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Evaluation of the Effects of Canagliflozin on Renal and Cardiovascular Outcomes in Participants With Diabetic Nephropathy (CREDENCE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02065791
Recruitment Status : Completed
First Posted : February 19, 2014
Results First Posted : November 20, 2019
Last Update Posted : December 5, 2019
Sponsor:
Collaborator:
The George Institute for Global Health, Australia
Information provided by (Responsible Party):
Janssen Research & Development, LLC

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Conditions Diabetes Mellitus, Type 2
Diabetic Nephropathy
Interventions Drug: Canagliflozin
Drug: Placebo
Enrollment 4401
Recruitment Details  
Pre-assignment Details A total of 12900 participants were pre-screened, of those, 8932 were screened. A total of 4401 participants were randomized, with 2199 and 2202 participants assigned to placebo and canagliflozin 100 milligrams (mg), respectively.
Arm/Group Title Placebo Canagliflozin 100 mg
Hide Arm/Group Description Participants received matching placebo orally once daily. Participants received canagliflozin 100 milligram (mg) orally once daily.
Period Title: Overall Study
Started 2199 2202
Treated 2197 2200
Completed 2174 2187
Not Completed 25 15
Reason Not Completed
Closed Site             1             1
Withdrawal by Subject             11             5
Lost to Follow-up             13             9
Arm/Group Title Placebo Canagliflozin 100 mg Total
Hide Arm/Group Description Participants received matching placebo orally once daily. Participants received canagliflozin 100 milligram (mg) orally once daily. Total of all reporting groups
Overall Number of Baseline Participants 2199 2202 4401
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 2199 participants 2202 participants 4401 participants
63.2  (9.23) 62.9  (9.17) 63  (9.2)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 2199 participants 2202 participants 4401 participants
Female
732
  33.3%
762
  34.6%
1494
  33.9%
Male
1467
  66.7%
1440
  65.4%
2907
  66.1%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 2199 participants 2202 participants 4401 participants
Hispanic or Latino
706
  32.1%
717
  32.6%
1423
  32.3%
Not Hispanic or Latino
1457
  66.3%
1436
  65.2%
2893
  65.7%
Unknown or Not Reported
36
   1.6%
49
   2.2%
85
   1.9%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 2199 participants 2202 participants 4401 participants
Asian
452
  20.6%
425
  19.3%
877
  19.9%
Black or African American
112
   5.1%
112
   5.1%
224
   5.1%
Hispanic or Latino
554
  25.2%
567
  25.7%
1121
  25.5%
Other
199
   9.0%
189
   8.6%
388
   8.8%
White Non-Hispanic
882
  40.1%
909
  41.3%
1791
  40.7%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 2199 participants 2202 participants 4401 participants
ARGENTINA
205
   9.3%
221
  10.0%
426
   9.7%
AUSTRALIA
18
   0.8%
20
   0.9%
38
   0.9%
BRAZIL
162
   7.4%
152
   6.9%
314
   7.1%
BULGARIA
13
   0.6%
16
   0.7%
29
   0.7%
CANADA
93
   4.2%
79
   3.6%
172
   3.9%
CHILE
30
   1.4%
22
   1.0%
52
   1.2%
CHINA
63
   2.9%
66
   3.0%
129
   2.9%
COLOMBIA
42
   1.9%
52
   2.4%
94
   2.1%
CZECH REPUBLIC
26
   1.2%
31
   1.4%
57
   1.3%
FRANCE
33
   1.5%
28
   1.3%
61
   1.4%
GERMANY
6
   0.3%
5
   0.2%
11
   0.2%
GUATEMALA
26
   1.2%
29
   1.3%
55
   1.2%
HUNGARY
68
   3.1%
67
   3.0%
135
   3.1%
INDIA
82
   3.7%
62
   2.8%
144
   3.3%
ITALY
39
   1.8%
51
   2.3%
90
   2.0%
JAPAN
53
   2.4%
57
   2.6%
110
   2.5%
LITHUANIA
3
   0.1%
4
   0.2%
7
   0.2%
MALAYSIA
72
   3.3%
63
   2.9%
135
   3.1%
MEXICO
152
   6.9%
151
   6.9%
303
   6.9%
NEW ZEALAND
30
   1.4%
31
   1.4%
61
   1.4%
PHILIPPINES
35
   1.6%
36
   1.6%
71
   1.6%
POLAND
27
   1.2%
23
   1.0%
50
   1.1%
ROMANIA
27
   1.2%
32
   1.5%
59
   1.3%
RUSSIAN FEDERATION
76
   3.5%
57
   2.6%
133
   3.0%
SERBIA
19
   0.9%
21
   1.0%
40
   0.9%
SLOVAKIA
32
   1.5%
34
   1.5%
66
   1.5%
SOUTH AFRICA
34
   1.5%
28
   1.3%
62
   1.4%
SOUTH KOREA
58
   2.6%
64
   2.9%
122
   2.8%
SPAIN
58
   2.6%
83
   3.8%
141
   3.2%
TAIWAN
22
   1.0%
15
   0.7%
37
   0.8%
UKRAINE
173
   7.9%
198
   9.0%
371
   8.4%
UNITED ARAB EMIRATES
0
   0.0%
1
   0.0%
1
   0.0%
UNITED KINGDOM
59
   2.7%
59
   2.7%
118
   2.7%
UNITED STATES
363
  16.5%
344
  15.6%
707
  16.1%
1.Primary Outcome
Title Primary Composite Endpoint of Doubling of Serum Creatinine (DoSC), End-stage Kidney Disease (ESKD), and Renal or Cardiovascular (CV) Death
Hide Description Primary composite endpoint is the composite of DoSC, ESKD, and renal or CV death. DoSC: from baseline average determination (sustained and confirmed by repeat central laboratory measure after at least 30 days and preferably within 60 days). ESKD: as initiation of maintenance dialysis for at least 30 days, or renal transplantation, or an estimated glomerular filtration rate (eGFR) value of less than (<)15 milliliters per minute per 1.73 square meter (mL/min/1.73 m^2) (sustained and confirmed by repeat central laboratory measure after at least 30 days and preferably within 60 days). Renal death: death in participants who had reached ESKD, died without initiating renal replacement therapy, and no other cause of death was determined via adjudication. Adjudication of these events by Endpoint Adjudication Committee (EAC) was performed in blinded fashion. Event rate estimated based on time to first occurrence of primary composite endpoint are presented.
Time Frame Up to 4.6 years
Hide Outcome Measure Data
Hide Analysis Population Description
The Intent-to-treat (ITT) population consisted of all randomized participants.
Arm/Group Title Placebo Canagliflozin 100 mg
Hide Arm/Group Description:
Participants received matching placebo orally once daily.
Participants received canagliflozin 100 milligram (mg) orally once daily.
Overall Number of Participants Analyzed 2199 2202
Measure Type: Number
Unit of Measure: Event rate per 1000 participant-years
61.24 43.21
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Canagliflozin 100 mg
Comments Comparison for canagliflozin versus placebo is reported here.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method Cox Proportional Hazard
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.70
Confidence Interval (2-Sided) 95%
0.59 to 0.82
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Composite Endpoint of CV Death and Hospitalized Heart Failure (HHF)
Hide Description The composite endpoint included CV death and HHF. CV death included death due to myocardial infarction (MI), stroke, heart failure, sudden death, death during a CV procedure or as a result of procedure-related complications, or death due to other CV causes. For analytic purposes, undetermined causes of death were considered CV deaths. In determining whether a death event was CV in nature, the EAC took into consideration both the proximate and underlying causes. Adjudication of these events by the EAC was performed in a blinded fashion. Event rate estimated based on the time to the first occurrence of the composite endpoint of CV death and HHF are presented.
Time Frame Up to 4.6 years
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population consisted of all randomized participants.
Arm/Group Title Placebo Canagliflozin 100 mg
Hide Arm/Group Description:
Participants received matching placebo orally once daily.
Participants received canagliflozin 100 milligram (mg) orally once daily.
Overall Number of Participants Analyzed 2199 2202
Measure Type: Number
Unit of Measure: Event rate per 1000 participant-years
45.44 31.47
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Canagliflozin 100 mg
Comments Comparison for canagliflozin versus placebo is reported here.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.0001
Comments [Not Specified]
Method Cox proportional hazard
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.69
Confidence Interval (2-Sided) 95%
0.57 to 0.83
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Major Adverse Cardiac Event (MACE)
Hide Description The composite endpoint included CV death, non-fatal MI, and non-fatal stroke (that is, 3-point MACE). Adjudication of these events by the EAC was performed in a blinded fashion. Event rate estimated based on the time to the first occurrence of MACE are presented.
Time Frame Up to 4.6 years
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population consisted of all randomized participants.
Arm/Group Title Placebo Canagliflozin 100 mg
Hide Arm/Group Description:
Participants received matching placebo orally once daily.
Participants received canagliflozin 100 milligram (mg) orally once daily.
Overall Number of Participants Analyzed 2199 2202
Measure Type: Number
Unit of Measure: Event rate per 1000 participant-years
48.67 38.71
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Canagliflozin 100 mg
Comments Comparison for canagliflozin versus placebo is reported here.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.0121
Comments [Not Specified]
Method Cox proportional hazard
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.80
Confidence Interval (2-Sided) 95%
0.67 to 0.95
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Hospitalized Heart Failure (HHF)
Hide Description Adjudication of these events by the Endpoint Adjudication Committee (EAC) was performed in a blinded fashion. Event rate estimated based on the time to the first occurrence of hospitalized heart failure are presented.
Time Frame Up to 4.6 years
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population consisted of all randomized participants.
Arm/Group Title Placebo Canagliflozin 100 mg
Hide Arm/Group Description:
Participants received matching placebo orally once daily.
Participants received canagliflozin 100 milligram (mg) orally once daily.
Overall Number of Participants Analyzed 2199 2202
Measure Type: Number
Unit of Measure: Event rate per 1000 participant-years
25.33 15.65
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Canagliflozin 100 mg
Comments Comparison for canagliflozin versus placebo is reported here.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.0003
Comments [Not Specified]
Method Cox proportional hazards
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.61
Confidence Interval (2-Sided) 95%
0.47 to 0.80
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Renal Composite Endpoint
Hide Description The renal composite endpoint included composite of DoSC, ESKD and Renal death. DoSC: from the baseline average determination (sustained and confirmed by repeat central laboratory measure after at least 30 days and preferably within 60 days). ESKD: initiation of maintenance dialysis for at least 30 days, or renal transplantation, or an eGFR value of <15 mL/min/1.73 m^2 (sustained and confirmed by repeat central laboratory measure after at least 30 days and preferably within 60 days). Renal death: death in participants who have reached ESKD, died without initiating renal replacement therapy, and no other cause of death was determined via adjudication. Adjudication of these events by the EAC was performed in a blinded fashion. Event rate estimated based on the time to the first occurrence of the renal composite endpoint are presented.
Time Frame Up to 4.6 years
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population consisted of all randomized participant.
Arm/Group Title Placebo Canagliflozin 100 mg
Hide Arm/Group Description:
Participants received matching placebo orally once daily.
Participants received canagliflozin 100 milligram (mg) orally once daily.
Overall Number of Participants Analyzed 2199 2202
Measure Type: Number
Unit of Measure: Event rate per 1000 participant-years
40.36 26.99
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Canagliflozin 100 mg
Comments Comparison for canagliflozin versus placebo is reported here.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Cox proportional hazards
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.66
Confidence Interval (2-Sided) 95%
0.53 to 0.81
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Cardiovascular (CV) Death
Hide Description CV death included death due to MI, stroke, heart failure, sudden death, death during a CV procedure or as a result of procedure-related complications, or death due to other CV causes. For analytic purposes, undetermined causes of death were considered CV deaths. In determining whether a death event was a CV in nature, the EAC took into consideration both the proximate and underlying causes. Adjudication of these events by the EAC was performed in a blinded fashion. Event rate estimated based on the time to the first occurrence of CV death are presented.
Time Frame Up to 4.6 years
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population consisted of all randomized participants.
Arm/Group Title Placebo Canagliflozin 100 mg
Hide Arm/Group Description:
Participants received matching placebo orally once daily.
Participants received canagliflozin 100 milligram (mg) orally once daily.
Overall Number of Participants Analyzed 2199 2202
Measure Type: Number
Unit of Measure: Event rate per 1000 participant-years
24.38 19.01
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Canagliflozin 100 mg
Comments Comparison for canagliflozin versus placebo is reported here.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.0502
Comments [Not Specified]
Method Cox proportional hazards
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.78
Confidence Interval (2-Sided) 95%
0.61 to 1.00
Estimation Comments [Not Specified]
7.Secondary Outcome
Title All-cause Mortality
Hide Description Adjudication of these events by Endpoint Adjudication Committee (EAC) was performed in a blinded fashion. Event rate estimated based on time to first occurrence of all-cause mortality are presented.
Time Frame Up to 4.6 years
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population consisted of all randomized participants.
Arm/Group Title Placebo Canagliflozin 100 mg
Hide Arm/Group Description:
Participants received matching placebo orally once daily.
Participants received canagliflozin 100 milligram (mg) orally once daily.
Overall Number of Participants Analyzed 2199 2202
Measure Type: Number
Unit of Measure: Event rate per 1000 participant-years
35.00 29.04
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Canagliflozin 100 mg
Comments Comparison for canagliflozin versus placebo is reported here.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.0727
Comments [Not Specified]
Method Cox proportional hazard
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.83
Confidence Interval (2-Sided) 95%
0.68 to 1.02
Estimation Comments [Not Specified]
8.Secondary Outcome
Title CV Composite Endpoint
Hide Description The CV composite endpoint included the CV death, non-fatal MI, non-fatal stroke, hospitalized heart failure, and hospitalized unstable angina. CV death included death due to MI, stroke, heart failure, sudden death, death during a CV procedure or as a result of procedure-related complications, or death due to other CV causes. For analytic purposes, undetermined causes of death were considered CV deaths. In determining whether a death event was a CV in nature, the EAC took into consideration both the proximate and underlying causes. Adjudication of these events by the EAC was performed in a blinded fashion. Event rate estimated based on the time to the first occurrence of the CV composite endpoint are presented.
Time Frame Up to 4.6 years
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population consisted of all randomized participant.
Arm/Group Title Placebo Canagliflozin 100 mg
Hide Arm/Group Description:
Participants received matching placebo orally once daily.
Participants received canagliflozin 100 milligram (mg) orally once daily.
Overall Number of Participants Analyzed 2199 2202
Measure Type: Number
Unit of Measure: Event rate per 1000 participant-years
66.95 49.35
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Canagliflozin 100 mg
Comments Comparison for canagliflozin versus placebo is reported here.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0001
Comments [Not Specified]
Method Cox proportional hazards
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.74
Confidence Interval (2-Sided) 95%
0.63 to 0.86
Estimation Comments [Not Specified]
Time Frame Up to 4.6 years
Adverse Event Reporting Description Safety population included all randomized participants who received at least 1 dose of study drug.
 
Arm/Group Title Placebo Canagliflozin 100 mg
Hide Arm/Group Description Participants received matching placebo orally once daily. Participants received canagliflozin 100 milligram (mg) orally once daily.
All-Cause Mortality
Placebo Canagliflozin 100 mg
Affected / at Risk (%) Affected / at Risk (%)
Total   193/2197 (8.78%)   164/2200 (7.45%) 
Hide Serious Adverse Events
Placebo Canagliflozin 100 mg
Affected / at Risk (%) Affected / at Risk (%)
Total   806/2197 (36.69%)   737/2200 (33.50%) 
Blood and lymphatic system disorders     
Anaemia * 1  10/2197 (0.46%)  7/2200 (0.32%) 
Anaemia Vitamin B12 Deficiency * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Bicytopenia * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Disseminated Intravascular Coagulation * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Haemorrhagic Anaemia * 1  2/2197 (0.09%)  2/2200 (0.09%) 
Hypochromic Anaemia * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Iron Deficiency Anaemia * 1  0/2197 (0.00%)  2/2200 (0.09%) 
Lymphadenopathy * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Nephrogenic Anaemia * 1  2/2197 (0.09%)  1/2200 (0.05%) 
Normochromic Normocytic Anaemia * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Normocytic Anaemia * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Pancytopenia * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Thrombocytopenia * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Cardiac disorders     
Acute Coronary Syndrome * 1  8/2197 (0.36%)  12/2200 (0.55%) 
Acute Left Ventricular Failure * 1  4/2197 (0.18%)  0/2200 (0.00%) 
Acute Myocardial Infarction * 1  38/2197 (1.73%)  38/2200 (1.73%) 
Angina Pectoris * 1  14/2197 (0.64%)  21/2200 (0.95%) 
Angina Unstable * 1  29/2197 (1.32%)  17/2200 (0.77%) 
Arrhythmia * 1  1/2197 (0.05%)  2/2200 (0.09%) 
Arteriosclerosis Coronary Artery * 1  3/2197 (0.14%)  4/2200 (0.18%) 
Atrial Fibrillation * 1  19/2197 (0.86%)  16/2200 (0.73%) 
Atrial Flutter * 1  2/2197 (0.09%)  2/2200 (0.09%) 
Atrioventricular Block * 1  2/2197 (0.09%)  2/2200 (0.09%) 
Atrioventricular Block Complete * 1  2/2197 (0.09%)  1/2200 (0.05%) 
Atrioventricular Block First Degree * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Bradycardia * 1  3/2197 (0.14%)  2/2200 (0.09%) 
Brugada Syndrome * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Cardiac Arrest * 1  7/2197 (0.32%)  5/2200 (0.23%) 
Cardiac Asthma * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Cardiac Disorder * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Cardiac Failure * 1  50/2197 (2.28%)  34/2200 (1.55%) 
Cardiac Failure Acute * 1  6/2197 (0.27%)  6/2200 (0.27%) 
Cardiac Failure Chronic * 1  4/2197 (0.18%)  2/2200 (0.09%) 
Cardiac Failure Congestive * 1  48/2197 (2.18%)  24/2200 (1.09%) 
Cardiac Fibrillation * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Cardiac Tamponade * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Cardio-Respiratory Arrest * 1  3/2197 (0.14%)  4/2200 (0.18%) 
Cardiogenic Shock * 1  8/2197 (0.36%)  2/2200 (0.09%) 
Cardiomyopathy * 1  2/2197 (0.09%)  0/2200 (0.00%) 
Cardiorenal Syndrome * 1  1/2197 (0.05%)  1/2200 (0.05%) 
Chronic Left Ventricular Failure * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Chronic Right Ventricular Failure * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Cor Pulmonale * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Coronary Artery Disease * 1  23/2197 (1.05%)  9/2200 (0.41%) 
Coronary Artery Insufficiency * 1  2/2197 (0.09%)  1/2200 (0.05%) 
Coronary Artery Occlusion * 1  0/2197 (0.00%)  3/2200 (0.14%) 
Coronary Artery Stenosis * 1  5/2197 (0.23%)  3/2200 (0.14%) 
Hypertensive Heart Disease * 1  0/2197 (0.00%)  2/2200 (0.09%) 
Ischaemic Cardiomyopathy * 1  6/2197 (0.27%)  4/2200 (0.18%) 
Left Ventricular Failure * 1  5/2197 (0.23%)  3/2200 (0.14%) 
Mitral Valve Incompetence * 1  3/2197 (0.14%)  1/2200 (0.05%) 
Myocardial Infarction * 1  27/2197 (1.23%)  22/2200 (1.00%) 
Myocardial Ischaemia * 1  8/2197 (0.36%)  8/2200 (0.36%) 
Myocarditis * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Pericardial Effusion * 1  2/2197 (0.09%)  2/2200 (0.09%) 
Pericardial Haemorrhage * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Pericarditis * 1  1/2197 (0.05%)  1/2200 (0.05%) 
Pulseless Electrical Activity * 1  1/2197 (0.05%)  1/2200 (0.05%) 
Right Ventricular Failure * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Sinus Node Dysfunction * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Supraventricular Tachycardia * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Tricuspid Valve Incompetence * 1  2/2197 (0.09%)  0/2200 (0.00%) 
Ventricular Arrhythmia * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Ventricular Extrasystoles * 1  1/2197 (0.05%)  2/2200 (0.09%) 
Ventricular Fibrillation * 1  2/2197 (0.09%)  1/2200 (0.05%) 
Ventricular Tachycardia * 1  2/2197 (0.09%)  1/2200 (0.05%) 
Ear and labyrinth disorders     
Vertigo * 1  3/2197 (0.14%)  2/2200 (0.09%) 
Vertigo Positional * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Endocrine disorders     
Goitre * 1  0/2197 (0.00%)  2/2200 (0.09%) 
Hyperparathyroidism * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Hyperthyroidism * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Hypothyroidism * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Inappropriate Antidiuretic Hormone Secretion * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Thyroid Mass * 1  0/2197 (0.00%)  2/2200 (0.09%) 
Eye disorders     
Amaurosis * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Angle Closure Glaucoma * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Cataract * 1  9/2197 (0.41%)  8/2200 (0.36%) 
Cataract Subcapsular * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Diabetic Retinopathy * 1  4/2197 (0.18%)  7/2200 (0.32%) 
Eye Haemorrhage * 1  3/2197 (0.14%)  1/2200 (0.05%) 
Eyelid Ptosis * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Glaucoma * 1  2/2197 (0.09%)  1/2200 (0.05%) 
Keratitis * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Maculopathy * 1  0/2197 (0.00%)  2/2200 (0.09%) 
Neovascular Age-Related Macular Degeneration * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Optic Ischaemic Neuropathy * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Retinal Detachment * 1  2/2197 (0.09%)  3/2200 (0.14%) 
Rhegmatogenous Retinal Detachment * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Tractional Retinal Detachment * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Uveitis * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Vision Blurred * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Visual Impairment * 1  2/2197 (0.09%)  1/2200 (0.05%) 
Vitreous Adhesions * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Vitreous Haemorrhage * 1  1/2197 (0.05%)  4/2200 (0.18%) 
Gastrointestinal disorders     
Abdominal Fat Apron * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Abdominal Incarcerated Hernia * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Abdominal Pain * 1  2/2197 (0.09%)  0/2200 (0.00%) 
Abdominal Pain Lower * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Abdominal Pain Upper * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Anal Fistula * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Anal Haemorrhage * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Chronic Gastritis * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Colitis * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Colitis Ischaemic * 1  2/2197 (0.09%)  0/2200 (0.00%) 
Constipation * 1  2/2197 (0.09%)  0/2200 (0.00%) 
Diabetic Gastroparesis * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Diarrhoea * 1  2/2197 (0.09%)  3/2200 (0.14%) 
Diverticulum * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Diverticulum Intestinal * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Diverticulum Intestinal Haemorrhagic * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Duodenal Ulcer * 1  1/2197 (0.05%)  2/2200 (0.09%) 
Duodenal Ulcer Haemorrhage * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Duodenitis * 1  0/2197 (0.00%)  2/2200 (0.09%) 
Enteritis * 1  3/2197 (0.14%)  0/2200 (0.00%) 
Enterocolitis * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Enterovesical Fistula * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Epulis * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Faeces Discoloured * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Food Poisoning * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Gastric Ulcer * 1  0/2197 (0.00%)  2/2200 (0.09%) 
Gastritis * 1  1/2197 (0.05%)  3/2200 (0.14%) 
Gastrointestinal Haemorrhage * 1  6/2197 (0.27%)  4/2200 (0.18%) 
Gastrooesophageal Reflux Disease * 1  2/2197 (0.09%)  0/2200 (0.00%) 
Haematemesis * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Haemorrhoidal Haemorrhage * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Ileus * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Incarcerated Inguinal Hernia * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Inguinal Hernia * 1  1/2197 (0.05%)  4/2200 (0.18%) 
Intestinal Obstruction * 1  1/2197 (0.05%)  7/2200 (0.32%) 
Intestinal Perforation * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Large Intestine Polyp * 1  2/2197 (0.09%)  1/2200 (0.05%) 
Leukoplakia Oral * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Lower Gastrointestinal Haemorrhage * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Melaena * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Obstructive Pancreatitis * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Pancreatitis * 1  0/2197 (0.00%)  4/2200 (0.18%) 
Pancreatitis Acute * 1  3/2197 (0.14%)  3/2200 (0.14%) 
Peptic Ulcer * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Peptic Ulcer Haemorrhage * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Rectal Haemorrhage * 1  1/2197 (0.05%)  1/2200 (0.05%) 
Rectal Polyp * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Small Intestinal Haemorrhage * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Small Intestinal Obstruction * 1  2/2197 (0.09%)  1/2200 (0.05%) 
Subileus * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Swollen Tongue * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Umbilical Hernia * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Upper Gastrointestinal Haemorrhage * 1  1/2197 (0.05%)  4/2200 (0.18%) 
Vomiting * 1  4/2197 (0.18%)  1/2200 (0.05%) 
General disorders     
Asthenia * 1  2/2197 (0.09%)  0/2200 (0.00%) 
Atrophy * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Cardiac Death * 1  1/2197 (0.05%)  3/2200 (0.14%) 
Chest Discomfort * 1  1/2197 (0.05%)  1/2200 (0.05%) 
Chest Pain * 1  3/2197 (0.14%)  1/2200 (0.05%) 
Complication Associated with Device * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Critical Illness * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Cyst * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Death * 1  6/2197 (0.27%)  7/2200 (0.32%) 
Drowning * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Gait Disturbance * 1  0/2197 (0.00%)  1/2200 (0.05%) 
General Physical Health Deterioration * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Generalised Oedema * 1  2/2197 (0.09%)  2/2200 (0.09%) 
Incarcerated Hernia * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Influenza Like Illness * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Localised Oedema * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Multiple Organ Dysfunction Syndrome * 1  2/2197 (0.09%)  1/2200 (0.05%) 
Necrobiosis * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Non-Cardiac Chest Pain * 1  2/2197 (0.09%)  8/2200 (0.36%) 
Oedema Peripheral * 1  4/2197 (0.18%)  3/2200 (0.14%) 
Peripheral Swelling * 1  3/2197 (0.14%)  1/2200 (0.05%) 
Pyrexia * 1  1/2197 (0.05%)  2/2200 (0.09%) 
Sudden Cardiac Death * 1  2/2197 (0.09%)  2/2200 (0.09%) 
Sudden Death * 1  8/2197 (0.36%)  3/2200 (0.14%) 
Systemic Inflammatory Response Syndrome * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Hepatobiliary disorders     
Bile Duct Obstruction * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Bile Duct Stone * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Cholangitis * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Cholangitis Acute * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Cholangitis Sclerosing * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Cholecystitis * 1  5/2197 (0.23%)  2/2200 (0.09%) 
Cholecystitis Acute * 1  4/2197 (0.18%)  5/2200 (0.23%) 
Cholecystitis Chronic * 1  1/2197 (0.05%)  3/2200 (0.14%) 
Cholelithiasis * 1  2/2197 (0.09%)  5/2200 (0.23%) 
Hepatic Cirrhosis * 1  2/2197 (0.09%)  1/2200 (0.05%) 
Hepatic Function Abnormal * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Ischaemic Hepatitis * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Immune system disorders     
Anaphylactic Reaction * 1  1/2197 (0.05%)  1/2200 (0.05%) 
Drug Hypersensitivity * 1  2/2197 (0.09%)  0/2200 (0.00%) 
Infections and infestations     
Abdominal Abscess * 1  1/2197 (0.05%)  1/2200 (0.05%) 
Abdominal Sepsis * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Abdominal Wall Abscess * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Abscess Limb * 1  0/2197 (0.00%)  3/2200 (0.14%) 
Acute Hepatitis B * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Appendicitis * 1  3/2197 (0.14%)  2/2200 (0.09%) 
Appendicitis Perforated * 1  3/2197 (0.14%)  0/2200 (0.00%) 
Arteriovenous Fistula Site Infection * 1  2/2197 (0.09%)  0/2200 (0.00%) 
Arthritis Bacterial * 1  1/2197 (0.05%)  2/2200 (0.09%) 
Atypical Pneumonia * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Bacteraemia * 1  1/2197 (0.05%)  1/2200 (0.05%) 
Bacterial Pyelonephritis * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Bacterial Sepsis * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Bronchiolitis * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Bronchitis * 1  7/2197 (0.32%)  5/2200 (0.23%) 
Bronchitis Viral * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Campylobacter Colitis * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Cellulitis * 1  26/2197 (1.18%)  18/2200 (0.82%) 
Cellulitis Staphylococcal * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Chronic Sinusitis * 1  2/2197 (0.09%)  0/2200 (0.00%) 
Clostridium Difficile Colitis * 1  1/2197 (0.05%)  2/2200 (0.09%) 
Clostridium Difficile Infection * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Cystitis * 1  0/2197 (0.00%)  2/2200 (0.09%) 
Dengue Fever * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Device Related Infection * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Diabetic Foot Infection * 1  4/2197 (0.18%)  3/2200 (0.14%) 
Diabetic Gangrene * 1  2/2197 (0.09%)  5/2200 (0.23%) 
Diverticulitis * 1  2/2197 (0.09%)  4/2200 (0.18%) 
Dysentery * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Ear Infection * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Empyema * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Endocarditis * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Endophthalmitis * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Enteritis Infectious * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Enterobacter Infection * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Enterocolitis Bacterial * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Epididymitis * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Erysipelas * 1  5/2197 (0.23%)  2/2200 (0.09%) 
Escherichia Sepsis * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Furuncle * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Gangrene * 1  15/2197 (0.68%)  10/2200 (0.45%) 
Gas Gangrene * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Gastroenteritis * 1  19/2197 (0.86%)  6/2200 (0.27%) 
Gastroenteritis Bacterial * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Gastroenteritis Viral * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Gastrointestinal Bacterial Infection * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Giardiasis * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Graft Infection * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Groin Abscess * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Haemophilus Infection * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Hepatic Echinococciasis * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Herpes Zoster * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Infected Skin Ulcer * 1  6/2197 (0.27%)  5/2200 (0.23%) 
Infection in An Immunocompromised Host * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Infective Exacerbation of Chronic Obstructive Airways Disease * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Influenza * 1  1/2197 (0.05%)  3/2200 (0.14%) 
Intervertebral Discitis * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Keratitis Fungal * 1  2/2197 (0.09%)  0/2200 (0.00%) 
Laryngitis * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Liver Abscess * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Localised Infection * 1  6/2197 (0.27%)  6/2200 (0.27%) 
Lower Respiratory Tract Infection * 1  3/2197 (0.14%)  2/2200 (0.09%) 
Lung Infection * 1  3/2197 (0.14%)  2/2200 (0.09%) 
Mediastinitis * 1  2/2197 (0.09%)  0/2200 (0.00%) 
Meningitis * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Meningitis Bacterial * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Necrotising Fasciitis * 1  0/2197 (0.00%)  2/2200 (0.09%) 
Onychomycosis * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Opisthorchiasis * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Orchitis * 1  1/2197 (0.05%)  1/2200 (0.05%) 
Osteomyelitis * 1  11/2197 (0.50%)  11/2200 (0.50%) 
Osteomyelitis Acute * 1  0/2197 (0.00%)  2/2200 (0.09%) 
Osteomyelitis Chronic * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Perineal Abscess * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Periodontitis * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Pharyngeal Abscess * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Pneumonia * 1  86/2197 (3.91%)  63/2200 (2.86%) 
Pneumonia Bacterial * 1  2/2197 (0.09%)  0/2200 (0.00%) 
Pneumonia Influenzal * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Pneumonia Pneumococcal * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Pneumonia Staphylococcal * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Pneumonia Streptococcal * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Pneumonia Viral * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Postoperative Wound Infection * 1  3/2197 (0.14%)  2/2200 (0.09%) 
Pseudomonas Bronchitis * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Pulmonary Sepsis * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Pyelonephritis * 1  5/2197 (0.23%)  3/2200 (0.14%) 
Pyelonephritis Acute * 1  2/2197 (0.09%)  4/2200 (0.18%) 
Pyelonephritis Chronic * 1  2/2197 (0.09%)  0/2200 (0.00%) 
Rectal Abscess * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Respiratory Syncytial Virus Bronchiolitis * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Respiratory Tract Infection * 1  2/2197 (0.09%)  2/2200 (0.09%) 
Respiratory Tract Infection Viral * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Rhinitis * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Scrotal Abscess * 1  1/2197 (0.05%)  1/2200 (0.05%) 
Scrub Typhus * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Sepsis * 1  12/2197 (0.55%)  11/2200 (0.50%) 
Septic Shock * 1  12/2197 (0.55%)  5/2200 (0.23%) 
Soft Tissue Infection * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Staphylococcal Bacteraemia * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Staphylococcal Infection * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Staphylococcal Sepsis * 1  2/2197 (0.09%)  2/2200 (0.09%) 
Streptococcal Infection * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Subcutaneous Abscess * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Tonsillitis * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Tooth Abscess * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Tracheobronchitis * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Upper Respiratory Tract Infection * 1  3/2197 (0.14%)  3/2200 (0.14%) 
Urinary Tract Infection * 1  21/2197 (0.96%)  25/2200 (1.14%) 
Urinary Tract Infection Fungal * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Urosepsis * 1  3/2197 (0.14%)  3/2200 (0.14%) 
Viral Infection * 1  1/2197 (0.05%)  1/2200 (0.05%) 
Viral Upper Respiratory Tract Infection * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Wound Infection * 1  1/2197 (0.05%)  6/2200 (0.27%) 
Injury, poisoning and procedural complications     
Anaesthetic Complication * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Ankle Fracture * 1  3/2197 (0.14%)  0/2200 (0.00%) 
Cervical Vertebral Fracture * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Chest Injury * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Clavicle Fracture * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Concussion * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Contusion * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Coronary Artery Reocclusion * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Coronary Vascular Graft Occlusion * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Craniocerebral Injury * 1  1/2197 (0.05%)  1/2200 (0.05%) 
Expired Product Administered * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Facial Bones Fracture * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Fall * 1  3/2197 (0.14%)  1/2200 (0.05%) 
Femoral Neck Fracture * 1  2/2197 (0.09%)  4/2200 (0.18%) 
Femur Fracture * 1  1/2197 (0.05%)  5/2200 (0.23%) 
Fibula Fracture * 1  0/2197 (0.00%)  2/2200 (0.09%) 
Foot Fracture * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Foreign Body in Eye * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Fracture Displacement * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Head Injury * 1  1/2197 (0.05%)  1/2200 (0.05%) 
Hip Fracture * 1  5/2197 (0.23%)  3/2200 (0.14%) 
Humerus Fracture * 1  2/2197 (0.09%)  4/2200 (0.18%) 
Joint Dislocation * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Joint Injury * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Ligament Rupture * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Ligament Sprain * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Limb Injury * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Meniscus Injury * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Muscle Injury * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Muscle Strain * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Overdose * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Patella Fracture * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Post Procedural Complication * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Post Procedural Haematoma * 1  1/2197 (0.05%)  1/2200 (0.05%) 
Post Procedural Haemorrhage * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Postoperative Thrombosis * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Postoperative Wound Complication * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Procedural Intestinal Perforation * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Procedural Pain * 1  1/2197 (0.05%)  1/2200 (0.05%) 
Pubis Fracture * 1  0/2197 (0.00%)  2/2200 (0.09%) 
Radius Fracture * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Rib Fracture * 1  2/2197 (0.09%)  1/2200 (0.05%) 
Road Traffic Accident * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Soft Tissue Injury * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Spinal Compression Fracture * 1  1/2197 (0.05%)  1/2200 (0.05%) 
Spinal Fracture * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Sternal Fracture * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Stress Fracture * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Subarachnoid Haemorrhage * 1  1/2197 (0.05%)  1/2200 (0.05%) 
Subdural Haematoma * 1  3/2197 (0.14%)  3/2200 (0.14%) 
Subdural Haemorrhage * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Thermal Burn * 1  1/2197 (0.05%)  2/2200 (0.09%) 
Thoracic Vertebral Fracture * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Tibia Fracture * 1  0/2197 (0.00%)  2/2200 (0.09%) 
Traumatic Intracranial Haemorrhage * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Ulna Fracture * 1  0/2197 (0.00%)  2/2200 (0.09%) 
Vascular Graft Occlusion * 1  0/2197 (0.00%)  2/2200 (0.09%) 
Wound * 1  5/2197 (0.23%)  0/2200 (0.00%) 
Wound Dehiscence * 1  1/2197 (0.05%)  1/2200 (0.05%) 
Wound Haemorrhage * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Wrist Fracture * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Investigations     
Aspiration Bronchial * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Biopsy Kidney * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Blood Creatine Phosphokinase Increased * 1  0/2197 (0.00%)  2/2200 (0.09%) 
Blood Creatinine Increased * 1  20/2197 (0.91%)  7/2200 (0.32%) 
Blood Glucose Increased * 1  2/2197 (0.09%)  1/2200 (0.05%) 
Blood Osmolarity Decreased * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Blood Urea Increased * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Ejection Fraction Decreased * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Glomerular Filtration Rate Decreased * 1  1/2197 (0.05%)  5/2200 (0.23%) 
Haemoglobin Decreased * 1  1/2197 (0.05%)  0/2200 (0.00%) 
International Normalised Ratio Increased * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Troponin Increased * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Weight Decreased * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Metabolism and nutrition disorders     
Cachexia * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Dehydration * 1  8/2197 (0.36%)  4/2200 (0.18%) 
Diabetes Mellitus * 1  10/2197 (0.46%)  5/2200 (0.23%) 
Diabetes Mellitus Inadequate Control * 1  12/2197 (0.55%)  7/2200 (0.32%) 
Diabetic Ketoacidosis * 1  2/2197 (0.09%)  9/2200 (0.41%) 
Diabetic Ketosis * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Diabetic Metabolic Decompensation * 1  3/2197 (0.14%)  1/2200 (0.05%) 
Electrolyte Imbalance * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Fluid Overload * 1  4/2197 (0.18%)  3/2200 (0.14%) 
Fluid Retention * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Hypercalcaemia * 1  1/2197 (0.05%)  1/2200 (0.05%) 
Hyperglycaemia * 1  11/2197 (0.50%)  1/2200 (0.05%) 
Hyperglycaemic Hyperosmolar Nonketotic Syndrome * 1  2/2197 (0.09%)  1/2200 (0.05%) 
Hyperkalaemia * 1  10/2197 (0.46%)  10/2200 (0.45%) 
Hyperlipidaemia * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Hypoglycaemia * 1  11/2197 (0.50%)  17/2200 (0.77%) 
Hypokalaemia * 1  3/2197 (0.14%)  0/2200 (0.00%) 
Hyponatraemia * 1  4/2197 (0.18%)  3/2200 (0.14%) 
Hypophagia * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Hypoproteinaemia * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Ketoacidosis * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Lactic Acidosis * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Metabolic Acidosis * 1  6/2197 (0.27%)  2/2200 (0.09%) 
Metabolic Disorder * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Obesity * 1  1/2197 (0.05%)  2/2200 (0.09%) 
Type 2 Diabetes Mellitus * 1  2/2197 (0.09%)  1/2200 (0.05%) 
Musculoskeletal and connective tissue disorders     
Arthralgia * 1  2/2197 (0.09%)  1/2200 (0.05%) 
Back Pain * 1  1/2197 (0.05%)  2/2200 (0.09%) 
Cervical Spinal Stenosis * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Chest Wall Haematoma * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Gouty Arthritis * 1  2/2197 (0.09%)  0/2200 (0.00%) 
Haemarthrosis * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Intervertebral Disc Degeneration * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Intervertebral Disc Displacement * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Intervertebral Disc Protrusion * 1  5/2197 (0.23%)  2/2200 (0.09%) 
Lumbar Spinal Stenosis * 1  5/2197 (0.23%)  1/2200 (0.05%) 
Muscular Weakness * 1  1/2197 (0.05%)  2/2200 (0.09%) 
Musculoskeletal Chest Pain * 1  1/2197 (0.05%)  2/2200 (0.09%) 
Musculoskeletal Pain * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Neuropathic Arthropathy * 1  3/2197 (0.14%)  0/2200 (0.00%) 
Osteitis * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Osteitis Deformans * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Osteoarthritis * 1  11/2197 (0.50%)  10/2200 (0.45%) 
Osteochondrosis * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Pain in Extremity * 1  2/2197 (0.09%)  2/2200 (0.09%) 
Periarthritis * 1  2/2197 (0.09%)  2/2200 (0.09%) 
Rotator Cuff Syndrome * 1  1/2197 (0.05%)  1/2200 (0.05%) 
Spinal Column Stenosis * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Spinal Disorder * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Spinal Osteoarthritis * 1  0/2197 (0.00%)  4/2200 (0.18%) 
Spondylolisthesis * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Symphysiolysis * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Systemic Lupus Erythematosus * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Trigger Finger * 1  2/2197 (0.09%)  0/2200 (0.00%) 
Vertebral Foraminal Stenosis * 1  1/2197 (0.05%)  1/2200 (0.05%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Acute Leukaemia * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Adenocarcinoma Gastric * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Adenocarcinoma of Colon * 1  1/2197 (0.05%)  2/2200 (0.09%) 
B-Cell Lymphoma * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Basal Cell Carcinoma * 1  0/2197 (0.00%)  2/2200 (0.09%) 
Benign Neoplasm of Bladder * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Bladder Cancer * 1  4/2197 (0.18%)  5/2200 (0.23%) 
Bladder Neoplasm * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Bladder Transitional Cell Carcinoma * 1  2/2197 (0.09%)  0/2200 (0.00%) 
Brain Cancer Metastatic * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Brain Neoplasm * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Breast Cancer * 1  2/2197 (0.09%)  3/2200 (0.14%) 
Cholangiocarcinoma * 1  0/2197 (0.00%)  2/2200 (0.09%) 
Chronic Lymphocytic Leukaemia * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Colon Adenoma * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Colon Cancer * 1  1/2197 (0.05%)  6/2200 (0.27%) 
Colon Neoplasm * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Diffuse Large B-Cell Lymphoma * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Endometrial Adenocarcinoma * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Endometrial Cancer * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Gastric Cancer * 1  1/2197 (0.05%)  3/2200 (0.14%) 
Gastric Neoplasm * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Hepatic Neoplasm * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Hepatocellular Carcinoma * 1  3/2197 (0.14%)  0/2200 (0.00%) 
Invasive Breast Carcinoma * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Invasive Ductal Breast Carcinoma * 1  1/2197 (0.05%)  2/2200 (0.09%) 
Invasive Lobular Breast Carcinoma * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Large Intestine Benign Neoplasm * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Laryngeal Cancer * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Lung Adenocarcinoma * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Lung Cancer Metastatic * 1  0/2197 (0.00%)  2/2200 (0.09%) 
Lung Neoplasm * 1  1/2197 (0.05%)  2/2200 (0.09%) 
Lung Neoplasm Malignant * 1  3/2197 (0.14%)  2/2200 (0.09%) 
Malignant Melanoma * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Malignant Neoplasm of Unknown Primary Site * 1  1/2197 (0.05%)  1/2200 (0.05%) 
Meningioma Malignant * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Metastases to Bone * 1  0/2197 (0.00%)  2/2200 (0.09%) 
Metastases to Liver * 1  2/2197 (0.09%)  2/2200 (0.09%) 
Metastatic Renal Cell Carcinoma * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Myelodysplastic Syndrome * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Neuroendocrine Tumour * 1  2/2197 (0.09%)  0/2200 (0.00%) 
Non-Hodgkin's Lymphoma Stage Ii * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Oesophageal Adenocarcinoma * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Oropharyngeal Squamous Cell Carcinoma * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Ovarian Cancer * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Ovarian Endometrioid Carcinoma * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Pancreatic Carcinoma * 1  1/2197 (0.05%)  1/2200 (0.05%) 
Pancreatic Carcinoma Metastatic * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Pancreatic Neoplasm * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Papillary Thyroid Cancer * 1  1/2197 (0.05%)  1/2200 (0.05%) 
Peritoneal Carcinoma Metastatic * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Pituitary Tumour Benign * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Plasma Cell Myeloma * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Prostate Cancer * 1  4/2197 (0.18%)  8/2200 (0.36%) 
Prostatic Adenoma * 1  0/2197 (0.00%)  2/2200 (0.09%) 
Rectal Adenocarcinoma * 1  1/2197 (0.05%)  1/2200 (0.05%) 
Rectal Adenoma * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Rectal Cancer * 1  1/2197 (0.05%)  1/2200 (0.05%) 
Rectosigmoid Cancer * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Renal Cell Carcinoma * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Renal Cell Carcinoma Stage I * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Renal Neoplasm * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Renal Oncocytoma * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Salivary Gland Neoplasm * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Squamous Cell Carcinoma * 1  1/2197 (0.05%)  1/2200 (0.05%) 
Squamous Cell Carcinoma of Lung * 1  1/2197 (0.05%)  1/2200 (0.05%) 
Squamous Cell Carcinoma of Skin * 1  0/2197 (0.00%)  2/2200 (0.09%) 
Squamous Cell Carcinoma of the Vulva * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Tongue Neoplasm Malignant Stage Unspecified * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Transitional Cell Cancer of Renal Pelvis and Ureter Metastatic * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Transitional Cell Cancer of the Renal Pelvis and Ureter * 1  0/2197 (0.00%)  2/2200 (0.09%) 
Transitional Cell Carcinoma * 1  0/2197 (0.00%)  3/2200 (0.14%) 
Uterine Cancer * 1  1/2197 (0.05%)  1/2200 (0.05%) 
Uterine Leiomyoma * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Nervous system disorders     
Amputation Stump Pain * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Basilar Migraine * 1  1/2197 (0.05%)  1/2200 (0.05%) 
Brain Injury * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Brain Oedema * 1  0/2197 (0.00%)  2/2200 (0.09%) 
Carotid Artery Occlusion * 1  1/2197 (0.05%)  1/2200 (0.05%) 
Carotid Artery Stenosis * 1  8/2197 (0.36%)  4/2200 (0.18%) 
Carpal Tunnel Syndrome * 1  0/2197 (0.00%)  2/2200 (0.09%) 
Cauda Equina Syndrome * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Cerebellar Haemorrhage * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Cerebellar Infarction * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Cerebellar Stroke * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Cerebral Haematoma * 1  1/2197 (0.05%)  1/2200 (0.05%) 
Cerebral Haemorrhage * 1  4/2197 (0.18%)  1/2200 (0.05%) 
Cerebral Hypoperfusion * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Cerebral Infarction * 1  7/2197 (0.32%)  6/2200 (0.27%) 
Cerebral Ischaemia * 1  2/2197 (0.09%)  2/2200 (0.09%) 
Cerebrovascular Accident * 1  36/2197 (1.64%)  30/2200 (1.36%) 
Cervical Radiculopathy * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Chronic Inflammatory Demyelinating Polyradiculoneuropathy * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Clonus * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Dementia * 1  1/2197 (0.05%)  2/2200 (0.09%) 
Depressed Level of Consciousness * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Diabetic Autonomic Neuropathy * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Diabetic Hyperosmolar Coma * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Diabetic Neuropathy * 1  2/2197 (0.09%)  1/2200 (0.05%) 
Dizziness * 1  1/2197 (0.05%)  1/2200 (0.05%) 
Dural Arteriovenous Fistula * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Embolic Cerebral Infarction * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Embolic Stroke * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Encephalopathy * 1  0/2197 (0.00%)  2/2200 (0.09%) 
Epilepsy * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Facial Paralysis * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Generalised Tonic-Clonic Seizure * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Haemorrhage Intracranial * 1  1/2197 (0.05%)  1/2200 (0.05%) 
Haemorrhagic Stroke * 1  4/2197 (0.18%)  3/2200 (0.14%) 
Haemorrhagic Transformation Stroke * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Headache * 1  1/2197 (0.05%)  1/2200 (0.05%) 
Hemiparesis * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Hypoglycaemic Coma * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Hypoglycaemic Encephalopathy * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Hypoxic-Ischaemic Encephalopathy * 1  2/2197 (0.09%)  1/2200 (0.05%) 
Intracranial Mass * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Ischaemic Cerebral Infarction * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Ischaemic Neuropathy * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Ischaemic Stroke * 1  17/2197 (0.77%)  14/2200 (0.64%) 
Lacunar Infarction * 1  4/2197 (0.18%)  4/2200 (0.18%) 
Language Disorder * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Lumbar Radiculopathy * 1  1/2197 (0.05%)  1/2200 (0.05%) 
Lumbosacral Radiculopathy * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Metabolic Encephalopathy * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Myelopathy * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Paraesthesia * 1  1/2197 (0.05%)  1/2200 (0.05%) 
Paraparesis * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Parkinson's Disease * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Peripheral Sensorimotor Neuropathy * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Piriformis Syndrome * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Polyneuropathy * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Presyncope * 1  1/2197 (0.05%)  1/2200 (0.05%) 
Progressive Supranuclear Palsy * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Radicular Syndrome * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Radiculopathy * 1  2/2197 (0.09%)  0/2200 (0.00%) 
Sciatica * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Seizure * 1  1/2197 (0.05%)  2/2200 (0.09%) 
Somnolence * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Spinal Cord Compression * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Status Epilepticus * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Syncope * 1  3/2197 (0.14%)  4/2200 (0.18%) 
Tension Headache * 1  0/2197 (0.00%)  2/2200 (0.09%) 
Thalamic Infarction * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Transient Ischaemic Attack * 1  4/2197 (0.18%)  10/2200 (0.45%) 
Vascular Encephalopathy * 1  2/2197 (0.09%)  1/2200 (0.05%) 
Vasculitis Cerebral * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Vertebral Artery Stenosis * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Vith Nerve Paralysis * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Pregnancy, puerperium and perinatal conditions     
Abortion Spontaneous * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Retained Products of Conception * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Product Issues     
Device Malfunction * 1  2/2197 (0.09%)  0/2200 (0.00%) 
Psychiatric disorders     
Affective Disorder * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Completed Suicide * 1  1/2197 (0.05%)  1/2200 (0.05%) 
Confusional State * 1  0/2197 (0.00%)  2/2200 (0.09%) 
Delirium * 1  3/2197 (0.14%)  1/2200 (0.05%) 
Disorientation * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Mental Status Changes * 1  2/2197 (0.09%)  0/2200 (0.00%) 
Substance-Induced Psychotic Disorder * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Suicide Attempt * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Renal and urinary disorders     
Acute Kidney Injury * 1  50/2197 (2.28%)  41/2200 (1.86%) 
Anuria * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Azotaemia * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Bladder Cyst * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Calculus Urinary * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Chronic Kidney Disease * 1  12/2197 (0.55%)  12/2200 (0.55%) 
Diabetic Nephropathy * 1  10/2197 (0.46%)  12/2200 (0.55%) 
End Stage Renal Disease * 1  23/2197 (1.05%)  16/2200 (0.73%) 
Glomerulonephritis Chronic * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Haematuria * 1  3/2197 (0.14%)  1/2200 (0.05%) 
Hydronephrosis * 1  2/2197 (0.09%)  0/2200 (0.00%) 
Nephrolithiasis * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Nephropathy * 1  4/2197 (0.18%)  1/2200 (0.05%) 
Nephrotic Syndrome * 1  1/2197 (0.05%)  2/2200 (0.09%) 
Neurogenic Bladder * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Renal Artery Stenosis * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Renal Colic * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Renal Failure * 1  9/2197 (0.41%)  5/2200 (0.23%) 
Renal Impairment * 1  7/2197 (0.32%)  10/2200 (0.45%) 
Renal Injury * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Renal Tubular Necrosis * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Stress Urinary Incontinence * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Ureterolithiasis * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Urethral Stenosis * 1  1/2197 (0.05%)  1/2200 (0.05%) 
Urinary Retention * 1  1/2197 (0.05%)  2/2200 (0.09%) 
Urinary Tract Obstruction * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Reproductive system and breast disorders     
Acquired Phimosis * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Adenomyosis * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Benign Prostatic Hyperplasia * 1  4/2197 (0.18%)  3/2200 (0.14%) 
Cervix Disorder * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Cystocele * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Erectile Dysfunction * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Genital Swelling * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Ovarian Cyst * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Postmenopausal Haemorrhage * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Prostatitis * 1  1/2197 (0.05%)  1/2200 (0.05%) 
Rectocele * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Uterine Prolapse * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Uterovaginal Prolapse * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Vaginal Prolapse * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Respiratory, thoracic and mediastinal disorders     
Acute Pulmonary Oedema * 1  8/2197 (0.36%)  6/2200 (0.27%) 
Acute Respiratory Distress Syndrome * 1  1/2197 (0.05%)  1/2200 (0.05%) 
Acute Respiratory Failure * 1  6/2197 (0.27%)  5/2200 (0.23%) 
Apnoeic Attack * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Asthma * 1  0/2197 (0.00%)  2/2200 (0.09%) 
Bronchiectasis * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Bronchitis Chronic * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Bronchospasm * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Chronic Obstructive Pulmonary Disease * 1  16/2197 (0.73%)  9/2200 (0.41%) 
Chronic Respiratory Failure * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Cough * 1  0/2197 (0.00%)  2/2200 (0.09%) 
Dyspnoea * 1  3/2197 (0.14%)  3/2200 (0.14%) 
Dyspnoea at Rest * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Emphysema * 1  1/2197 (0.05%)  1/2200 (0.05%) 
Epistaxis * 1  2/2197 (0.09%)  0/2200 (0.00%) 
Hiccups * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Hydrothorax * 1  1/2197 (0.05%)  1/2200 (0.05%) 
Hypoxia * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Laryngeal Haematoma * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Nasal Polyps * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Nasal Septum Perforation * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Pickwickian Syndrome * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Pleural Effusion * 1  6/2197 (0.27%)  3/2200 (0.14%) 
Pleuritic Pain * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Pneumonia Aspiration * 1  2/2197 (0.09%)  0/2200 (0.00%) 
Pulmonary Arterial Hypertension * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Pulmonary Congestion * 1  1/2197 (0.05%)  1/2200 (0.05%) 
Pulmonary Embolism * 1  3/2197 (0.14%)  7/2200 (0.32%) 
Pulmonary Fibrosis * 1  0/2197 (0.00%)  4/2200 (0.18%) 
Pulmonary Infarction * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Pulmonary Mass * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Pulmonary Oedema * 1  7/2197 (0.32%)  3/2200 (0.14%) 
Respiratory Depression * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Respiratory Distress * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Respiratory Failure * 1  10/2197 (0.46%)  10/2200 (0.45%) 
Sleep Apnoea Syndrome * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Vocal Cord Leukoplakia * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Skin and subcutaneous tissue disorders     
Angioedema * 1  1/2197 (0.05%)  2/2200 (0.09%) 
Diabetic Foot * 1  10/2197 (0.46%)  15/2200 (0.68%) 
Diabetic Ulcer * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Drug Eruption * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Eczema * 1  1/2197 (0.05%)  1/2200 (0.05%) 
Erythema * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Idiopathic Angioedema * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Neuropathic Ulcer * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Psoriasis * 1  1/2197 (0.05%)  1/2200 (0.05%) 
Rash Generalised * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Skin Ulcer * 1  8/2197 (0.36%)  18/2200 (0.82%) 
Surgical and medical procedures     
Hospitalisation * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Vascular disorders     
Accelerated Hypertension * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Aortic Dissection * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Aortic Stenosis * 1  5/2197 (0.23%)  3/2200 (0.14%) 
Arterial Disorder * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Arterial Insufficiency * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Arteriosclerosis * 1  3/2197 (0.14%)  1/2200 (0.05%) 
Circulatory Collapse * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Deep Vein Thrombosis * 1  7/2197 (0.32%)  2/2200 (0.09%) 
Diabetic Vascular Disorder * 1  2/2197 (0.09%)  0/2200 (0.00%) 
Embolism * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Embolism Arterial * 1  2/2197 (0.09%)  0/2200 (0.00%) 
Extremity Necrosis * 1  8/2197 (0.36%)  9/2200 (0.41%) 
Haematoma * 1  1/2197 (0.05%)  2/2200 (0.09%) 
Hypertension * 1  7/2197 (0.32%)  7/2200 (0.32%) 
Hypertensive Crisis * 1  9/2197 (0.41%)  9/2200 (0.41%) 
Hypertensive Emergency * 1  2/2197 (0.09%)  1/2200 (0.05%) 
Hypotension * 1  3/2197 (0.14%)  4/2200 (0.18%) 
Intermittent Claudication * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Leriche Syndrome * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Lymphoedema * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Necrosis Ischaemic * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Orthostatic Hypotension * 1  5/2197 (0.23%)  2/2200 (0.09%) 
Peripheral Arterial Occlusive Disease * 1  11/2197 (0.50%)  10/2200 (0.45%) 
Peripheral Artery Occlusion * 1  0/2197 (0.00%)  2/2200 (0.09%) 
Peripheral Ischaemia * 1  5/2197 (0.23%)  3/2200 (0.14%) 
Peripheral Vascular Disorder * 1  1/2197 (0.05%)  5/2200 (0.23%) 
Peripheral Venous Disease * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Post Thrombotic Syndrome * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Shock Haemorrhagic * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Subclavian Artery Stenosis * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Thrombophlebitis Superficial * 1  2/2197 (0.09%)  2/2200 (0.09%) 
Thrombosis * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Vascular Occlusion * 1  0/2197 (0.00%)  1/2200 (0.05%) 
Venous Haemorrhage * 1  1/2197 (0.05%)  0/2200 (0.00%) 
Venous Thrombosis Limb * 1  1/2197 (0.05%)  0/2200 (0.00%) 
1
Term from vocabulary, MedDRA Version 21.0
*
Indicates events were collected by non-systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 2%
Placebo Canagliflozin 100 mg
Affected / at Risk (%) Affected / at Risk (%)
Total   1447/2197 (65.86%)   1320/2200 (60.00%) 
Blood and lymphatic system disorders     
Anaemia * 1  136/2197 (6.19%)  77/2200 (3.50%) 
Ear and labyrinth disorders     
Vertigo * 1  50/2197 (2.28%)  46/2200 (2.09%) 
Eye disorders     
Cataract * 1  80/2197 (3.64%)  58/2200 (2.64%) 
Diabetic Retinopathy * 1  55/2197 (2.50%)  65/2200 (2.95%) 
Gastrointestinal disorders     
Constipation * 1  82/2197 (3.73%)  80/2200 (3.64%) 
Diarrhoea * 1  105/2197 (4.78%)  91/2200 (4.14%) 
Nausea * 1  52/2197 (2.37%)  54/2200 (2.45%) 
Vomiting * 1  48/2197 (2.18%)  41/2200 (1.86%) 
General disorders     
Oedema Peripheral * 1  199/2197 (9.06%)  119/2200 (5.41%) 
Infections and infestations     
Bronchitis * 1  86/2197 (3.91%)  83/2200 (3.77%) 
Gastroenteritis * 1  51/2197 (2.32%)  49/2200 (2.23%) 
Influenza * 1  88/2197 (4.01%)  87/2200 (3.95%) 
Nasopharyngitis * 1  133/2197 (6.05%)  130/2200 (5.91%) 
Onychomycosis * 1  33/2197 (1.50%)  45/2200 (2.05%) 
Pneumonia * 1  52/2197 (2.37%)  41/2200 (1.86%) 
Respiratory Tract Infection * 1  44/2197 (2.00%)  19/2200 (0.86%) 
Upper Respiratory Tract Infection * 1  117/2197 (5.33%)  90/2200 (4.09%) 
Urinary Tract Infection * 1  185/2197 (8.42%)  202/2200 (9.18%) 
Injury, poisoning and procedural complications     
Limb Injury * 1  45/2197 (2.05%)  43/2200 (1.95%) 
Investigations     
Blood Creatinine Increased * 1  185/2197 (8.42%)  140/2200 (6.36%) 
Glomerular Filtration Rate Decreased * 1  80/2197 (3.64%)  63/2200 (2.86%) 
Metabolism and nutrition disorders     
Diabetes Mellitus * 1  44/2197 (2.00%)  24/2200 (1.09%) 
Hyperglycaemia * 1  74/2197 (3.37%)  54/2200 (2.45%) 
Hyperkalaemia * 1  152/2197 (6.92%)  129/2200 (5.86%) 
Hyperuricaemia * 1  75/2197 (3.41%)  64/2200 (2.91%) 
Hypoglycaemia * 1  227/2197 (10.33%)  213/2200 (9.68%) 
Musculoskeletal and connective tissue disorders     
Arthralgia * 1  83/2197 (3.78%)  81/2200 (3.68%) 
Back Pain * 1  99/2197 (4.51%)  94/2200 (4.27%) 
Pain in Extremity * 1  54/2197 (2.46%)  56/2200 (2.55%) 
Nervous system disorders     
Diabetic Neuropathy * 1  69/2197 (3.14%)  56/2200 (2.55%) 
Headache * 1  65/2197 (2.96%)  69/2200 (3.14%) 
Renal and urinary disorders     
Acute Kidney Injury * 1  51/2197 (2.32%)  50/2200 (2.27%) 
End Stage Renal Disease * 1  52/2197 (2.37%)  30/2200 (1.36%) 
Renal Impairment * 1  61/2197 (2.78%)  42/2200 (1.91%) 
Respiratory, thoracic and mediastinal disorders     
Cough * 1  81/2197 (3.69%)  80/2200 (3.64%) 
Dyspnoea * 1  46/2197 (2.09%)  35/2200 (1.59%) 
Skin and subcutaneous tissue disorders     
Skin Ulcer * 1  70/2197 (3.19%)  85/2200 (3.86%) 
Vascular disorders     
Hypertension * 1  193/2197 (8.78%)  144/2200 (6.55%) 
Hypotension * 1  30/2197 (1.37%)  57/2200 (2.59%) 
1
Term from vocabulary, MedDRA Version 21.0
*
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.
If an investigator wishes to publish information from the study, 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 by the sponsor in writing, the investigator will withhold such publication for up to an additional 60 days.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Senior Director
Organization: Janssen Research & Development, LLC
Phone: 844-434-4210
EMail: ClinicalTrialDisclosure@its.jnj.com
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT02065791    
Other Study ID Numbers: CR103517
2013-004494-28 ( EudraCT Number )
28431754DNE3001 ( Other Identifier: Janssen Research & Development, LLC )
First Submitted: February 17, 2014
First Posted: February 19, 2014
Results First Submitted: October 30, 2019
Results First Posted: November 20, 2019
Last Update Posted: December 5, 2019