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Efficacy and Safety of Rivaroxaban for the Prevention of Stroke in Subjects With Non-Valvular Atrial Fibrillation

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ClinicalTrials.gov Identifier: NCT00494871
Recruitment Status : Completed
First Posted : July 2, 2007
Results First Posted : April 19, 2012
Last Update Posted : April 20, 2015
Sponsor:
Collaborator:
Janssen R&D, L.L.C.
Information provided by (Responsible Party):
Bayer

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Prevention
Condition Atrial Fibrillation
Interventions Drug: Rivaroxaban (Xarelto, BAY59-7939)
Drug: Warfarin
Drug: Rivaroxaban placebo
Drug: Warfarin placebo
Enrollment 1280
Recruitment Details The first participant entered the study on 08 Jun 2007, and the last participant completed the study on 19 Jan 2010. The study was conducted at 167 centers in Japan. 164 study centers enrolled at least 1 participant.
Pre-assignment Details In total, 1439 participants were screened for study eligibility; 159 participants were screening failures and were not randomized. Therefore, 1280 participants (640 in each group) were randomized.
Arm/Group Title Rivaroxaban (Xarelto, BAY59-7939) Warfarin
Hide Arm/Group Description Participants received once daily (OD) a rivaroxaban 15 mg tablet and a warfarin placebo tablet during the double-blind treatment period Participants received OD a warfarin potassium tablet and a rivaroxaban placebo tablet during the double-blind treatment period
Period Title: Double-blind (DB) Treatment Period
Started 640 640
Started Treatment 639 [1] 639 [1]
Completed 480 468
Not Completed 160 172
Reason Not Completed
Adverse Event             73             70
Withdrawal by Subject             26             35
Death             8             3
Physician Decision             4             13
Lost to Follow-up             4             1
Protocol Violation             9             9
Clinical Endpoint Reached             18             28
Non-compliant with Study Medication             3             1
Protocol Driven Decision Point             12             8
Site Closed by Investigator             1             2
Site Closed by Sponsor             1             1
Drop out before Treatment Start             1             1
[1]
Safety population
Period Title: Follow-up (FU) Period
Started 639 [1] 639 [1]
Entered FU and Valid for Safety 628 [2] 630 [2]
Completed 610 616
Not Completed 29 23
Reason Not Completed
Adverse Event             1             1
Death             13             12
Lost to Follow-up             6             2
Physician Decision             0             1
Protocol Violation             1             0
Withdrawal by Subject             5             5
Clinical Endpoint Reached             3             2
[1]
All treated participants were to enter FU period, whether or not they completed the DB period
[2]
Safety population
Arm/Group Title Rivaroxaban (Xarelto, BAY59-7939) Warfarin Total
Hide Arm/Group Description Participants received once daily (OD) a rivaroxaban 15 mg tablet and a warfarin placebo tablet during the double-blind treatment period Participants received OD a warfarin potassium tablet and a rivaroxaban placebo tablet during the double-blind treatment period Total of all reporting groups
Overall Number of Baseline Participants 640 640 1280
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 640 participants 640 participants 1280 participants
71.0  (8.3) 71.2  (7.9) 71.1  (8.1)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 640 participants 640 participants 1280 participants
Female
110
  17.2%
140
  21.9%
250
  19.5%
Male
530
  82.8%
500
  78.1%
1030
  80.5%
CL(CR) [creatinine clearance]  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 640 participants 640 participants 1280 participants
<50 mL/min 141 143 284
50 to <80 mL/min 329 329 658
≥80 mL/min 170 168 338
1.Primary Outcome
Title Event Rate of the Composite Endpoint of Adjudicated Major Bleeding or Adjudicated Non-major Clinically Relevant Bleeding
Hide Description Major bleeding: clinically overt bleeding (COB) associated with a fall in hemoglobin ≥2 g/dL, leading to transfusion ≥2 units of packed red blood cells or whole blood, occurring in a critical site or contributing to death. Non-major clinically relevant bleeding: COB that does not meet the definition of major bleeding, but requires medical intervention or unscheduled contact with the physician, (temporary) discontinuation of the study treatment, discomfort to the subject such as pain, or impairment of activities of daily life.
Time Frame Up to 2 days after the last dose
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The safety analysis population consisted of randomized participants who took at least one dose of study treatment (639 in each treatment group).
Arm/Group Title Rivaroxaban (Xarelto, BAY59-7939) Warfarin
Hide Arm/Group Description:
Participants received once daily (OD) a rivaroxaban 15 mg tablet and a warfarin placebo tablet during the double-blind treatment period
Participants received OD a warfarin potassium tablet and a rivaroxaban placebo tablet during the double-blind treatment period
Overall Number of Participants Analyzed 639 639
Measure Type: Number
Unit of Measure: Events per 100 patient-years
18.04 16.42
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rivaroxaban (Xarelto, BAY59-7939), Warfarin
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments Non-inferiority margin of 2.0
Statistical Test of Hypothesis P-Value 0.025
Comments [Not Specified]
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.11
Confidence Interval (2-Sided) 95%
0.87 to 1.42
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Event Rate of the Composite Endpoint of Adjudicated Stroke and Non-central Nervous System (CNS) Systemic Embolism
Hide Description This is the principal efficacy endpoint. Stroke included hemorrhagic, ischemic infarction and unknown. Arterial emboli in the following areas were "non-CNS systemic embolism”: peripheral arterial in the upper and lower extremities, renal, mesenteric, splenic, hepatic, ocular/retinal and others. Pulmonary embolism or myocardial infarction was excluded.
Time Frame Up to 2 days after the last dose
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The per-protocol analysis population consisted of randomized participants excluding those who had specific pre-defined major protocol deviations (637 in each treatment group).
Arm/Group Title Rivaroxaban (Xarelto, BAY59-7939) Warfarin
Hide Arm/Group Description:
Participants received once daily (OD) a rivaroxaban 15 mg tablet and a warfarin placebo tablet during the double-blind treatment period
Participants received OD a warfarin potassium tablet and a rivaroxaban placebo tablet during the double-blind treatment period
Overall Number of Participants Analyzed 637 637
Measure Type: Number
Unit of Measure: Events per 100 patient-years
1.26 2.61
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rivaroxaban (Xarelto, BAY59-7939), Warfarin
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.49
Confidence Interval (2-Sided) 95%
0.24 to 1.00
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Event Rate of the Composite Endpoint of Adjudicated Stroke, Non-CNS Systemic Embolism, and Vascular Death
Hide Description Stroke included hemorrhagic, ischemic infarction and unknown. Arterial emboli in the following areas were "non-CNS systemic embolism”: peripheral arterial in the upper and lower extremities, renal, mesenteric, splenic, hepatic, ocular/retinal and others. Pulmonary embolism or myocardial infarction was excluded. Any death that was not clearly non-vascular.
Time Frame Up to 2 days after the last dose
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The per-protocol analysis population consisted of randomized participants excluding those who had specific pre-defined major protocol deviations (637 in each treatment group).
Arm/Group Title Rivaroxaban (Xarelto, BAY59-7939) Warfarin
Hide Arm/Group Description:
Participants received once daily (OD) a rivaroxaban 15 mg tablet and a warfarin placebo tablet during the double-blind treatment period
Participants received OD a warfarin potassium tablet and a rivaroxaban placebo tablet during the double-blind treatment period
Overall Number of Participants Analyzed 637 637
Measure Type: Number
Unit of Measure: Events per 100 patient-years
1.83 2.85
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rivaroxaban (Xarelto, BAY59-7939), Warfarin
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.65
Confidence Interval (2-Sided) 95%
0.34 to 1.22
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Event Rate of the Composite Endpoint of Adjudicated Stroke, Non-CNS Systemic Embolism, Myocardial Infarction, and Vascular Death
Hide Description Stroke included hemorrhagic, ischemic infarction and unknown. Arterial emboli in the following areas were "non-CNS systemic embolism”: peripheral arterial in the upper and lower extremities, renal, mesenteric, splenic, hepatic, ocular/retinal and others. Pulmonary embolism or myocardial infarction was excluded. Myocardial infarction: assessed based on either cardiac biomarkers, new abnormal Q waves appeared on electrocardiogram for ≥2 leads, or autopsy confirmation. Any death that was not clearly non-vascular.
Time Frame Up to 2 days after the last dose
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The per-protocol analysis population consisted of randomized participants excluding those who had specific pre-defined major protocol deviations (637 in each treatment group).
Arm/Group Title Rivaroxaban (Xarelto, BAY59-7939) Warfarin
Hide Arm/Group Description:
Participants received once daily (OD) a rivaroxaban 15 mg tablet and a warfarin placebo tablet during the double-blind treatment period
Participants received OD a warfarin potassium tablet and a rivaroxaban placebo tablet during the double-blind treatment period
Overall Number of Participants Analyzed 637 637
Measure Type: Number
Unit of Measure: Events per 100 patient-years
2.18 2.97
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rivaroxaban (Xarelto, BAY59-7939), Warfarin
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.74
Confidence Interval (2-Sided) 95%
0.41 to 1.34
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Event Rate of Stroke
Hide Description All events were adjudicated and confirmed by a central independent committee blinded to treatment. Stroke included hemorrhagic (Stroke with local collections of intraparenchymal blood. Subarachnoid hemorrhage, subdural hemorrhage, and epidural hemorrhage were excluded.), ischemic infarction (Stroke without focal collection of intracranial blood) and unknown (No imaging data and anatomic findings were available.).
Time Frame Up to 2 days after the last dose
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The per-protocol analysis population consisted of randomized participants excluding those who had specific pre-defined major protocol deviations (637 in each treatment group).
Arm/Group Title Rivaroxaban (Xarelto, BAY59-7939) Warfarin
Hide Arm/Group Description:
Participants received once daily (OD) a rivaroxaban 15 mg tablet and a warfarin placebo tablet during the double-blind treatment period
Participants received OD a warfarin potassium tablet and a rivaroxaban placebo tablet during the double-blind treatment period
Overall Number of Participants Analyzed 637 637
Measure Type: Number
Unit of Measure: Events per 100 patient-years
1.15 2.49
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rivaroxaban (Xarelto, BAY59-7939), Warfarin
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.46
Confidence Interval (2-Sided) 95%
0.22 to 0.98
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Event Rate of Non-CNS Systemic Embolism
Hide Description All events were adjudicated and confirmed by a central independent committee blinded to treatment. Non-CNS systemic embolism was abrupt vascular insufficiency associated with clinical or radiological evidence of arterial occlusion in the absence of other likely mechanisms (such as trauma, atherosclerosis, and instrumentation). Arterial emboli in the following areas were "non-CNS systemic embolism”: peripheral arterial in the upper and lower extremities, renal, mesenteric, splenic, hepatic, ocular/retinal and others. Pulmonary embolism or myocardial infarction was excluded from this category.
Time Frame Up to 2 days after the last dose
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The per-protocol analysis population consisted of randomized participants excluding those who had specific pre-defined major protocol deviations (637 in each treatment group).
Arm/Group Title Rivaroxaban (Xarelto, BAY59-7939) Warfarin
Hide Arm/Group Description:
Participants received once daily (OD) a rivaroxaban 15 mg tablet and a warfarin placebo tablet during the double-blind treatment period
Participants received OD a warfarin potassium tablet and a rivaroxaban placebo tablet during the double-blind treatment period
Overall Number of Participants Analyzed 637 637
Measure Type: Number
Unit of Measure: Events per 100 patient-years
0.11 0.12
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rivaroxaban (Xarelto, BAY59-7939), Warfarin
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.99
Confidence Interval (2-Sided) 95%
0.06 to 15.85
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Event Rate of Myocardial Infarction
Hide Description All events were adjudicated and confirmed by a central independent committee blinded to treatment. Myocardial infarction was assessed based on either cardiac bio-markers (troponin I, troponin T, or creatine kinase-muscle and brain subunit isozyme), new abnormal Q waves appeared on ECG for 2 or more leads, or autopsy confirmation.
Time Frame Up to 2 days after the last dose
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The per-protocol analysis population consisted of randomized participants excluding those who had specific pre-defined major protocol deviations (637 in each treatment group).
Arm/Group Title Rivaroxaban (Xarelto, BAY59-7939) Warfarin
Hide Arm/Group Description:
Participants received once daily (OD) a rivaroxaban 15 mg tablet and a warfarin placebo tablet during the double-blind treatment period
Participants received OD a warfarin potassium tablet and a rivaroxaban placebo tablet during the double-blind treatment period
Overall Number of Participants Analyzed 637 637
Measure Type: Number
Unit of Measure: Events per 100 patient-years
0.34 0.12
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rivaroxaban (Xarelto, BAY59-7939), Warfarin
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 2.93
Confidence Interval (2-Sided) 95%
0.30 to 28.16
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Event Rate of Vascular Death
Hide Description All events were adjudicated and confirmed by a central independent committee blinded to treatment. Any death that was not clearly non-vascular (e.g., deaths due to spontaneous bleeding, myocardial infarction, stroke, cardiac failure, and arrhythmia)
Time Frame Up to 2 days after the last dose
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The per-protocol analysis population consisted of randomized participants excluding those who had specific pre-defined major protocol deviations (637 in each treatment group).
Arm/Group Title Rivaroxaban (Xarelto, BAY59-7939) Warfarin
Hide Arm/Group Description:
Participants received once daily (OD) a rivaroxaban 15 mg tablet and a warfarin placebo tablet during the double-blind treatment period
Participants received OD a warfarin potassium tablet and a rivaroxaban placebo tablet during the double-blind treatment period
Overall Number of Participants Analyzed 637 637
Measure Type: Number
Unit of Measure: Events per 100 patient-years
0.69 0.24
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rivaroxaban (Xarelto, BAY59-7939), Warfarin
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 2.97
Confidence Interval (2-Sided) 95%
0.60 to 14.70
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Event Rate of Stroke With Serious Residual Disability
Hide Description All events were adjudicated and confirmed by a central independent committee blinded to treatment. A stroke was considered disabling if the participant’s modified Rankin score was between 3 and 5, inclusive.
Time Frame Up to 2 days after the last dose
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The per-protocol analysis population consisted of randomized participants excluding those who had specific pre-defined major protocol deviations (637 in each treatment group).
Arm/Group Title Rivaroxaban (Xarelto, BAY59-7939) Warfarin
Hide Arm/Group Description:
Participants received once daily (OD) a rivaroxaban 15 mg tablet and a warfarin placebo tablet during the double-blind treatment period
Participants received OD a warfarin potassium tablet and a rivaroxaban placebo tablet during the double-blind treatment period
Overall Number of Participants Analyzed 637 637
Measure Type: Number
Unit of Measure: Events per 100 patient-years
0.57 1.19
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rivaroxaban (Xarelto, BAY59-7939), Warfarin
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.48
Confidence Interval (2-Sided) 95%
0.16 to 1.40
Estimation Comments [Not Specified]
10.Secondary Outcome
Title Event Rate of All-cause Death
Hide Description All events were adjudicated and confirmed by a central independent committee blinded to treatment. All-cause death included vascular death and non-vascular death.
Time Frame Up to 2 days after the last dose
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The per-protocol analysis population consisted of randomized participants excluding those who had specific pre-defined major protocol deviations (637 in each treatment group).
Arm/Group Title Rivaroxaban (Xarelto, BAY59-7939) Warfarin
Hide Arm/Group Description:
Participants received once daily (OD) a rivaroxaban 15 mg tablet and a warfarin placebo tablet during the double-blind treatment period
Participants received OD a warfarin potassium tablet and a rivaroxaban placebo tablet during the double-blind treatment period
Overall Number of Participants Analyzed 637 637
Measure Type: Number
Unit of Measure: Events per 100 patient-years
0.80 0.59
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rivaroxaban (Xarelto, BAY59-7939), Warfarin
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.37
Confidence Interval (2-Sided) 95%
0.43 to 4.31
Estimation Comments [Not Specified]
11.Secondary Outcome
Title Event Rate of Adjudicated Major Bleeding
Hide Description All events were adjudicated and confirmed by a central independent committee blinded to treatment. Major bleeding was clinically overt bleeding associated with a fall in hemoglobin of 2 g/dL or higher, 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.
Time Frame Up to 2 days after the last dose
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The safety analysis population consisted of randomized participants who took at least one dose of study treatment (639 in each treatment group).
Arm/Group Title Rivaroxaban (Xarelto, BAY59-7939) Warfarin
Hide Arm/Group Description:
Participants received once daily (OD) a rivaroxaban 15 mg tablet and a warfarin placebo tablet during the double-blind treatment period
Participants received OD a warfarin potassium tablet and a rivaroxaban placebo tablet during the double-blind treatment period
Overall Number of Participants Analyzed 639 639
Measure Type: Number
Unit of Measure: Events per 100 patient-years
3.00 3.59
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rivaroxaban (Xarelto, BAY59-7939), Warfarin
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.85
Confidence Interval (2-Sided) 95%
0.50 to 1.43
Estimation Comments [Not Specified]
12.Secondary Outcome
Title Event Rate Adjudicated Non-major Clinically Relevant Bleeding
Hide Description All events were adjudicated and confirmed by a central independent committee blinded to treatment. Non-major clinically relevant bleeding was clinically overt bleeding that does not meet the definition of major bleeding, but requires medical intervention or unscheduled contact with the physician, (temporary) discontinuation of the study treatment, discomfort to the subject such as pain, or impairment of activities of daily life.
Time Frame Up to 2 days after the last dose
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The safety analysis population consisted of randomized participants who took at least one dose of study treatment (639 in each treatment group).
Arm/Group Title Rivaroxaban (Xarelto, BAY59-7939) Warfarin
Hide Arm/Group Description:
Participants received once daily (OD) a rivaroxaban 15 mg tablet and a warfarin placebo tablet during the double-blind treatment period
Participants received OD a warfarin potassium tablet and a rivaroxaban placebo tablet during the double-blind treatment period
Overall Number of Participants Analyzed 639 639
Measure Type: Number
Unit of Measure: Events per 100 patient-years
15.42 12.99
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rivaroxaban (Xarelto, BAY59-7939), Warfarin
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.20
Confidence Interval (2-Sided) 95%
0.92 to 1.56
Estimation Comments [Not Specified]
Time Frame Reporting Group (RG) 1 + 2: Safety data collected start with the first dose of study drug up to 2 days after the last dose; Reporting Group (RG) 3 + 4: Safety data collected from last dose plus 2 days to end of trial.
Adverse Event Reporting Description RG3: During follow-up period, participants could be transitioned from study drug to an open-label warfarin or other appropriate therapy.
 
Arm/Group Title RG1: Rivaroxaban Double-blind (DB) Period RG2: Warfarin DB Period RG3: Rivaroxaban Follow-up (FU) Period RG4: Warfarin FU Period
Hide Arm/Group Description Participants orally administered a rivaroxaban 15 mg tablet (a 10 mg tablet for participants with creatinine clearance of 30 to 49 mL/min, inclusive, at screening) and a warfarin placebo tablet once daily (OD) during the double-blind treatment period. Safety data collected start with the first dose of study drug up to 2 days after the last dose Participants orally administered a warfarin potassium tablet and a rivaroxaban placebo tablet OD during the double-blind treatment period. Safety data collected start with the first dose of study drug up to 2 days after the last dose Participants orally administered a rivaroxaban 15 mg tablet (a 10 mg tablet for participants with creatinine clearance of 30 to 49 mL/min, inclusive, at screening) and a warfarin placebo tablet once daily (OD) during the double-blind treatment period. Safety data collected from last dose plus 2 days to end of trial Participants orally administered a warfarin potassium tablet and a rivaroxaban placebo tablet OD during the double-blind treatment period. Safety data collected from last dose plus 2 days to end of trial
All-Cause Mortality
RG1: Rivaroxaban Double-blind (DB) Period RG2: Warfarin DB Period RG3: Rivaroxaban Follow-up (FU) Period RG4: Warfarin FU Period
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
RG1: Rivaroxaban Double-blind (DB) Period RG2: Warfarin DB Period RG3: Rivaroxaban Follow-up (FU) Period RG4: Warfarin FU Period
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   151/639 (23.63%)      155/639 (24.26%)      50/628 (7.96%)      37/630 (5.87%)    
Blood and lymphatic system disorders         
Anaemia * 1  1/639 (0.16%)  1 3/639 (0.47%)  3 2/628 (0.32%)  2 0/630 (0.00%)  0
Disseminated intravascular coagulation * 1  0/639 (0.00%)  0 0/639 (0.00%)  0 2/628 (0.32%)  2 0/630 (0.00%)  0
Hypoprothrombinaemia * 1  0/639 (0.00%)  0 0/639 (0.00%)  0 2/628 (0.32%)  2 0/630 (0.00%)  0
Iron deficiency anaemia * 1  0/639 (0.00%)  0 1/639 (0.16%)  1 0/628 (0.00%)  0 0/630 (0.00%)  0
Thrombocytopenia * 1  1/639 (0.16%)  1 0/639 (0.00%)  0 0/628 (0.00%)  0 0/630 (0.00%)  0
Cardiac disorders         
Acute myocardial infarction * 1  2/639 (0.31%)  2 1/639 (0.16%)  1 0/628 (0.00%)  0 1/630 (0.16%)  1
Angina pectoris * 1  1/639 (0.16%)  1 2/639 (0.31%)  3 0/628 (0.00%)  0 0/630 (0.00%)  0
Angina unstable * 1  2/639 (0.31%)  2 0/639 (0.00%)  0 2/628 (0.32%)  2 1/630 (0.16%)  1
Aortic valve incompetence * 1  1/639 (0.16%)  1 0/639 (0.00%)  0 0/628 (0.00%)  0 1/630 (0.16%)  1
Atrial fibrillation * 1  4/639 (0.63%)  5 2/639 (0.31%)  2 0/628 (0.00%)  0 1/630 (0.16%)  1
Atrial flutter * 1  1/639 (0.16%)  1 0/639 (0.00%)  0 0/628 (0.00%)  0 1/630 (0.16%)  1
Atrioventricular block complete * 1  0/639 (0.00%)  0 1/639 (0.16%)  1 0/628 (0.00%)  0 0/630 (0.00%)  0
Bradycardia * 1  0/639 (0.00%)  0 1/639 (0.16%)  1 1/628 (0.16%)  1 0/630 (0.00%)  0
Cardiac arrest * 1  0/639 (0.00%)  0 1/639 (0.16%)  1 0/628 (0.00%)  0 1/630 (0.16%)  1
Cardiac failure * 1  12/639 (1.88%)  12 11/639 (1.72%)  18 3/628 (0.48%)  3 4/630 (0.63%)  4
Cardiac failure acute * 1  0/639 (0.00%)  0 1/639 (0.16%)  3 0/628 (0.00%)  0 0/630 (0.00%)  0
Cardiac failure chronic * 1  3/639 (0.47%)  3 3/639 (0.47%)  3 0/628 (0.00%)  0 0/630 (0.00%)  0
Cardiac failure congestive * 1  2/639 (0.31%)  2 3/639 (0.47%)  3 1/628 (0.16%)  1 1/630 (0.16%)  1
Cardio-respiratory arrest * 1  0/639 (0.00%)  0 2/639 (0.31%)  2 1/628 (0.16%)  1 0/630 (0.00%)  0
Cor pulmonale * 1  0/639 (0.00%)  0 0/639 (0.00%)  0 1/628 (0.16%)  1 0/630 (0.00%)  0
Mitral valve incompetence * 1  1/639 (0.16%)  1 0/639 (0.00%)  0 0/628 (0.00%)  0 2/630 (0.32%)  2
Myocardial ischaemia * 1  0/639 (0.00%)  0 0/639 (0.00%)  0 1/628 (0.16%)  1 0/630 (0.00%)  0
Sick sinus syndrome * 1  0/639 (0.00%)  0 2/639 (0.31%)  2 0/628 (0.00%)  0 0/630 (0.00%)  0
Ventricular tachycardia * 1  2/639 (0.31%)  2 1/639 (0.16%)  1 0/628 (0.00%)  0 0/630 (0.00%)  0
Ear and labyrinth disorders         
Vertigo * 1  1/639 (0.16%)  1 1/639 (0.16%)  1 0/628 (0.00%)  0 0/630 (0.00%)  0
Auditory meatus external erosion * 1  0/639 (0.00%)  0 1/639 (0.16%)  1 0/628 (0.00%)  0 0/630 (0.00%)  0
Sudden hearing loss * 1  1/639 (0.16%)  1 2/639 (0.31%)  2 0/628 (0.00%)  0 0/630 (0.00%)  0
Eye disorders         
Cataract * 1  9/639 (1.41%)  10 7/639 (1.10%)  8 0/628 (0.00%)  0 0/630 (0.00%)  0
Glaucoma * 1  1/639 (0.16%)  1 0/639 (0.00%)  0 0/628 (0.00%)  0 0/630 (0.00%)  0
Macular degeneration * 1  0/639 (0.00%)  0 1/639 (0.16%)  1 0/628 (0.00%)  0 0/630 (0.00%)  0
Retinal detachment * 1  1/639 (0.16%)  1 0/639 (0.00%)  0 0/628 (0.00%)  0 0/630 (0.00%)  0
Retinal haemorrhage * 1  1/639 (0.16%)  1 0/639 (0.00%)  0 0/628 (0.00%)  0 0/630 (0.00%)  0
Macular hole * 1  0/639 (0.00%)  0 1/639 (0.16%)  1 0/628 (0.00%)  0 0/630 (0.00%)  0
Gastrointestinal disorders         
Abdominal pain * 1  1/639 (0.16%)  1 0/639 (0.00%)  0 0/628 (0.00%)  0 0/630 (0.00%)  0
Anal polyp * 1  0/639 (0.00%)  0 1/639 (0.16%)  1 0/628 (0.00%)  0 0/630 (0.00%)  0
Colonic polyp * 1  5/639 (0.78%)  5 9/639 (1.41%)  12 0/628 (0.00%)  0 1/630 (0.16%)  1
Dental caries * 1  1/639 (0.16%)  1 0/639 (0.00%)  0 0/628 (0.00%)  0 0/630 (0.00%)  0
Diarrhoea * 1  1/639 (0.16%)  1 0/639 (0.00%)  0 0/628 (0.00%)  0 0/630 (0.00%)  0
Diverticulum intestinal haemorrhagic * 1  0/639 (0.00%)  0 3/639 (0.47%)  3 0/628 (0.00%)  0 0/630 (0.00%)  0
Duodenal ulcer haemorrhage * 1  0/639 (0.00%)  0 1/639 (0.16%)  1 0/628 (0.00%)  0 0/630 (0.00%)  0
Enterocolitis * 1  1/639 (0.16%)  1 2/639 (0.31%)  2 0/628 (0.00%)  0 0/630 (0.00%)  0
Gastric ulcer * 1  2/639 (0.31%)  2 1/639 (0.16%)  1 0/628 (0.00%)  0 0/630 (0.00%)  0
Gastric ulcer haemorrhage * 1  3/639 (0.47%)  3 2/639 (0.31%)  2 0/628 (0.00%)  0 0/630 (0.00%)  0
Gastrointestinal haemorrhage * 1  0/639 (0.00%)  0 4/639 (0.63%)  4 0/628 (0.00%)  0 0/630 (0.00%)  0
Gingival bleeding * 1  0/639 (0.00%)  0 1/639 (0.16%)  1 0/628 (0.00%)  0 0/630 (0.00%)  0
Haemorrhoids * 1  1/639 (0.16%)  1 0/639 (0.00%)  0 0/628 (0.00%)  0 0/630 (0.00%)  0
Ileus * 1  0/639 (0.00%)  0 4/639 (0.63%)  4 0/628 (0.00%)  0 0/630 (0.00%)  0
Inguinal hernia * 1  1/639 (0.16%)  1 2/639 (0.31%)  2 0/628 (0.00%)  0 1/630 (0.16%)  1
Intestinal obstruction * 1  0/639 (0.00%)  0 1/639 (0.16%)  1 0/628 (0.00%)  0 0/630 (0.00%)  0
Large intestine perforation * 1  0/639 (0.00%)  0 1/639 (0.16%)  1 0/628 (0.00%)  0 0/630 (0.00%)  0
Mallory-Weiss syndrome * 1  1/639 (0.16%)  1 0/639 (0.00%)  0 0/628 (0.00%)  0 0/630 (0.00%)  0
Melaena * 1  1/639 (0.16%)  1 1/639 (0.16%)  2 1/628 (0.16%)  1 0/630 (0.00%)  0
Mouth haemorrhage * 1  0/639 (0.00%)  0 1/639 (0.16%)  1 0/628 (0.00%)  0 0/630 (0.00%)  0
Nausea * 1  1/639 (0.16%)  1 1/639 (0.16%)  1 0/628 (0.00%)  0 0/630 (0.00%)  0
Pancreatitis acute * 1  1/639 (0.16%)  1 0/639 (0.00%)  0 0/628 (0.00%)  0 0/630 (0.00%)  0
Periodontal disease * 1  1/639 (0.16%)  1 0/639 (0.00%)  0 0/628 (0.00%)  0 0/630 (0.00%)  0
Periodontitis * 1  1/639 (0.16%)  1 3/639 (0.47%)  4 0/628 (0.00%)  0 0/630 (0.00%)  0
Peritonitis * 1  0/639 (0.00%)  0 1/639 (0.16%)  1 0/628 (0.00%)  0 0/630 (0.00%)  0
Rectal polyp * 1  1/639 (0.16%)  1 0/639 (0.00%)  0 0/628 (0.00%)  0 0/630 (0.00%)  0
Tooth loss * 1  0/639 (0.00%)  0 0/639 (0.00%)  0 0/628 (0.00%)  0 1/630 (0.16%)  1
Upper gastrointestinal haemorrhage * 1  1/639 (0.16%)  1 0/639 (0.00%)  0 0/628 (0.00%)  0 0/630 (0.00%)  0
Vomiting * 1  0/639 (0.00%)  0 1/639 (0.16%)  1 0/628 (0.00%)  0 0/630 (0.00%)  0
Subileus * 1  1/639 (0.16%)  1 0/639 (0.00%)  0 0/628 (0.00%)  0 0/630 (0.00%)  0
Mechanical ileus * 1  0/639 (0.00%)  0 1/639 (0.16%)  1 0/628 (0.00%)  0 0/630 (0.00%)  0
General disorders         
Malaise * 1  0/639 (0.00%)  0 2/639 (0.31%)  2 0/628 (0.00%)  0 0/630 (0.00%)  0
Oedema * 1  0/639 (0.00%)  0 1/639 (0.16%)  1 0/628 (0.00%)  0 0/630 (0.00%)  0
Oedema peripheral * 1  0/639 (0.00%)  0 0/639 (0.00%)  0 0/628 (0.00%)  0 1/630 (0.16%)  1
Pyrexia * 1  0/639 (0.00%)  0 1/639 (0.16%)  1 0/628 (0.00%)  0 1/630 (0.16%)  1
Sudden death * 1  4/639 (0.63%)  4 2/639 (0.31%)  2 3/628 (0.48%)  3 0/630 (0.00%)  0
Sudden cardiac death * 1  1/639 (0.16%)  1 0/639 (0.00%)  0 1/628 (0.16%)  1 0/630 (0.00%)  0
Catheter site haemorrhage * 1  0/639 (0.00%)  0 1/639 (0.16%)  1 0/628 (0.00%)  0 0/630 (0.00%)  0
Hepatobiliary disorders         
Bile duct stone * 1  0/639 (0.00%)  0 2/639 (0.31%)  2 0/628 (0.00%)  0 0/630 (0.00%)  0
Cholangitis acute * 1  1/639 (0.16%)  1 0/639 (0.00%)  0 0/628 (0.00%)  0 0/630 (0.00%)  0
Cholecystitis * 1  0/639 (0.00%)  0 0/639 (0.00%)  0 0/628 (0.00%)  0 1/630 (0.16%)  1
Cholecystitis acute * 1  0/639 (0.00%)  0 1/639 (0.16%)  1 1/628 (0.16%)  1 1/630 (0.16%)  1
Cholelithiasis * 1  0/639 (0.00%)  0 0/639 (0.00%)  0 0/628 (0.00%)  0 1/630 (0.16%)  1
Hepatic function abnormal * 1  2/639 (0.31%)  2 1/639 (0.16%)  1 0/628 (0.00%)  0 0/630 (0.00%)  0
Liver disorder * 1  0/639 (0.00%)  0 0/639 (0.00%)  0 1/628 (0.16%)  1 0/630 (0.00%)  0
Immune system disorders         
Anaphylactic reaction * 1  1/639 (0.16%)  1 0/639 (0.00%)  0 0/628 (0.00%)  0 0/630 (0.00%)  0
Infections and infestations         
Appendicitis * 1  1/639 (0.16%)  1 0/639 (0.00%)  0 0/628 (0.00%)  0 0/630 (0.00%)  0
Bronchitis * 1  1/639 (0.16%)  1 1/639 (0.16%)  1 0/628 (0.00%)  0 0/630 (0.00%)  0
Bronchopneumonia * 1  0/639 (0.00%)  0 1/639 (0.16%)  1 0/628 (0.00%)  0 0/630 (0.00%)  0
Cellulitis * 1  2/639 (0.31%)  2 1/639 (0.16%)  1 0/628 (0.00%)  0 0/630 (0.00%)  0
Diverticulitis * 1  0/639 (0.00%)  0 1/639 (0.16%)  1 0/628 (0.00%)  0 0/630 (0.00%)  0
Gastroenteritis * 1  3/639 (0.47%)  3 1/639 (0.16%)  1 0/628 (0.00%)  0 0/630 (0.00%)  0
Gastroenteritis viral * 1  1/639 (0.16%)  1 0/639 (0.00%)  0 0/628 (0.00%)  0 0/630 (0.00%)  0
Herpes zoster * 1  1/639 (0.16%)  1 1/639 (0.16%)  1 0/628 (0.00%)  0 0/630 (0.00%)  0
Liver abscess * 1  0/639 (0.00%)  0 0/639 (0.00%)  0 1/628 (0.16%)  1 0/630 (0.00%)  0
Meningitis bacterial * 1  1/639 (0.16%)  1 0/639 (0.00%)  0 0/628 (0.00%)  0 0/630 (0.00%)  0
Otitis media * 1  0/639 (0.00%)  0 1/639 (0.16%)  1 0/628 (0.00%)  0 0/630 (0.00%)  0
Pneumonia * 1  14/639 (2.19%)  15 10/639 (1.56%)  11 3/628 (0.48%)  3 3/630 (0.48%)  3
Pyelonephritis * 1  0/639 (0.00%)  0 1/639 (0.16%)  1 0/628 (0.00%)  0 0/630 (0.00%)  0
Sepsis * 1  0/639 (0.00%)  0 2/639 (0.31%)  2 2/628 (0.32%)  2 1/630 (0.16%)  1
Subcutaneous abscess * 1  0/639 (0.00%)  0 1/639 (0.16%)  1 0/628 (0.00%)  0 0/630 (0.00%)  0
Urinary tract infection * 1  2/639 (0.31%)  2 0/639 (0.00%)  0 0/628 (0.00%)  0 0/630 (0.00%)  0
Anal abscess * 1  1/639 (0.16%)  1 1/639 (0.16%)  1 0/628 (0.00%)  0 0/630 (0.00%)  0
Lung infection * 1  1/639 (0.16%)  1 0/639 (0.00%)  0 0/628 (0.00%)  0 0/630 (0.00%)  0
Enterocolitis viral * 1  1/639 (0.16%)  1 1/639 (0.16%)  1 0/628 (0.00%)  0 0/630 (0.00%)  0
Infective spondylitis * 1  0/639 (0.00%)  0 1/639 (0.16%)  1 1/628 (0.16%)  1 0/630 (0.00%)  0
Injury, poisoning and procedural complications         
Accident * 1  0/639 (0.00%)  0 1/639 (0.16%)  1 0/628 (0.00%)  0 0/630 (0.00%)  0
Accidental exposure * 1  1/639 (0.16%)  1 0/639 (0.00%)  0 0/628 (0.00%)  0 0/630 (0.00%)  0
Femur fracture * 1  2/639 (0.31%)  2 0/639 (0.00%)  0 0/628 (0.00%)  0 0/630 (0.00%)  0
Fibula fracture * 1  0/639 (0.00%)  0 2/639 (0.31%)  2 0/628 (0.00%)  0 0/630 (0.00%)  0
Patella fracture * 1  1/639 (0.16%)  1 0/639 (0.00%)  0 0/628 (0.00%)  0 0/630 (0.00%)  0
Radius fracture * 1  0/639 (0.00%)  0 1/639 (0.16%)  1 0/628 (0.00%)  0 0/630 (0.00%)  0
Rib fracture * 1  1/639 (0.16%)  1 1/639 (0.16%)  1 0/628 (0.00%)  0 0/630 (0.00%)  0
Road traffic accident * 1  0/639 (0.00%)  0 1/639 (0.16%)  1 0/628 (0.00%)  0 0/630 (0.00%)  0
Spinal compression fracture * 1  4/639 (0.63%)  6 2/639 (0.31%)  2 0/628 (0.00%)  0 0/630 (0.00%)  0
Spinal cord injury * 1  1/639 (0.16%)  1 0/639 (0.00%)  0 0/628 (0.00%)  0 0/630 (0.00%)  0
Spinal cord injury cervical * 1  0/639 (0.00%)  0 1/639 (0.16%)  1 0/628 (0.00%)  0 0/630 (0.00%)  0
Subdural haematoma * 1  1/639 (0.16%)  1 0/639 (0.00%)  0 1/628 (0.16%)  1 0/630 (0.00%)  0
Tendon rupture * 1  1/639 (0.16%)  1 0/639 (0.00%)  0 0/628 (0.00%)  0 0/630 (0.00%)  0
Therapeutic agent toxicity * 1  1/639 (0.16%)  1 2/639 (0.31%)  2 0/628 (0.00%)  0 0/630 (0.00%)  0
Tibia fracture * 1  0/639 (0.00%)  0 2/639 (0.31%)  2 0/628 (0.00%)  0 0/630 (0.00%)  0
Ulna fracture * 1  0/639 (0.00%)  0 1/639 (0.16%)  1 0/628 (0.00%)  0 0/630 (0.00%)  0
Muscle strain * 1  1/639 (0.16%)  1 0/639 (0.00%)  0 0/628 (0.00%)  0 0/630 (0.00%)  0
Contusion * 1  2/639 (0.31%)  2 0/639 (0.00%)  0 0/628 (0.00%)  0 0/630 (0.00%)  0
Post procedural haemorrhage * 1  1/639 (0.16%)  1 1/639 (0.16%)  1 0/628 (0.00%)  0 1/630 (0.16%)  1
Brain contusion * 1  1/639 (0.16%)  1 1/639 (0.16%)  1 0/628 (0.00%)  0 0/630 (0.00%)  0
Thermal burn * 1  0/639 (0.00%)  0 0/639 (0.00%)  0 0/628 (0.00%)  0 1/630 (0.16%)  1
Coronary artery restenosis * 1  1/639 (0.16%)  1 0/639 (0.00%)  0 0/628 (0.00%)  0 0/630 (0.00%)  0
Skin laceration * 1  1/639 (0.16%)  1 0/639 (0.00%)  0 0/628 (0.00%)  0 0/630 (0.00%)  0
Ligament injury * 1  1/639 (0.16%)  1 0/639 (0.00%)  0 0/628 (0.00%)  0 0/630 (0.00%)  0
Skull fracture * 1  0/639 (0.00%)  0 1/639 (0.16%)  1 0/628 (0.00%)  0 0/630 (0.00%)  0
Investigations         
Blood pressure decreased * 1  2/639 (0.31%)  2 1/639 (0.16%)  1 0/628 (0.00%)  0 0/630 (0.00%)  0
Haemoglobin decreased * 1  0/639 (0.00%)  0 1/639 (0.16%)  1 0/628 (0.00%)  0 0/630 (0.00%)  0
International normalised ratio increased * 1  0/639 (0.00%)  0 0/639 (0.00%)  0 3/628 (0.48%)  3 0/630 (0.00%)  0
Metabolism and nutrition disorders         
Dehydration * 1  0/639 (0.00%)  0 1/639 (0.16%)  1 0/628 (0.00%)  0 0/630 (0.00%)  0
Diabetes mellitus * 1  4/639 (0.63%)  6 1/639 (0.16%)  1 0/628 (0.00%)  0 0/630 (0.00%)  0
Hyperkalaemia * 1  0/639 (0.00%)  0 0/639 (0.00%)  0 0/628 (0.00%)  0 1/630 (0.16%)  1
Hyponatraemia * 1  0/639 (0.00%)  0 1/639 (0.16%)  1 0/628 (0.00%)  0 0/630 (0.00%)  0
Hypoproteinaemia * 1  1/639 (0.16%)  1 0/639 (0.00%)  0 0/628 (0.00%)  0 0/630 (0.00%)  0
Decreased appetite * 1  0/639 (0.00%)  0 1/639 (0.16%)  1 0/628 (0.00%)  0 0/630 (0.00%)  0
Musculoskeletal and connective tissue disorders         
Back pain * 1  1/639 (0.16%)  1 0/639 (0.00%)  0 0/628 (0.00%)  0 0/630 (0.00%)  0
Bursitis * 1  1/639 (0.16%)  1 0/639 (0.00%)  0 0/628 (0.00%)  0 0/630 (0.00%)  0
Chondrocalcinosis pyrophosphate * 1  1/639 (0.16%)  1 1/639 (0.16%)  1 1/628 (0.16%)  1 0/630 (0.00%)  0
Compartment syndrome * 1  1/639 (0.16%)  1 0/639 (0.00%)  0 0/628 (0.00%)  0 0/630 (0.00%)  0
Haemarthrosis * 1  1/639 (0.16%)  1 0/639 (0.00%)  0 0/628 (0.00%)  0 0/630 (0.00%)  0
Joint effusion * 1  1/639 (0.16%)  1 0/639 (0.00%)  0 0/628 (0.00%)  0 0/630 (0.00%)  0
Lumbar spinal stenosis * 1  0/639 (0.00%)  0 1/639 (0.16%)  1 0/628 (0.00%)  0 0/630 (0.00%)  0
Muscle haemorrhage * 1  1/639 (0.16%)  1 1/639 (0.16%)  1 0/628 (0.00%)  0 0/630 (0.00%)  0
Neck pain * 1  1/639 (0.16%)  1 0/639 (0.00%)  0 0/628 (0.00%)  0 0/630 (0.00%)  0
Pain in extremity * 1  1/639 (0.16%)  2 0/639 (0.00%)  0 0/628 (0.00%)  0 0/630 (0.00%)  0
Periarthritis * 1  0/639 (0.00%)  0 1/639 (0.16%)  1 0/628 (0.00%)  0 0/630 (0.00%)  0
Polymyalgia rheumatica * 1  0/639 (0.00%)  0 1/639 (0.16%)  1 0/628 (0.00%)  0 0/630 (0.00%)  0
Rhabdomyolysis * 1  0/639 (0.00%)  0 1/639 (0.16%)  1 0/628 (0.00%)  0 0/630 (0.00%)  0
Spinal osteoarthritis * 1  0/639 (0.00%)  0 1/639 (0.16%)  1 0/628 (0.00%)  0 0/630 (0.00%)  0
Intervertebral disc protrusion * 1  0/639 (0.00%)  0 1/639 (0.16%)  1 0/628 (0.00%)  0 0/630 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)         
Bladder cancer * 1  0/639 (0.00%)  0 2/639 (0.31%)  2 0/628 (0.00%)  0 0/630 (0.00%)  0
Bladder neoplasm * 1  0/639 (0.00%)  0 0/639 (0.00%)  0 0/628 (0.00%)  0 1/630 (0.16%)  1
Colon cancer * 1  0/639 (0.00%)  0 1/639 (0.16%)  1 1/628 (0.16%)  1 1/630 (0.16%)  1
Gastric cancer * 1  2/639 (0.31%)  2 4/639 (0.63%)  4 2/628 (0.32%)  2 2/630 (0.32%)  2
Lipoma * 1  1/639 (0.16%)  1 0/639 (0.00%)  0 0/628 (0.00%)  0 0/630 (0.00%)  0
Lymphoma * 1  1/639 (0.16%)  1 0/639 (0.00%)  0 0/628 (0.00%)  0 0/630 (0.00%)  0
Malignant ascites * 1  0/639 (0.00%)  0 1/639 (0.16%)  1 0/628 (0.00%)  0 0/630 (0.00%)  0
Malignant pleural effusion * 1  0/639 (0.00%)  0 1/639 (0.16%)  1 0/628 (0.00%)  0 0/630 (0.00%)  0
Metastases to liver * 1  0/639 (0.00%)  0 1/639 (0.16%)  1 0/628 (0.00%)  0 0/630 (0.00%)  0
Metastases to lung * 1  0/639 (0.00%)  0 2/639 (0.31%)  2 0/628 (0.00%)  0 0/630 (0.00%)  0
Metastases to lymph nodes * 1  0/639 (0.00%)  0 0/639 (0.00%)  0 1/628 (0.16%)  1 0/630 (0.00%)  0
Metastases to neck * 1  0/639 (0.00%)  0 1/639 (0.16%)  1 0/628 (0.00%)  0 0/630 (0.00%)  0
Nasal sinus cancer * 1  0/639 (0.00%)  0 0/639 (0.00%)  0 0/628 (0.00%)  0 1/630 (0.16%)  1
Oesophageal carcinoma * 1  1/639 (0.16%)  1 1/639 (0.16%)  1 0/628 (0.00%)  0 0/630 (0.00%)  0
Rectal cancer * 1  1/639 (0.16%)  1 1/639 (0.16%)  1 2/628 (0.32%)  2 0/630 (0.00%)  0
Small cell lung cancer stage unspecified * 1  2/639 (0.31%)  2 0/639 (0.00%)  0 0/628 (0.00%)  0 0/630 (0.00%)  0
Uterine cancer * 1  0/639 (0.00%)  0 1/639 (0.16%)  1 0/628 (0.00%)  0 0/630 (0.00%)  0
Tumour haemorrhage * 1  0/639 (0.00%)  0 1/639 (0.16%)  1 0/628 (0.00%)  0 0/630 (0.00%)  0
Lung neoplasm malignant * 1  0/639 (0.00%)  0 1/639 (0.16%)  1 1/628 (0.16%)  1 0/630 (0.00%)  0
Large intestine carcinoma * 1  2/639 (0.31%)  2 1/639 (0.16%)  1 1/628 (0.16%)  1 1/630 (0.16%)  1
Prostate cancer * 1  3/639 (0.47%)  3 0/639 (0.00%)  0 1/628 (0.16%)  1 1/630 (0.16%)  1
Nervous system disorders         
Brain stem haemorrhage * 1  0/639 (0.00%)  0 2/639 (0.31%)  2 0/628 (0.00%)  0 0/630 (0.00%)  0
Carotid artery stenosis * 1  1/639 (0.16%)  1 0/639 (0.00%)  0 1/628 (0.16%)  1 0/630 (0.00%)  0
Cerebral haemorrhage * 1  1/639 (0.16%)  1 1/639 (0.16%)  1 1/628 (0.16%)  1 0/630 (0.00%)  0
Cholinergic syndrome * 1  0/639 (0.00%)  0 1/639 (0.16%)  1 0/628 (0.00%)  0 0/630 (0.00%)  0
Convulsion * 1  0/639 (0.00%)  0 3/639 (0.47%)  4 1/628 (0.16%)  1 0/630 (0.00%)  0
Dizziness * 1  1/639 (0.16%)  1 1/639 (0.16%)  1 0/628 (0.00%)  0 0/630 (0.00%)  0
Epilepsy * 1  4/639 (0.63%)  5 1/639 (0.16%)  1 1/628 (0.16%)  1 0/630 (0.00%)  0
Facial palsy * 1  0/639 (0.00%)  0 1/639 (0.16%)  1 0/628 (0.00%)  0 0/630 (0.00%)  0
Haemorrhage intracranial * 1  0/639 (0.00%)  0 0/639 (0.00%)  0 1/628 (0.16%)  1 0/630 (0.00%)  0
Haemorrhagic cerebral infarction * 1  0/639 (0.00%)  0 0/639 (0.00%)  0 2/628 (0.32%)  2 1/630 (0.16%)  1
Hemiplegia * 1  0/639 (0.00%)  0 1/639 (0.16%)  1 0/628 (0.00%)  0 0/630 (0.00%)  0
Hypertensive encephalopathy * 1  1/639 (0.16%)  1 0/639 (0.00%)  0 0/628 (0.00%)  0 0/630 (0.00%)  0
Loss of consciousness * 1  0/639 (0.00%)  0 1/639 (0.16%)  1 1/628 (0.16%)  1 0/630 (0.00%)  0
Subarachnoid haemorrhage * 1  0/639 (0.00%)  0 1/639 (0.16%)  1 0/628 (0.00%)  0 0/630 (0.00%)  0
Syncope * 1  1/639 (0.16%)  1 0/639 (0.00%)  0 0/628 (0.00%)  0 0/630 (0.00%)  0
Transient ischaemic attack * 1  2/639 (0.31%)  2 2/639 (0.31%)  2 1/628 (0.16%)  1 2/630 (0.32%)  2
Vertebral artery stenosis * 1  0/639 (0.00%)  0 0/639 (0.00%)  0 0/628 (0.00%)  0 1/630 (0.16%)  1
Carotid artery occlusion * 1  1/639 (0.16%)  1 0/639 (0.00%)  0 0/628 (0.00%)  0 0/630 (0.00%)  0
Thalamus haemorrhage * 1  1/639 (0.16%)  1 1/639 (0.16%)  1 0/628 (0.00%)  0 0/630 (0.00%)  0
Putamen haemorrhage * 1  1/639 (0.16%)  1 0/639 (0.00%)  0 0/628 (0.00%)  0 0/630 (0.00%)  0
Ischaemic stroke * 1  9/639 (1.41%)  9 18/639 (2.82%)  18 10/628 (1.59%)  12 4/630 (0.63%)  4
Postresuscitation encephalopathy * 1  0/639 (0.00%)  0 1/639 (0.16%)  1 0/628 (0.00%)  0 0/630 (0.00%)  0
Psychiatric disorders         
Psychosomatic disease * 1  0/639 (0.00%)  0 1/639 (0.16%)  1 0/628 (0.00%)  0 0/630 (0.00%)  0
Renal and urinary disorders         
Acute prerenal failure * 1  0/639 (0.00%)  0 1/639 (0.16%)  1 0/628 (0.00%)  0 0/630 (0.00%)  0
Haematuria * 1  1/639 (0.16%)  1 0/639 (0.00%)  0 0/628 (0.00%)  0 0/630 (0.00%)  0
Nephrolithiasis * 1  1/639 (0.16%)  2 0/639 (0.00%)  0 0/628 (0.00%)  0 0/630 (0.00%)  0
Renal artery stenosis * 1  0/639 (0.00%)  0 1/639 (0.16%)  1 0/628 (0.00%)  0 0/630 (0.00%)  0
Renal failure * 1  0/639 (0.00%)  0 1/639 (0.16%)  1 0/628 (0.00%)  0 0/630 (0.00%)  0
Renal failure acute * 1  1/639 (0.16%)  1 1/639 (0.16%)  1 0/628 (0.00%)  0 0/630 (0.00%)  0
Renal impairment * 1  1/639 (0.16%)  1 0/639 (0.00%)  0 0/628 (0.00%)  0 0/630 (0.00%)  0
Renal embolism * 1  1/639 (0.16%)  1 1/639 (0.16%)  1 0/628 (0.00%)  0 0/630 (0.00%)  0
Reproductive system and breast disorders         
Prostatitis * 1  0/639 (0.00%)  0 1/639 (0.16%)  1 0/628 (0.00%)  0 0/630 (0.00%)  0
Respiratory, thoracic and mediastinal disorders         
Acute respiratory distress syndrome * 1  1/639 (0.16%)  1 0/639 (0.00%)  0 0/628 (0.00%)  0 0/630 (0.00%)  0
Asthma * 1  3/639 (0.47%)  3 1/639 (0.16%)  5 0/628 (0.00%)  0 0/630 (0.00%)  0
Epistaxis * 1  2/639 (0.31%)  2 1/639 (0.16%)  1 0/628 (0.00%)  0 0/630 (0.00%)  0
Haemoptysis * 1  0/639 (0.00%)  0 0/639 (0.00%)  0 1/628 (0.16%)  1 0/630 (0.00%)  0
Haemothorax * 1  0/639 (0.00%)  0 1/639 (0.16%)  1 0/628 (0.00%)  0 0/630 (0.00%)  0
Interstitial lung disease * 1  2/639 (0.31%)  2 3/639 (0.47%)  3 0/628 (0.00%)  0 1/630 (0.16%)  1
Pleural effusion * 1  1/639 (0.16%)  1 0/639 (0.00%)  0 0/628 (0.00%)  0 0/630 (0.00%)  0
Pleurisy * 1  1/639 (0.16%)  1 0/639 (0.00%)  0 0/628 (0.00%)  0 0/630 (0.00%)  0
Pneumonia aspiration * 1  1/639 (0.16%)  1 0/639 (0.00%)  0 0/628 (0.00%)  0 0/630 (0.00%)  0
Pneumothorax * 1  1/639 (0.16%)  1 0/639 (0.00%)  0 0/628 (0.00%)  0 0/630 (0.00%)  0
Pulmonary oedema * 1  0/639 (0.00%)  0 0/639 (0.00%)  0 0/628 (0.00%)  0 1/630 (0.16%)  1
Status asthmaticus * 1  1/639 (0.16%)  1 0/639 (0.00%)  0 0/628 (0.00%)  0 0/630 (0.00%)  0
Upper respiratory tract inflammation * 1  1/639 (0.16%)  1 0/639 (0.00%)  0 0/628 (0.00%)  0 0/630 (0.00%)  0
Bronchial haemorrhage * 1  0/639 (0.00%)  0 0/639 (0.00%)  0 1/628 (0.16%)  1 0/630 (0.00%)  0
Skin and subcutaneous tissue disorders         
Eczema * 1  0/639 (0.00%)  0 0/639 (0.00%)  0 1/628 (0.16%)  1 0/630 (0.00%)  0
Haemorrhage subcutaneous * 1  0/639 (0.00%)  0 1/639 (0.16%)  1 0/628 (0.00%)  0 0/630 (0.00%)  0
Rash * 1  0/639 (0.00%)  0 1/639 (0.16%)  1 0/628 (0.00%)  0 0/630 (0.00%)  0
Vascular disorders         
Aortic aneurysm * 1  1/639 (0.16%)  1 0/639 (0.00%)  0 0/628 (0.00%)  0 0/630 (0.00%)  0
Aortic dissection * 1  2/639 (0.31%)  2 0/639 (0.00%)  0 0/628 (0.00%)  0 0/630 (0.00%)  0
Haematoma * 1  0/639 (0.00%)  0 0/639 (0.00%)  0 0/628 (0.00%)  0 1/630 (0.16%)  1
Shock haemorrhagic * 1  1/639 (0.16%)  1 0/639 (0.00%)  0 1/628 (0.16%)  1 0/630 (0.00%)  0
Peripheral embolism * 1  0/639 (0.00%)  0 1/639 (0.16%)  1 0/628 (0.00%)  0 0/630 (0.00%)  0
Arteriosclerosis obliterans * 1  0/639 (0.00%)  0 2/639 (0.31%)  2 0/628 (0.00%)  0 0/630 (0.00%)  0
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (12.1)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
RG1: Rivaroxaban Double-blind (DB) Period RG2: Warfarin DB Period RG3: Rivaroxaban Follow-up (FU) Period RG4: Warfarin FU Period
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   474/639 (74.18%)      470/639 (73.55%)      73/628 (11.62%)      61/630 (9.68%)    
Cardiac disorders         
Cardiac failure * 1  36/639 (5.63%)  39 29/639 (4.54%)  35 5/628 (0.80%)  6 2/630 (0.32%)  2
Eye disorders         
Conjunctival haemorrhage * 1  26/639 (4.07%)  32 42/639 (6.57%)  57 9/628 (1.43%)  9 1/630 (0.16%)  1
Gastrointestinal disorders         
Constipation * 1  38/639 (5.95%)  46 32/639 (5.01%)  40 12/628 (1.91%)  12 8/630 (1.27%)  8
Dental caries * 1  28/639 (4.38%)  32 34/639 (5.32%)  35 1/628 (0.16%)  1 0/630 (0.00%)  0
Diarrhoea * 1  57/639 (8.92%)  71 40/639 (6.26%)  47 3/628 (0.48%)  3 6/630 (0.95%)  6
Gingival bleeding * 1  54/639 (8.45%)  72 31/639 (4.85%)  38 1/628 (0.16%)  1 2/630 (0.32%)  2
Infections and infestations         
Nasopharyngitis * 1  206/639 (32.24%)  378 232/639 (36.31%)  412 16/628 (2.55%)  16 15/630 (2.38%)  16
Injury, poisoning and procedural complications         
Contusion * 1  58/639 (9.08%)  82 56/639 (8.76%)  80 4/628 (0.64%)  4 4/630 (0.63%)  4
Wound haemorrhage * 1  33/639 (5.16%)  38 27/639 (4.23%)  31 1/628 (0.16%)  1 1/630 (0.16%)  1
Metabolism and nutrition disorders         
Diabetes mellitus * 1  43/639 (6.73%)  48 31/639 (4.85%)  34 0/628 (0.00%)  0 1/630 (0.16%)  1
Musculoskeletal and connective tissue disorders         
Back pain * 1  50/639 (7.82%)  57 56/639 (8.76%)  60 5/628 (0.80%)  5 7/630 (1.11%)  7
Nervous system disorders         
Headache * 1  24/639 (3.76%)  29 39/639 (6.10%)  43 6/628 (0.96%)  6 2/630 (0.32%)  3
Respiratory, thoracic and mediastinal disorders         
Epistaxis * 1  102/639 (15.96%)  203 59/639 (9.23%)  86 6/628 (0.96%)  8 8/630 (1.27%)  8
Upper respiratory tract inflammation * 1  55/639 (8.61%)  76 74/639 (11.58%)  102 3/628 (0.48%)  3 1/630 (0.16%)  1
Skin and subcutaneous tissue disorders         
Eczema * 1  37/639 (5.79%)  50 43/639 (6.73%)  49 2/628 (0.32%)  2 1/630 (0.16%)  1
Haemorrhage subcutaneous * 1  67/639 (10.49%)  147 79/639 (12.36%)  175 9/628 (1.43%)  9 6/630 (0.95%)  7
Vascular disorders         
Hypertension * 1  24/639 (3.76%)  25 32/639 (5.01%)  36 3/628 (0.48%)  3 2/630 (0.32%)  2
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (12.1)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Therapeutic Area Head
Organization: BAYER
Publications of Results:
Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT00494871     History of Changes
Other Study ID Numbers: 12620
First Submitted: June 29, 2007
First Posted: July 2, 2007
Results First Submitted: March 28, 2012
Results First Posted: April 19, 2012
Last Update Posted: April 20, 2015