Trial Outcomes & Findings for 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 (NCT NCT00439725)
NCT ID: NCT00439725
Last Updated: 2014-11-04
Results Overview
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.
COMPLETED
PHASE3
1197 participants
6- or 12-month study treatment period
2014-11-04
Participant Flow
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.
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).
Participant milestones
| Measure |
Rivaroxaban (Xarelto, BAY59-7939)
Participants were to receive rivaroxaban 20 mg oral tablet once daily
|
Placebo
Participants were to receive matching placebo oral tablet once daily
|
|---|---|---|
|
Treatment Period
STARTED
|
602
|
595
|
|
Treatment Period
Participants Received Treatment
|
598
|
590
|
|
Treatment Period
COMPLETED
|
366
|
349
|
|
Treatment Period
NOT COMPLETED
|
236
|
246
|
|
Observational Period
STARTED
|
577
|
560
|
|
Observational Period
COMPLETED
|
569
|
553
|
|
Observational Period
NOT COMPLETED
|
8
|
7
|
Reasons for withdrawal
| Measure |
Rivaroxaban (Xarelto, BAY59-7939)
Participants were to receive rivaroxaban 20 mg oral tablet once daily
|
Placebo
Participants were to receive matching placebo oral tablet once daily
|
|---|---|---|
|
Treatment Period
Withdrawal by Subject
|
22
|
19
|
|
Treatment Period
Study terminated by sponsor
|
156
|
148
|
|
Treatment Period
Site closed by investigator
|
1
|
2
|
|
Treatment Period
Adverse Event
|
39
|
18
|
|
Treatment Period
Physician Decision
|
1
|
1
|
|
Treatment Period
Protocol Violation
|
2
|
1
|
|
Treatment Period
Clinical endpoint reached
|
6
|
50
|
|
Treatment Period
Technical problems
|
1
|
0
|
|
Treatment Period
Lost to Follow-up
|
1
|
1
|
|
Treatment Period
Participant convenience
|
1
|
0
|
|
Treatment Period
Protocol driven decision point
|
1
|
1
|
|
Treatment Period
Death
|
1
|
1
|
|
Treatment Period
Participant did not receive treatment
|
4
|
4
|
|
Observational Period
Withdrawal by Subject
|
2
|
2
|
|
Observational Period
Lost to Follow-up
|
0
|
1
|
|
Observational Period
Death
|
0
|
2
|
|
Observational Period
Study termination by sponsor
|
1
|
1
|
|
Observational Period
Clinical endpoint reached
|
3
|
1
|
|
Observational Period
Technical problems
|
1
|
0
|
|
Observational Period
Participant convenience
|
1
|
0
|
Baseline Characteristics
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
Baseline characteristics by cohort
| Measure |
Rivaroxaban (Xarelto, BAY59-7939)
n=602 Participants
Participants were to receive rivaroxaban 20 mg oral tablet once daily
|
Placebo
n=594 Participants
Participants were to receive matching placebo oral tablet once daily
|
Total
n=1196 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
58.2 years
STANDARD_DEVIATION 15.6 • n=39 Participants
|
58.4 years
STANDARD_DEVIATION 16.0 • n=41 Participants
|
58.3 years
STANDARD_DEVIATION 15.8 • n=35 Participants
|
|
Age, Customized
18 - 40 years
|
87 participants
n=39 Participants
|
94 participants
n=41 Participants
|
181 participants
n=35 Participants
|
|
Age, Customized
>40 - <65 years
|
273 participants
n=39 Participants
|
280 participants
n=41 Participants
|
553 participants
n=35 Participants
|
|
Age, Customized
65 - 75 years
|
153 participants
n=39 Participants
|
121 participants
n=41 Participants
|
274 participants
n=35 Participants
|
|
Age, Customized
>75 years
|
89 participants
n=39 Participants
|
99 participants
n=41 Participants
|
188 participants
n=35 Participants
|
|
Sex: Female, Male
Female
|
248 Participants
n=39 Participants
|
255 Participants
n=41 Participants
|
503 Participants
n=35 Participants
|
|
Sex: Female, Male
Male
|
354 Participants
n=39 Participants
|
339 Participants
n=41 Participants
|
693 Participants
n=35 Participants
|
PRIMARY outcome
Timeframe: 6- or 12-month study treatment periodPopulation: 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.
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.
Outcome measures
| Measure |
Rivaroxaban (Xarelto, BAY59-7939)
n=602 Participants
Participants were to receive rivaroxaban 20 mg oral tablet once daily
|
Placebo
n=594 Participants
Participants were to receive matching placebo oral tablet once daily
|
|---|---|---|
|
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
|
1.3 Percentage of participants
|
7.1 Percentage of participants
|
SECONDARY outcome
Timeframe: 6- or 12-month study treatment periodPopulation: 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.
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.
Outcome measures
| Measure |
Rivaroxaban (Xarelto, BAY59-7939)
n=602 Participants
Participants were to receive rivaroxaban 20 mg oral tablet once daily
|
Placebo
n=594 Participants
Participants were to receive matching placebo oral tablet once daily
|
|---|---|---|
|
Percentage of Participants With the Composite Variable Comprising Recurrent DVT, Non-fatal PE and All Cause Mortality Until the Intended End of Study Treatment
|
1.3 Percentage of participants
|
7.2 Percentage of participants
|
SECONDARY outcome
Timeframe: 6- or 12-month study treatment periodPopulation: 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.
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.
Outcome measures
| Measure |
Rivaroxaban (Xarelto, BAY59-7939)
n=602 Participants
Participants were to receive rivaroxaban 20 mg oral tablet once daily
|
Placebo
n=594 Participants
Participants were to receive matching placebo oral tablet once daily
|
|---|---|---|
|
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
|
1.5 Percentage of participants
|
7.4 Percentage of participants
|
SECONDARY outcome
Timeframe: 6- or 12-month study treatment periodPopulation: 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.
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.
Outcome measures
| Measure |
Rivaroxaban (Xarelto, BAY59-7939)
n=602 Participants
Participants were to receive rivaroxaban 20 mg oral tablet once daily
|
Placebo
n=594 Participants
Participants were to receive matching placebo oral tablet once daily
|
|---|---|---|
|
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
|
2.0 Percentage of participants
|
7.1 Percentage of participants
|
SECONDARY outcome
Timeframe: 6- or 12-month study treatment periodPopulation: 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.
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.
Outcome measures
| Measure |
Rivaroxaban (Xarelto, BAY59-7939)
n=602 Participants
Participants were to receive rivaroxaban 20 mg oral tablet once daily
|
Placebo
n=594 Participants
Participants were to receive matching placebo oral tablet once daily
|
|---|---|---|
|
Percentage of Participants With Recurrent VTE (PE or DVT) Until the Intended End of Study Treatment
|
1.2 Percentage of participants
|
7.1 Percentage of participants
|
SECONDARY outcome
Timeframe: 6- or 12-month study treatment periodPopulation: 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.
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.
Outcome measures
| Measure |
Rivaroxaban (Xarelto, BAY59-7939)
n=602 Participants
Participants were to receive rivaroxaban 20 mg oral tablet once daily
|
Placebo
n=594 Participants
Participants were to receive matching placebo oral tablet once daily
|
|---|---|---|
|
Percentage of Participants With Recurrent DVT Until the Intended End of Study Treatment
|
0.8 Percentage of participants
|
5.2 Percentage of participants
|
SECONDARY outcome
Timeframe: 6- or 12-month study treatment periodPopulation: 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.
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.
Outcome measures
| Measure |
Rivaroxaban (Xarelto, BAY59-7939)
n=598 Participants
Participants were to receive rivaroxaban 20 mg oral tablet once daily
|
Placebo
n=590 Participants
Participants were to receive matching placebo oral tablet once daily
|
|---|---|---|
|
Percentage of Participants With Major Bleeding
Treatment-emergent (time window: 2 days)
|
0.7 Percentage of participants
|
0.0 Percentage of participants
|
|
Percentage of Participants With Major Bleeding
All post-randomization
|
0.7 Percentage of participants
|
0.2 Percentage of participants
|
SECONDARY outcome
Timeframe: 6- or 12-month study treatment periodPopulation: 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.
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
Outcome measures
| Measure |
Rivaroxaban (Xarelto, BAY59-7939)
n=598 Participants
Participants were to receive rivaroxaban 20 mg oral tablet once daily
|
Placebo
n=590 Participants
Participants were to receive matching placebo oral tablet once daily
|
|---|---|---|
|
Percentage of Participants With Clinically Relevant Bleeding
Treatment-emergent (time window: 2 days)
|
6.0 Percentage of participants
|
1.2 Percentage of participants
|
|
Percentage of Participants With Clinically Relevant Bleeding
All post-randomization
|
6.0 Percentage of participants
|
1.9 Percentage of participants
|
SECONDARY outcome
Timeframe: 6- or 12-month study treatment periodPopulation: 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.
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)
Outcome measures
| Measure |
Rivaroxaban (Xarelto, BAY59-7939)
n=598 Participants
Participants were to receive rivaroxaban 20 mg oral tablet once daily
|
Placebo
n=590 Participants
Participants were to receive matching placebo oral tablet once daily
|
|---|---|---|
|
Percentage of Participants With All Death
Treatment-emergent (time window: 2 days)
|
0.2 Percentage of participants
|
0.2 Percentage of participants
|
|
Percentage of Participants With All Death
All post-randomization
|
0.2 Percentage of participants
|
0.3 Percentage of participants
|
SECONDARY outcome
Timeframe: 6- or 12-month study treatment periodPopulation: 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.
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)
Outcome measures
| Measure |
Rivaroxaban (Xarelto, BAY59-7939)
n=598 Participants
Participants were to receive rivaroxaban 20 mg oral tablet once daily
|
Placebo
n=590 Participants
Participants were to receive matching placebo oral tablet once daily
|
|---|---|---|
|
Percentage of Participants With Other Vascular Events
On treatment (time window: 1 day)
|
0.5 Percentage of participants
|
0.7 Percentage of participants
|
|
Percentage of Participants With Other Vascular Events
All post-randomization
|
0.8 Percentage of participants
|
0.7 Percentage of participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 6- or 12-month study treatment periodPopulation: 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.
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.
Outcome measures
| Measure |
Rivaroxaban (Xarelto, BAY59-7939)
n=602 Participants
Participants were to receive rivaroxaban 20 mg oral tablet once daily
|
Placebo
n=594 Participants
Participants were to receive matching placebo oral tablet once daily
|
|---|---|---|
|
Percentage of Participants With Death (PE) Until the Intended End of Study Treatment
|
0.0 Percentage of participants
|
0.2 Percentage of participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 6- or 12-month study treatment periodPopulation: 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.
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.
Outcome measures
| Measure |
Rivaroxaban (Xarelto, BAY59-7939)
n=602 Participants
Participants were to receive rivaroxaban 20 mg oral tablet once daily
|
Placebo
n=594 Participants
Participants were to receive matching placebo oral tablet once daily
|
|---|---|---|
|
Percentage of Participants With Death (PE Cannot be Excluded) Until the Intended End of Study Treatment
|
0.2 Percentage of participants
|
0.0 Percentage of participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 6- or 12-month study treatment periodPopulation: 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.
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.
Outcome measures
| Measure |
Rivaroxaban (Xarelto, BAY59-7939)
n=602 Participants
Participants were to receive rivaroxaban 20 mg oral tablet once daily
|
Placebo
n=594 Participants
Participants were to receive matching placebo oral tablet once daily
|
|---|---|---|
|
Percentage of Participants With Symptomatic Recurrent PE Until the Intended End of Study Treatment
|
0.3 Percentage of participants
|
2.2 Percentage of participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 30 days observational period after last intake of study medicationPopulation: Intention-to-treat (ITT) population entering observational period. Participants were analyzed according to the treatment assigned at randomization.
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.
Outcome measures
| Measure |
Rivaroxaban (Xarelto, BAY59-7939)
n=577 Participants
Participants were to receive rivaroxaban 20 mg oral tablet once daily
|
Placebo
n=559 Participants
Participants were to receive matching placebo oral tablet once daily
|
|---|---|---|
|
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
|
1.2 Percentage of participants
|
0.9 Percentage of participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 30 days observational period after last intake of study medicationPopulation: Intention-to-treat (ITT) population entering observational period. Participants were analyzed according to the treatment assigned at randomization.
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.
Outcome measures
| Measure |
Rivaroxaban (Xarelto, BAY59-7939)
n=577 Participants
Participants were to receive rivaroxaban 20 mg oral tablet once daily
|
Placebo
n=559 Participants
Participants were to receive matching placebo oral tablet once daily
|
|---|---|---|
|
Percentage of Participants With Symptomatic Recurrent PE During Observational Period
|
0.3 Percentage of participants
|
0.2 Percentage of participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 30 days observational period after last intake of study medicationPopulation: Intention-to-treat (ITT) population entering observational period. Participants were analyzed according to the treatment assigned at randomization.
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.
Outcome measures
| Measure |
Rivaroxaban (Xarelto, BAY59-7939)
n=577 Participants
Participants were to receive rivaroxaban 20 mg oral tablet once daily
|
Placebo
n=559 Participants
Participants were to receive matching placebo oral tablet once daily
|
|---|---|---|
|
Percentage of Participants With the Composite Variable Comprising Recurrent DVT, Non-fatal PE and All Cause Mortality During Observational Period
|
1.2 Percentage of participants
|
1.1 Percentage of participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 30 days observational period after last intake of study medicationPopulation: Intention-to-treat (ITT) population entering observational period. Participants were analyzed according to the treatment assigned at randomization.
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.
Outcome measures
| Measure |
Rivaroxaban (Xarelto, BAY59-7939)
n=577 Participants
Participants were to receive rivaroxaban 20 mg oral tablet once daily
|
Placebo
n=559 Participants
Participants were to receive matching placebo oral tablet once daily
|
|---|---|---|
|
Percentage of Participants With the Composite Variable Comprising Recurrent DVT, Non-fatal PE, All Cause Mortality, Strokes and Myocardial Infarctions During Observational Period
|
1.4 Percentage of participants
|
1.1 Percentage of participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 30 days observational period after last intake of study medicationPopulation: Intention-to-treat (ITT) population entering observational period. Participants were analyzed according to the treatment assigned at randomization.
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.
Outcome measures
| Measure |
Rivaroxaban (Xarelto, BAY59-7939)
n=577 Participants
Participants were to receive rivaroxaban 20 mg oral tablet once daily
|
Placebo
n=559 Participants
Participants were to receive matching placebo oral tablet once daily
|
|---|---|---|
|
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
|
1.2 Percentage of participants
|
0.9 Percentage of participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 30 days observational period after last intake of study medicationPopulation: Intention-to-treat (ITT) population entering observational period. Participants were analyzed according to the treatment assigned at randomization.
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.
Outcome measures
| Measure |
Rivaroxaban (Xarelto, BAY59-7939)
n=577 Participants
Participants were to receive rivaroxaban 20 mg oral tablet once daily
|
Placebo
n=559 Participants
Participants were to receive matching placebo oral tablet once daily
|
|---|---|---|
|
Percentage of Participants With Recurrent VTE (PE or DVT) During Observational Period
|
1.2 Percentage of participants
|
0.9 Percentage of participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 30 days observational period after last intake of study medicationPopulation: Intention-to-treat (ITT) population entering observational period. Participants were analyzed according to the treatment assigned at randomization.
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.
Outcome measures
| Measure |
Rivaroxaban (Xarelto, BAY59-7939)
n=577 Participants
Participants were to receive rivaroxaban 20 mg oral tablet once daily
|
Placebo
n=559 Participants
Participants were to receive matching placebo oral tablet once daily
|
|---|---|---|
|
Percentage of Participants With Recurrent DVT During Observational Period
|
0.9 Percentage of participants
|
0.7 Percentage of participants
|
Adverse Events
Rivaroxaban (Xarelto, BAY59-7939)
Placebo
Serious adverse events
| Measure |
Rivaroxaban (Xarelto, BAY59-7939)
n=598 participants at risk
Participants were to receive rivaroxaban 20 mg oral tablet once daily
|
Placebo
n=590 participants at risk
Participants were to receive matching placebo oral tablet once daily
|
|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
0.17%
1/598
|
0.17%
1/590
|
|
Cardiac disorders
Acute myocardial infarction
|
0.17%
1/598
|
0.17%
1/590
|
|
Cardiac disorders
Angina unstable
|
0.50%
3/598
|
0.00%
0/590
|
|
Cardiac disorders
Atrial fibrillation
|
0.50%
3/598
|
0.68%
4/590
|
|
Cardiac disorders
Bradycardia
|
0.17%
1/598
|
0.17%
1/590
|
|
Cardiac disorders
Cardiac arrest
|
0.17%
1/598
|
0.00%
0/590
|
|
Cardiac disorders
Cardiac failure
|
0.00%
0/598
|
0.17%
1/590
|
|
Cardiac disorders
Cardiac failure congestive
|
0.17%
1/598
|
0.00%
0/590
|
|
Cardiac disorders
Cardiomyopathy
|
0.00%
0/598
|
0.17%
1/590
|
|
Cardiac disorders
Sick sinus syndrome
|
0.00%
0/598
|
0.17%
1/590
|
|
Cardiac disorders
Supraventricular tachycardia
|
0.00%
0/598
|
0.17%
1/590
|
|
Gastrointestinal disorders
Abdominal pain
|
0.17%
1/598
|
0.17%
1/590
|
|
Gastrointestinal disorders
Abdominal pain upper
|
0.33%
2/598
|
0.00%
0/590
|
|
Gastrointestinal disorders
Colitis
|
0.00%
0/598
|
0.17%
1/590
|
|
Gastrointestinal disorders
Colitis ischaemic
|
0.00%
0/598
|
0.17%
1/590
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/598
|
0.17%
1/590
|
|
Gastrointestinal disorders
Diverticulum
|
0.00%
0/598
|
0.17%
1/590
|
|
Gastrointestinal disorders
Gastric ulcer
|
0.17%
1/598
|
0.00%
0/590
|
|
Gastrointestinal disorders
Gastritis
|
0.17%
1/598
|
0.00%
0/590
|
|
Gastrointestinal disorders
Gastrointestinal haemorrhage
|
0.33%
2/598
|
0.00%
0/590
|
|
Gastrointestinal disorders
Haemorrhoids
|
0.00%
0/598
|
0.17%
1/590
|
|
Gastrointestinal disorders
Inguinal hernia
|
0.00%
0/598
|
0.17%
1/590
|
|
Gastrointestinal disorders
Intestinal obstruction
|
0.17%
1/598
|
0.00%
0/590
|
|
Gastrointestinal disorders
Large intestinal ulcer
|
0.00%
0/598
|
0.17%
1/590
|
|
Gastrointestinal disorders
Melaena
|
0.17%
1/598
|
0.00%
0/590
|
|
Gastrointestinal disorders
Rectal haemorrhage
|
0.17%
1/598
|
0.17%
1/590
|
|
Gastrointestinal disorders
Abdominal hernia obstructive
|
0.00%
0/598
|
0.17%
1/590
|
|
General disorders
Asthenia
|
0.00%
0/598
|
0.17%
1/590
|
|
General disorders
Chest pain
|
0.33%
2/598
|
0.51%
3/590
|
|
General disorders
Non-cardiac chest pain
|
0.00%
0/598
|
0.17%
1/590
|
|
Hepatobiliary disorders
Cholecystitis
|
0.17%
1/598
|
0.17%
1/590
|
|
Hepatobiliary disorders
Cholelithiasis
|
0.17%
1/598
|
0.00%
0/590
|
|
Immune system disorders
Antiphospholipid syndrome
|
0.17%
1/598
|
0.00%
0/590
|
|
Infections and infestations
Appendicitis
|
0.17%
1/598
|
0.00%
0/590
|
|
Infections and infestations
Bronchitis
|
0.00%
0/598
|
0.51%
3/590
|
|
Infections and infestations
Cellulitis
|
0.17%
1/598
|
0.17%
1/590
|
|
Infections and infestations
Gastroenteritis
|
0.33%
2/598
|
0.00%
0/590
|
|
Infections and infestations
Herpes zoster
|
0.00%
0/598
|
0.17%
1/590
|
|
Infections and infestations
Intestinal gangrene
|
0.00%
0/598
|
0.17%
1/590
|
|
Infections and infestations
Localised infection
|
0.17%
1/598
|
0.00%
0/590
|
|
Infections and infestations
Lung abscess
|
0.17%
1/598
|
0.00%
0/590
|
|
Infections and infestations
Pharyngitis
|
0.00%
0/598
|
0.17%
1/590
|
|
Infections and infestations
Pneumonia
|
0.50%
3/598
|
0.00%
0/590
|
|
Infections and infestations
Urinary tract infection
|
0.17%
1/598
|
0.17%
1/590
|
|
Infections and infestations
Postoperative abscess
|
0.17%
1/598
|
0.00%
0/590
|
|
Infections and infestations
Abdominal abscess
|
0.17%
1/598
|
0.00%
0/590
|
|
Infections and infestations
Respiratory tract infection
|
0.17%
1/598
|
0.00%
0/590
|
|
Injury, poisoning and procedural complications
Humerus fracture
|
0.00%
0/598
|
0.17%
1/590
|
|
Injury, poisoning and procedural complications
Joint dislocation
|
0.17%
1/598
|
0.00%
0/590
|
|
Injury, poisoning and procedural complications
Rib fracture
|
0.17%
1/598
|
0.00%
0/590
|
|
Injury, poisoning and procedural complications
Soft tissue injury
|
0.00%
0/598
|
0.17%
1/590
|
|
Injury, poisoning and procedural complications
Drug exposure during pregnancy
|
0.00%
0/598
|
0.17%
1/590
|
|
Injury, poisoning and procedural complications
Traumatic fracture
|
0.00%
0/598
|
0.17%
1/590
|
|
Injury, poisoning and procedural complications
Post procedural haemorrhage
|
0.17%
1/598
|
0.00%
0/590
|
|
Injury, poisoning and procedural complications
Skull fracture
|
0.17%
1/598
|
0.00%
0/590
|
|
Investigations
Alanine aminotransferase increased
|
0.33%
2/598
|
0.00%
0/590
|
|
Investigations
Aspartate aminotransferase increased
|
0.33%
2/598
|
0.00%
0/590
|
|
Investigations
Liver function test abnormal
|
0.00%
0/598
|
0.17%
1/590
|
|
Investigations
Hepatic enzyme increased
|
0.33%
2/598
|
0.00%
0/590
|
|
Metabolism and nutrition disorders
Diabetic ketoacidosis
|
0.00%
0/598
|
0.17%
1/590
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
0.17%
1/598
|
0.00%
0/590
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
0.17%
1/598
|
0.00%
0/590
|
|
Musculoskeletal and connective tissue disorders
Costochondritis
|
0.00%
0/598
|
0.17%
1/590
|
|
Musculoskeletal and connective tissue disorders
Joint stiffness
|
0.00%
0/598
|
0.17%
1/590
|
|
Musculoskeletal and connective tissue disorders
Osteoarthritis
|
0.17%
1/598
|
0.17%
1/590
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.17%
1/598
|
0.17%
1/590
|
|
Musculoskeletal and connective tissue disorders
Rheumatoid arthritis
|
0.17%
1/598
|
0.17%
1/590
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
0.00%
0/598
|
0.17%
1/590
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma
|
0.17%
1/598
|
0.00%
0/590
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon cancer
|
0.00%
0/598
|
0.17%
1/590
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Endometrial cancer
|
0.00%
0/598
|
0.17%
1/590
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Hepatic neoplasm
|
0.17%
1/598
|
0.00%
0/590
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant melanoma in situ
|
0.00%
0/598
|
0.17%
1/590
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to liver
|
0.17%
1/598
|
0.00%
0/590
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to spine
|
0.17%
1/598
|
0.00%
0/590
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Sarcoma
|
0.17%
1/598
|
0.00%
0/590
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Squamous cell carcinoma of skin
|
0.17%
1/598
|
0.00%
0/590
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Benign vascular neoplasm
|
0.00%
0/598
|
0.17%
1/590
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colorectal cancer
|
0.00%
0/598
|
0.17%
1/590
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Oesophageal neoplasm
|
0.17%
1/598
|
0.00%
0/590
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Vaginal neoplasm
|
0.00%
0/598
|
0.17%
1/590
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastatic squamous cell carcinoma
|
0.17%
1/598
|
0.00%
0/590
|
|
Nervous system disorders
Epilepsy
|
0.33%
2/598
|
0.17%
1/590
|
|
Nervous system disorders
Syncope
|
0.33%
2/598
|
0.17%
1/590
|
|
Nervous system disorders
Transient ischaemic attack
|
0.17%
1/598
|
0.00%
0/590
|
|
Nervous system disorders
Ischaemic stroke
|
0.00%
0/598
|
0.17%
1/590
|
|
Nervous system disorders
Metabolic encephalopathy
|
0.17%
1/598
|
0.00%
0/590
|
|
Pregnancy, puerperium and perinatal conditions
Abortion missed
|
0.17%
1/598
|
0.00%
0/590
|
|
Pregnancy, puerperium and perinatal conditions
Pregnancy
|
0.17%
1/598
|
0.00%
0/590
|
|
Psychiatric disorders
Anxiety
|
0.00%
0/598
|
0.17%
1/590
|
|
Psychiatric disorders
Depression
|
0.17%
1/598
|
0.00%
0/590
|
|
Renal and urinary disorders
Haematuria
|
0.17%
1/598
|
0.00%
0/590
|
|
Renal and urinary disorders
Hydronephrosis
|
0.00%
0/598
|
0.17%
1/590
|
|
Renal and urinary disorders
Renal failure acute
|
0.17%
1/598
|
0.00%
0/590
|
|
Reproductive system and breast disorders
Menometrorrhagia
|
0.17%
1/598
|
0.00%
0/590
|
|
Reproductive system and breast disorders
Metrorrhagia
|
0.17%
1/598
|
0.00%
0/590
|
|
Reproductive system and breast disorders
Vaginal prolapse
|
0.00%
0/598
|
0.17%
1/590
|
|
Respiratory, thoracic and mediastinal disorders
Acute pulmonary oedema
|
0.17%
1/598
|
0.00%
0/590
|
|
Respiratory, thoracic and mediastinal disorders
Bronchospasm
|
0.17%
1/598
|
0.00%
0/590
|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
|
0.50%
3/598
|
0.00%
0/590
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.33%
2/598
|
0.00%
0/590
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
0.00%
0/598
|
0.17%
1/590
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
0.00%
0/598
|
0.17%
1/590
|
|
Respiratory, thoracic and mediastinal disorders
Sleep apnoea syndrome
|
0.00%
0/598
|
0.17%
1/590
|
|
Skin and subcutaneous tissue disorders
Stevens-Johnson syndrome
|
0.00%
0/598
|
0.17%
1/590
|
|
Surgical and medical procedures
Anal fistula excision
|
0.00%
0/598
|
0.17%
1/590
|
|
Surgical and medical procedures
Appendicectomy
|
0.17%
1/598
|
0.00%
0/590
|
|
Surgical and medical procedures
Bladder calculus removal
|
0.17%
1/598
|
0.00%
0/590
|
|
Vascular disorders
Circulatory collapse
|
0.17%
1/598
|
0.00%
0/590
|
|
Vascular disorders
Haematoma
|
0.00%
0/598
|
0.17%
1/590
|
|
Vascular disorders
Hypertension
|
0.33%
2/598
|
0.17%
1/590
|
|
Vascular disorders
Thrombophlebitis
|
0.17%
1/598
|
0.00%
0/590
|
|
Vascular disorders
Peripheral arterial occlusive disease
|
0.00%
0/598
|
0.17%
1/590
|
Other adverse events
| Measure |
Rivaroxaban (Xarelto, BAY59-7939)
n=598 participants at risk
Participants were to receive rivaroxaban 20 mg oral tablet once daily
|
Placebo
n=590 participants at risk
Participants were to receive matching placebo oral tablet once daily
|
|---|---|---|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
5.2%
31/598
|
6.4%
38/590
|
|
Infections and infestations
Nasopharyngitis
|
5.5%
33/598
|
5.4%
32/590
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60