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Trial record 100 of 10799 for:    Placebo AND once

Once - Daily Oral Direct Factor Xa Inhibitor Rivaroxaban In The Long-Term Prevention Of Recurrent Symptomatic Venous Thromboembolism In Patients With Symptomatic Deep-Vein Thrombosis Or Pulmonary Embolism. The Einstein-Extension Study

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ClinicalTrials.gov Identifier: NCT00439725
Recruitment Status : Completed
First Posted : February 26, 2007
Results First Posted : April 12, 2012
Last Update Posted : November 4, 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: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Prevention
Condition Venous Thromboembolism
Interventions Drug: Rivaroxaban (Xarelto, BAY59-7939)
Drug: Placebo
Enrollment 1197
Recruitment Details Participants with confirmed symptomatic deep vein thrombosis or pulmonary embolism, who either had been treated for 6 or 12 months with warfarin or acenocoumarol or rivaroxaban in study NCT00440193, or who had been treated for 6 to 14 months with warfarin or acenocoumarol outside study NCT00440193, were recruited at specialized study sites.
Pre-assignment Details Out of 1200 participants screened, 3 failed screening (2 due to withdrawal of consent and 1 due to a protocol violation), and 1197 participants were randomized (602 to rivaroxaban and 595 to placebo).
Arm/Group Title Rivaroxaban (Xarelto, BAY59-7939) Placebo
Hide Arm/Group Description Participants were to receive rivaroxaban 20 mg oral tablet once daily Participants were to receive matching placebo oral tablet once daily
Period Title: Treatment Period
Started 602 595
Participants Received Treatment 598 [1] 590 [1]
Completed 366 349
Not Completed 236 246
Reason Not Completed
Withdrawal by Subject             22             19
Study terminated by sponsor             156             148
Site closed by investigator             1             2
Adverse Event             39             18
Physician Decision             1             1
Protocol Violation             2             1
Clinical endpoint reached             6             50
Technical problems             1             0
Lost to Follow-up             1             1
Participant convenience             1             0
Protocol driven decision point             1             1
Death             1             1
Participant did not receive treatment             4             4
[1]
Safety population
Period Title: Observational Period
Started 577 [1] 560 [1]
Completed 569 553
Not Completed 8 7
Reason Not Completed
Withdrawal by Subject             2             2
Lost to Follow-up             0             1
Death             0             2
Study termination by sponsor             1             1
Clinical endpoint reached             3             1
Technical problems             1             0
Participant convenience             1             0
[1]
All participants who took any study medication and entered the observational period.
Arm/Group Title Rivaroxaban (Xarelto, BAY59-7939) Placebo Total
Hide Arm/Group Description Participants were to receive rivaroxaban 20 mg oral tablet once daily Participants were to receive matching placebo oral tablet once daily Total of all reporting groups
Overall Number of Baseline Participants 602 594 1196
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous   [1] 
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 602 participants 594 participants 1196 participants
58.2  (15.6) 58.4  (16.0) 58.3  (15.8)
[1]
Measure Description: Number of participants analyzed for Baseline is intention-to-treat (ITT) population.
Age, Customized   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 602 participants 594 participants 1196 participants
18 - 40 years 87 94 181
>40 - <65 years 273 280 553
65 - 75 years 153 121 274
>75 years 89 99 188
[1]
Measure Description: Number of participants analyzed for Baseline is intention-to-treat (ITT) population.
Sex: Female, Male   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 602 participants 594 participants 1196 participants
Female
248
  41.2%
255
  42.9%
503
  42.1%
Male
354
  58.8%
339
  57.1%
693
  57.9%
[1]
Measure Description: Number of participants analyzed for Baseline is 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. For definition of DVT/PE, kindly refer to the link in the Protocol section.
Time Frame 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) Placebo
Hide Arm/Group Description:
Participants were to receive rivaroxaban 20 mg oral tablet once daily
Participants were to receive matching placebo oral tablet once daily
Overall Number of Participants Analyzed 602 594
Measure Type: Number
Unit of Measure: Percentage of participants
1.3 7.1
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rivaroxaban (Xarelto, BAY59-7939), Placebo
Comments The rivaroxaban to comparator hazard ratio was computed with a 95% CI (confidence interval) (two-sided testing).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments 1st test in a hierarchy, a p-value of less than 0.05 would be considered significant.
Method Regression, Cox
Comments Stratified by intended treatment duration, adjusted for pre-treatment
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.185
Confidence Interval 95%
0.087 to 0.393
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.3858
Estimation Comments [Not Specified]
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), or lung scintigraphy (for PE), and/or case summaries.
Time Frame 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) Placebo
Hide Arm/Group Description:
Participants were to receive rivaroxaban 20 mg oral tablet once daily
Participants were to receive matching placebo oral tablet once daily
Overall Number of Participants Analyzed 602 594
Measure Type: Number
Unit of Measure: Percentage of participants
1.3 7.2
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rivaroxaban (Xarelto, BAY59-7939), Placebo
Comments The rivaroxaban to comparator hazard ratio was computed with a 95% CI (two-sided testing).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments 2nd test in a hierarchy, a p-value of less than 0.05 would be considered significant. If the 1st test in hierarchy was significant.
Method Regression, Cox
Comments Stratified by intended treatment duration, adjusted for pre-treatment
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.180
Confidence Interval 95%
0.085 to 0.383
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.3850
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Percentage of Participants With the Composite Variable Comprising Recurrent DVT, Non-fatal PE, All Cause Mortality, Strokes and Myocardial Infarctions 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), results/films/images of confirmatory testing, and/or case summaries.
Time Frame 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) Placebo
Hide Arm/Group Description:
Participants were to receive rivaroxaban 20 mg oral tablet once daily
Participants were to receive matching placebo oral tablet once daily
Overall Number of Participants Analyzed 602 594
Measure Type: Number
Unit of Measure: Percentage of participants
1.5 7.4
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rivaroxaban (Xarelto, BAY59-7939), Placebo
Comments The rivaroxaban to comparator hazard ratio was computed with a 95% CI (two-sided testing).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments 3rd test in a hierarchy, a p-value of less than 0.05 would be considered significant. If the previous tests in hierarchy were significant
Method Regression, Cox
Comments Stratified by intended treatment duration, adjusted for pre-treatment
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.198
Confidence Interval 95%
0.096 to 0.405
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.3659
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Percentage of Participants With Net Clinical Benefit as Composite of Recurrent DVT or Non-fatal or Fatal PE and Major Bleeding Events 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 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) Placebo
Hide Arm/Group Description:
Participants were to receive rivaroxaban 20 mg oral tablet once daily
Participants were to receive matching placebo oral tablet once daily
Overall Number of Participants Analyzed 602 594
Measure Type: Number
Unit of Measure: Percentage of participants
2.0 7.1
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rivaroxaban (Xarelto, BAY59-7939), Placebo
Comments The rivaroxaban to comparator hazard ratio was computed with a 95% CI (two-sided testing).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments 4th test in a hierarchy, a p-value of less than 0.05 would be considered significant. If the previous tests in hierarchy were significant
Method Regression, Cox
Comments Stratified by intended treatment duration, adjusted for pre-treatment
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.278
Confidence Interval 95%
0.146 to 0.528
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.3274
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Percentage of Participants With Recurrent VTE (PE or 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 (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), results/films/images of confirmatory testing, and/or case summaries.
Time Frame 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) Placebo
Hide Arm/Group Description:
Participants were to receive rivaroxaban 20 mg oral tablet once daily
Participants were to receive matching placebo oral tablet once daily
Overall Number of Participants Analyzed 602 594
Measure Type: Number
Unit of Measure: Percentage of participants
1.2 7.1
6.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 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) Placebo
Hide Arm/Group Description:
Participants were to receive rivaroxaban 20 mg oral tablet once daily
Participants were to receive matching placebo oral tablet once daily
Overall Number of Participants Analyzed 602 594
Measure Type: Number
Unit of Measure: Percentage of participants
0.8 5.2
7.Secondary Outcome
Title Percentage of Participants With Major Bleeding
Hide Description All events were adjudicated and confirmed by a central independent adjudication committee (CIAC) blinded to treatment. Major bleeding event was overt bleeding associated with a 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. Treatment-emergent [after intake of first tablet of study medication as randomized but not more than 2 days after stop of study medication (referred to as time window: 2 days)] events and all events post randomization were reported.
Time Frame 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 study treatment. For this population, participants were analyzed according to the treatment they received.
Arm/Group Title Rivaroxaban (Xarelto, BAY59-7939) Placebo
Hide Arm/Group Description:
Participants were to receive rivaroxaban 20 mg oral tablet once daily
Participants were to receive matching placebo oral tablet once daily
Overall Number of Participants Analyzed 598 590
Measure Type: Number
Unit of Measure: Percentage of participants
Treatment-emergent (time window: 2 days) 0.7 0.0
All post-randomization 0.7 0.2
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rivaroxaban (Xarelto, BAY59-7939), Placebo
Comments The rivaroxaban to comparator hazard ratio was computed with a 95% CI (two-sided testing), comparison was done for the treatment emergent (within two days after end of treatment) bleeding events.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1121
Comments No adjustment for multiple comparison.
Method Log Rank
Comments [Not Specified]
8.Secondary Outcome
Title Percentage of Participants With Clinically Relevant Bleeding
Hide Description All events adjudicated/confirmed by CIAC blinded to treatment. Clinically relevant bleeding included major bleeding (definition: see outcome 7) 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 daily life activities. Treatment-emergent events (after intake of 1st study medication tablet as randomized up to 2 days after stop of study medication [‘time window: 2 days’]) and all events post randomization were reported
Time Frame 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 study treatment. For this population, participants were analyzed according to the treatment they received.
Arm/Group Title Rivaroxaban (Xarelto, BAY59-7939) Placebo
Hide Arm/Group Description:
Participants were to receive rivaroxaban 20 mg oral tablet once daily
Participants were to receive matching placebo oral tablet once daily
Overall Number of Participants Analyzed 598 590
Measure Type: Number
Unit of Measure: Percentage of participants
Treatment-emergent (time window: 2 days) 6.0 1.2
All post-randomization 6.0 1.9
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rivaroxaban (Xarelto, BAY59-7939), Placebo
Comments The rivaroxaban to comparator hazard ratio was computed with a 95% CI (two-sided testing), comparison was done for the treatment emergent (within two days after end of treatment) bleeding events.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments No adjustment for multiple comparison, a p-value of less than 0.05 would be considered significant.
Method Regression, Cox
Comments Stratified by intended treatment duration, adjusted for pre-treatment done for treatment-emergent (time window: 2 days)
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 5.185
Confidence Interval 95%
2.307 to 11.652
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.4131
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Percentage of Participants With All Death
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. Treatment-emergent events and all events post randomization were reported. Treatment-emergent: after intake of first tablet of study medication as randomized but not more than 2 days after stop of study medication (referred to as time window: 2 days)
Time Frame 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 study treatment. For this population, participants were analyzed according to the treatment they received.
Arm/Group Title Rivaroxaban (Xarelto, BAY59-7939) Placebo
Hide Arm/Group Description:
Participants were to receive rivaroxaban 20 mg oral tablet once daily
Participants were to receive matching placebo oral tablet once daily
Overall Number of Participants Analyzed 598 590
Measure Type: Number
Unit of Measure: Percentage of participants
Treatment-emergent (time window: 2 days) 0.2 0.2
All post-randomization 0.2 0.3
10.Secondary Outcome
Title Percentage of Participants With Other Vascular Events
Hide Description All pre-defined vascular events (acute coronary syndromes, ischemic stroke, transient ischemic attack, non-central nervous system systemic embolism and vascular death) were adjudicated/confirmed by a central independent adjudication committee blinded to treatment, based on results/films/images of confirmatory testing, and/or case summaries. On treatment events and all events post randomization were reported. On treatment: after intake of first tablet of study medication as randomized but not more than 1 day after stop of study medication (referred to as time window: 1 day)
Time Frame 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 study treatment. For this population, participants were analyzed according to the treatment they received.
Arm/Group Title Rivaroxaban (Xarelto, BAY59-7939) Placebo
Hide Arm/Group Description:
Participants were to receive rivaroxaban 20 mg oral tablet once daily
Participants were to receive matching placebo oral tablet once daily
Overall Number of Participants Analyzed 598 590
Measure Type: Number
Unit of Measure: Percentage of participants
On treatment (time window: 1 day) 0.5 0.7
All post-randomization 0.8 0.7
11.Other Pre-specified Outcome
Title Percentage of Participants With Death (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 autopsy, results/films/images of confirmatory testing, and/or case summaries.
Time Frame 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) Placebo
Hide Arm/Group Description:
Participants were to receive rivaroxaban 20 mg oral tablet once daily
Participants were to receive matching placebo oral tablet once daily
Overall Number of Participants Analyzed 602 594
Measure Type: Number
Unit of Measure: Percentage of participants
0.0 0.2
12.Other Pre-specified Outcome
Title Percentage of Participants With Death (PE Cannot be Excluded) 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 unexplained death for which DVT/PE could not be ruled out, results/films/images of confirmatory testing, and/or case summaries.
Time Frame 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) Placebo
Hide Arm/Group Description:
Participants were to receive rivaroxaban 20 mg oral tablet once daily
Participants were to receive matching placebo oral tablet once daily
Overall Number of Participants Analyzed 602 594
Measure Type: Number
Unit of Measure: Percentage of participants
0.2 0.0
13.Other Pre-specified Outcome
Title Percentage of Participants With Symptomatic 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 either spiral computed tomography (CT) scanning, pulmonary angiography, ventilation/perfusion lung scan, lung scintigraphy, results/films/images of confirmatory testing, and/or case summaries.
Time Frame 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) Placebo
Hide Arm/Group Description:
Participants were to receive rivaroxaban 20 mg oral tablet once daily
Participants were to receive matching placebo oral tablet once daily
Overall Number of Participants Analyzed 602 594
Measure Type: Number
Unit of Measure: Percentage of participants
0.3 2.2
14.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 30 days observational period after last intake of study medication
Hide Outcome Measure Data
Hide Analysis Population Description
Intention-to-treat (ITT) population entering observational period. Participants were analyzed according to the treatment assigned at randomization.
Arm/Group Title Rivaroxaban (Xarelto, BAY59-7939) Placebo
Hide Arm/Group Description:
Participants were to receive rivaroxaban 20 mg oral tablet once daily
Participants were to receive matching placebo oral tablet once daily
Overall Number of Participants Analyzed 577 559
Measure Type: Number
Unit of Measure: Percentage of participants
1.2 0.9
15.Other Pre-specified Outcome
Title Percentage of Participants With Symptomatic Recurrent 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 spiral computed tomography (CT) scanning, pulmonary angiography, ventilation/perfusion lung scan, lung scintigraphy, results/films/images of confirmatory testing, and/or case summaries.
Time Frame 30 days observational period after last intake of study medication
Hide Outcome Measure Data
Hide Analysis Population Description
Intention-to-treat (ITT) population entering observational period. Participants were analyzed according to the treatment assigned at randomization.
Arm/Group Title Rivaroxaban (Xarelto, BAY59-7939) Placebo
Hide Arm/Group Description:
Participants were to receive rivaroxaban 20 mg oral tablet once daily
Participants were to receive matching placebo oral tablet once daily
Overall Number of Participants Analyzed 577 559
Measure Type: Number
Unit of Measure: Percentage of participants
0.3 0.2
16.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 30 days observational period after last intake of study medication
Hide Outcome Measure Data
Hide Analysis Population Description
Intention-to-treat (ITT) population entering observational period. Participants were analyzed according to the treatment assigned at randomization.
Arm/Group Title Rivaroxaban (Xarelto, BAY59-7939) Placebo
Hide Arm/Group Description:
Participants were to receive rivaroxaban 20 mg oral tablet once daily
Participants were to receive matching placebo oral tablet once daily
Overall Number of Participants Analyzed 577 559
Measure Type: Number
Unit of Measure: Percentage of participants
1.2 1.1
17.Other Pre-specified Outcome
Title Percentage of Participants With the Composite Variable Comprising Recurrent DVT, Non-fatal PE, All Cause Mortality, Strokes and Myocardial Infarctions 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 30 days observational period after last intake of study medication
Hide Outcome Measure Data
Hide Analysis Population Description
Intention-to-treat (ITT) population entering observational period. Participants were analyzed according to the treatment assigned at randomization.
Arm/Group Title Rivaroxaban (Xarelto, BAY59-7939) Placebo
Hide Arm/Group Description:
Participants were to receive rivaroxaban 20 mg oral tablet once daily
Participants were to receive matching placebo oral tablet once daily
Overall Number of Participants Analyzed 577 559
Measure Type: Number
Unit of Measure: Percentage of participants
1.4 1.1
18.Other Pre-specified Outcome
Title Percentage of Participants With Net Clinical Benefit as Composite of Recurrent DVT or Non-fatal or Fatal PE and Major Bleeding Events During Observational Period
Hide Description Events were adjudicated/confirmed by a central independent adjudication committee blinded to treatment, based on either compression ultrasound, venography, spiral CT 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 or more units, occurring in a critical site or contributing to death.
Time Frame 30 days observational period after last intake of study medication
Hide Outcome Measure Data
Hide Analysis Population Description
Intention-to-treat (ITT) population entering observational period. Participants were analyzed according to the treatment assigned at randomization.
Arm/Group Title Rivaroxaban (Xarelto, BAY59-7939) Placebo
Hide Arm/Group Description:
Participants were to receive rivaroxaban 20 mg oral tablet once daily
Participants were to receive matching placebo oral tablet once daily
Overall Number of Participants Analyzed 577 559
Measure Type: Number
Unit of Measure: Percentage of participants
1.2 0.9
19.Other Pre-specified Outcome
Title Percentage of Participants With Recurrent VTE (PE or 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 (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), results/films/images of confirmatory testing, and/or case summaries.
Time Frame 30 days observational period after last intake of study medication
Hide Outcome Measure Data
Hide Analysis Population Description
Intention-to-treat (ITT) population entering observational period. Participants were analyzed according to the treatment assigned at randomization.
Arm/Group Title Rivaroxaban (Xarelto, BAY59-7939) Placebo
Hide Arm/Group Description:
Participants were to receive rivaroxaban 20 mg oral tablet once daily
Participants were to receive matching placebo oral tablet once daily
Overall Number of Participants Analyzed 577 559
Measure Type: Number
Unit of Measure: Percentage of participants
1.2 0.9
20.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 or venography, results/films/images of confirmatory testing, and/or case summaries.
Time Frame 30 days observational period after last intake of study medication
Hide Outcome Measure Data
Hide Analysis Population Description
Intention-to-treat (ITT) population entering observational period. Participants were analyzed according to the treatment assigned at randomization.
Arm/Group Title Rivaroxaban (Xarelto, BAY59-7939) Placebo
Hide Arm/Group Description:
Participants were to receive rivaroxaban 20 mg oral tablet once daily
Participants were to receive matching placebo oral tablet once daily
Overall Number of Participants Analyzed 577 559
Measure Type: Number
Unit of Measure: Percentage of participants
0.9 0.7
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Rivaroxaban (Xarelto, BAY59-7939) Placebo
Hide Arm/Group Description Participants were to receive rivaroxaban 20 mg oral tablet once daily Participants were to receive matching placebo oral tablet once daily
All-Cause Mortality
Rivaroxaban (Xarelto, BAY59-7939) Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Rivaroxaban (Xarelto, BAY59-7939) Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   59/598 (9.87%)   52/590 (8.81%) 
Blood and lymphatic system disorders     
Anaemia * 1  1/598 (0.17%)  1/590 (0.17%) 
Cardiac disorders     
Acute myocardial infarction * 1  1/598 (0.17%)  1/590 (0.17%) 
Angina unstable * 1  3/598 (0.50%)  0/590 (0.00%) 
Atrial fibrillation * 1  3/598 (0.50%)  4/590 (0.68%) 
Bradycardia * 1  1/598 (0.17%)  1/590 (0.17%) 
Cardiac arrest * 1  1/598 (0.17%)  0/590 (0.00%) 
Cardiac failure * 1  0/598 (0.00%)  1/590 (0.17%) 
Cardiac failure congestive * 1  1/598 (0.17%)  0/590 (0.00%) 
Cardiomyopathy * 1  0/598 (0.00%)  1/590 (0.17%) 
Sick sinus syndrome * 1  0/598 (0.00%)  1/590 (0.17%) 
Supraventricular tachycardia * 1  0/598 (0.00%)  1/590 (0.17%) 
Gastrointestinal disorders     
Abdominal pain * 1  1/598 (0.17%)  1/590 (0.17%) 
Abdominal pain upper * 1  2/598 (0.33%)  0/590 (0.00%) 
Colitis * 1  0/598 (0.00%)  1/590 (0.17%) 
Colitis ischaemic * 1  0/598 (0.00%)  1/590 (0.17%) 
Constipation * 1  0/598 (0.00%)  1/590 (0.17%) 
Diverticulum * 1  0/598 (0.00%)  1/590 (0.17%) 
Gastric ulcer * 1  1/598 (0.17%)  0/590 (0.00%) 
Gastritis * 1  1/598 (0.17%)  0/590 (0.00%) 
Gastrointestinal haemorrhage * 1  2/598 (0.33%)  0/590 (0.00%) 
Haemorrhoids * 1  0/598 (0.00%)  1/590 (0.17%) 
Inguinal hernia * 1  0/598 (0.00%)  1/590 (0.17%) 
Intestinal obstruction * 1  1/598 (0.17%)  0/590 (0.00%) 
Large intestinal ulcer * 1  0/598 (0.00%)  1/590 (0.17%) 
Melaena * 1  1/598 (0.17%)  0/590 (0.00%) 
Rectal haemorrhage * 1  1/598 (0.17%)  1/590 (0.17%) 
Abdominal hernia obstructive * 1  0/598 (0.00%)  1/590 (0.17%) 
General disorders     
Asthenia * 1  0/598 (0.00%)  1/590 (0.17%) 
Chest pain * 1  2/598 (0.33%)  3/590 (0.51%) 
Non-cardiac chest pain * 1  0/598 (0.00%)  1/590 (0.17%) 
Hepatobiliary disorders     
Cholecystitis * 1  1/598 (0.17%)  1/590 (0.17%) 
Cholelithiasis * 1  1/598 (0.17%)  0/590 (0.00%) 
Immune system disorders     
Antiphospholipid syndrome * 1  1/598 (0.17%)  0/590 (0.00%) 
Infections and infestations     
Appendicitis * 1  1/598 (0.17%)  0/590 (0.00%) 
Bronchitis * 1  0/598 (0.00%)  3/590 (0.51%) 
Cellulitis * 1  1/598 (0.17%)  1/590 (0.17%) 
Gastroenteritis * 1  2/598 (0.33%)  0/590 (0.00%) 
Herpes zoster * 1  0/598 (0.00%)  1/590 (0.17%) 
Intestinal gangrene * 1  0/598 (0.00%)  1/590 (0.17%) 
Localised infection * 1  1/598 (0.17%)  0/590 (0.00%) 
Lung abscess * 1  1/598 (0.17%)  0/590 (0.00%) 
Pharyngitis * 1  0/598 (0.00%)  1/590 (0.17%) 
Pneumonia * 1  3/598 (0.50%)  0/590 (0.00%) 
Urinary tract infection * 1  1/598 (0.17%)  1/590 (0.17%) 
Postoperative abscess * 1  1/598 (0.17%)  0/590 (0.00%) 
Abdominal abscess * 1  1/598 (0.17%)  0/590 (0.00%) 
Respiratory tract infection * 1  1/598 (0.17%)  0/590 (0.00%) 
Injury, poisoning and procedural complications     
Humerus fracture * 1  0/598 (0.00%)  1/590 (0.17%) 
Joint dislocation * 1  1/598 (0.17%)  0/590 (0.00%) 
Rib fracture * 1  1/598 (0.17%)  0/590 (0.00%) 
Soft tissue injury * 1  0/598 (0.00%)  1/590 (0.17%) 
Drug exposure during pregnancy * 1  0/598 (0.00%)  1/590 (0.17%) 
Traumatic fracture * 1  0/598 (0.00%)  1/590 (0.17%) 
Post procedural haemorrhage * 1  1/598 (0.17%)  0/590 (0.00%) 
Skull fracture * 1  1/598 (0.17%)  0/590 (0.00%) 
Investigations     
Alanine aminotransferase increased * 1  2/598 (0.33%)  0/590 (0.00%) 
Aspartate aminotransferase increased * 1  2/598 (0.33%)  0/590 (0.00%) 
Liver function test abnormal * 1  0/598 (0.00%)  1/590 (0.17%) 
Hepatic enzyme increased * 1  2/598 (0.33%)  0/590 (0.00%) 
Metabolism and nutrition disorders     
Diabetic ketoacidosis * 1  0/598 (0.00%)  1/590 (0.17%) 
Hyperglycaemia * 1  1/598 (0.17%)  0/590 (0.00%) 
Hyponatraemia * 1  1/598 (0.17%)  0/590 (0.00%) 
Musculoskeletal and connective tissue disorders     
Costochondritis * 1  0/598 (0.00%)  1/590 (0.17%) 
Joint stiffness * 1  0/598 (0.00%)  1/590 (0.17%) 
Osteoarthritis * 1  1/598 (0.17%)  1/590 (0.17%) 
Pain in extremity * 1  1/598 (0.17%)  1/590 (0.17%) 
Rheumatoid arthritis * 1  1/598 (0.17%)  1/590 (0.17%) 
Musculoskeletal chest pain * 1  0/598 (0.00%)  1/590 (0.17%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Adenocarcinoma * 1  1/598 (0.17%)  0/590 (0.00%) 
Colon cancer * 1  0/598 (0.00%)  1/590 (0.17%) 
Endometrial cancer * 1  0/598 (0.00%)  1/590 (0.17%) 
Hepatic neoplasm * 1  1/598 (0.17%)  0/590 (0.00%) 
Malignant melanoma in situ * 1  0/598 (0.00%)  1/590 (0.17%) 
Metastases to liver * 1  1/598 (0.17%)  0/590 (0.00%) 
Metastases to spine * 1  1/598 (0.17%)  0/590 (0.00%) 
Sarcoma * 1  1/598 (0.17%)  0/590 (0.00%) 
Squamous cell carcinoma of skin * 1  1/598 (0.17%)  0/590 (0.00%) 
Benign vascular neoplasm * 1  0/598 (0.00%)  1/590 (0.17%) 
Colorectal cancer * 1  0/598 (0.00%)  1/590 (0.17%) 
Oesophageal neoplasm * 1  1/598 (0.17%)  0/590 (0.00%) 
Vaginal neoplasm * 1  0/598 (0.00%)  1/590 (0.17%) 
Metastatic squamous cell carcinoma * 1  1/598 (0.17%)  0/590 (0.00%) 
Nervous system disorders     
Epilepsy * 1  2/598 (0.33%)  1/590 (0.17%) 
Syncope * 1  2/598 (0.33%)  1/590 (0.17%) 
Transient ischaemic attack * 1  1/598 (0.17%)  0/590 (0.00%) 
Ischaemic stroke * 1  0/598 (0.00%)  1/590 (0.17%) 
Metabolic encephalopathy * 1  1/598 (0.17%)  0/590 (0.00%) 
Pregnancy, puerperium and perinatal conditions     
Abortion missed * 1  1/598 (0.17%)  0/590 (0.00%) 
Pregnancy * 1  1/598 (0.17%)  0/590 (0.00%) 
Psychiatric disorders     
Anxiety * 1  0/598 (0.00%)  1/590 (0.17%) 
Depression * 1  1/598 (0.17%)  0/590 (0.00%) 
Renal and urinary disorders     
Haematuria * 1  1/598 (0.17%)  0/590 (0.00%) 
Hydronephrosis * 1  0/598 (0.00%)  1/590 (0.17%) 
Renal failure acute * 1  1/598 (0.17%)  0/590 (0.00%) 
Reproductive system and breast disorders     
Menometrorrhagia * 1  1/598 (0.17%)  0/590 (0.00%) 
Metrorrhagia * 1  1/598 (0.17%)  0/590 (0.00%) 
Vaginal prolapse * 1  0/598 (0.00%)  1/590 (0.17%) 
Respiratory, thoracic and mediastinal disorders     
Acute pulmonary oedema * 1  1/598 (0.17%)  0/590 (0.00%) 
Bronchospasm * 1  1/598 (0.17%)  0/590 (0.00%) 
Chronic obstructive pulmonary disease * 1  3/598 (0.50%)  0/590 (0.00%) 
Dyspnoea * 1  2/598 (0.33%)  0/590 (0.00%) 
Pulmonary embolism * 1  0/598 (0.00%)  1/590 (0.17%) 
Respiratory failure * 1  0/598 (0.00%)  1/590 (0.17%) 
Sleep apnoea syndrome * 1  0/598 (0.00%)  1/590 (0.17%) 
Skin and subcutaneous tissue disorders     
Stevens-Johnson syndrome * 1  0/598 (0.00%)  1/590 (0.17%) 
Surgical and medical procedures     
Anal fistula excision * 1  0/598 (0.00%)  1/590 (0.17%) 
Appendicectomy * 1  1/598 (0.17%)  0/590 (0.00%) 
Bladder calculus removal * 1  1/598 (0.17%)  0/590 (0.00%) 
Vascular disorders     
Circulatory collapse * 1  1/598 (0.17%)  0/590 (0.00%) 
Haematoma * 1  0/598 (0.00%)  1/590 (0.17%) 
Hypertension * 1  2/598 (0.33%)  1/590 (0.17%) 
Thrombophlebitis * 1  1/598 (0.17%)  0/590 (0.00%) 
Peripheral arterial occlusive disease * 1  0/598 (0.00%)  1/590 (0.17%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (12.0)
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) Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   63/598 (10.54%)   65/590 (11.02%) 
Infections and infestations     
Nasopharyngitis * 1  33/598 (5.52%)  32/590 (5.42%) 
Musculoskeletal and connective tissue disorders     
Pain in extremity * 1  31/598 (5.18%)  38/590 (6.44%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (12.0)
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
Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT00439725     History of Changes
Other Study ID Numbers: 11899
2006-004494-96 ( EudraCT Number )
First Submitted: February 23, 2007
First Posted: February 26, 2007
Results First Submitted: January 31, 2012
Results First Posted: April 12, 2012
Last Update Posted: November 4, 2014