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A Study to Assess the Effectiveness and Safety of Rivaroxaban in Reducing the Risk of Death, Myocardial Infarction or Stroke in Participants With Heart Failure and Coronary Artery Disease Following an Episode of Decompensated Heart Failure (COMMANDER HF)

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ClinicalTrials.gov Identifier: NCT01877915
Recruitment Status : Completed
First Posted : June 14, 2013
Results First Posted : May 10, 2019
Last Update Posted : May 10, 2019
Sponsor:
Collaborator:
Bayer
Information provided by (Responsible Party):
Janssen Research & Development, LLC

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Conditions Heart Failure
Coronary Artery Disease
Interventions Drug: Rivaroxaban
Drug: Placebo
Other: Standard of care for heart failure and coronary artery disease
Enrollment 5081
Recruitment Details  
Pre-assignment Details A total of 3 participants randomized twice were only counted once in the ITT analysis set (comprised of 5,022 participants).
Arm/Group Title Rivaroxaban Placebo
Hide Arm/Group Description Participants received 2.5 milligram (mg) tablet of rivaroxaban orally twice daily with standard of care for heart failure and coronary artery disease (as prescribed by the participant's managing physician). Participants received matching placebo orally twice daily with standard of care for heart failure and coronary artery disease (as prescribed by the participant's managing physician).
Period Title: Overall Study
Started 2507 2515
Completed 2453 2447
Not Completed 54 68
Reason Not Completed
Lost to Follow-up             10             9
Withdrawal by Subject             42             55
Other             2             4
Arm/Group Title Rivaroxaban Placebo Total
Hide Arm/Group Description Participants received 2.5 milligram (mg) tablet of rivaroxaban orally twice daily with standard of care for heart failure and coronary artery disease (as prescribed by the participant's managing physician). Participants received matching placebo orally twice daily with standard of care for heart failure and coronary artery disease (as prescribed by the participant's managing physician). Total of all reporting groups
Overall Number of Baseline Participants 2507 2515 5022
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 2507 participants 2515 participants 5022 participants
66.5  (10.07) 66.3  (10.27) 66.4  (10.17)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 2507 participants 2515 participants 5022 participants
Female
551
  22.0%
599
  23.8%
1150
  22.9%
Male
1956
  78.0%
1916
  76.2%
3872
  77.1%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 2507 participants 2515 participants 5022 participants
Hispanic or Latino
309
  12.3%
300
  11.9%
609
  12.1%
Not Hispanic or Latino
2186
  87.2%
2203
  87.6%
4389
  87.4%
Unknown or Not Reported
12
   0.5%
12
   0.5%
24
   0.5%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 2507 participants 2515 participants 5022 participants
American Indian or Alaska Native
11
   0.4%
10
   0.4%
21
   0.4%
Asian
362
  14.4%
365
  14.5%
727
  14.5%
Native Hawaiian or Other Pacific Islander
2
   0.1%
0
   0.0%
2
   0.0%
Black or African American
29
   1.2%
36
   1.4%
65
   1.3%
White
2063
  82.3%
2065
  82.1%
4128
  82.2%
More than one race
4
   0.2%
5
   0.2%
9
   0.2%
Unknown or Not Reported
36
   1.4%
34
   1.4%
70
   1.4%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 2507 participants 2515 participants 5022 participants
Asian
362
  14.4%
365
  14.5%
727
  14.5%
Black or African American
29
   1.2%
36
   1.4%
65
   1.3%
Other
59
   2.4%
56
   2.2%
115
   2.3%
White Hispanic or Latino
258
  10.3%
251
  10.0%
509
  10.1%
White Non-Hispanic
1799
  71.8%
1807
  71.8%
3606
  71.8%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 2507 participants 2515 participants 5022 participants
ARGENTINA
76
   3.0%
76
   3.0%
152
   3.0%
AUSTRALIA
7
   0.3%
7
   0.3%
14
   0.3%
BRAZIL
80
   3.2%
80
   3.2%
160
   3.2%
BULGARIA
314
  12.5%
314
  12.5%
628
  12.5%
CANADA
14
   0.6%
14
   0.6%
28
   0.6%
CHINA
186
   7.4%
186
   7.4%
372
   7.4%
CZECH REPUBLIC
35
   1.4%
34
   1.4%
69
   1.4%
DENMARK
9
   0.4%
9
   0.4%
18
   0.4%
FRANCE
10
   0.4%
10
   0.4%
20
   0.4%
GERMANY
32
   1.3%
32
   1.3%
64
   1.3%
GREECE
8
   0.3%
8
   0.3%
16
   0.3%
HUNGARY
69
   2.8%
69
   2.7%
138
   2.7%
ITALY
35
   1.4%
36
   1.4%
71
   1.4%
JAPAN
133
   5.3%
132
   5.2%
265
   5.3%
LATVIA
12
   0.5%
13
   0.5%
25
   0.5%
LITHUANIA
17
   0.7%
18
   0.7%
35
   0.7%
MALAYSIA
17
   0.7%
17
   0.7%
34
   0.7%
MEXICO
73
   2.9%
73
   2.9%
146
   2.9%
NETHERLANDS
1
   0.0%
2
   0.1%
3
   0.1%
POLAND
288
  11.5%
290
  11.5%
578
  11.5%
PORTUGAL
20
   0.8%
22
   0.9%
42
   0.8%
ROMANIA
200
   8.0%
198
   7.9%
398
   7.9%
RUSSIAN FEDERATION
274
  10.9%
276
  11.0%
550
  11.0%
SLOVAKIA
41
   1.6%
41
   1.6%
82
   1.6%
SOUTH AFRICA
8
   0.3%
8
   0.3%
16
   0.3%
SOUTH KOREA
24
   1.0%
24
   1.0%
48
   1.0%
SPAIN
89
   3.6%
89
   3.5%
178
   3.5%
SWEDEN
2
   0.1%
3
   0.1%
5
   0.1%
TURKEY
96
   3.8%
96
   3.8%
192
   3.8%
UKRAINE
264
  10.5%
265
  10.5%
529
  10.5%
UNITED KINGDOM
13
   0.5%
12
   0.5%
25
   0.5%
UNITED STATES
60
   2.4%
61
   2.4%
121
   2.4%
1.Primary Outcome
Title Event Rate of All-Cause Mortality, Myocardial Infarction (MI), or Stroke
Hide Description Event Rate of all-cause mortality (ACM), MI, or stroke were assessed. Event rate estimated based on the time to the first occurrence of the event were reported in the study. Event Rate / (100 patient [pt]-year [yr]) = 100*n/(total risk exposure), where n is the number of events.
Time Frame Up to Global treatment end date (approximately 54 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat analysis set included all randomized unique participants who signed a valid informed consent. Participants were analyzed according to the treatment group assigned, irrespective of the actual treatment received.
Arm/Group Title Rivaroxaban Placebo
Hide Arm/Group Description:
Participants received 2.5 milligram (mg) tablet of rivaroxaban orally twice daily with standard of care for heart failure and coronary artery disease (as prescribed by the participant's managing physician).
Participants received matching placebo orally twice daily with standard of care for heart failure and coronary artery disease (as prescribed by the participant's managing physician).
Overall Number of Participants Analyzed 2507 2515
Measure Type: Number
Unit of Measure: Event rate per 100 patient-year
13.44 14.27
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rivaroxaban, Placebo
Comments Statistical Analysis 1
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.270
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.94
Confidence Interval (2-Sided) 95%
0.84 to 1.05
Estimation Comments [Not Specified]
2.Primary Outcome
Title Event Rate of Either Fatal Bleeding or Bleeding Into a Critical Space With Potential for Permanent Disability
Hide Description Event rate of either fatal bleeding or bleeding into critical space with potential for permanent disability were assessed. Fatal bleeding event was death within 7 days after a bleeding event which required hospitalization or met International Society on Thrombosis and Haemostasis(ISTH) major bleeding definition criteria. Fatal bleeding events included those met criteria in 3 categories: 1: Any ISTH major bleeding event consider primary cause of death by investigator; 2: Any ISTH major bleeding event not considered to be primary cause of death by investigator but resulted in death within 7 days;3: Any bleeding event resulted in hospital stay and death within 7 days. Bleeding into critical space with potential for permanent disability included 7 critical spaces: intracranial, intraspinal, intraocular. Event rate estimated based on time to first occurrence of event were reported in the study. Event Rate / (100 pt-yr) = 100*n/(total risk exposure), where n is the number of events.
Time Frame Up to 227 Weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Analysis Set included all intent-to-treat participants who received at least one dose of study drug. Here 'N' signifies number of participants who were evaluable for this outcome measure.
Arm/Group Title Rivaroxaban Placebo
Hide Arm/Group Description:
Participants received 2.5 milligram (mg) tablet of rivaroxaban orally twice daily with standard of care for heart failure and coronary artery disease (as prescribed by the participant's managing physician).
Participants received matching placebo orally twice daily with standard of care for heart failure and coronary artery disease (as prescribed by the participant's managing physician).
Overall Number of Participants Analyzed 2499 2509
Measure Type: Number
Unit of Measure: Event rate per 100 patient-year
Fatal Bleeding 0.22 0.22
Critical Space Bleeding with Permanent Disability 0.32 0.48
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rivaroxaban, Placebo
Comments Statistical Analysis 1 (Fatal Bleeding)
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.951
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.03
Confidence Interval (2-Sided) 95%
0.41 to 2.59
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Rivaroxaban, Placebo
Comments Statistical Analysis 2 (Bleeding in Critical Space with Potential for Permanent Disability)
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.253
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.67
Confidence Interval (2-Sided) 95%
0.33 to 1.34
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Event Rate of Cardio Vascular Death or Re-Hospitalization for Worsening of Heart Failure (RHHF)
Hide Description Event rate of cardio vascular (CV) death or re-hospitalization for worsening of heart failure were assessed. Event rate estimated based on the time to the first occurrence of the event were reported in the study. Event Rate / (100 pt-yr) = 100*n/(total risk exposure), where n is the number of events.
Time Frame Up to Global treatment end date (approximately 54 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat analysis set included all randomized unique participants who signed a valid informed consent. Participants were analyzed according to the treatment group assigned, irrespective of the actual treatment received.
Arm/Group Title Rivaroxaban Placebo
Hide Arm/Group Description:
Participants received 2.5 milligram (mg) tablet of rivaroxaban orally twice daily with standard of care for heart failure and coronary artery disease (as prescribed by the participant's managing physician).
Participants received matching placebo orally twice daily with standard of care for heart failure and coronary artery disease (as prescribed by the participant's managing physician).
Overall Number of Participants Analyzed 2507 2515
Measure Type: Number
Unit of Measure: Event rate per 100 patient-year
23.32 23.46
4.Secondary Outcome
Title Event Rate of Cardio Vascular Death
Hide Description Event rate of cardio vascular death were assessed. CV death included deaths due to spontaneous bleeding, MI, stroke, worsening HF and arrhythmias, death due to CV procedures and sudden death. Event rate estimated based on the time to the first occurrence of the event were reported in the study. Event Rate / (100 pt-yr) = 100*n/(total risk exposure), where n is the number of events.
Time Frame Up to Global treatment end date (approximately 54 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat analysis set included all randomized unique participants who signed a valid informed consent. Participants were analyzed according to the treatment group assigned, irrespective of the actual treatment received.
Arm/Group Title Rivaroxaban Placebo
Hide Arm/Group Description:
Participants received 2.5 milligram (mg) tablet of rivaroxaban orally twice daily with standard of care for heart failure and coronary artery disease (as prescribed by the participant's managing physician).
Participants received matching placebo orally twice daily with standard of care for heart failure and coronary artery disease (as prescribed by the participant's managing physician).
Overall Number of Participants Analyzed 2507 2515
Measure Type: Number
Unit of Measure: Event rate per 100 patient-year
9.46 9.96
5.Secondary Outcome
Title Event Rate of Re-Hospitalization for Worsening of Heart Failure
Hide Description Event rate of re-hospitalization for worsening of heart failure were assessed. Event rate estimated based on the time to the first occurrence of the event were reported in the study. Event Rate / (100 pt-yr) = 100*n/(total risk exposure), where n is the number of events.
Time Frame Up to Global treatment end date (approximately 54 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat analysis set included all randomized unique participants who signed a valid informed consent. Participants were analyzed according to the treatment group assigned, irrespective of the actual treatment received.
Arm/Group Title Rivaroxaban Placebo
Hide Arm/Group Description:
Participants received 2.5 milligram (mg) tablet of rivaroxaban orally twice daily with standard of care for heart failure and coronary artery disease (as prescribed by the participant's managing physician).
Participants received matching placebo orally twice daily with standard of care for heart failure and coronary artery disease (as prescribed by the participant's managing physician).
Overall Number of Participants Analyzed 2507 2515
Measure Type: Number
Unit of Measure: Event rate per 100 patient-year
17.24 17.45
6.Secondary Outcome
Title Event Rate of Re-Hospitalization for Cardio Vascular Events (RHCV)
Hide Description Event rate due to cardio vascular events were assessed. Hospitalization for a CV Event required that participants be hospitalized (in-patient or emergency department) for greater than 24 hours and must have met the following criterion:Discharge summary with primary reason for admission listed as CV in nature (example, bleeding, arrhythmia, ACS, MI) other than HF which was captured in the HF re-hospitalization. Event rate estimated based on the time to the first occurrence of the event were reported in the study. Event Rate / (100 pt-yr) = 100*n/(total risk exposure), where n is the number of events.
Time Frame Up to Global treatment end date (approximately 54 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat analysis set included all randomized unique participants who signed a valid informed consent. Participants were analyzed according to the treatment group assigned, irrespective of the actual treatment received.
Arm/Group Title Rivaroxaban Placebo
Hide Arm/Group Description:
Participants received 2.5 milligram (mg) tablet of rivaroxaban orally twice daily with standard of care for heart failure and coronary artery disease (as prescribed by the participant's managing physician).
Participants received matching placebo orally twice daily with standard of care for heart failure and coronary artery disease (as prescribed by the participant's managing physician).
Overall Number of Participants Analyzed 2507 2515
Measure Type: Number
Unit of Measure: Event rate per 100 patient-year
13.30 14.04
7.Secondary Outcome
Title Event Rate of All-Cause Mortality (ACM) or Re-Hospitalization for Worsening Heart Failure
Hide Description Event rate of all-Cause Mortality (ACM) or re-Hospitalization for worsening heart failure were assessed. Event rate estimated based on the time to the first occurrence of the event were reported in the study. Event Rate / (100 pt-yr) = 100*n/(total risk exposure), where n is the number of events.
Time Frame Up to Global treatment end date (approximately 54 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat analysis set included all randomized unique participants who signed a valid informed consent. Participants were analyzed according to the treatment group assigned, irrespective of the actual treatment received.
Arm/Group Title Rivaroxaban Placebo
Hide Arm/Group Description:
Participants received 2.5 milligram (mg) tablet of rivaroxaban orally twice daily with standard of care for heart failure and coronary artery disease (as prescribed by the participant's managing physician).
Participants received matching placebo orally twice daily with standard of care for heart failure and coronary artery disease (as prescribed by the participant's managing physician).
Overall Number of Participants Analyzed 2507 2515
Measure Type: Number
Unit of Measure: Event rate per 100 patient-year
24.84 24.57
8.Secondary Outcome
Title Event Rate of Bleeding Events That Requiring Hospitalization
Hide Description Event rate of bleeding events and required Hospitalization were assessed. Event rate estimated based on the time to the first occurrence of the event were reported in the study. Event Rate / (100 pt-yr) = 100*n/(total risk exposure), where n is the number of events.
Time Frame Up to 227 Weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Analysis Set included all intent-to-treat participants who received at least one dose of study drug. Here 'N' signifies number of participants who were evaluable for this outcome measure.
Arm/Group Title Rivaroxaban Placebo
Hide Arm/Group Description:
Participants received 2.5 milligram (mg) tablet of rivaroxaban orally twice daily with standard of care for heart failure and coronary artery disease (as prescribed by the participant's managing physician).
Participants received matching placebo orally twice daily with standard of care for heart failure and coronary artery disease (as prescribed by the participant's managing physician).
Overall Number of Participants Analyzed 2499 2509
Measure Type: Number
Unit of Measure: Event rate per 100 patient-year
1.52 1.16
9.Secondary Outcome
Title Event Rate of International Society on Thrombosis and Haemostasis (ISTH) Major Bleeding Event
Hide Description Event rate of ISTH major bleeding event were assessed. Event rate estimated based on the time to the first occurrence of the event were reported in the study. Event Rate / (100 pt-yr) = 100*n/(total risk exposure), where n is the number of events.
Time Frame Up to 227 Weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Analysis Set included all intent-to-treat participants who received at least one dose of study drug. Here 'N' signifies number of participants who were evaluable for this outcome measure.
Arm/Group Title Rivaroxaban Placebo
Hide Arm/Group Description:
Participants received 2.5 milligram (mg) tablet of rivaroxaban orally twice daily with standard of care for heart failure and coronary artery disease (as prescribed by the participant's managing physician).
Participants received matching placebo orally twice daily with standard of care for heart failure and coronary artery disease (as prescribed by the participant's managing physician).
Overall Number of Participants Analyzed 2499 2509
Measure Type: Number
Unit of Measure: Event rate per 100 patient-year
2.04 1.21
Time Frame Up to 54 Months
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Rivaroxaban Placebo
Hide Arm/Group Description Participants received 2.5 milligram (mg) tablet of rivaroxaban orally twice daily with standard of care for heart failure and coronary artery disease (as prescribed by the participant's managing physician). Participants received matching placebo orally twice daily with standard of care for heart failure and coronary artery disease (as prescribed by the participant's managing physician).
All-Cause Mortality
Rivaroxaban Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   565/2507 (22.54%)   571/2515 (22.70%) 
Show Serious Adverse Events Hide Serious Adverse Events
Rivaroxaban Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   479/2507 (19.11%)   451/2515 (17.93%) 
Blood and lymphatic system disorders     
Anaemia * 1  12/2507 (0.48%)  7/2515 (0.28%) 
Anaemia Vitamin B12 Deficiency * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Aplastic Anaemia * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Disseminated Intravascular Coagulation * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Iron Deficiency Anaemia * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Lymphadenopathy * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Thrombocytopenia * 1  0/2507 (0.00%)  3/2515 (0.12%) 
Cardiac disorders     
Atrial Fibrillation * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Cardiac Failure * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Cardiac Ventricular Thrombosis * 1  1/2507 (0.04%)  1/2515 (0.04%) 
Cardiogenic Shock * 1  0/2507 (0.00%)  2/2515 (0.08%) 
Cardiorenal Syndrome * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Myocarditis * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Palpitations * 1  1/2507 (0.04%)  1/2515 (0.04%) 
Congenital, familial and genetic disorders     
Arteriovenous Malformation * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Buried Penis Syndrome * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Hydrocele * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Ear and labyrinth disorders     
Vertigo * 1  1/2507 (0.04%)  2/2515 (0.08%) 
Vertigo Positional * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Endocrine disorders     
Basedow's Disease * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Hypothyroidism * 1  1/2507 (0.04%)  1/2515 (0.04%) 
Eye disorders     
Cataract * 1  7/2507 (0.28%)  2/2515 (0.08%) 
Cataract Nuclear * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Diabetic Retinopathy * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Macular Hole * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Ophthalmoplegia * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Retinal Detachment * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Retinopathy Hypertensive * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Subretinal Fibrosis * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Visual Acuity Reduced * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Gastrointestinal disorders     
Abdominal Adhesions * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Abdominal Pain * 1  6/2507 (0.24%)  7/2515 (0.28%) 
Abdominal Pain Upper * 1  1/2507 (0.04%)  1/2515 (0.04%) 
Abdominal Tenderness * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Anal Fissure * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Ascites * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Chronic Gastritis * 1  3/2507 (0.12%)  1/2515 (0.04%) 
Coeliac Disease * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Colitis * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Constipation * 1  2/2507 (0.08%)  1/2515 (0.04%) 
Dental Caries * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Diarrhoea * 1  4/2507 (0.16%)  2/2515 (0.08%) 
Diverticulum Intestinal * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Duodenal Obstruction * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Duodenal Ulcer * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Dyspepsia * 1  2/2507 (0.08%)  3/2515 (0.12%) 
Dysphagia * 1  1/2507 (0.04%)  1/2515 (0.04%) 
Enteritis * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Erosive Duodenitis * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Food Poisoning * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Gastric Ulcer * 1  1/2507 (0.04%)  3/2515 (0.12%) 
Gastritis * 1  2/2507 (0.08%)  4/2515 (0.16%) 
Gastritis Erosive * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Gastrointestinal Angiodysplasia * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Gastrointestinal Disorder * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Gastrointestinal Necrosis * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Gastrooesophageal Reflux Disease * 1  3/2507 (0.12%)  1/2515 (0.04%) 
Gastrooesophageal Sphincter Insufficiency * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Hernial Eventration * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Ileus * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Ileus Paralytic * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Incarcerated Inguinal Hernia * 1  1/2507 (0.04%)  2/2515 (0.08%) 
Incarcerated Umbilical Hernia * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Inflammatory Bowel Disease * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Inguinal Hernia * 1  7/2507 (0.28%)  9/2515 (0.36%) 
Intestinal Infarction * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Intestinal Obstruction * 1  5/2507 (0.20%)  0/2515 (0.00%) 
Ischaemic Enteritis * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Large Intestinal Obstruction * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Large Intestine Polyp * 1  4/2507 (0.16%)  1/2515 (0.04%) 
Nausea * 1  2/2507 (0.08%)  1/2515 (0.04%) 
Pancreatic Disorder * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Pancreatic Necrosis * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Pancreatitis Acute * 1  3/2507 (0.12%)  3/2515 (0.12%) 
Pancreatitis Chronic * 1  2/2507 (0.08%)  1/2515 (0.04%) 
Small Intestinal Obstruction * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Subileus * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Ulcerative Gastritis * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Volvulus of Small Bowel * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Vomiting * 1  3/2507 (0.12%)  2/2515 (0.08%) 
General disorders     
Asthenia * 1  5/2507 (0.20%)  1/2515 (0.04%) 
Chest Discomfort * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Chest Pain * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Death * 1  0/2507 (0.00%)  3/2515 (0.12%) 
Disuse Syndrome * 1  1/2507 (0.04%)  1/2515 (0.04%) 
Drug Withdrawal Syndrome * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Fatigue * 1  0/2507 (0.00%)  2/2515 (0.08%) 
General Physical Health Deterioration * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Heteroplasia * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Hyperthermia Malignant * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Impaired Healing * 1  1/2507 (0.04%)  1/2515 (0.04%) 
Multiple Organ Dysfunction Syndrome * 1  5/2507 (0.20%)  3/2515 (0.12%) 
Non-Cardiac Chest Pain * 1  7/2507 (0.28%)  6/2515 (0.24%) 
Pain * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Pyrexia * 1  4/2507 (0.16%)  4/2515 (0.16%) 
Soft Tissue Inflammation * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Sudden Death * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Hepatobiliary disorders     
Acute Hepatic Failure * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Bile Duct Stone * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Biliary Colic * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Biliary Dilatation * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Cardiac Cirrhosis * 1  2/2507 (0.08%)  1/2515 (0.04%) 
Cholangitis * 1  3/2507 (0.12%)  1/2515 (0.04%) 
Cholangitis Acute * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Cholecystitis * 1  10/2507 (0.40%)  5/2515 (0.20%) 
Cholecystitis Acute * 1  1/2507 (0.04%)  7/2515 (0.28%) 
Cholecystitis Chronic * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Cholelithiasis * 1  2/2507 (0.08%)  3/2515 (0.12%) 
Cirrhosis Alcoholic * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Hepatic Cirrhosis * 1  0/2507 (0.00%)  2/2515 (0.08%) 
Hepatic Failure * 1  2/2507 (0.08%)  1/2515 (0.04%) 
Hepatic Function Abnormal * 1  1/2507 (0.04%)  1/2515 (0.04%) 
Hepatic Lesion * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Hepatitis Acute * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Hepatorenal Failure * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Jaundice * 1  1/2507 (0.04%)  1/2515 (0.04%) 
Liver Disorder * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Portal Hypertension * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Immune system disorders     
Hypersensitivity * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Sarcoidosis * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Infections and infestations     
Abdominal Abscess * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Abscess * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Abscess Limb * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Abscess Soft Tissue * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Anal Abscess * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Appendicitis * 1  3/2507 (0.12%)  1/2515 (0.04%) 
Arthritis Bacterial * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Bacterial Infection * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Bacterial Sepsis * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Bronchitis * 1  12/2507 (0.48%)  9/2515 (0.36%) 
Bronchitis Bacterial * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Bursitis Infective * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Carbuncle * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Cellulitis * 1  7/2507 (0.28%)  7/2515 (0.28%) 
Cellulitis Gangrenous * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Cholecystitis Infective * 1  2/2507 (0.08%)  0/2515 (0.00%) 
Chronic Tonsillitis * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Clostridium Difficile Colitis * 1  1/2507 (0.04%)  1/2515 (0.04%) 
Clostridium Difficile Infection * 1  0/2507 (0.00%)  2/2515 (0.08%) 
Cystitis * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Dengue Fever * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Device Related Infection * 1  1/2507 (0.04%)  1/2515 (0.04%) 
Diabetic Foot Infection * 1  2/2507 (0.08%)  1/2515 (0.04%) 
Diabetic Gangrene * 1  1/2507 (0.04%)  3/2515 (0.12%) 
Diverticulitis * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Douglas' Abscess * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Encephalitis * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Endocarditis * 1  1/2507 (0.04%)  2/2515 (0.08%) 
Enteritis Infectious * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Enterobacter Infection * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Epididymitis * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Erysipelas * 1  2/2507 (0.08%)  1/2515 (0.04%) 
Escherichia Bacteraemia * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Escherichia Infection * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Escherichia Pyelonephritis * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Escherichia Sepsis * 1  0/2507 (0.00%)  3/2515 (0.12%) 
Escherichia Urinary Tract Infection * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Gangrene * 1  7/2507 (0.28%)  4/2515 (0.16%) 
Gastritis Viral * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Gastroenteritis * 1  6/2507 (0.24%)  4/2515 (0.16%) 
Gastroenteritis Shigella * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Gastroenteritis Viral * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Haemorrhagic Pneumonia * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Hepatitis E * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Herpes Zoster * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Herpes Zoster Infection Neurological * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Infected Dermal Cyst * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Infected Skin Ulcer * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Infection * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Infective Spondylitis * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Influenza * 1  7/2507 (0.28%)  2/2515 (0.08%) 
Intervertebral Discitis * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Localised Infection * 1  3/2507 (0.12%)  1/2515 (0.04%) 
Lower Respiratory Tract Infection * 1  2/2507 (0.08%)  0/2515 (0.00%) 
Lung Abscess * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Lung Infection * 1  8/2507 (0.32%)  6/2515 (0.24%) 
Medical Device Site Infection * 1  1/2507 (0.04%)  3/2515 (0.12%) 
Meningitis * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Myiasis * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Osteomyelitis * 1  4/2507 (0.16%)  1/2515 (0.04%) 
Pancreas Infection * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Parotid Abscess * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Periodontitis * 1  2/2507 (0.08%)  1/2515 (0.04%) 
Peritonitis * 1  5/2507 (0.20%)  3/2515 (0.12%) 
Pharyngeal Abscess * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Pharyngitis * 1  2/2507 (0.08%)  0/2515 (0.00%) 
Pneumonia * 1  68/2507 (2.71%)  72/2515 (2.86%) 
Pneumonia Bacterial * 1  1/2507 (0.04%)  5/2515 (0.20%) 
Pneumonia Klebsiella * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Pneumonia Staphylococcal * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Post Procedural Infection * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Postoperative Wound Infection * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Pulmonary Tuberculosis * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Pyelonephritis * 1  2/2507 (0.08%)  0/2515 (0.00%) 
Pyelonephritis Acute * 1  0/2507 (0.00%)  3/2515 (0.12%) 
Pyuria * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Respiratory Tract Infection * 1  10/2507 (0.40%)  8/2515 (0.32%) 
Sepsis * 1  16/2507 (0.64%)  7/2515 (0.28%) 
Septic Shock * 1  4/2507 (0.16%)  6/2515 (0.24%) 
Sinusitis * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Staphylococcal Sepsis * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Syphilis * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Tracheitis * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Upper Respiratory Tract Infection * 1  5/2507 (0.20%)  1/2515 (0.04%) 
Urinary Tract Infection * 1  14/2507 (0.56%)  9/2515 (0.36%) 
Urinary Tract Infection Bacterial * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Urosepsis * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Viral Myocarditis * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Wound Infection * 1  1/2507 (0.04%)  2/2515 (0.08%) 
Injury, poisoning and procedural complications     
Accidental Overdose * 1  2/2507 (0.08%)  2/2515 (0.08%) 
Alcohol Poisoning * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Ankle Fracture * 1  1/2507 (0.04%)  1/2515 (0.04%) 
Bone Fissure * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Burns Third Degree * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Cervical Vertebral Fracture * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Contusion * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Craniocerebral Injury * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Fall * 1  5/2507 (0.20%)  3/2515 (0.12%) 
Femoral Neck Fracture * 1  1/2507 (0.04%)  3/2515 (0.12%) 
Femur Fracture * 1  8/2507 (0.32%)  4/2515 (0.16%) 
Fibula Fracture * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Foot Fracture * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Foreign Body * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Gun Shot Wound * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Hand Fracture * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Head Injury * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Hip Fracture * 1  6/2507 (0.24%)  1/2515 (0.04%) 
Humerus Fracture * 1  0/2507 (0.00%)  2/2515 (0.08%) 
Intentional Overdose * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Limb Injury * 1  1/2507 (0.04%)  1/2515 (0.04%) 
Lower Limb Fracture * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Multiple Fractures * 1  2/2507 (0.08%)  1/2515 (0.04%) 
Patella Fracture * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Pneumothorax Traumatic * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Post Procedural Complication * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Postoperative Renal Failure * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Postoperative Wound Complication * 1  2/2507 (0.08%)  0/2515 (0.00%) 
Radiation Pneumonitis * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Radius Fracture * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Rib Fracture * 1  1/2507 (0.04%)  1/2515 (0.04%) 
Road Traffic Accident * 1  3/2507 (0.12%)  3/2515 (0.12%) 
Spinal Compression Fracture * 1  2/2507 (0.08%)  3/2515 (0.12%) 
Tendon Rupture * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Thermal Burn * 1  2/2507 (0.08%)  3/2515 (0.12%) 
Thoracic Vertebral Fracture * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Tibia Fracture * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Ulna Fracture * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Wound Dehiscence * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Investigations     
Biopsy Pleura * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Biopsy Prostate * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Blood Creatine Phosphokinase Increased * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Blood Creatinine Increased * 1  0/2507 (0.00%)  2/2515 (0.08%) 
Blood Glucose Abnormal * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Blood Glucose Fluctuation * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Hepatic Enzyme Increased * 1  3/2507 (0.12%)  0/2515 (0.00%) 
Liver Function Test Increased * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Oesophagogastroduodenoscopy * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Platelet Count Decreased * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Metabolism and nutrition disorders     
Acidosis * 1  1/2507 (0.04%)  1/2515 (0.04%) 
Cachexia * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Decreased Appetite * 1  0/2507 (0.00%)  2/2515 (0.08%) 
Dehydration * 1  1/2507 (0.04%)  3/2515 (0.12%) 
Diabetes Mellitus * 1  7/2507 (0.28%)  8/2515 (0.32%) 
Diabetes Mellitus Inadequate Control * 1  9/2507 (0.36%)  3/2515 (0.12%) 
Diabetic Ketosis * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Diabetic Metabolic Decompensation * 1  2/2507 (0.08%)  4/2515 (0.16%) 
Electrolyte Imbalance * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Fluid Retention * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Hypercalcaemia * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Hyperglycaemia * 1  3/2507 (0.12%)  3/2515 (0.12%) 
Hyperglycaemic Hyperosmolar Nonketotic Syndrome * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Hyperkalaemia * 1  4/2507 (0.16%)  7/2515 (0.28%) 
Hypervolaemia * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Hypoglycaemia * 1  5/2507 (0.20%)  5/2515 (0.20%) 
Hypokalaemia * 1  1/2507 (0.04%)  1/2515 (0.04%) 
Hyponatraemia * 1  0/2507 (0.00%)  5/2515 (0.20%) 
Hypovolaemia * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Insulin-Requiring Type 2 Diabetes Mellitus * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Lactic Acidosis * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Metabolic Disorder * 1  1/2507 (0.04%)  1/2515 (0.04%) 
Type 1 Diabetes Mellitus * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Type 2 Diabetes Mellitus * 1  5/2507 (0.20%)  3/2515 (0.12%) 
Musculoskeletal and connective tissue disorders     
Arthralgia * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Arthritis * 1  2/2507 (0.08%)  0/2515 (0.00%) 
Back Pain * 1  0/2507 (0.00%)  3/2515 (0.12%) 
Foot Deformity * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Gouty Arthritis * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Intervertebral Disc Degeneration * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Intervertebral Disc Disorder * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Intervertebral Disc Protrusion * 1  4/2507 (0.16%)  1/2515 (0.04%) 
Lumbar Spinal Stenosis * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Muscle Spasms * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Muscular Weakness * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Musculoskeletal Chest Pain * 1  1/2507 (0.04%)  2/2515 (0.08%) 
Myopathy * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Osteitis * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Osteoarthritis * 1  0/2507 (0.00%)  4/2515 (0.16%) 
Osteochondrosis * 1  1/2507 (0.04%)  1/2515 (0.04%) 
Pain in Extremity * 1  1/2507 (0.04%)  1/2515 (0.04%) 
Polymyalgia Rheumatica * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Rheumatoid Arthritis * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Spinal Osteoarthritis * 1  2/2507 (0.08%)  0/2515 (0.00%) 
Spinal Pain * 1  1/2507 (0.04%)  2/2515 (0.08%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Acute Myeloid Leukaemia * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Adenocarcinoma of Colon * 1  1/2507 (0.04%)  1/2515 (0.04%) 
Bladder Cancer * 1  6/2507 (0.24%)  3/2515 (0.12%) 
Bladder Cancer Recurrent * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Brain Neoplasm * 1  1/2507 (0.04%)  1/2515 (0.04%) 
Breast Cancer Stage Ii * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Breast Neoplasm * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Bronchial Carcinoma * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Cervix Carcinoma * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Chronic Lymphocytic Leukaemia * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Clear Cell Renal Cell Carcinoma * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Colon Cancer * 1  7/2507 (0.28%)  3/2515 (0.12%) 
Colon Cancer Metastatic * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Colon Cancer Recurrent * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Colon Neoplasm * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Colorectal Adenocarcinoma * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Colorectal Cancer * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Ear Neoplasm Malignant * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Endometrial Cancer Metastatic * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Epiglottic Carcinoma * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Gallbladder Cancer * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Gastric Cancer * 1  2/2507 (0.08%)  0/2515 (0.00%) 
Gastric Cancer Recurrent * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Gastrooesophageal Cancer * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Hepatic Cancer * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Hepatic Cancer Stage Iv * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Hypopharyngeal Cancer * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Intestinal Adenocarcinoma * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Lipoma * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Lung Adenocarcinoma * 1  0/2507 (0.00%)  2/2515 (0.08%) 
Lung Cancer Metastatic * 1  1/2507 (0.04%)  2/2515 (0.08%) 
Lung Carcinoma Cell Type Unspecified Stage Ii * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Lung Neoplasm * 1  1/2507 (0.04%)  4/2515 (0.16%) 
Lung Neoplasm Malignant * 1  7/2507 (0.28%)  7/2515 (0.28%) 
Lymphoma * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Malignant Melanoma * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Malignant Neoplasm of Unknown Primary Site * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Meningioma * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Metastases to Bone * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Metastases to Central Nervous System * 1  1/2507 (0.04%)  1/2515 (0.04%) 
Metastases to Liver * 1  4/2507 (0.16%)  1/2515 (0.04%) 
Metastases to Lung * 1  0/2507 (0.00%)  2/2515 (0.08%) 
Metastatic Neoplasm * 1  2/2507 (0.08%)  0/2515 (0.00%) 
Metastatic Renal Cell Carcinoma * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Monoclonal Gammopathy * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Neoplasm Malignant * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Neoplasm of Orbit * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Non-Hodgkin's Lymphoma * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Oesophageal Adenocarcinoma * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Oropharyngeal Squamous Cell Carcinoma * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Pancreatic Carcinoma * 1  2/2507 (0.08%)  1/2515 (0.04%) 
Pancreatic Carcinoma Metastatic * 1  0/2507 (0.00%)  2/2515 (0.08%) 
Plasma Cell Myeloma * 1  1/2507 (0.04%)  2/2515 (0.08%) 
Prostate Cancer * 1  4/2507 (0.16%)  4/2515 (0.16%) 
Prostate Cancer Metastatic * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Prostate Cancer Stage Iv * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Prostatic Adenoma * 1  1/2507 (0.04%)  1/2515 (0.04%) 
Rectal Adenocarcinoma * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Rectal Cancer Stage Iii * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Rectal Neoplasm * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Renal Cancer * 1  2/2507 (0.08%)  2/2515 (0.08%) 
Renal Cancer Metastatic * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Renal Cell Carcinoma * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Renal Neoplasm * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Small Cell Carcinoma * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Small Intestine Carcinoma * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Squamous Cell Carcinoma * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Testis Cancer * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Throat Cancer * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Thyroid Cancer * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Tongue Neoplasm * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Tongue Neoplasm Malignant Stage Unspecified * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Transitional Cell Carcinoma * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Nervous system disorders     
Amyotrophic Lateral Sclerosis * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Brain Injury * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Brain Oedema * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Carpal Tunnel Syndrome * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Cervicobrachial Syndrome * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Dementia * 1  2/2507 (0.08%)  0/2515 (0.00%) 
Diabetic Neuropathy * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Dizziness Postural * 1  1/2507 (0.04%)  1/2515 (0.04%) 
Encephalopathy * 1  1/2507 (0.04%)  1/2515 (0.04%) 
Epilepsy * 1  2/2507 (0.08%)  1/2515 (0.04%) 
Headache * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Hemianopia * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Hypoglycaemic Coma * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Hypoxic-Ischaemic Encephalopathy * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Intercostal Neuralgia * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Ischaemic Neuropathy * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Loss of Consciousness * 1  2/2507 (0.08%)  1/2515 (0.04%) 
Lumbosacral Radiculopathy * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Metabolic Encephalopathy * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Neuroglycopenia * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Neuropathy Peripheral * 1  2/2507 (0.08%)  0/2515 (0.00%) 
Sciatica * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Seizure * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Syncope * 1  6/2507 (0.24%)  3/2515 (0.12%) 
Transient Ischaemic Attack * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Vertebrobasilar Insufficiency * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Product Issues     
Device Dislocation * 1  0/2507 (0.00%)  2/2515 (0.08%) 
Psychiatric disorders     
Alcohol Abuse * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Alcohol Withdrawal Syndrome * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Alcoholism * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Antisocial Personality Disorder * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Anxiety Disorder * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Confusional State * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Delirium * 1  1/2507 (0.04%)  1/2515 (0.04%) 
Depression * 1  2/2507 (0.08%)  1/2515 (0.04%) 
Illness Anxiety Disorder * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Major Depression * 1  1/2507 (0.04%)  2/2515 (0.08%) 
Psychotic Disorder Due to A General Medical Condition * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Self-Injurious Ideation * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Suicidal Ideation * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Suicide Attempt * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Renal and urinary disorders     
Acute Kidney Injury * 1  17/2507 (0.68%)  28/2515 (1.11%) 
Calculus Urinary * 1  1/2507 (0.04%)  1/2515 (0.04%) 
Chronic Kidney Disease * 1  14/2507 (0.56%)  7/2515 (0.28%) 
Diabetic Nephropathy * 1  1/2507 (0.04%)  1/2515 (0.04%) 
Dysuria * 1  1/2507 (0.04%)  0/2515 (0.00%) 
End Stage Renal Disease * 1  2/2507 (0.08%)  1/2515 (0.04%) 
Glomerulonephritis * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Iga Nephropathy * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Nephrolithiasis * 1  3/2507 (0.12%)  0/2515 (0.00%) 
Nephropathy Toxic * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Nephrotic Syndrome * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Prerenal Failure * 1  2/2507 (0.08%)  0/2515 (0.00%) 
Renal Artery Stenosis * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Renal Colic * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Renal Failure * 1  12/2507 (0.48%)  12/2515 (0.48%) 
Renal Impairment * 1  4/2507 (0.16%)  9/2515 (0.36%) 
Ureterolithiasis * 1  2/2507 (0.08%)  0/2515 (0.00%) 
Urethral Stenosis * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Urinary Retention * 1  3/2507 (0.12%)  1/2515 (0.04%) 
Urinary Tract Disorder * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Urinary Tract Obstruction * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Reproductive system and breast disorders     
Benign Prostatic Hyperplasia * 1  4/2507 (0.16%)  1/2515 (0.04%) 
Cystocele * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Gynaecomastia * 1  1/2507 (0.04%)  1/2515 (0.04%) 
Ovarian Cyst Torsion * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Prostatitis * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Uterine Polyp * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Respiratory, thoracic and mediastinal disorders     
Acute Pulmonary Oedema * 1  0/2507 (0.00%)  3/2515 (0.12%) 
Acute Respiratory Failure * 1  2/2507 (0.08%)  2/2515 (0.08%) 
Asthma * 1  5/2507 (0.20%)  2/2515 (0.08%) 
Atelectasis * 1  1/2507 (0.04%)  1/2515 (0.04%) 
Bronchiectasis * 1  2/2507 (0.08%)  0/2515 (0.00%) 
Bronchitis Chronic * 1  4/2507 (0.16%)  1/2515 (0.04%) 
Bronchospasm * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Chronic Obstructive Pulmonary Disease * 1  15/2507 (0.60%)  16/2515 (0.64%) 
Cough * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Dyspnoea * 1  4/2507 (0.16%)  2/2515 (0.08%) 
Dyspnoea Paroxysmal Nocturnal * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Emphysema * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Hypoxia * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Interstitial Lung Disease * 1  1/2507 (0.04%)  2/2515 (0.08%) 
Lung Disorder * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Lung Infiltration * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Necrotising Bronchiolitis * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Pleural Effusion * 1  3/2507 (0.12%)  2/2515 (0.08%) 
Pleurisy * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Pneumonia Aspiration * 1  4/2507 (0.16%)  1/2515 (0.04%) 
Pneumothorax * 1  1/2507 (0.04%)  1/2515 (0.04%) 
Pulmonary Fibrosis * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Pulmonary Hypertension * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Pulmonary Mass * 1  2/2507 (0.08%)  1/2515 (0.04%) 
Pulmonary Oedema * 1  0/2507 (0.00%)  3/2515 (0.12%) 
Respiratory Arrest * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Respiratory Failure * 1  9/2507 (0.36%)  5/2515 (0.20%) 
Respiratory Tract Inflammation * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Sleep Apnoea Syndrome * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Vocal Cord Thickening * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Skin and subcutaneous tissue disorders     
Angioedema * 1  1/2507 (0.04%)  1/2515 (0.04%) 
Decubitus Ulcer * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Diabetic Foot * 1  6/2507 (0.24%)  4/2515 (0.16%) 
Dyshidrotic Eczema * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Hypersensitivity Vasculitis * 1  0/2507 (0.00%)  2/2515 (0.08%) 
Necrobiosis Lipoidica Diabeticorum * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Rash Generalised * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Rash Macular * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Skin Lesion * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Skin Ulcer * 1  1/2507 (0.04%)  2/2515 (0.08%) 
Toxic Epidermal Necrolysis * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Surgical and medical procedures     
Anal Sphincterotomy * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Bile Duct Stent Removal * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Breast Tumour Excision * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Cataract Operation * 1  3/2507 (0.12%)  2/2515 (0.08%) 
Chemotherapy * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Cyst Removal * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Debridement * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Diabetes Mellitus Management * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Drug Therapy * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Hernia Repair * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Ileostomy * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Inguinal Hernia Repair * 1  2/2507 (0.08%)  0/2515 (0.00%) 
Insertion of Ambulatory Peritoneal Catheter * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Leg Amputation * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Peripheral Artery Bypass * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Prosthetic Vessel Implantation * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Removal of Ambulatory Peritoneal Catheter * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Spinal Fusion Surgery * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Spinal Laminectomy * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Transurethral Prostatectomy * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Vascular disorders     
Aortic Aneurysm * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Aortic Dissection * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Arterial Haemorrhage * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Arteriosclerosis * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Circulatory Collapse * 1  2/2507 (0.08%)  1/2515 (0.04%) 
Cryoglobulinaemia * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Diabetic Vascular Disorder * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Extremity Necrosis * 1  3/2507 (0.12%)  0/2515 (0.00%) 
Hypertension * 1  0/2507 (0.00%)  2/2515 (0.08%) 
Hypotension * 1  4/2507 (0.16%)  2/2515 (0.08%) 
Hypovolaemic Shock * 1  2/2507 (0.08%)  0/2515 (0.00%) 
Orthostatic Hypotension * 1  0/2507 (0.00%)  2/2515 (0.08%) 
Peripheral Arterial Occlusive Disease * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Peripheral Ischaemia * 1  2/2507 (0.08%)  0/2515 (0.00%) 
Peripheral Vascular Disorder * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Phlebitis Superficial * 1  0/2507 (0.00%)  1/2515 (0.04%) 
Subclavian Artery Stenosis * 1  1/2507 (0.04%)  0/2515 (0.00%) 
Thrombophlebitis * 1  1/2507 (0.04%)  0/2515 (0.00%) 
1
Term from vocabulary, MedDRA Version 20.1
*
Indicates events were collected by non-systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 2%
Rivaroxaban Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   53/2507 (2.11%)   60/2515 (2.39%) 
Infections and infestations     
Nasopharyngitis * 1  53/2507 (2.11%)  60/2515 (2.39%) 
1
Term from vocabulary, MedDRA Version 20.1
*
Indicates events were collected by non-systematic assessment
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.
A copy of the manuscript must be provided to the sponsor for review at least 60 days before submission for publication or presentation. If requested in writing, such publication will be withheld for up to an additional 60 days.
Results Point of Contact
Name/Title: SENIOR DIRECTOR, CLINICAL LEADER CV
Organization: Janssen Research & Development, LLC
Phone: 844-434-4210
Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT01877915     History of Changes
Other Study ID Numbers: CR101940
RIVAROXHFA3001 ( Other Identifier: Janssen Research & Development, LLC )
2013-000046-19 ( EudraCT Number )
First Submitted: June 12, 2013
First Posted: June 14, 2013
Results First Submitted: April 18, 2019
Results First Posted: May 10, 2019
Last Update Posted: May 10, 2019