrated doses to achieve a target international normalized ratio (INR) of 2.5 (range: 2.0 to 3.0)
Overall Number of Participants Analyzed 1731 1718
Measure Type: Number
Unit of Measure: Percentage of participants
4.0 5.1
Show Statistical Analysis 1 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 0.044
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 0.72
Confidence Interval 95%
0.53 to 0.99
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.1616
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
Show Outcome Measure DataHide 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 were to receive rivaroxaban 15 mg oral tablet twice daily for 3 weeks, followed by 20 mg once daily
Participants were to receive 1.0 mg/kg enoxaparin twice daily (subcutaneous) for at least 5 days, plus vitamin K antagonist (VKA) (oral) at individually titrated doses to achieve a target international normalized ratio (INR) of 2.5 (range: 2.0 to 3.0)
Overall Number of Participants Analyzed 1731 1718
Measure Type: Number
Unit of Measure: Percentage of participants
2.9 4.2
Show Statistical Analysis 1 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 0.027
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 0.67
Confidence Interval 95%
0.47 to 0.95
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.1828
Estimation Comments The standard error of the log hazard ratio was estimated.
4.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
Show Outcome Measure DataHide 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 were to receive rivaroxaban 15 mg oral tablet twice daily for 3 weeks, followed by 20 mg once daily
Participants were to receive 1.0 mg/kg enoxaparin twice daily (subcutaneous) for at least 5 days, plus vitamin K antagonist (VKA) (oral) at individually titrated doses to achieve a target international normalized ratio (INR) of 2.5 (range: 2.0 to 3.0)
Overall Number of Participants Analyzed 1731 1718
Measure Type: Number
Unit of Measure: Percentage of participants
0.9 1.6
5.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
Show Outcome Measure DataHide 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 were to receive rivaroxaban 15 mg oral tablet twice daily for 3 weeks, followed by 20 mg once daily
Participants were to receive 1.0 mg/kg enoxaparin twice daily (subcutaneous) for at least 5 days, plus vitamin K antagonist (VKA) (oral) at individually titrated doses to achieve a target international normalized ratio (INR) of 2.5 (range: 2.0 to 3.0)
Overall Number of Participants Analyzed 1718 1711
Measure Type: Number
Unit of Measure: Percentage of participants
8.1 8.1
Show Statistical Analysis 1 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 0.77
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 0.97
Confidence Interval 95%
0.76 to 1.22
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.1204
Estimation Comments The standard error of the log hazard ratio was estimated.
6.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
Show Outcome Measure DataHide 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 were to receive rivaroxaban 15 mg oral tablet twice daily for 3 weeks, followed by 20 mg once daily
Participants were to receive 1.0 mg/kg enoxaparin twice daily (subcutaneous) for at least 5 days, plus vitamin K antagonist (VKA) (oral) at individually titrated doses to achieve a target international normalized ratio (INR) of 2.5 (range: 2.0 to 3.0)
Overall Number of Participants Analyzed 1718 1711
Measure Type: Number
Unit of Measure: Percentage of participants
All post-randomization 2.4 3.0
Treatment-emergent (time window: 2 days) 1.0 1.1
Treatment-emergent (time window: 7 days) 1.2 1.5
7.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
Show Outcome Measure DataHide 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 were to receive rivaroxaban 15 mg oral tablet twice daily for 3 weeks, followed by 20 mg once daily
Participants were to receive 1.0 mg/kg enoxaparin twice daily (subcutaneous) for at least 5 days, plus vitamin K antagonist (VKA) (oral) at individually titrated doses to achieve a target international normalized ratio (INR) of 2.5 (range: 2.0 to 3.0)
Overall Number of Participants Analyzed 1718 1711
Measure Type: Number
Unit of Measure: Percentage of participants
0.7 0.8
8.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
Show Outcome Measure DataHide 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 were to receive rivaroxaban 15 mg oral tablet twice daily for 3 weeks, followed by 20 mg once daily
Participants were to receive 1.0 mg/kg enoxaparin twice daily (subcutaneous) for at least 5 days, plus vitamin K antagonist (VKA) (oral) at individually titrated doses to achieve a target international normalized ratio (INR) of 2.5 (range: 2.0 to 3.0)
Overall Number of Participants Analyzed 1731 1718
Measure Type: Number
Unit of Measure: Percentage of participants
Death (PE) 0.06 0
Death (PE cannot be excluded) 0.2 0.3
Symptomatic PE and DVT 0.06 0
Symptomatic recurrent PE only 1.2 1.0
Symptomatic recurrent DVT only 0.8 1.6
Death (bleeding) 0.06 0.3
Death (cardiovascular) 0.1 0.2
Death (other) 1.8 2.0
Major bleeding 0.9 1.3
9.Other Pre-specified 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]) 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), results/films/images of confirmatory testing, and/or case summaries.
Time Frame Up to 30 days after the last intake of study medication
Show Outcome Measure DataHide 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 were to receive rivaroxaban 15 mg oral tablet twice daily for 3 weeks, followed by 20 mg once daily
Participants were to receive 1.0 mg/kg enoxaparin twice daily (subcutaneous) for at least 5 days, plus vitamin K antagonist (VKA) (oral) at individually titrated doses to achieve a target international normalized ratio (INR) of 2.5 (range: 2.0 to 3.0)
Overall Number of Participants Analyzed 1425 1408
Measure Type: Number
Unit of Measure: Percentage of participants
0.8 0.5
10.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
Show Outcome Measure DataHide 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 were to receive rivaroxaban 15 mg oral tablet twice daily for 3 weeks, followed by 20 mg once daily
Participants were to receive 1.0 mg/kg enoxaparin twice daily (subcutaneous) for at least 5 days, plus vitamin K antagonist (VKA) (oral) at individually titrated doses to achieve a target international normalized ratio (INR) of 2.5 (range: 2.0 to 3.0)
Overall Number of Participants Analyzed 1430 1413
Measure Type: Number
Unit of Measure: Percentage of participants
2.2 1.8
11.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 or 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
Show Outcome Measure DataHide 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 were to receive rivaroxaban 15 mg oral tablet twice daily for 3 weeks, followed by 20 mg once daily
Participants were to receive 1.0 mg/kg enoxaparin twice daily (subcutaneous) for at least 5 days, plus vitamin K antagonist (VKA) (oral) at individually titrated doses to achieve a target international normalized ratio (INR) of 2.5 (range: 2.0 to 3.0)
Overall Number of Participants Analyzed 1425 1410
Measure Type: Number
Unit of Measure: Percentage of participants
1.1 1.1
12.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
Show Outcome Measure DataHide 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 were to receive rivaroxaban 15 mg oral tablet twice daily for 3 weeks, followed by 20 mg once daily
Participants were to receive 1.0 mg/kg enoxaparin twice daily (subcutaneous) for at least 5 days, plus vitamin K antagonist (VKA) (oral) at individually titrated doses to achieve a target international normalized ratio (INR) of 2.5 (range: 2.0 to 3.0)
Overall Number of Participants Analyzed 1425 1408
Measure Type: Number
Unit of Measure: Percentage of participants
0.6 0.3
13.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
Show Outcome Measure DataHide 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 were to receive rivaroxaban 15 mg oral tablet twice daily for 3 weeks, followed by 20 mg once daily
Participants were to receive 1.0 mg/kg enoxaparin twice daily (subcutaneous) for at least 5 days, plus vitamin K antagonist (VKA) (oral) at individually titrated doses to achieve a target international normalized ratio (INR) of 2.5 (range: 2.0 to 3.0)
Overall Number of Participants Analyzed 1425 1408
Measure Type: Number
Unit of Measure: Percentage of participants
Death (PE) 0 0
Death (PE cannot be excluded) 0.07 0.07
Symptomatic PE and DVT 0 0
Symptomatic recurrent PE only 0.3 0.1
Symptomatic recurrent DVT only 0.6 0.3
Death (bleeding) 0.07 0.1
Death (cardiovascular) 0.07 0.3
Death (other) 1.3 0.8
Major bleeding 0.2 0.6
14.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. Major bleeding was overt 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 confirmed by independent committee blinded to treatment, based on compression ultrasound, venography, spiral CT scan, pulmonary angiography, ventilation/perfusion lung scan, lung scintigraphy, autopsy, results/films/images of confirmatory testing and/or case summaries
Time Frame 3-, 6- or 12-month study treatment period
Show Outcome Measure DataHide 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 were to receive rivaroxaban 15 mg oral tablet twice daily for 3 weeks, followed by 20 mg once daily
Participants were to receive 1.0 mg/kg enoxaparin twice daily (subcutaneous) for at least 5 days, plus vitamin K antagonist (VKA) (oral) at individually titrated doses to achieve a target international normalized ratio (INR) of 2.5 (range: 2.0 to 3.0)
Overall Number of Participants Analyzed 1731 1718
Measure Type: Number
Unit of Measure: Percentage of participants
3.6 4.7
15.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, cardiovascular death, myocardial infarctions, stroke, or non CNS systemic embolism. Major bleeding was 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 (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
Show Outcome Measure DataHide 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 were to receive rivaroxaban 15 mg oral tablet twice daily for 3 weeks, followed by 20 mg once daily
Participants were to receive 1.0 mg/kg enoxaparin twice daily (subcutaneous) for at least 5 days, plus vitamin K antagonist (VKA) (oral) at individually titrated doses to achieve a target international normalized ratio (INR) of 2.5 (range: 2.0 to 3.0)
Overall Number of Participants Analyzed 1426 1410
Measure Type: Number
Unit of Measure: Percentage of participants
1.2 1.3
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Rivaroxaban (Xarelto, BAY59-7939) Enoxaparin/VKA
Hide Arm/Group Description Participants were to receive rivaroxaban 15 mg oral tablet twice daily for 3 weeks, followed by 20 mg once daily Participants were to receive 1.0 mg/kg enoxaparin twice daily (subcutaneous) for at least 5 days, plus vitamin K antagonist (VKA) (oral) at individually titrated doses to achieve a target international normalized ratio (INR) of 2.5 (range: 2.0 to 3.0)
All-Cause Mortality
Rivaroxaban (Xarelto, BAY59-7939) Enoxaparin/VKA
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Rivaroxaban (Xarelto, BAY59-7939) Enoxaparin/VKA
Affected / at Risk (%) Affected / at Risk (%)
Total   222/1718 (12.92%)   252/1711 (14.73%) 
Blood and lymphatic system disorders     
Anaemia * 1  11/1718 (0.64%)  8/1711 (0.47%) 
Febrile neutropenia * 1  1/1718 (0.06%)  0/1711 (0.00%) 
Lymphadenopathy mediastinal * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Microcytic anaemia * 1  1/1718 (0.06%)  0/1711 (0.00%) 
Normochromic normocytic anaemia * 1  1/1718 (0.06%)  0/1711 (0.00%) 
Splenic haemorrhage * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Thrombocytopenia * 1  2/1718 (0.12%)  1/1711 (0.06%) 
Autoimmune thrombocytopenia * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Haemorrhagic anaemia * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Spontaneous haematoma * 1  1/1718 (0.06%)  0/1711 (0.00%) 
Cardiac disorders     
Acute myocardial infarction * 1  5/1718 (0.29%)  1/1711 (0.06%) 
Angina pectoris * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Angina unstable * 1  1/1718 (0.06%)  3/1711 (0.18%) 
Arrhythmia * 1  1/1718 (0.06%)  0/1711 (0.00%) 
Atrial fibrillation * 1  2/1718 (0.12%)  3/1711 (0.18%) 
Atrial flutter * 1  1/1718 (0.06%)  0/1711 (0.00%) 
Atrioventricular block second degree * 1  1/1718 (0.06%)  0/1711 (0.00%) 
Bradycardia * 1  1/1718 (0.06%)  0/1711 (0.00%) 
Cardiac arrest * 1  0/1718 (0.00%)  3/1711 (0.18%) 
Cardiac failure * 1  1/1718 (0.06%)  1/1711 (0.06%) 
Cardiac failure chronic * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Cardiac failure congestive * 1  0/1718 (0.00%)  2/1711 (0.12%) 
Cardio-respiratory arrest * 1  1/1718 (0.06%)  0/1711 (0.00%) 
Myocardial infarction * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Myocardial ischaemia * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Pericarditis * 1  1/1718 (0.06%)  0/1711 (0.00%) 
Right ventricular failure * 1  1/1718 (0.06%)  0/1711 (0.00%) 
Sick sinus syndrome * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Sinus arrhythmia * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Tachycardia * 1  1/1718 (0.06%)  0/1711 (0.00%) 
Ventricular tachycardia * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Tachyarrhythmia * 1  1/1718 (0.06%)  0/1711 (0.00%) 
Acute coronary syndrome * 1  1/1718 (0.06%)  0/1711 (0.00%) 
Cardiac disorder * 1  1/1718 (0.06%)  0/1711 (0.00%) 
Aortic valve disease * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Congenital, familial and genetic disorders     
Phimosis * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Ear and labyrinth disorders     
Ear haemorrhage * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Vertigo * 1  2/1718 (0.12%)  1/1711 (0.06%) 
Sudden hearing loss * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Endocrine disorders     
Basedow's disease * 1  1/1718 (0.06%)  0/1711 (0.00%) 
Goitre * 1  1/1718 (0.06%)  0/1711 (0.00%) 
Eye disorders     
Blepharochalasis * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Conjunctival haemorrhage * 1  0/1718 (0.00%)  2/1711 (0.12%) 
Eye haemorrhage * 1  1/1718 (0.06%)  0/1711 (0.00%) 
Hyphaema * 1  1/1718 (0.06%)  0/1711 (0.00%) 
Maculopathy * 1  1/1718 (0.06%)  0/1711 (0.00%) 
Retinal detachment * 1  1/1718 (0.06%)  0/1711 (0.00%) 
Vitreous detachment * 1  1/1718 (0.06%)  0/1711 (0.00%) 
Vitreous haemorrhage * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Gastrointestinal disorders     
Abdominal discomfort * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Abdominal pain * 1  3/1718 (0.17%)  1/1711 (0.06%) 
Abdominal pain upper * 1  1/1718 (0.06%)  0/1711 (0.00%) 
Ascites * 1  1/1718 (0.06%)  0/1711 (0.00%) 
Colitis ulcerative * 1  1/1718 (0.06%)  1/1711 (0.06%) 
Colonic polyp * 1  0/1718 (0.00%)  2/1711 (0.12%) 
Constipation * 1  1/1718 (0.06%)  0/1711 (0.00%) 
Crohn's disease * 1  0/1718 (0.00%)  4/1711 (0.23%) 
Diarrhoea * 1  1/1718 (0.06%)  0/1711 (0.00%) 
Duodenal ulcer * 1  0/1718 (0.00%)  2/1711 (0.12%) 
Food poisoning * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Gastric ulcer perforation * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Gastritis * 1  1/1718 (0.06%)  1/1711 (0.06%) 
Gastrointestinal haemorrhage * 1  4/1718 (0.23%)  0/1711 (0.00%) 
Gastrointestinal necrosis * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Gingival bleeding * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Haematemesis * 1  1/1718 (0.06%)  3/1711 (0.18%) 
Haematochezia * 1  0/1718 (0.00%)  2/1711 (0.12%) 
Haemorrhoids * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Inguinal hernia, obstructive * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Intestinal dilatation * 1  1/1718 (0.06%)  0/1711 (0.00%) 
Intestinal obstruction * 1  2/1718 (0.12%)  1/1711 (0.06%) 
Intestinal perforation * 1  1/1718 (0.06%)  0/1711 (0.00%) 
Large intestine perforation * 1  1/1718 (0.06%)  1/1711 (0.06%) 
Melaena * 1  1/1718 (0.06%)  1/1711 (0.06%) 
Nausea * 1  1/1718 (0.06%)  0/1711 (0.00%) 
Oesophageal ulcer haemorrhage * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Oesophagitis * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Pancreatic cyst * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Pancreatitis * 1  1/1718 (0.06%)  2/1711 (0.12%) 
Pancreatitis acute * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Rectal haemorrhage * 1  5/1718 (0.29%)  4/1711 (0.23%) 
Rectal polyp * 1  1/1718 (0.06%)  0/1711 (0.00%) 
Reflux oesophagitis * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Retroperitoneal fibrosis * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Small intestinal obstruction * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Upper gastrointestinal haemorrhage * 1  0/1718 (0.00%)  2/1711 (0.12%) 
Vomiting * 1  1/1718 (0.06%)  1/1711 (0.06%) 
Lower gastrointestinal haemorrhage * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Enterocutaneous fistula * 1  2/1718 (0.12%)  0/1711 (0.00%) 
Abdominal wall cyst * 1  1/1718 (0.06%)  0/1711 (0.00%) 
Haemorrhoidal haemorrhage * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Intra-abdominal haematoma * 1  1/1718 (0.06%)  0/1711 (0.00%) 
Hernial eventration * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Intestinal mass * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Intestinal haemorrhage * 1  0/1718 (0.00%)  1/1711 (0.06%) 
General disorders     
Chest pain * 1  3/1718 (0.17%)  1/1711 (0.06%) 
Death * 1  2/1718 (0.12%)  1/1711 (0.06%) 
Generalised oedema * 1  1/1718 (0.06%)  0/1711 (0.00%) 
Impaired healing * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Malaise * 1  1/1718 (0.06%)  1/1711 (0.06%) 
Multi-organ failure * 1  3/1718 (0.17%)  2/1711 (0.12%) 
Oedema peripheral * 1  3/1718 (0.17%)  0/1711 (0.00%) 
Pelvic mass * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Pyrexia * 1  3/1718 (0.17%)  2/1711 (0.12%) 
Sudden death * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Sudden cardiac death * 1  1/1718 (0.06%)  0/1711 (0.00%) 
General physical health deterioration * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Systemic inflammatory response syndrome * 1  1/1718 (0.06%)  0/1711 (0.00%) 
Medical device complication * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Device occlusion * 1  1/1718 (0.06%)  0/1711 (0.00%) 
Hepatobiliary disorders     
Acute hepatic failure * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Biliary colic * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Cholangitis * 1  1/1718 (0.06%)  0/1711 (0.00%) 
Cholecystitis * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Cholecystitis acute * 1  0/1718 (0.00%)  2/1711 (0.12%) 
Cholelithiasis * 1  1/1718 (0.06%)  0/1711 (0.00%) 
Hepatic failure * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Hepatic steatosis * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Hepatitis acute * 1  1/1718 (0.06%)  0/1711 (0.00%) 
Jaundice cholestatic * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Hepatic mass * 1  1/1718 (0.06%)  0/1711 (0.00%) 
Immune system disorders     
Liver transplant rejection * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Infections and infestations     
Abscess * 1  1/1718 (0.06%)  0/1711 (0.00%) 
Appendicitis * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Bacteraemia * 1  1/1718 (0.06%)  0/1711 (0.00%) 
Bronchitis * 1  1/1718 (0.06%)  0/1711 (0.00%) 
Bronchopneumonia * 1  3/1718 (0.17%)  1/1711 (0.06%) 
Cellulitis * 1  3/1718 (0.17%)  4/1711 (0.23%) 
Dengue fever * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Diverticulitis * 1  1/1718 (0.06%)  0/1711 (0.00%) 
Endocarditis staphylococcal * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Epiglottitis * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Erysipelas * 1  0/1718 (0.00%)  2/1711 (0.12%) 
Escherichia sepsis * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Gastroenteritis * 1  0/1718 (0.00%)  4/1711 (0.23%) 
Influenza * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Lobar pneumonia * 1  1/1718 (0.06%)  3/1711 (0.18%) 
Lower respiratory tract infection * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Mastitis * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Paronychia * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Pneumonia * 1  5/1718 (0.29%)  10/1711 (0.58%) 
Postoperative wound infection * 1  1/1718 (0.06%)  1/1711 (0.06%) 
Pulmonary tuberculosis * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Pyelonephritis * 1  1/1718 (0.06%)  0/1711 (0.00%) 
Sepsis * 1  2/1718 (0.12%)  7/1711 (0.41%) 
Septic shock * 1  1/1718 (0.06%)  4/1711 (0.23%) 
Tracheobronchitis * 1  1/1718 (0.06%)  0/1711 (0.00%) 
Urinary tract infection * 1  5/1718 (0.29%)  3/1711 (0.18%) 
Viral infection * 1  1/1718 (0.06%)  0/1711 (0.00%) 
Anal abscess * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Incision site abscess * 1  1/1718 (0.06%)  0/1711 (0.00%) 
Abscess limb * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Pulmonary sepsis * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Bacterial sepsis * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Infective exacerbation of chronic obstructive airways disease * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Cardiac valve vegetation * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Cerebral toxoplasmosis * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Infective aneurysm * 1  1/1718 (0.06%)  0/1711 (0.00%) 
Wound abscess * 1  1/1718 (0.06%)  0/1711 (0.00%) 
Abdominal abscess * 1  0/1718 (0.00%)  2/1711 (0.12%) 
Pneumonia bacterial * 1  0/1718 (0.00%)  2/1711 (0.12%) 
Lung infection * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Respiratory tract infection * 1  1/1718 (0.06%)  2/1711 (0.12%) 
Device related infection * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Incision site infection * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Post procedural sepsis * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Injury, poisoning and procedural complications     
Accident * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Alcohol poisoning * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Ankle fracture * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Cartilage injury * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Clavicle fracture * 1  1/1718 (0.06%)  0/1711 (0.00%) 
Drug toxicity * 1  1/1718 (0.06%)  0/1711 (0.00%) 
Femoral neck fracture * 1  0/1718 (0.00%)  2/1711 (0.12%) 
Femur fracture * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Humerus fracture * 1  2/1718 (0.12%)  0/1711 (0.00%) 
Joint dislocation * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Overdose * 1  1/1718 (0.06%)  1/1711 (0.06%) 
Pneumothorax traumatic * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Radiation pneumonitis * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Radius fracture * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Rib fracture * 1  1/1718 (0.06%)  0/1711 (0.00%) 
Spinal compression fracture * 1  1/1718 (0.06%)  1/1711 (0.06%) 
Subdural haematoma * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Therapeutic agent toxicity * 1  0/1718 (0.00%)  2/1711 (0.12%) 
Ulna fracture * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Wound dehiscence * 1  1/1718 (0.06%)  0/1711 (0.00%) 
Vascular pseudoaneurysm * 1  1/1718 (0.06%)  0/1711 (0.00%) 
Thoracic vertebral fracture * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Contusion * 1  2/1718 (0.12%)  1/1711 (0.06%) 
Post procedural haemorrhage * 1  1/1718 (0.06%)  2/1711 (0.12%) 
Induced abortion haemorrhage * 1  1/1718 (0.06%)  0/1711 (0.00%) 
Traumatic haemorrhage * 1  1/1718 (0.06%)  0/1711 (0.00%) 
Skin laceration * 1  1/1718 (0.06%)  1/1711 (0.06%) 
Gastrointestinal disorder postoperative * 1  1/1718 (0.06%)  0/1711 (0.00%) 
Ligament injury * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Post procedural haematuria * 1  1/1718 (0.06%)  0/1711 (0.00%) 
Investigations     
Alanine aminotransferase increased * 1  2/1718 (0.12%)  6/1711 (0.35%) 
Blood bilirubin increased * 1  1/1718 (0.06%)  0/1711 (0.00%) 
Chest X-ray abnormal * 1  0/1718 (0.00%)  1/1711 (0.06%) 
International normalised ratio increased * 1  0/1718 (0.00%)  5/1711 (0.29%) 
Liver function test abnormal * 1  2/1718 (0.12%)  4/1711 (0.23%) 
Weight decreased * 1  1/1718 (0.06%)  0/1711 (0.00%) 
Transaminases increased * 1  2/1718 (0.12%)  0/1711 (0.00%) 
Hepatic enzyme increased * 1  1/1718 (0.06%)  5/1711 (0.29%) 
International normalised ratio fluctuation * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Metabolism and nutrition disorders     
Dehydration * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Diabetes mellitus inadequate control * 1  1/1718 (0.06%)  0/1711 (0.00%) 
Diabetic ketoacidosis * 1  1/1718 (0.06%)  0/1711 (0.00%) 
Hypoglycaemia * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Hypokalaemia * 1  1/1718 (0.06%)  0/1711 (0.00%) 
Hypoproteinaemia * 1  1/1718 (0.06%)  0/1711 (0.00%) 
Tetany * 1  1/1718 (0.06%)  0/1711 (0.00%) 
Metabolic disorder * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Diabetic foot * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Musculoskeletal and connective tissue disorders     
Arthralgia * 1  1/1718 (0.06%)  0/1711 (0.00%) 
Arthritis * 1  0/1718 (0.00%)  2/1711 (0.12%) 
Back pain * 1  3/1718 (0.17%)  2/1711 (0.12%) 
Bursitis * 1  1/1718 (0.06%)  0/1711 (0.00%) 
Haemarthrosis * 1  0/1718 (0.00%)  2/1711 (0.12%) 
Muscle haemorrhage * 1  0/1718 (0.00%)  3/1711 (0.18%) 
Musculoskeletal pain * 1  1/1718 (0.06%)  0/1711 (0.00%) 
Myalgia * 1  1/1718 (0.06%)  0/1711 (0.00%) 
Osteoarthritis * 1  1/1718 (0.06%)  0/1711 (0.00%) 
Osteoporosis * 1  1/1718 (0.06%)  0/1711 (0.00%) 
Pain in extremity * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Pathological fracture * 1  1/1718 (0.06%)  0/1711 (0.00%) 
Rotator cuff syndrome * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Synovitis * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Systemic lupus erythematosus * 1  1/1718 (0.06%)  0/1711 (0.00%) 
Joint range of motion decreased * 1  1/1718 (0.06%)  0/1711 (0.00%) 
Intervertebral disc protrusion * 1  1/1718 (0.06%)  1/1711 (0.06%) 
Musculoskeletal chest pain * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Juvenile arthritis * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Foot deformity * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Acute leukaemia * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Angiosarcoma * 1  1/1718 (0.06%)  0/1711 (0.00%) 
Basal cell carcinoma * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Bile duct cancer * 1  1/1718 (0.06%)  0/1711 (0.00%) 
Bladder cancer * 1  2/1718 (0.12%)  0/1711 (0.00%) 
Breast cancer * 1  3/1718 (0.17%)  1/1711 (0.06%) 
Cervix carcinoma * 1  2/1718 (0.12%)  7/1711 (0.41%) 
Cervix carcinoma stage III * 1  1/1718 (0.06%)  0/1711 (0.00%) 
Colon cancer * 1  2/1718 (0.12%)  4/1711 (0.23%) 
Endometrial cancer * 1  1/1718 (0.06%)  1/1711 (0.06%) 
Gastric cancer * 1  1/1718 (0.06%)  1/1711 (0.06%) 
Gastric cancer recurrent * 1  1/1718 (0.06%)  0/1711 (0.00%) 
Hepatic neoplasm malignant * 1  2/1718 (0.12%)  2/1711 (0.12%) 
Large cell carcinoma of the respiratory tract stage unspecified * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Lung adenocarcinoma * 1  0/1718 (0.00%)  3/1711 (0.18%) 
Lung carcinoma cell type unspecified recurrent * 1  1/1718 (0.06%)  0/1711 (0.00%) 
Lymphoma * 1  3/1718 (0.17%)  0/1711 (0.00%) 
Malignant melanoma * 1  1/1718 (0.06%)  0/1711 (0.00%) 
Meningioma * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Metastases to liver * 1  2/1718 (0.12%)  4/1711 (0.23%) 
Metastases to lung * 1  1/1718 (0.06%)  2/1711 (0.12%) 
Metastases to lymph nodes * 1  2/1718 (0.12%)  1/1711 (0.06%) 
Non-Hodgkin's lymphoma * 1  2/1718 (0.12%)  0/1711 (0.00%) 
Oesophageal adenocarcinoma * 1  1/1718 (0.06%)  0/1711 (0.00%) 
Oesophageal carcinoma * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Ovarian cancer * 1  2/1718 (0.12%)  2/1711 (0.12%) 
Pancreatic carcinoma * 1  3/1718 (0.17%)  0/1711 (0.00%) 
Pancreatic carcinoma metastatic * 1  0/1718 (0.00%)  2/1711 (0.12%) 
Prostate cancer metastatic * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Rectal cancer * 1  1/1718 (0.06%)  2/1711 (0.12%) 
Rectal cancer recurrent * 1  1/1718 (0.06%)  0/1711 (0.00%) 
Renal cell carcinoma recurrent * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Rhabdomyosarcoma * 1  1/1718 (0.06%)  0/1711 (0.00%) 
Uterine cancer * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Uterine leiomyoma * 1  1/1718 (0.06%)  0/1711 (0.00%) 
Waldenstrom's macroglobulinaemia * 1  1/1718 (0.06%)  0/1711 (0.00%) 
Lung cancer metastatic * 1  1/1718 (0.06%)  0/1711 (0.00%) 
Metastases to peritoneum * 1  1/1718 (0.06%)  0/1711 (0.00%) 
Lymphoma cutis * 1  1/1718 (0.06%)  0/1711 (0.00%) 
Ear neoplasm malignant * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Cervix cancer metastatic * 1  1/1718 (0.06%)  0/1711 (0.00%) 
Hepatic cancer metastatic * 1  1/1718 (0.06%)  0/1711 (0.00%) 
Breast cancer metastatic * 1  1/1718 (0.06%)  0/1711 (0.00%) 
Retroperitoneal neoplasm * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Ovarian cancer metastatic * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Lung neoplasm malignant * 1  2/1718 (0.12%)  3/1711 (0.18%) 
Large intestine carcinoma * 1  1/1718 (0.06%)  0/1711 (0.00%) 
Metastases to central nervous system * 1  1/1718 (0.06%)  1/1711 (0.06%) 
Small cell lung cancer metastatic * 1  1/1718 (0.06%)  0/1711 (0.00%) 
Prostate cancer * 1  1/1718 (0.06%)  1/1711 (0.06%) 
Metastatic neoplasm * 1  2/1718 (0.12%)  1/1711 (0.06%) 
Ovarian epithelial cancer * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Pelvic neoplasm * 1  1/1718 (0.06%)  0/1711 (0.00%) 
Colorectal cancer * 1  2/1718 (0.12%)  0/1711 (0.00%) 
Renal neoplasm * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Non-small cell lung cancer * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Lung neoplasm * 1  2/1718 (0.12%)  1/1711 (0.06%) 
Penis carcinoma * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Metastatic squamous cell carcinoma * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Ovarian cancer recurrent * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Bladder transitional cell carcinoma stage I * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Renal cell carcinoma * 1  1/1718 (0.06%)  0/1711 (0.00%) 
Nervous system disorders     
Cerebral haemorrhage * 1  1/1718 (0.06%)  1/1711 (0.06%) 
Dizziness * 1  0/1718 (0.00%)  2/1711 (0.12%) 
Epilepsy * 1  1/1718 (0.06%)  1/1711 (0.06%) 
Facial palsy * 1  1/1718 (0.06%)  0/1711 (0.00%) 
Grand mal convulsion * 1  1/1718 (0.06%)  0/1711 (0.00%) 
Haemorrhage intracranial * 1  1/1718 (0.06%)  1/1711 (0.06%) 
Headache * 1  1/1718 (0.06%)  1/1711 (0.06%) 
Hypoglycaemic coma * 1  1/1718 (0.06%)  0/1711 (0.00%) 
Migraine * 1  1/1718 (0.06%)  0/1711 (0.00%) 
Mononeuritis * 1  1/1718 (0.06%)  0/1711 (0.00%) 
Multiple sclerosis * 1  1/1718 (0.06%)  0/1711 (0.00%) 
Neuralgia * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Presyncope * 1  1/1718 (0.06%)  0/1711 (0.00%) 
Syncope * 1  1/1718 (0.06%)  2/1711 (0.12%) 
Transient ischaemic attack * 1  1/1718 (0.06%)  4/1711 (0.23%) 
IIIrd nerve paresis * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Cognitive disorder * 1  1/1718 (0.06%)  0/1711 (0.00%) 
Ischaemic stroke * 1  4/1718 (0.23%)  7/1711 (0.41%) 
Parkinson's disease * 1  1/1718 (0.06%)  0/1711 (0.00%) 
Metabolic encephalopathy * 1  1/1718 (0.06%)  0/1711 (0.00%) 
Complex regional pain syndrome * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Cerebral arteriosclerosis * 1  1/1718 (0.06%)  0/1711 (0.00%) 
Pregnancy, puerperium and perinatal conditions     
Abortion * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Post abortion haemorrhage * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Psychiatric disorders     
Acute psychosis * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Alcohol abuse * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Completed suicide * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Confusional state * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Depression * 1  3/1718 (0.17%)  2/1711 (0.12%) 
Panic attack * 1  1/1718 (0.06%)  1/1711 (0.06%) 
Suicide attempt * 1  1/1718 (0.06%)  0/1711 (0.00%) 
Major depression * 1  1/1718 (0.06%)  0/1711 (0.00%) 
Psychotic disorder * 1  1/1718 (0.06%)  0/1711 (0.00%) 
Renal and urinary disorders     
Anuria * 1  1/1718 (0.06%)  0/1711 (0.00%) 
Calculus ureteric * 1  1/1718 (0.06%)  0/1711 (0.00%) 
Cystitis haemorrhagic * 1  1/1718 (0.06%)  0/1711 (0.00%) 
Haematuria * 1  4/1718 (0.23%)  8/1711 (0.47%) 
Hydronephrosis * 1  0/1718 (0.00%)  2/1711 (0.12%) 
Nephrolithiasis * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Nephrotic syndrome * 1  1/1718 (0.06%)  0/1711 (0.00%) 
Renal colic * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Renal failure * 1  1/1718 (0.06%)  0/1711 (0.00%) 
Renal failure acute * 1  1/1718 (0.06%)  3/1711 (0.18%) 
Reproductive system and breast disorders     
Menorrhagia * 1  5/1718 (0.29%)  1/1711 (0.06%) 
Ovarian cyst * 1  1/1718 (0.06%)  1/1711 (0.06%) 
Pelvic pain * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Penile swelling * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Prostatitis * 1  1/1718 (0.06%)  0/1711 (0.00%) 
Scrotal swelling * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Uterine polyp * 1  1/1718 (0.06%)  0/1711 (0.00%) 
Vaginal haemorrhage * 1  3/1718 (0.17%)  2/1711 (0.12%) 
Postmenopausal haemorrhage * 1  1/1718 (0.06%)  0/1711 (0.00%) 
Haemorrhagic ovarian cyst * 1  1/1718 (0.06%)  0/1711 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Asthma * 1  1/1718 (0.06%)  3/1711 (0.18%) 
Chronic obstructive pulmonary disease * 1  4/1718 (0.23%)  2/1711 (0.12%) 
Cough * 1  2/1718 (0.12%)  0/1711 (0.00%) 
Dyspnoea * 1  2/1718 (0.12%)  5/1711 (0.29%) 
Dyspnoea at rest * 1  1/1718 (0.06%)  0/1711 (0.00%) 
Epistaxis * 1  1/1718 (0.06%)  1/1711 (0.06%) 
Haemoptysis * 1  1/1718 (0.06%)  2/1711 (0.12%) 
Haemothorax * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Interstitial lung disease * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Lung disorder * 1  1/1718 (0.06%)  0/1711 (0.00%) 
Pleural effusion * 1  1/1718 (0.06%)  1/1711 (0.06%) 
Pulmonary embolism * 1  1/1718 (0.06%)  2/1711 (0.12%) 
Pulmonary fibrosis * 1  1/1718 (0.06%)  0/1711 (0.00%) 
Pulmonary oedema * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Respiratory distress * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Respiratory failure * 1  1/1718 (0.06%)  1/1711 (0.06%) 
Tachypnoea * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Wegener's granulomatosis * 1  1/1718 (0.06%)  0/1711 (0.00%) 
Pulmonary mass * 1  1/1718 (0.06%)  0/1711 (0.00%) 
Sputum retention * 1  1/1718 (0.06%)  0/1711 (0.00%) 
Skin and subcutaneous tissue disorders     
Dermatitis exfoliative * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Drug eruption * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Henoch-Schonlein purpura * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Leukocytoclastic vasculitis * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Scar * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Skin ulcer * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Surgical and medical procedures     
Abortion induced * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Bladder catheter removal * 1  1/1718 (0.06%)  0/1711 (0.00%) 
Uterine polypectomy * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Ileostomy closure * 1  1/1718 (0.06%)  0/1711 (0.00%) 
Vascular disorders     
Aortic aneurysm * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Arterial thrombosis limb * 1  1/1718 (0.06%)  1/1711 (0.06%) 
Arteriosclerosis * 1  0/1718 (0.00%)  2/1711 (0.12%) 
Circulatory collapse * 1  1/1718 (0.06%)  0/1711 (0.00%) 
Haematoma * 1  1/1718 (0.06%)  4/1711 (0.23%) 
Hypertension * 1  2/1718 (0.12%)  0/1711 (0.00%) 
Hypertensive crisis * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Hypotension * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Jugular vein thrombosis * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Lymphoedema * 1  1/1718 (0.06%)  0/1711 (0.00%) 
Peripheral ischaemia * 1  1/1718 (0.06%)  2/1711 (0.12%) 
Peripheral vascular disorder * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Shock * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Thrombophlebitis superficial * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Thrombosis * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Post thrombotic syndrome * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Shock haemorrhagic * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Femoral artery occlusion * 1  1/1718 (0.06%)  0/1711 (0.00%) 
Iliac artery stenosis * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Peripheral artery aneurysm * 1  1/1718 (0.06%)  0/1711 (0.00%) 
Extremity necrosis * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Arterial haemorrhage * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Peripheral embolism * 1  0/1718 (0.00%)  1/1711 (0.06%) 
Peripheral arterial occlusive disease * 1  2/1718 (0.12%)  0/1711 (0.00%) 
May-Thurner syndrome * 1  0/1718 (0.00%)  1/1711 (0.06%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 13.0
Show Other (Not Including Serious) Adverse Events 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   241/1718 (14.03%)   212/1711 (12.39%) 
Infections and infestations     
Nasopharyngitis * 1  100/1718 (5.82%)  91/1711 (5.32%) 
Nervous system disorders     
Headache * 1  91/1718 (5.30%)  70/1711 (4.09%) 
Respiratory, thoracic and mediastinal disorders     
Epistaxis * 1  90/1718 (5.24%)  74/1711 (4.32%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 13.0
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.
Results Point of Contact
Name/Title: Therapeutic Area Head
Organization: BAYER
Publications of Results:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT00440193     History of Changes
Other Study ID Numbers: 11702a
2006-004495-13 ( EudraCT Number )
11702b ( Other Identifier: Company internal )
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