Trial Outcomes & Findings for Regulation of Coagulation in Orthopedic Surgery to Prevent Deep Vein Thromboembolism (DVT) and Pulmonary Embolism (PE). A Study of BAY59-7939 in the Prevention of Venous Thrombo Embolism (VTE) in Subjects Undergoing Elective Total Knee Replacement. (NCT NCT00362232)
NCT ID: NCT00362232
Last Updated: 2014-11-04
Results Overview
Blinded, adjudicated assessment of bilateral venography, clinical signs of deep vein thrombosis (DVT) and pulmonary embolism (PE), ultrasound, clinical chemistry and coagulation factors, autopsy report, electrocardiogram (ECG), pulmonary angiography, perfusion/ventilation lung scintigraphy, chest radiography, computed tomography
COMPLETED
PHASE3
3148 participants
Up to 16 days after surgery
2014-11-04
Participant Flow
The recruitment period was from 16 Jun 2006 to 31 Jan 2008.
3418 subjects were screened; 270 subjects were screening failures and were not randomized; 3148 subjects were randomized; 114 subjects did not receive medication; 3034 subjects received medication and were included in the safety population
Participant milestones
| Measure |
Rivaroxaban 10 mg Once Daily (OD) (Xarelto, BAY59-7939)
Rivaroxaban (Xarelto, BAY59-7939) 10 mg tablet administered once daily (od) in the evening plus placebo syringes of enoxaparin twice a day (bid) administered once in the morning and once in the evening.
|
Enoxaparin 30 mg Twice a Day (Bid)
Placebo tablet of rivaroxaban administered once daily in the evening plus syringes of enoxaparin active substance 30 mg twice a day administered once in the morning and once in the evening.
|
|---|---|---|
|
Treatment (12 +/- 2 Days)
STARTED
|
1584
|
1564
|
|
Treatment (12 +/- 2 Days)
Received Treatment
|
1526
|
1508
|
|
Treatment (12 +/- 2 Days)
COMPLETED
|
1425
|
1413
|
|
Treatment (12 +/- 2 Days)
NOT COMPLETED
|
159
|
151
|
|
Follow-up (30 (+ 5) Days)
STARTED
|
1471
|
1455
|
|
Follow-up (30 (+ 5) Days)
COMPLETED
|
1433
|
1416
|
|
Follow-up (30 (+ 5) Days)
NOT COMPLETED
|
38
|
39
|
Reasons for withdrawal
| Measure |
Rivaroxaban 10 mg Once Daily (OD) (Xarelto, BAY59-7939)
Rivaroxaban (Xarelto, BAY59-7939) 10 mg tablet administered once daily (od) in the evening plus placebo syringes of enoxaparin twice a day (bid) administered once in the morning and once in the evening.
|
Enoxaparin 30 mg Twice a Day (Bid)
Placebo tablet of rivaroxaban administered once daily in the evening plus syringes of enoxaparin active substance 30 mg twice a day administered once in the morning and once in the evening.
|
|---|---|---|
|
Treatment (12 +/- 2 Days)
Adverse Event
|
62
|
56
|
|
Treatment (12 +/- 2 Days)
Death
|
1
|
3
|
|
Treatment (12 +/- 2 Days)
Lost to Follow-up
|
3
|
1
|
|
Treatment (12 +/- 2 Days)
Physician Decision
|
2
|
5
|
|
Treatment (12 +/- 2 Days)
Protocol Violation
|
22
|
21
|
|
Treatment (12 +/- 2 Days)
Withdrawal by Subject
|
49
|
47
|
|
Treatment (12 +/- 2 Days)
Noncompliance to Study Drug
|
9
|
0
|
|
Treatment (12 +/- 2 Days)
Technical Problems
|
1
|
0
|
|
Treatment (12 +/- 2 Days)
Clinical Endpoint Reached
|
10
|
18
|
|
Follow-up (30 (+ 5) Days)
Adverse Event
|
2
|
3
|
|
Follow-up (30 (+ 5) Days)
Death
|
1
|
1
|
|
Follow-up (30 (+ 5) Days)
Lost to Follow-up
|
27
|
28
|
|
Follow-up (30 (+ 5) Days)
Withdrawal by Subject
|
8
|
7
|
Baseline Characteristics
Regulation of Coagulation in Orthopedic Surgery to Prevent Deep Vein Thromboembolism (DVT) and Pulmonary Embolism (PE). A Study of BAY59-7939 in the Prevention of Venous Thrombo Embolism (VTE) in Subjects Undergoing Elective Total Knee Replacement.
Baseline characteristics by cohort
| Measure |
Rivaroxaban 10 mg Once Daily (OD) (Xarelto, BAY59-7939)
n=1526 Participants
Rivaroxaban (Xarelto, BAY59-7939) 10 mg tablet administered once daily (od) in the evening plus placebo syringes of enoxaparin twice a day (bid) administered once in the morning and once in the evening.
|
Enoxaparin 30 mg Twice a Day (Bid)
n=1508 Participants
Placebo tablet of rivaroxaban administered once daily in the evening plus syringes of enoxaparin active substance 30 mg twice a day administered once in the morning and once in the evening.
|
Total
n=3034 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
64.4 years
STANDARD_DEVIATION 9.7 • n=99 Participants
|
64.7 years
STANDARD_DEVIATION 9.7 • n=107 Participants
|
64.5 years
STANDARD_DEVIATION 9.7 • n=206 Participants
|
|
Sex: Female, Male
Female
|
1007 Participants
n=99 Participants
|
967 Participants
n=107 Participants
|
1974 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
519 Participants
n=99 Participants
|
541 Participants
n=107 Participants
|
1060 Participants
n=206 Participants
|
|
Race/Ethnicity, Customized
White
|
1008 participants
n=99 Participants
|
1032 participants
n=107 Participants
|
2040 participants
n=206 Participants
|
|
Race/Ethnicity, Customized
Black
|
88 participants
n=99 Participants
|
65 participants
n=107 Participants
|
153 participants
n=206 Participants
|
|
Race/Ethnicity, Customized
Asian
|
289 participants
n=99 Participants
|
289 participants
n=107 Participants
|
578 participants
n=206 Participants
|
|
Race/Ethnicity, Customized
American Indian
|
1 participants
n=99 Participants
|
4 participants
n=107 Participants
|
5 participants
n=206 Participants
|
|
Race/Ethnicity, Customized
Hispanic
|
137 participants
n=99 Participants
|
116 participants
n=107 Participants
|
253 participants
n=206 Participants
|
|
Race/Ethnicity, Customized
Uncodable
|
2 participants
n=99 Participants
|
2 participants
n=107 Participants
|
4 participants
n=206 Participants
|
|
Weight
=< 50 kg
|
22 participants
n=99 Participants
|
28 participants
n=107 Participants
|
50 participants
n=206 Participants
|
|
Weight
> 50 - 70 kg
|
367 participants
n=99 Participants
|
358 participants
n=107 Participants
|
725 participants
n=206 Participants
|
|
Weight
> 70 - 90 kg
|
629 participants
n=99 Participants
|
616 participants
n=107 Participants
|
1245 participants
n=206 Participants
|
|
Weight
> 90 - 110 kg
|
322 participants
n=99 Participants
|
343 participants
n=107 Participants
|
665 participants
n=206 Participants
|
|
Weight
> 110 kg
|
185 participants
n=99 Participants
|
162 participants
n=107 Participants
|
347 participants
n=206 Participants
|
PRIMARY outcome
Timeframe: Up to 16 days after surgeryPopulation: The primary efficacy analysis was based on the per protocol (PP) population and included subjects who were valid for the modified intent to treat (MITT) population, had an adequate assessment of thromboembolism that, in case of a positive finding, was done not later than 36 hours after stop of study drug, and had no major protocol deviations.
Blinded, adjudicated assessment of bilateral venography, clinical signs of deep vein thrombosis (DVT) and pulmonary embolism (PE), ultrasound, clinical chemistry and coagulation factors, autopsy report, electrocardiogram (ECG), pulmonary angiography, perfusion/ventilation lung scintigraphy, chest radiography, computed tomography
Outcome measures
| Measure |
Rivaroxaban 10 mg Once Daily (OD) (Xarelto, BAY59-7939)
n=864 Participants
Rivaroxaban (Xarelto, BAY59-7939) 10 mg tablet administered once daily (od) in the evening plus placebo syringes of enoxaparin twice a day (bid) administered once in the morning and once in the evening.
|
Enoxaparin 30 mg Twice a Day (Bid)
n=878 Participants
Placebo tablet of rivaroxaban administered once daily in the evening plus syringes of enoxaparin active substance 30 mg twice a day administered once in the morning and once in the evening.
|
|---|---|---|
|
Composite Endpoint of Total Venous Thrombo Embolism (VTE) i.e.: Any Deep Vein Thromboembolism (DVT) (Proximal and/or Distal), Non Fatal Pulmonary Embolism (PE), Death of All Causes Per Protocol Population
|
6.71 Percentage of participants
|
9.34 Percentage of participants
|
PRIMARY outcome
Timeframe: Up to 16 days after surgeryPopulation: A subject was considered valid for the MITT analysis if the subject was valid for the safety analysis, had undergone the appropriate surgery, and had an adequate assessment of thromboembolism
Blinded, adjudicated assessment of bilateral venography, clinical signs of deep vein thrombosis (DVT) and pulmonary embolism (PE), ultrasound, clinical chemistry and coagulation factors, autopsy report, electrocardiogram (ECG), pulmonary angiography, perfusion/ventilation lung scintigraphy, chest radiography, computed tomography
Outcome measures
| Measure |
Rivaroxaban 10 mg Once Daily (OD) (Xarelto, BAY59-7939)
n=965 Participants
Rivaroxaban (Xarelto, BAY59-7939) 10 mg tablet administered once daily (od) in the evening plus placebo syringes of enoxaparin twice a day (bid) administered once in the morning and once in the evening.
|
Enoxaparin 30 mg Twice a Day (Bid)
n=959 Participants
Placebo tablet of rivaroxaban administered once daily in the evening plus syringes of enoxaparin active substance 30 mg twice a day administered once in the morning and once in the evening.
|
|---|---|---|
|
Composite Endpoint of Total VTE i.e.: Any DVT (Proximal and/or Distal), Non Fatal PE, Death of All Causes Per Modified Intent to Treat Population.
|
6.94 Percentage of participants
|
10.11 Percentage of participants
|
SECONDARY outcome
Timeframe: Up to 16 days after surgeryPopulation: The PP population included subjects who were valid for the modified intent to treat (MITT) population, had an adequate assessment of thromboembolism that, in case of a positive finding, was done not later than 36 hours after stop of study drug, and had no major protocol deviations.
Blinded, adjudicated assessment of bilateral venography, clinical signs of deep vein thrombosis (DVT) and pulmonary embolism (PE), ultrasound, clinical chemistry and coagulation factors, autopsy report, electrocardiogram (ECG), pulmonary angiography, perfusion/ventilation lung scintigraphy, chest radiography, computed tomography
Outcome measures
| Measure |
Rivaroxaban 10 mg Once Daily (OD) (Xarelto, BAY59-7939)
n=1011 Participants
Rivaroxaban (Xarelto, BAY59-7939) 10 mg tablet administered once daily (od) in the evening plus placebo syringes of enoxaparin twice a day (bid) administered once in the morning and once in the evening.
|
Enoxaparin 30 mg Twice a Day (Bid)
n=1020 Participants
Placebo tablet of rivaroxaban administered once daily in the evening plus syringes of enoxaparin active substance 30 mg twice a day administered once in the morning and once in the evening.
|
|---|---|---|
|
Incidence of the Composite Endpoint Comprising Proximal DVT, Non-fatal PE and VTE- Related Death (Major VTE) Per Protocol Population of Major VTE
|
1.09 percentage of participants
|
1.47 percentage of participants
|
SECONDARY outcome
Timeframe: Up to 16 days after surgeryPopulation: A subject was considered valid for the MITT analysis if the subject was valid for the safety analysis, had undergone the appropriate surgery, and had an adequate assessment of thromboembolism
Blinded, adjudicated assessment of bilateral venography, clinical signs of deep vein thrombosis (DVT) and pulmonary embolism (PE), ultrasound, clinical chemistry and coagulation factors, autopsy report, electrocardiogram (ECG), pulmonary angiography, perfusion/ventilation lung scintigraphy, chest radiography, computed tomography
Outcome measures
| Measure |
Rivaroxaban 10 mg Once Daily (OD) (Xarelto, BAY59-7939)
n=1122 Participants
Rivaroxaban (Xarelto, BAY59-7939) 10 mg tablet administered once daily (od) in the evening plus placebo syringes of enoxaparin twice a day (bid) administered once in the morning and once in the evening.
|
Enoxaparin 30 mg Twice a Day (Bid)
n=1112 Participants
Placebo tablet of rivaroxaban administered once daily in the evening plus syringes of enoxaparin active substance 30 mg twice a day administered once in the morning and once in the evening.
|
|---|---|---|
|
Incidence of the Composite Endpoint Comprising Proximal DVT, Non-fatal PE and VTE- Related Death (Major VTE) Per Modified Intent to Treat Population of Major VTE.
|
1.16 percentage of participants
|
1.98 percentage of participants
|
SECONDARY outcome
Timeframe: Up to 16 days after surgeryPopulation: The PP population included subjects who were valid for the modified intent to treat (MITT) population, had an adequate assessment of thromboembolism that, in case of a positive finding, was done not later than 36 hours after stop of study drug, and had no major protocol deviations
Blinded, adjudicated assessment of bilateral venography, clinical signs of DVT and PE, ultrasound, clinical chemistry and coagulation factors, autopsy report, electrocardiogram (ECG), pulmonary angiography, perfusion/ventilation lung scintigraphy, chest radiography, computed tomography
Outcome measures
| Measure |
Rivaroxaban 10 mg Once Daily (OD) (Xarelto, BAY59-7939)
n=864 Participants
Rivaroxaban (Xarelto, BAY59-7939) 10 mg tablet administered once daily (od) in the evening plus placebo syringes of enoxaparin twice a day (bid) administered once in the morning and once in the evening.
|
Enoxaparin 30 mg Twice a Day (Bid)
n=878 Participants
Placebo tablet of rivaroxaban administered once daily in the evening plus syringes of enoxaparin active substance 30 mg twice a day administered once in the morning and once in the evening.
|
|---|---|---|
|
Incidence of Symptomatic VTE (DVT, PE) Per Protocol Population.
|
1.04 percentage of participants
|
1.48 percentage of participants
|
SECONDARY outcome
Timeframe: Up to 16 days after surgeryPopulation: A subject was considered valid for the MITT analysis if the subject was valid for the safety analysis, had undergone the appropriate surgery, and had an adequate assessment of thromboembolism
Blinded, adjudicated assessment of bilateral venography, clinical signs of DVT and PE, ultrasound, clinical chemistry and coagulation factors, autopsy report, electrocardiogram (ECG), pulmonary angiography, perfusion/ventilation lung scintigraphy, chest radiography, computed tomography
Outcome measures
| Measure |
Rivaroxaban 10 mg Once Daily (OD) (Xarelto, BAY59-7939)
n=965 Participants
Rivaroxaban (Xarelto, BAY59-7939) 10 mg tablet administered once daily (od) in the evening plus placebo syringes of enoxaparin twice a day (bid) administered once in the morning and once in the evening.
|
Enoxaparin 30 mg Twice a Day (Bid)
n=959 Participants
Placebo tablet of rivaroxaban administered once daily in the evening plus syringes of enoxaparin active substance 30 mg twice a day administered once in the morning and once in the evening.
|
|---|---|---|
|
Incidence of Symptomatic VTE (DVT, PE) Per Modified Intent to Treat Population.
|
1.14 percentage of participants
|
1.88 percentage of participants
|
SECONDARY outcome
Timeframe: Up to 16 days after surgeryPopulation: The PP population included subjects who were valid for the modified intent to treat (MITT) population, had an adequate assessment of thromboembolism that, in case of a positive finding, was done not later than 36 hours after stop of study drug, and had no major protocol deviations
Blinded, adjudicated assessment of bilateral venography, clinical signs of DVT and PE, ultrasound, clinical chemistry and coagulation factors, autopsy report, electrocardiogram (ECG), pulmonary angiography, perfusion/ventilation lung scintigraphy, chest radiography, computed tomography
Outcome measures
| Measure |
Rivaroxaban 10 mg Once Daily (OD) (Xarelto, BAY59-7939)
n=864 Participants
Rivaroxaban (Xarelto, BAY59-7939) 10 mg tablet administered once daily (od) in the evening plus placebo syringes of enoxaparin twice a day (bid) administered once in the morning and once in the evening.
|
Enoxaparin 30 mg Twice a Day (Bid)
n=878 Participants
Placebo tablet of rivaroxaban administered once daily in the evening plus syringes of enoxaparin active substance 30 mg twice a day administered once in the morning and once in the evening.
|
|---|---|---|
|
Incidence of DVT (Proximal, Distal) Per Protocol Population.
|
6.37 percentage of participants
|
8.66 percentage of participants
|
SECONDARY outcome
Timeframe: Up to 16 days after surgeryPopulation: A subject was considered valid for the MITT analysis if the subject was valid for the safety analysis, had undergone the appropriate surgery, and had an adequate assessment of thromboembolism
Blinded, adjudicated assessment of bilateral venography, clinical signs of DVT and PE, ultrasound, clinical chemistry and coagulation factors, autopsy report, electrocardiogram (ECG), pulmonary angiography, perfusion/ventilation lung scintigraphy, chest radiography, computed tomography
Outcome measures
| Measure |
Rivaroxaban 10 mg Once Daily (OD) (Xarelto, BAY59-7939)
n=965 Participants
Rivaroxaban (Xarelto, BAY59-7939) 10 mg tablet administered once daily (od) in the evening plus placebo syringes of enoxaparin twice a day (bid) administered once in the morning and once in the evening.
|
Enoxaparin 30 mg Twice a Day (Bid)
n=959 Participants
Placebo tablet of rivaroxaban administered once daily in the evening plus syringes of enoxaparin active substance 30 mg twice a day administered once in the morning and once in the evening.
|
|---|---|---|
|
Incidence of DVT (Proximal, Distal) Per Modified Intent to Treat Population.
|
6.32 percentage of participants
|
8.97 percentage of participants
|
SECONDARY outcome
Timeframe: Up to 47 days after surgeryPopulation: The PP population included subjects who were valid for the modified intent to treat (MITT) population, had an adequate assessment of thromboembolism that, in case of a positive finding, was done not later than 36 hours after stop of study drug, and had no major protocol deviations
Blinded, adjudicated assessment of bilateral venography, clinical signs of DVT and PE, ultrasound, clinical chemistry and coagulation factors, autopsy report, electrocardiogram (ECG), pulmonary angiography, perfusion/ventilation lung scintigraphy, chest radiography, computed tomography
Outcome measures
| Measure |
Rivaroxaban 10 mg Once Daily (OD) (Xarelto, BAY59-7939)
n=864 Participants
Rivaroxaban (Xarelto, BAY59-7939) 10 mg tablet administered once daily (od) in the evening plus placebo syringes of enoxaparin twice a day (bid) administered once in the morning and once in the evening.
|
Enoxaparin 30 mg Twice a Day (Bid)
n=878 Participants
Placebo tablet of rivaroxaban administered once daily in the evening plus syringes of enoxaparin active substance 30 mg twice a day administered once in the morning and once in the evening.
|
|---|---|---|
|
Incidence of Symptomatic VTE During Follow-up Per Protocol Population.
|
0.35 percentage of participants
|
0.11 percentage of participants
|
SECONDARY outcome
Timeframe: Up to 47 days after surgeryPopulation: A subject was considered valid for the MITT analysis if the subject was valid for the safety analysis, had undergone the appropriate surgery, and had an adequate assessment of thromboembolism
Blinded, adjudicated assessment of bilateral venography, clinical signs of DVT and PE, ultrasound, clinical chemistry and coagulation factors, autopsy report, electrocardiogram (ECG), pulmonary angiography, perfusion/ventilation lung scintigraphy, chest radiography, computed tomography
Outcome measures
| Measure |
Rivaroxaban 10 mg Once Daily (OD) (Xarelto, BAY59-7939)
n=965 Participants
Rivaroxaban (Xarelto, BAY59-7939) 10 mg tablet administered once daily (od) in the evening plus placebo syringes of enoxaparin twice a day (bid) administered once in the morning and once in the evening.
|
Enoxaparin 30 mg Twice a Day (Bid)
n=959 Participants
Placebo tablet of rivaroxaban administered once daily in the evening plus syringes of enoxaparin active substance 30 mg twice a day administered once in the morning and once in the evening.
|
|---|---|---|
|
Incidence of Symptomatic VTE During Follow-up Per Modified Intent to Treat Population.
|
0.31 percentage of participants
|
0.21 percentage of participants
|
SECONDARY outcome
Timeframe: Up to 47 days after surgeryPopulation: The net clinical benefit population comprised all subjects either valid for MITT analysis of major VTE or who showed treatment-emergent major bleeding.
Blinded, adjudicated assessment of bilateral venography, clinical signs of DVT and PE, ultrasound, clinical chemistry and coagulation factors, autopsy report, electrocardiogram (ECG), pulmonary angiography, perfusion/ventilation lung scintigraphy, chest radiography, computed tomography, anesthesia and surgery reports, number of transfusions
Outcome measures
| Measure |
Rivaroxaban 10 mg Once Daily (OD) (Xarelto, BAY59-7939)
n=1130 Participants
Rivaroxaban (Xarelto, BAY59-7939) 10 mg tablet administered once daily (od) in the evening plus placebo syringes of enoxaparin twice a day (bid) administered once in the morning and once in the evening.
|
Enoxaparin 30 mg Twice a Day (Bid)
n=1114 Participants
Placebo tablet of rivaroxaban administered once daily in the evening plus syringes of enoxaparin active substance 30 mg twice a day administered once in the morning and once in the evening.
|
|---|---|---|
|
The Composite Endpoint Comprising Major VTE and Treatment-emergent Major Bleeding Per Subjects Valid for Analysis of Net Clinical Benefit
|
2.04 percentage of participants
|
2.33 percentage of participants
|
SECONDARY outcome
Timeframe: Up to 16 days after surgeryPopulation: The PP population included subjects who were valid for the modified intent to treat (MITT) population, had an adequate assessment of thromboembolism that, in case of a positive finding, was done not later than 36 hours after stop of study drug, and had no major protocol deviations
Blinded, adjudicated assessment of bilateral venography, clinical signs of DVT and PE, ultrasound, clinical chemistry and coagulation factors, autopsy report, electrocardiogram (ECG), pulmonary angiography, perfusion/ventilation lung scintigraphy, chest radiography, computed tomography
Outcome measures
| Measure |
Rivaroxaban 10 mg Once Daily (OD) (Xarelto, BAY59-7939)
n=864 Participants
Rivaroxaban (Xarelto, BAY59-7939) 10 mg tablet administered once daily (od) in the evening plus placebo syringes of enoxaparin twice a day (bid) administered once in the morning and once in the evening.
|
Enoxaparin 30 mg Twice a Day (Bid)
n=878 Participants
Placebo tablet of rivaroxaban administered once daily in the evening plus syringes of enoxaparin active substance 30 mg twice a day administered once in the morning and once in the evening.
|
|---|---|---|
|
Incidence of the Composite Endpoint That Results From the Primary Endpoint by Substituting VTE Related Death for All Death Per Protocol Population.
|
6.71 percentage of participants
|
9.11 percentage of participants
|
SECONDARY outcome
Timeframe: Up to 16 days after surgeryPopulation: A subject was considered valid for the MITT analysis if the subject was valid for the safety analysis, had undergone the appropriate surgery, and had an adequate assessment of thromboembolism
Blinded, adjudicated assessment of bilateral venography, clinical signs of DVT and PE, ultrasound, clinical chemistry and coagulation factors, autopsy report, electrocardiogram (ECG), pulmonary angiography, perfusion/ventilation lung scintigraphy, chest radiography, computed tomography
Outcome measures
| Measure |
Rivaroxaban 10 mg Once Daily (OD) (Xarelto, BAY59-7939)
n=965 Participants
Rivaroxaban (Xarelto, BAY59-7939) 10 mg tablet administered once daily (od) in the evening plus placebo syringes of enoxaparin twice a day (bid) administered once in the morning and once in the evening.
|
Enoxaparin 30 mg Twice a Day (Bid)
n=959 Participants
Placebo tablet of rivaroxaban administered once daily in the evening plus syringes of enoxaparin active substance 30 mg twice a day administered once in the morning and once in the evening.
|
|---|---|---|
|
Incidence of the Composite Endpoint That Results From the Primary Endpoint by Substituting VTE Related Death for All Death Per Modified Intent to Treat Population.
|
6.84 percentage of participants
|
9.80 percentage of participants
|
SECONDARY outcome
Timeframe: Up to 16 days after surgeryPopulation: The PP population included subjects who were valid for the modified intent to treat (MITT) population, had an adequate assessment of thromboembolism that, in case of a positive finding, was done not later than 36 hours after stop of study drug, and had no major protocol deviations
Blinded, adjudicated assessment of bilateral venography, clinical signs of DVT and PE, ultrasound, clinical chemistry and coagulation factors, autopsy report, electrocardiogram (ECG), pulmonary angiography, perfusion/ventilation lung scintigraphy, chest radiography, computed tomography
Outcome measures
| Measure |
Rivaroxaban 10 mg Once Daily (OD) (Xarelto, BAY59-7939)
n=1011 Participants
Rivaroxaban (Xarelto, BAY59-7939) 10 mg tablet administered once daily (od) in the evening plus placebo syringes of enoxaparin twice a day (bid) administered once in the morning and once in the evening.
|
Enoxaparin 30 mg Twice a Day (Bid)
n=1020 Participants
Placebo tablet of rivaroxaban administered once daily in the evening plus syringes of enoxaparin active substance 30 mg twice a day administered once in the morning and once in the evening.
|
|---|---|---|
|
Incidence of the Composite Endpoint That Results From Major VTE by Substituting All Cause Mortality for VTE-related Death Per Protocol of Major VTE Population.
|
1.09 percentage of participants
|
1.67 percentage of participants
|
SECONDARY outcome
Timeframe: Up to 16 days after surgeryPopulation: A subject was considered valid for the MITT analysis if the subject was valid for the safety analysis, had undergone the appropriate surgery, and had an adequate assessment of thromboembolism
Blinded, adjudicated assessment of bilateral venography, clinical signs of DVT and PE, ultrasound, clinical chemistry and coagulation factors, autopsy report, electrocardiogram (ECG), pulmonary angiography, perfusion/ventilation lung scintigraphy, chest radiography, computed tomography
Outcome measures
| Measure |
Rivaroxaban 10 mg Once Daily (OD) (Xarelto, BAY59-7939)
n=1122 Participants
Rivaroxaban (Xarelto, BAY59-7939) 10 mg tablet administered once daily (od) in the evening plus placebo syringes of enoxaparin twice a day (bid) administered once in the morning and once in the evening.
|
Enoxaparin 30 mg Twice a Day (Bid)
n=1112 Participants
Placebo tablet of rivaroxaban administered once daily in the evening plus syringes of enoxaparin active substance 30 mg twice a day administered once in the morning and once in the evening.
|
|---|---|---|
|
Incidence of the Composite Endpoint That Results From Major VTE by Substituting All Cause Mortality for VTE-related Death Per Modified Intent to Treat of Major VTE Population.
|
1.25 percentage of participants
|
2.25 percentage of participants
|
SECONDARY outcome
Timeframe: from start of double-blind study medication to last dose of double-blind study medication plus two days. The average duration of double-blind treatment was 12 days in each treatment group (safety population).Population: The safety population comprised those subjects who received at least 1 dose of study drug.
Blinded, adjudicated assessments of all available information (eg, anesthesia and surgery reports, laboratory results, number of transfusions, autopsy report)
Outcome measures
| Measure |
Rivaroxaban 10 mg Once Daily (OD) (Xarelto, BAY59-7939)
n=1526 Participants
Rivaroxaban (Xarelto, BAY59-7939) 10 mg tablet administered once daily (od) in the evening plus placebo syringes of enoxaparin twice a day (bid) administered once in the morning and once in the evening.
|
Enoxaparin 30 mg Twice a Day (Bid)
n=1508 Participants
Placebo tablet of rivaroxaban administered once daily in the evening plus syringes of enoxaparin active substance 30 mg twice a day administered once in the morning and once in the evening.
|
|---|---|---|
|
Treatment-emergent Major Bleedings Per Safety Population.
|
0.66 percentage of participants
|
0.27 percentage of participants
|
Adverse Events
Rivaroxaban 10 mg Once Daily (OD) (Xarelto, BAY59-7939)
Enoxaparin 30 mg Twice a Day (Bid)
Serious adverse events
| Measure |
Rivaroxaban 10 mg Once Daily (OD) (Xarelto, BAY59-7939)
n=1526 participants at risk
Rivaroxaban (Xarelto, BAY59-7939) 10 mg tablet administered once daily (od) in the evening plus placebo syringes of enoxaparin twice a day (bid) administered once in the morning and once in the evening.
|
Enoxaparin 30 mg Twice a Day (Bid)
n=1508 participants at risk
Placebo tablet of rivaroxaban administered once daily in the evening plus syringes of enoxaparin active substance 30 mg twice a day administered once in the morning and once in the evening.
|
|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
0.13%
2/1526
|
0.20%
3/1508
|
|
Blood and lymphatic system disorders
Haemorrhagic anaemia
|
0.07%
1/1526
|
0.00%
0/1508
|
|
Blood and lymphatic system disorders
Leukopenia
|
0.00%
0/1526
|
0.07%
1/1508
|
|
Blood and lymphatic system disorders
Neutropenia
|
0.00%
0/1526
|
0.07%
1/1508
|
|
Blood and lymphatic system disorders
Thrombocythaemia
|
0.07%
1/1526
|
0.00%
0/1508
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
0.07%
1/1526
|
0.00%
0/1508
|
|
Cardiac disorders
Acute myocardial infarction
|
0.07%
1/1526
|
0.07%
1/1508
|
|
Cardiac disorders
Angina pectoris
|
0.13%
2/1526
|
0.07%
1/1508
|
|
Cardiac disorders
Atrial fibrillation
|
0.00%
0/1526
|
0.27%
4/1508
|
|
Cardiac disorders
Atrial tachycardia
|
0.00%
0/1526
|
0.07%
1/1508
|
|
Cardiac disorders
Atrioventricular block complete
|
0.07%
1/1526
|
0.00%
0/1508
|
|
Cardiac disorders
Bundle branch block left
|
0.07%
1/1526
|
0.00%
0/1508
|
|
Cardiac disorders
Cardiac arrest
|
0.07%
1/1526
|
0.13%
2/1508
|
|
Cardiac disorders
Cardiac failure congestive
|
0.13%
2/1526
|
0.13%
2/1508
|
|
Cardiac disorders
Cardio-respiratory arrest
|
0.07%
1/1526
|
0.00%
0/1508
|
|
Cardiac disorders
Myocardial infarction
|
0.07%
1/1526
|
0.40%
6/1508
|
|
Endocrine disorders
Adrenal haemorrhage
|
0.07%
1/1526
|
0.00%
0/1508
|
|
Gastrointestinal disorders
Abdominal pain
|
0.26%
4/1526
|
0.00%
0/1508
|
|
Gastrointestinal disorders
Abdominal pain lower
|
0.00%
0/1526
|
0.07%
1/1508
|
|
Gastrointestinal disorders
Colitis
|
0.00%
0/1526
|
0.07%
1/1508
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/1526
|
0.07%
1/1508
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/1526
|
0.07%
1/1508
|
|
Gastrointestinal disorders
Duodenitis haemorrhagic
|
0.07%
1/1526
|
0.00%
0/1508
|
|
Gastrointestinal disorders
Gastric haemorrhage
|
0.00%
0/1526
|
0.13%
2/1508
|
|
Gastrointestinal disorders
Gastritis
|
0.07%
1/1526
|
0.00%
0/1508
|
|
Gastrointestinal disorders
Gastritis erosive
|
0.07%
1/1526
|
0.00%
0/1508
|
|
Gastrointestinal disorders
Gastroduodenal haemorrhage
|
0.07%
1/1526
|
0.00%
0/1508
|
|
Gastrointestinal disorders
Gastrointestinal haemorrhage
|
0.07%
1/1526
|
0.07%
1/1508
|
|
Gastrointestinal disorders
Haematemesis
|
0.00%
0/1526
|
0.07%
1/1508
|
|
Gastrointestinal disorders
Haematochezia
|
0.07%
1/1526
|
0.00%
0/1508
|
|
Gastrointestinal disorders
Intestinal haemorrhage
|
0.00%
0/1526
|
0.07%
1/1508
|
|
Gastrointestinal disorders
Nausea
|
0.26%
4/1526
|
0.20%
3/1508
|
|
Gastrointestinal disorders
Oesophageal stenosis
|
0.07%
1/1526
|
0.00%
0/1508
|
|
Gastrointestinal disorders
Upper gastrointestinal haemorrhage
|
0.07%
1/1526
|
0.00%
0/1508
|
|
Gastrointestinal disorders
Vomiting
|
0.26%
4/1526
|
0.20%
3/1508
|
|
General disorders
Chest pain
|
0.20%
3/1526
|
0.40%
6/1508
|
|
General disorders
Death
|
0.07%
1/1526
|
0.00%
0/1508
|
|
General disorders
Generalised oedema
|
0.00%
0/1526
|
0.07%
1/1508
|
|
General disorders
Non-cardiac chest pain
|
0.00%
0/1526
|
0.07%
1/1508
|
|
General disorders
Oedema
|
0.07%
1/1526
|
0.07%
1/1508
|
|
General disorders
Oedema peripheral
|
0.07%
1/1526
|
0.27%
4/1508
|
|
General disorders
Pyrexia
|
0.07%
1/1526
|
0.13%
2/1508
|
|
Hepatobiliary disorders
Cholecystitis
|
0.00%
0/1526
|
0.07%
1/1508
|
|
Hepatobiliary disorders
Cholelithiasis
|
0.00%
0/1526
|
0.13%
2/1508
|
|
Hepatobiliary disorders
Hepatitis
|
0.00%
0/1526
|
0.07%
1/1508
|
|
Immune system disorders
Contrast media allergy
|
0.00%
0/1526
|
0.07%
1/1508
|
|
Immune system disorders
Drug hypersensitivity
|
0.07%
1/1526
|
0.00%
0/1508
|
|
Infections and infestations
Appendicitis
|
0.07%
1/1526
|
0.00%
0/1508
|
|
Infections and infestations
Arthritis infective
|
0.20%
3/1526
|
0.60%
9/1508
|
|
Infections and infestations
Cellulitis
|
0.26%
4/1526
|
0.27%
4/1508
|
|
Infections and infestations
Device related infection
|
0.00%
0/1526
|
0.07%
1/1508
|
|
Infections and infestations
Diverticulitis
|
0.20%
3/1526
|
0.00%
0/1508
|
|
Infections and infestations
Endocarditis bacterial
|
0.07%
1/1526
|
0.00%
0/1508
|
|
Infections and infestations
Gastroenteritis
|
0.07%
1/1526
|
0.07%
1/1508
|
|
Infections and infestations
Pneumonia
|
0.07%
1/1526
|
0.40%
6/1508
|
|
Infections and infestations
Post procedural infection
|
0.00%
0/1526
|
0.20%
3/1508
|
|
Infections and infestations
Postoperative wound infection
|
0.07%
1/1526
|
0.07%
1/1508
|
|
Infections and infestations
Sepsis
|
0.20%
3/1526
|
0.07%
1/1508
|
|
Infections and infestations
Septic shock
|
0.00%
0/1526
|
0.07%
1/1508
|
|
Infections and infestations
Staphylococcal infection
|
0.00%
0/1526
|
0.07%
1/1508
|
|
Infections and infestations
Urinary tract infection
|
0.13%
2/1526
|
0.07%
1/1508
|
|
Infections and infestations
Wound infection
|
0.13%
2/1526
|
0.07%
1/1508
|
|
Injury, poisoning and procedural complications
Allergic transfusion reaction
|
0.00%
0/1526
|
0.07%
1/1508
|
|
Injury, poisoning and procedural complications
Anaemia postoperative
|
0.13%
2/1526
|
0.13%
2/1508
|
|
Injury, poisoning and procedural complications
Contusion
|
0.00%
0/1526
|
0.07%
1/1508
|
|
Injury, poisoning and procedural complications
Device malfunction
|
0.00%
0/1526
|
0.07%
1/1508
|
|
Injury, poisoning and procedural complications
Incision site haemorrhage
|
0.13%
2/1526
|
0.00%
0/1508
|
|
Injury, poisoning and procedural complications
Operative haemorrhage
|
0.13%
2/1526
|
0.20%
3/1508
|
|
Injury, poisoning and procedural complications
Post procedural haematoma
|
0.07%
1/1526
|
0.00%
0/1508
|
|
Injury, poisoning and procedural complications
Post procedural haemorrhage
|
0.00%
0/1526
|
0.07%
1/1508
|
|
Injury, poisoning and procedural complications
Post procedural swelling
|
0.00%
0/1526
|
0.07%
1/1508
|
|
Injury, poisoning and procedural complications
Procedural pain
|
0.07%
1/1526
|
0.07%
1/1508
|
|
Injury, poisoning and procedural complications
Subdural haemorrhage
|
0.00%
0/1526
|
0.07%
1/1508
|
|
Injury, poisoning and procedural complications
Tendon rupture
|
0.07%
1/1526
|
0.00%
0/1508
|
|
Injury, poisoning and procedural complications
Thoracic vertebral fracture
|
0.00%
0/1526
|
0.07%
1/1508
|
|
Injury, poisoning and procedural complications
Transfusion reaction
|
0.07%
1/1526
|
0.00%
0/1508
|
|
Injury, poisoning and procedural complications
Wound dehiscence
|
0.07%
1/1526
|
0.07%
1/1508
|
|
Investigations
Alanine aminotransferase increased
|
0.00%
0/1526
|
0.20%
3/1508
|
|
Investigations
Aspartate aminotransferase increased
|
0.00%
0/1526
|
0.07%
1/1508
|
|
Investigations
Blood alkaline phosphatase increased
|
0.00%
0/1526
|
0.07%
1/1508
|
|
Investigations
Blood bilirubin increased
|
0.00%
0/1526
|
0.13%
2/1508
|
|
Investigations
Blood creatinine increased
|
0.07%
1/1526
|
0.00%
0/1508
|
|
Investigations
Body temperature increased
|
0.07%
1/1526
|
0.07%
1/1508
|
|
Investigations
Clostridium difficile toxin test positive
|
0.07%
1/1526
|
0.00%
0/1508
|
|
Investigations
Coagulation factor increased
|
0.00%
0/1526
|
0.07%
1/1508
|
|
Investigations
Gamma-glutamyltransferase increased
|
0.00%
0/1526
|
0.07%
1/1508
|
|
Investigations
Haematocrit decreased
|
0.00%
0/1526
|
0.07%
1/1508
|
|
Investigations
Haemoglobin decreased
|
0.07%
1/1526
|
0.00%
0/1508
|
|
Investigations
Hepatic enzyme increased
|
0.00%
0/1526
|
0.13%
2/1508
|
|
Investigations
International normalised ratio increased
|
0.00%
0/1526
|
0.07%
1/1508
|
|
Investigations
Liver function test abnormal
|
0.13%
2/1526
|
0.00%
0/1508
|
|
Investigations
Occult blood positive
|
0.00%
0/1526
|
0.07%
1/1508
|
|
Investigations
Oxygen saturation decreased
|
0.00%
0/1526
|
0.07%
1/1508
|
|
Investigations
Platelet count decreased
|
0.07%
1/1526
|
0.07%
1/1508
|
|
Metabolism and nutrition disorders
Dehydration
|
0.07%
1/1526
|
0.00%
0/1508
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
0.07%
1/1526
|
0.00%
0/1508
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
0.07%
1/1526
|
0.00%
0/1508
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
0.07%
1/1526
|
0.07%
1/1508
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.07%
1/1526
|
0.07%
1/1508
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/1526
|
0.07%
1/1508
|
|
Musculoskeletal and connective tissue disorders
Fluctuance
|
0.07%
1/1526
|
0.00%
0/1508
|
|
Musculoskeletal and connective tissue disorders
Haemarthrosis
|
0.07%
1/1526
|
0.00%
0/1508
|
|
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion
|
0.00%
0/1526
|
0.07%
1/1508
|
|
Musculoskeletal and connective tissue disorders
Joint swelling
|
0.07%
1/1526
|
0.00%
0/1508
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal stiffness
|
0.00%
0/1526
|
0.07%
1/1508
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.07%
1/1526
|
0.13%
2/1508
|
|
Musculoskeletal and connective tissue disorders
Soft tissue haemorrhage
|
0.00%
0/1526
|
0.07%
1/1508
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastatic neoplasm
|
0.00%
0/1526
|
0.07%
1/1508
|
|
Nervous system disorders
Cerebral infarction
|
0.07%
1/1526
|
0.00%
0/1508
|
|
Nervous system disorders
Cerebrovascular insufficiency
|
0.07%
1/1526
|
0.00%
0/1508
|
|
Nervous system disorders
Coma
|
0.00%
0/1526
|
0.07%
1/1508
|
|
Nervous system disorders
Convulsion
|
0.07%
1/1526
|
0.00%
0/1508
|
|
Nervous system disorders
Embolic stroke
|
0.07%
1/1526
|
0.00%
0/1508
|
|
Nervous system disorders
Encephalopathy
|
0.07%
1/1526
|
0.13%
2/1508
|
|
Nervous system disorders
Haemorrhagic stroke
|
0.07%
1/1526
|
0.00%
0/1508
|
|
Nervous system disorders
Ischaemic stroke
|
0.07%
1/1526
|
0.07%
1/1508
|
|
Nervous system disorders
Peroneal nerve palsy
|
0.07%
1/1526
|
0.00%
0/1508
|
|
Nervous system disorders
Somnolence
|
0.07%
1/1526
|
0.00%
0/1508
|
|
Nervous system disorders
Speech disorder
|
0.07%
1/1526
|
0.00%
0/1508
|
|
Psychiatric disorders
Confusional state
|
0.07%
1/1526
|
0.07%
1/1508
|
|
Psychiatric disorders
Delirium
|
0.13%
2/1526
|
0.00%
0/1508
|
|
Psychiatric disorders
Delirium tremens
|
0.00%
0/1526
|
0.07%
1/1508
|
|
Psychiatric disorders
Depression
|
0.07%
1/1526
|
0.00%
0/1508
|
|
Psychiatric disorders
Mental status changes
|
0.07%
1/1526
|
0.00%
0/1508
|
|
Psychiatric disorders
Panic attack
|
0.00%
0/1526
|
0.07%
1/1508
|
|
Renal and urinary disorders
Nephrolithiasis
|
0.00%
0/1526
|
0.07%
1/1508
|
|
Renal and urinary disorders
Obstructive uropathy
|
0.07%
1/1526
|
0.00%
0/1508
|
|
Renal and urinary disorders
Renal failure acute
|
0.33%
5/1526
|
0.27%
4/1508
|
|
Renal and urinary disorders
Renal failure chronic
|
0.00%
0/1526
|
0.07%
1/1508
|
|
Renal and urinary disorders
Renal impairment
|
0.07%
1/1526
|
0.00%
0/1508
|
|
Renal and urinary disorders
Urethral caruncle
|
0.07%
1/1526
|
0.00%
0/1508
|
|
Renal and urinary disorders
Urinary retention
|
0.07%
1/1526
|
0.00%
0/1508
|
|
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure
|
0.00%
0/1526
|
0.07%
1/1508
|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
|
0.07%
1/1526
|
0.00%
0/1508
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.07%
1/1526
|
0.27%
4/1508
|
|
Respiratory, thoracic and mediastinal disorders
Haemoptysis
|
0.07%
1/1526
|
0.00%
0/1508
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
0.07%
1/1526
|
0.13%
2/1508
|
|
Respiratory, thoracic and mediastinal disorders
Idiopathic pulmonary fibrosis
|
0.07%
1/1526
|
0.00%
0/1508
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonia aspiration
|
0.07%
1/1526
|
0.07%
1/1508
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
0.07%
1/1526
|
0.07%
1/1508
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
0.59%
9/1526
|
0.73%
11/1508
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary hypertension
|
0.00%
0/1526
|
0.07%
1/1508
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary oedema
|
0.07%
1/1526
|
0.13%
2/1508
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory depression
|
0.13%
2/1526
|
0.00%
0/1508
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory distress
|
0.07%
1/1526
|
0.00%
0/1508
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
0.13%
2/1526
|
0.07%
1/1508
|
|
Skin and subcutaneous tissue disorders
Blister
|
0.00%
0/1526
|
0.07%
1/1508
|
|
Vascular disorders
Arterial thrombosis limb
|
0.00%
0/1526
|
0.07%
1/1508
|
|
Vascular disorders
Deep vein thrombosis
|
0.85%
13/1526
|
1.5%
22/1508
|
|
Vascular disorders
Embolism venous
|
0.00%
0/1526
|
0.07%
1/1508
|
|
Vascular disorders
Haematoma
|
0.20%
3/1526
|
0.20%
3/1508
|
|
Vascular disorders
Haemorrhage
|
0.20%
3/1526
|
0.00%
0/1508
|
|
Vascular disorders
Hypertensive crisis
|
0.07%
1/1526
|
0.00%
0/1508
|
|
Vascular disorders
Hypotension
|
0.00%
0/1526
|
0.07%
1/1508
|
|
Vascular disorders
Hypovolaemic shock
|
0.00%
0/1526
|
0.07%
1/1508
|
|
Vascular disorders
Thrombophlebitis superficial
|
0.07%
1/1526
|
0.00%
0/1508
|
|
Vascular disorders
Wound haemorrhage
|
0.00%
0/1526
|
0.07%
1/1508
|
Other adverse events
| Measure |
Rivaroxaban 10 mg Once Daily (OD) (Xarelto, BAY59-7939)
n=1526 participants at risk
Rivaroxaban (Xarelto, BAY59-7939) 10 mg tablet administered once daily (od) in the evening plus placebo syringes of enoxaparin twice a day (bid) administered once in the morning and once in the evening.
|
Enoxaparin 30 mg Twice a Day (Bid)
n=1508 participants at risk
Placebo tablet of rivaroxaban administered once daily in the evening plus syringes of enoxaparin active substance 30 mg twice a day administered once in the morning and once in the evening.
|
|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
3.7%
57/1526
|
3.4%
51/1508
|
|
Blood and lymphatic system disorders
Thrombocythaemia
|
2.2%
33/1526
|
2.3%
35/1508
|
|
Cardiac disorders
Bradycardia
|
0.98%
15/1526
|
1.1%
16/1508
|
|
Cardiac disorders
Tachycardia
|
6.3%
96/1526
|
6.3%
95/1508
|
|
Gastrointestinal disorders
Abdominal pain
|
1.4%
21/1526
|
0.86%
13/1508
|
|
Gastrointestinal disorders
Abdominal pain upper
|
1.0%
16/1526
|
1.1%
16/1508
|
|
Gastrointestinal disorders
Constipation
|
16.9%
258/1526
|
17.6%
266/1508
|
|
Gastrointestinal disorders
Diarrhoea
|
4.0%
61/1526
|
3.6%
55/1508
|
|
Gastrointestinal disorders
Dyspepsia
|
2.8%
42/1526
|
3.1%
46/1508
|
|
Gastrointestinal disorders
Hyperchlorhydria
|
0.59%
9/1526
|
1.1%
17/1508
|
|
Gastrointestinal disorders
Nausea
|
17.8%
272/1526
|
18.7%
282/1508
|
|
Gastrointestinal disorders
Vomiting
|
10.3%
157/1526
|
8.7%
131/1508
|
|
General disorders
Asthenia
|
5.0%
77/1526
|
5.6%
84/1508
|
|
General disorders
Chest pain
|
1.0%
16/1526
|
1.6%
24/1508
|
|
General disorders
Chills
|
1.8%
28/1526
|
2.2%
33/1508
|
|
General disorders
Fatigue
|
5.2%
79/1526
|
5.2%
79/1508
|
|
General disorders
Oedema
|
2.8%
43/1526
|
2.5%
38/1508
|
|
General disorders
Oedema peripheral
|
15.4%
235/1526
|
17.0%
256/1508
|
|
General disorders
Pain
|
1.2%
19/1526
|
1.7%
25/1508
|
|
General disorders
Pyrexia
|
21.0%
320/1526
|
20.6%
310/1508
|
|
Infections and infestations
Urinary tract infection
|
2.6%
40/1526
|
2.6%
39/1508
|
|
Injury, poisoning and procedural complications
Anaemia postoperative
|
11.7%
178/1526
|
12.4%
187/1508
|
|
Injury, poisoning and procedural complications
Contusion
|
1.8%
27/1526
|
2.1%
31/1508
|
|
Injury, poisoning and procedural complications
Post procedural swelling
|
1.0%
16/1526
|
0.73%
11/1508
|
|
Injury, poisoning and procedural complications
Procedural nausea
|
1.7%
26/1526
|
1.5%
22/1508
|
|
Injury, poisoning and procedural complications
Procedural pain
|
11.3%
172/1526
|
12.3%
186/1508
|
|
Injury, poisoning and procedural complications
Wound secretion
|
1.2%
19/1526
|
0.99%
15/1508
|
|
Investigations
Alanine aminotransferase increased
|
1.6%
24/1526
|
3.0%
45/1508
|
|
Investigations
Aspartate aminotransferase increased
|
1.4%
22/1526
|
1.9%
28/1508
|
|
Investigations
Blood alkaline phosphatase increased
|
0.92%
14/1526
|
1.4%
21/1508
|
|
Investigations
Blood creatinine increased
|
1.1%
17/1526
|
1.2%
18/1508
|
|
Investigations
Blood lactate dehydrogenase increased
|
2.2%
33/1526
|
1.9%
29/1508
|
|
Investigations
Blood potassium decreased
|
1.2%
19/1526
|
1.6%
24/1508
|
|
Investigations
Body temperature increased
|
4.1%
63/1526
|
5.4%
81/1508
|
|
Investigations
Breath sounds abnormal
|
1.4%
22/1526
|
1.5%
22/1508
|
|
Investigations
Gamma-glutamyltransferase increased
|
2.6%
40/1526
|
3.4%
52/1508
|
|
Investigations
Haemoglobin decreased
|
2.9%
44/1526
|
2.2%
33/1508
|
|
Investigations
Lipase increased
|
1.0%
16/1526
|
1.1%
17/1508
|
|
Metabolism and nutrition disorders
Anorexia
|
1.2%
18/1526
|
1.9%
28/1508
|
|
Metabolism and nutrition disorders
Decreased appetite
|
1.0%
16/1526
|
1.3%
19/1508
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
2.7%
41/1526
|
3.5%
53/1508
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
3.1%
47/1526
|
4.4%
67/1508
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
1.0%
16/1526
|
1.4%
21/1508
|
|
Musculoskeletal and connective tissue disorders
Joint swelling
|
2.3%
35/1526
|
2.6%
39/1508
|
|
Musculoskeletal and connective tissue disorders
Joint warmth
|
1.4%
21/1526
|
1.2%
18/1508
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
6.3%
96/1526
|
5.8%
88/1508
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
8.6%
131/1526
|
7.9%
119/1508
|
|
Nervous system disorders
Dizziness
|
7.3%
111/1526
|
6.8%
102/1508
|
|
Nervous system disorders
Headache
|
3.2%
49/1526
|
3.1%
46/1508
|
|
Nervous system disorders
Hypoaesthesia
|
2.0%
30/1526
|
2.5%
38/1508
|
|
Nervous system disorders
Lethargy
|
1.0%
16/1526
|
0.86%
13/1508
|
|
Nervous system disorders
Somnolence
|
4.2%
64/1526
|
3.8%
58/1508
|
|
Psychiatric disorders
Anxiety
|
2.9%
44/1526
|
2.6%
39/1508
|
|
Psychiatric disorders
Confusional state
|
2.5%
38/1526
|
2.3%
35/1508
|
|
Psychiatric disorders
Insomnia
|
10.7%
163/1526
|
11.1%
168/1508
|
|
Renal and urinary disorders
Dysuria
|
1.2%
19/1526
|
0.80%
12/1508
|
|
Renal and urinary disorders
Pollakiuria
|
1.3%
20/1526
|
0.73%
11/1508
|
|
Renal and urinary disorders
Urinary retention
|
4.7%
72/1526
|
4.3%
65/1508
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
2.2%
33/1526
|
2.6%
39/1508
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
3.1%
47/1526
|
2.4%
36/1508
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
1.8%
27/1526
|
1.3%
19/1508
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
1.7%
26/1526
|
1.7%
26/1508
|
|
Respiratory, thoracic and mediastinal disorders
Pharyngolaryngeal pain
|
1.4%
22/1526
|
1.7%
26/1508
|
|
Respiratory, thoracic and mediastinal disorders
Wheezing
|
0.98%
15/1526
|
1.4%
21/1508
|
|
Skin and subcutaneous tissue disorders
Blister
|
2.4%
37/1526
|
1.7%
25/1508
|
|
Skin and subcutaneous tissue disorders
Ecchymosis
|
1.8%
28/1526
|
2.1%
31/1508
|
|
Skin and subcutaneous tissue disorders
Erythema
|
5.2%
79/1526
|
5.0%
75/1508
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
1.2%
18/1526
|
1.6%
24/1508
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
8.4%
128/1526
|
8.2%
123/1508
|
|
Skin and subcutaneous tissue disorders
Pruritus generalised
|
1.3%
20/1526
|
0.93%
14/1508
|
|
Skin and subcutaneous tissue disorders
Rash
|
2.4%
36/1526
|
2.7%
40/1508
|
|
Vascular disorders
Deep vein thrombosis
|
3.4%
52/1526
|
4.5%
68/1508
|
|
Vascular disorders
Hypertension
|
2.2%
34/1526
|
1.4%
21/1508
|
|
Vascular disorders
Hypotension
|
6.6%
100/1526
|
6.8%
102/1508
|
|
Vascular disorders
Thrombosis
|
1.6%
25/1526
|
1.5%
22/1508
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place