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Trial record 1 of 1 for:    H-030-014
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Study of a Candidate Clostridium Difficile Toxoid Vaccine in Subjects at Risk for C. Difficile Infection

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: NCT01887912
Recruitment Status : Terminated (The Independent Data Monitoring Committee (IDMC) concluded that the probability that the study will meet its primary objective is low.)
First Posted : June 27, 2013
Results First Posted : July 5, 2019
Last Update Posted : March 28, 2022
Sponsor:
Information provided by (Responsible Party):
Sanofi ( Sanofi Pasteur, a Sanofi Company )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Investigator, Outcomes Assessor);   Primary Purpose: Prevention
Condition Clostridium Difficile Infection
Interventions Biological: C. difficile Toxoid Vaccine
Biological: Placebo: 0.9% normal saline
Enrollment 9302
Recruitment Details Study participants were enrolled in the study from 30 July 2013 to 17 November 2017.
Pre-assignment Details A total of 9302 participants were enrolled and randomized in the study.
Arm/Group Title C. Difficile Vaccine Group Placebo Group
Hide Arm/Group Description Participants received 1 injection of 0.5 mL C. difficile toxoid vaccine at Days 0 (Injection 1), 7 (Injection 2), and 30 (Injection 3). Participants received 1 injection of 0.5 mL placebo matched to vaccine at Days 0 (Injection 1), 7 (Injection 2), and 30 (Injection 3).
Period Title: Overall Study
Started 6201 3101
Safety Population [1] 6113 3057
Completed 4809 2370
Not Completed 1392 731
Reason Not Completed
Serious adverse event             400             198
Other Adverse Event             34             15
Protocol Violation             67             37
Lost to Follow-up             163             74
Withdrawal by Subject             606             349
Other             122             58
[1]
Participants who had received the study or control vaccine, analyzed according to vaccine received
Arm/Group Title C. Difficile Vaccine Group Placebo Group Total
Hide Arm/Group Description Participants received 1 injection of 0.5 mL C. difficile toxoid vaccine at Days 0 (Injection 1), 7 (Injection 2), and 30 (Injection 3). Participants received 1 injection of 0.5 mL placebo matched to vaccine at Days 0 (Injection 1), 7 (Injection 2), and 30 (Injection 3). Total of all reporting groups
Overall Number of Baseline Participants 6201 3101 9302
Hide Baseline Analysis Population Description
Analysis was performed on all randomized participants.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 6201 participants 3101 participants 9302 participants
65.9  (8.86) 65.8  (8.87) 65.8  (8.86)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6201 participants 3101 participants 9302 participants
Female
2629
  42.4%
1294
  41.7%
3923
  42.2%
Male
3572
  57.6%
1807
  58.3%
5379
  57.8%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6201 participants 3101 participants 9302 participants
Hispanic or Latino
330
   5.3%
171
   5.5%
501
   5.4%
Not Hispanic or Latino
2780
  44.8%
1390
  44.8%
4170
  44.8%
Unknown or Not Reported
3091
  49.8%
1540
  49.7%
4631
  49.8%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6201 participants 3101 participants 9302 participants
American Indian or Alaska Native
6
   0.1%
6
   0.2%
12
   0.1%
Asian
795
  12.8%
398
  12.8%
1193
  12.8%
Native Hawaiian or Other Pacific Islander
5
   0.1%
4
   0.1%
9
   0.1%
Black or African American
206
   3.3%
102
   3.3%
308
   3.3%
White
2983
  48.1%
1487
  48.0%
4470
  48.1%
More than one race
8
   0.1%
5
   0.2%
13
   0.1%
Unknown or Not Reported
2198
  35.4%
1099
  35.4%
3297
  35.4%
1.Primary Outcome
Title Number of Participants With Symptomatic Polymerase Chain Reaction (PCR)-Confirmed Primary C. Difficile Infection (CDI) Cases
Hide Description Symptomatic PCR-confirmed CDI cases were defined as the number of participants with combination of clinical and laboratory findings. Clinical components were: >= 3 loose stools in <= 24 hours, loose stools (defined as type 6 [fluffy pieces with ragged edges, mushy] or type 7 [watery, no solid pieces] according to the Bristol Stool Chart) lasting >= 24 hours. Laboratory findings were: stool sample positive for C. difficile Toxin B by PCR at central laboratory or diagnosis of pseudomembranous colitis visualized at colonoscopy.
Time Frame Up to 3 years post injection 1
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on modified intent-to-treat (mITT) population which included all participants who received at least 1 injection and were analyzed according to the group to which they were randomized.
Arm/Group Title C. Difficile Vaccine Group Placebo Group
Hide Arm/Group Description:
Participants received 1 injection of 0.5 mL C. difficile toxoid vaccine at Days 0 (Injection 1), 7 (Injection 2), and 30 (Injection 3).
Participants received 1 injection of 0.5 mL placebo matched to vaccine at Days 0 (Injection 1), 7 (Injection 2), and 30 (Injection 3).
Overall Number of Participants Analyzed 6173 3085
Measure Type: Count of Participants
Unit of Measure: Participants
34 16
2.Secondary Outcome
Title Number of Participants With Severe PCR-Confirmed Primary CDI Cases
Hide Description Severe CDI cases were defined as number of participants with at least one of the following symptoms: fever >= 38.5 degree Celsius (°C), white blood cell count >= 15,000 cells/mm^3, ileus, pseudomembranous colitis, serum albumin <3 gram per deciliter, abdominal distension, abdominal tenderness, or admission to the intensive care unit within 7 days of CDI diagnosis.
Time Frame Up to 3 years post injection 1
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on participants with protocol-defined (PCR confirmed) primary CDI cases.
Arm/Group Title C. Difficile Vaccine Group Placebo Group
Hide Arm/Group Description:
Participants received 1 injection of 0.5 mL C. difficile toxoid vaccine at Days 0 (Injection 1), 7 (Injection 2), and 30 (Injection 3).
Participants received 1 injection of 0.5 mL placebo matched to vaccine at Days 0 (Injection 1), 7 (Injection 2), and 30 (Injection 3).
Overall Number of Participants Analyzed 34 16
Measure Type: Count of Participants
Unit of Measure: Participants
9 6
3.Secondary Outcome
Title Number of Participants With Loose Stool Episodes
Hide Description Loose stools were defined as type 6 (fluffy pieces with ragged edges, mushy) or type 7 (watery, no solid pieces) according to the Bristol Stool Chart. In this outcome measure, participants with number of loose stool episodes (categorized as: loose stool episodes less than 3, 3 to 6, 7 to 10, 11 to 15 and greater than 15) were reported.
Time Frame Up to 3 years post injection 1
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on participants with protocol-defined PCR confirmed CDI cases.
Arm/Group Title C. Difficile Vaccine Group Placebo Group
Hide Arm/Group Description:
Participants received 1 injection of 0.5 mL C. difficile toxoid vaccine at Days 0 (Injection 1), 7 (Injection 2), and 30 (Injection 3).
Participants received 1 injection of 0.5 mL placebo matched to vaccine at Days 0 (Injection 1), 7 (Injection 2), and 30 (Injection 3).
Overall Number of Participants Analyzed 34 16
Measure Type: Count of Participants
Unit of Measure: Participants
<3 0 0
3 to 6 7 4
7 to 10 7 2
11 to 15 7 4
>15 13 6
4.Secondary Outcome
Title Number of Participants With Symptomatic PCR Confirmed CDI Cases: Per-Protocol Population
Hide Description Symptomatic PCR confirmed CDI cases were defined as the number of participants with combination of clinical and laboratory findings. Clinical components were: >= 3 loose stools in <= 24 hours, loose stools (defined as type 6 [fluffy pieces with ragged edges, mushy] or type 7 [watery, no solid pieces] according to the Bristol Stool Chart) lasting >= 24 hours. Laboratory findings were: stool sample positive for C. difficile Toxin B by PCR at central laboratory or diagnosis of pseudomembranous colitis visualized at colonoscopy. Analysis was performed on per-protocol efficacy analysis set (PPEAS).
Time Frame Up to 3 years post injection 1
Hide Outcome Measure Data
Hide Analysis Population Description
PPEAS: participants who had at least 1 injection, no relevant protocol deviations (not meet inclusion criteria/ met exclusion criteria, not receive any vaccine/not received in proper time window, received different vaccine than randomized, preparation and / or administration of vaccine not done per protocol, received protocol-restricted therapy).
Arm/Group Title C. Difficile Vaccine Group Placebo Group
Hide Arm/Group Description:
Participants received 1 injection of 0.5 mL C. difficile toxoid vaccine at Days 0 (Injection 1), 7 (Injection 2), and 30 (Injection 3).
Participants received 1 injection of 0.5 mL placebo matched to vaccine at Days 0 (Injection 1), 7 (Injection 2), and 30 (Injection 3).
Overall Number of Participants Analyzed 4786 2378
Measure Type: Count of Participants
Unit of Measure: Participants
23 13
5.Secondary Outcome
Title Serum Antibody Concentrations Against Toxins A and B Measured by Enzyme-Linked Immunosorbent Assay (ELISA)
Hide Description Serum antibody concentrations against toxins A and B were measured by ELISA and expressed as geometric mean concentration (GMC). The 2-sided 95% Confidence Interval (CI) of GMC was based on the Student t-distribution. Analysis was performed on Per Protocol Immunogenicity Analysis Set, which included participants who had at least 1 injection, no relevant protocol deviations (not met inclusion criteria/ met exclusion criteria, not received vaccine/ not received in proper time window, received different vaccine than randomized, preparation and/ or administration of vaccine not per protocol, protocol-restricted therapy, not provided post-dose serology sample/serology sample did not produced a valid test result).
Time Frame Day 0, Day 14, Day 30, Day 60, Day 210, Day 390, Day 570, Day 750, Day 930, and Day 1110
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on Per Protocol Immunogenicity Analysis Set. Here, 'number analyzed' = participants with available data for each specified category.
Arm/Group Title C. Difficile Vaccine Group Placebo Group
Hide Arm/Group Description:
Participants received 1 injection of 0.5 mL C. difficile toxoid vaccine at Days 0 (Injection 1), 7 (Injection 2), and 30 (Injection 3).
Participants received 1 injection of 0.5 mL placebo matched to vaccine at Days 0 (Injection 1), 7 (Injection 2), and 30 (Injection 3).
Overall Number of Participants Analyzed 471 236
Geometric Mean (95% Confidence Interval)
Unit of Measure: ELISA units per milliliter (EU/mL)
Toxin A ImunnoglobulinG (IgG): Day 0 Number Analyzed 468 participants 230 participants
0.957
(0.897 to 1.02)
0.999
(0.912 to 1.09)
Toxin A IgG: Day 14 Number Analyzed 418 participants 214 participants
3.19
(2.68 to 3.80)
0.913
(0.849 to 0.983)
Toxin A IgG: Day 30 Number Analyzed 456 participants 230 participants
12.2
(10.4 to 14.3)
0.959
(0.889 to 1.03)
Toxin A IgG: Day 60 Number Analyzed 417 participants 212 participants
43.7
(38.1 to 50.2)
0.933
(0.867 to 1.00)
Toxin A IgG: Day 210 Number Analyzed 355 participants 182 participants
12.0
(10.5 to 13.8)
0.944
(0.865 to 1.03)
Toxin A IgG: Day 390 Number Analyzed 320 participants 159 participants
6.02
(5.23 to 6.93)
0.955
(0.856 to 1.06)
Toxin A IgG: Day 570 Number Analyzed 277 participants 145 participants
4.50
(3.86 to 5.25)
0.908
(0.834 to 0.989)
Toxin A IgG: Day 750 Number Analyzed 191 participants 93 participants
4.02
(3.38 to 4.78)
0.856
(0.776 to 0.944)
Toxin A IgG: Day 930 Number Analyzed 108 participants 66 participants
3.83
(3.02 to 4.85)
0.902
(0.796 to 1.02)
Toxin A IgG: Day 1110 Number Analyzed 59 participants 36 participants
3.75
(2.64 to 5.34)
1.09
(0.786 to 1.50)
Toxin B IgG: Day 0 Number Analyzed 468 participants 231 participants
1.40
(1.24 to 1.57)
1.49
(1.24 to 1.79)
Toxin B IgG: Day 14 Number Analyzed 419 participants 216 participants
4.36
(3.37 to 5.64)
1.56
(1.29 to 1.89)
Toxin B IgG: Day 30 Number Analyzed 455 participants 231 participants
10.0
(7.85 to 12.8)
1.46
(1.21 to 1.75)
Toxin B IgG: Day 60 Number Analyzed 417 participants 212 participants
24.8
(20.1 to 30.6)
1.42
(1.18 to 1.71)
Toxin B IgG: Day 210 Number Analyzed 354 participants 182 participants
6.62
(5.36 to 8.19)
1.31
(1.07 to 1.61)
Toxin B IgG: Day 390 Number Analyzed 319 participants 159 participants
3.98
(3.15 to 5.02)
1.24
(0.991 to 1.56)
Toxin B IgG: Day 570 Number Analyzed 277 participants 145 participants
3.37
(2.63 to 4.32)
1.15
(0.905 to 1.47)
Toxin B IgG: Day 750 Number Analyzed 191 participants 93 participants
2.86
(2.14 to 3.84)
1.11
(0.840 to 1.47)
Toxin B IgG: Day 930 Number Analyzed 108 participants 66 participants
2.42
(1.65 to 3.55)
1.13
(0.812 to 1.58)
Toxin B IgG: Day 1110 Number Analyzed 59 participants 36 participants
3.46
(2.06 to 5.81)
0.966
(0.592 to 1.58)
6.Secondary Outcome
Title Percentage of Participants With >= 2 and 4-Fold Rise in Serum Antibody Concentrations From Baseline Against Toxins A and B Measured by ELISA
Hide Description Percentage of Participants with >= 2 and 4-fold rise in serum antibody concentrations against toxins A and B were measured by ELISA. The 2-sided 95% Cl of the percentage was based on Exact method calculations.
Time Frame Day 60
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on Per Protocol Immunogenicity Analysis Set. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure and 'number analyzed' = participants with available data for each specified category.
Arm/Group Title C. Difficile Vaccine Group Placebo Group
Hide Arm/Group Description:
Participants received 1 injection of 0.5 mL C. difficile toxoid vaccine at Days 0 (Injection 1), 7 (Injection 2), and 30 (Injection 3).
Participants received 1 injection of 0.5 mL placebo matched to vaccine at Days 0 (Injection 1), 7 (Injection 2), and 30 (Injection 3).
Overall Number of Participants Analyzed 436 220
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
Toxin A IgG: >=2 Number Analyzed 433 participants 217 participants
93.3
(90.5 to 95.5)
0.9
(0.1 to 3.3)
Toxin A IgG: >=4 Number Analyzed 433 participants 217 participants
88.9
(85.6 to 91.7)
0.0
(0.0 to 1.7)
Toxin B IgG: >=2 Number Analyzed 433 participants 218 participants
82.2
(78.3 to 85.7)
4.6
(2.2 to 8.3)
Toxin B IgG: >=4 Number Analyzed 433 participants 218 participants
73.2
(68.8 to 77.3)
0.5
(0.0 to 2.5)
7.Secondary Outcome
Title Serum Antibody Concentrations Against Toxins A and B Measured by ELISA in Participants With CDI
Hide Description Serum antibody concentrations against toxins A and B were measured by ELISA and expressed as GMC. The 2-sided 95% CI GMC was based on the Student t-distribution. Symptomatic PCR-confirmed CDI cases were defined as the number of participants with combination of clinical and laboratory findings. Clinical components were: >= 3 loose stools in <= 24 hours, loose stools (defined as type 6 [fluffy pieces with ragged edges, mushy] or type 7 [watery, no solid pieces] according to the Bristol Stool Chart) lasting >= 24 hours. Laboratory findings were: stool sample positive for C. difficile Toxin B by PCR at central laboratory or diagnosis of pseudomembranous colitis visualized at colonoscopy.
Time Frame Day 0 and Day 60
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on participants with protocol-defined (PCR confirmed) primary CDI cases. Here, 'number analyzed' = participants with available data for each specified category.
Arm/Group Title C. Difficile Vaccine Group Placebo Group
Hide Arm/Group Description:
Participants received 1 injection of 0.5 mL C. difficile toxoid vaccine at Days 0 (Injection 1), 7 (Injection 2), and 30 (Injection 3).
Participants received 1 injection of 0.5 mL placebo matched to vaccine at Days 0 (Injection 1), 7 (Injection 2), and 30 (Injection 3).
Overall Number of Participants Analyzed 34 16
Geometric Mean (95% Confidence Interval)
Unit of Measure: EU/mL
Toxin A IgG: Day 0 Number Analyzed 33 participants 16 participants
1.15
(0.821 to 1.62)
1.04
(0.661 to 1.64)
Toxin A IgG: Day 60 Number Analyzed 30 participants 16 participants
42.1
(18.0 to 98.3)
1.06
(0.632 to 1.76)
Toxin B IgG: Day 0 Number Analyzed 33 participants 16 participants
1.41
(0.762 to 2.62)
1.05
(0.504 to 2.20)
Toxin B IgG: Day 60 Number Analyzed 30 participants 16 participants
19.3
(6.65 to 56.2)
1.13
(0.609 to 2.11)
8.Secondary Outcome
Title Serum Antibody Concentrations Against Toxins A and B Measured by Toxin Neutralization Assay (TNA)
Hide Description Serum antibody concentrations against toxins A and B were measured by TNA and expressed as geometric mean titer (GMT). The 2-sided 95% Cl of GMT was based on the Student t-distribution.
Time Frame Day 0, Day 14, Day 30, Day 60, Day 210, Day 390, Day 570, Day 750, Day 930, and Day 1110
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on Per Protocol Immunogenicity Analysis Set. Here, 'number analyzed' = participants with available data for each specified category.
Arm/Group Title C. Difficile Vaccine Group Placebo Group
Hide Arm/Group Description:
Participants received 1 injection of 0.5 mL C. difficile toxoid vaccine at Days 0 (Injection 1), 7 (Injection 2), and 30 (Injection 3).
Participants received 1 injection of 0.5 mL placebo matched to vaccine at Days 0 (Injection 1), 7 (Injection 2), and 30 (Injection 3).
Overall Number of Participants Analyzed 471 236
Geometric Mean (95% Confidence Interval)
Unit of Measure: Titer (1/dilution)
Toxin A TNA: Day 0 Number Analyzed 466 participants 231 participants
9.86
(9.22 to 10.5)
10.1
(9.12 to 11.2)
Toxin A TNA: Day 14 Number Analyzed 419 participants 216 participants
28.5
(22.7 to 35.8)
9.86
(8.96 to 10.8)
Toxin A TNA: Day 30 Number Analyzed 456 participants 231 participants
50.5
(40.9 to 62.3)
9.97
(9.09 to 10.9)
Toxin A TNA: Day 60 Number Analyzed 416 participants 212 participants
269
(226 to 322)
9.82
(8.95 to 10.8)
Toxin A TNA: Day 210 Number Analyzed 354 participants 181 participants
269
(228 to 317)
10.3
(9.09 to 11.7)
Toxin A TNA: Day 390 Number Analyzed 320 participants 159 participants
217
(183 to 259)
10.1
(8.86 to 11.5)
Toxin A TNA: Day 570 Number Analyzed 277 participants 145 participants
184
(153 to 223)
9.86
(8.76 to 11.1)
Toxin A TNA: Day 750 Number Analyzed 191 participants 93 participants
186
(148 to 234)
10.2
(8.66 to 12.0)
Toxin A TNA: Day 930 Number Analyzed 108 participants 66 participants
173
(125 to 240)
10.7
(8.57 to 13.4)
Toxin A TNA: Day 1110 Number Analyzed 59 participants 36 participants
212
(137 to 329)
10.2
(8.03 to 12.9)
Toxin B TNA: Day 0 Number Analyzed 466 participants 230 participants
12.3
(11.2 to 13.6)
13.2
(11.2 to 15.6)
Toxin B TNA: Day 14 Number Analyzed 419 participants 216 participants
32.7
(25.3 to 42.2)
13.3
(11.3 to 15.7)
Toxin B TNA: Day 30 Number Analyzed 456 participants 231 participants
37.8
(29.3 to 48.8)
13.4
(11.3 to 15.8)
Toxin B TNA: Day 60 Number Analyzed 416 participants 212 participants
43.9
(34.0 to 56.6)
14.3
(11.9 to 17.2)
Toxin B TNA: Day 210 Number Analyzed 354 participants 181 participants
41.4
(32.4 to 53.1)
13.2
(11.1 to 15.5)
Toxin B TNA: Day 390 Number Analyzed 319 participants 159 participants
38.4
(30.0 to 49.0)
13.5
(11.3 to 16.1)
Toxin B TNA: Day 570 Number Analyzed 277 participants 145 participants
35.7
(27.7 to 46.0)
13.7
(11.3 to 16.8)
Toxin B TNA: Day 750 Number Analyzed 191 participants 93 participants
34.3
(25.1 to 46.9)
14.6
(11.2 to 18.9)
Toxin B TNA: Day 930 Number Analyzed 108 participants 66 participants
31.0
(21.1 to 45.6)
17.0
(12.3 to 23.5)
Toxin B TNA: Day 1110 Number Analyzed 59 participants 36 participants
46.8
(26.1 to 84.1)
14.0
(9.05 to 21.7)
9.Secondary Outcome
Title Percentage of Participants With >= 2 and 4-Fold Rise in Serum Antibody Concentrations From Baseline Against Toxins A and B Measured by TNA
Hide Description Percentage of Participants with >= 2 and 4-fold rise in serum antibody concentrations against toxins A and B were measured by TNA. The 2-sided 95% CI of the percentage was based on Exact method calculations.
Time Frame Day 60
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on Per Protocol Immunogenicity Analysis Set. Here, "overall number of participants analyzed" signifies participants evaluable for this outcome measure and 'number analyzed' = participants with evaluable data for each specified category.
Arm/Group Title C. Difficile Vaccine Group Placebo Group
Hide Arm/Group Description:
Participants received 1 injection of 0.5 mL C. difficile toxoid vaccine at Days 0 (Injection 1), 7 (Injection 2), and 30 (Injection 3).
Participants received 1 injection of 0.5 mL placebo matched to vaccine at Days 0 (Injection 1), 7 (Injection 2), and 30 (Injection 3).
Overall Number of Participants Analyzed 436 220
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
Toxin A TNA: >=2 Number Analyzed 431 participants 218 participants
85.6
(81.9 to 88.8)
0.5
(0.0 to 2.5)
Toxin A TNA: >=4 Number Analyzed 431 participants 218 participants
78.2
(74.0 to 82.0)
0.5
(0.0 to 2.5)
Toxin B TNA: >=2 Number Analyzed 431 participants 217 participants
30.9
(26.5 to 35.5)
2.8
(1.0 to 5.9)
Toxin B TNA: >=4 Number Analyzed 431 participants 217 participants
27.4
(23.2 to 31.8)
1.8
(0.5 to 4.7)
10.Secondary Outcome
Title Serum Antibody Concentrations Against Toxins A and B Measured by TNA in Participants With CDI
Hide Description Serum antibody concentrations against toxins A and B were measured by TNA and were expressed as GMT. The 2-sided 95% CI GMC was based on the Student t-distribution. Symptomatic PCR confirmed CDI cases were defined as the number of participants with combination of clinical and laboratory findings. Clinical components were: >= 3 loose stools in <= 24 hours, loose stools (defined as type 6 [fluffy pieces with ragged edges, mushy] or type 7 [watery, no solid pieces] according to the Bristol Stool Chart) lasting >= 24 hours. Laboratory findings were: stool sample positive for C. difficile Toxin B by PCR at central laboratory or diagnosis of pseudomembranous colitis visualized at colonoscopy.
Time Frame Day 0 and Day 60
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on participants with protocol-defined (PCR confirmed) primary CDI cases. Here, 'number analyzed' = participants with available data for each specified category.
Arm/Group Title C. Difficile Vaccine Group Placebo Group
Hide Arm/Group Description:
Participants received 1 injection of 0.5 mL C. difficile toxoid vaccine at Days 0 (Injection 1), 7 (Injection 2), and 30 (Injection 3).
Participants received 1 injection of 0.5 mL placebo matched to vaccine at Days 0 (Injection 1), 7 (Injection 2), and 30 (Injection 3).
Overall Number of Participants Analyzed 34 16
Geometric Mean (95% Confidence Interval)
Unit of Measure: Titer (1/dilution)
Toxin A TNA: Day 0 Number Analyzed 33 participants 16 participants
12.4
(8.59 to 17.9)
12.0
(6.27 to 23.0)
Toxin A TNA: Day 60 Number Analyzed 30 participants 16 participants
176
(83.4 to 371)
10.7
(5.77 to 19.7)
Toxin B TNA: Day 0 Number Analyzed 33 participants 16 participants
16.7
(9.46 to 29.5)
11.1
(7.57 to 16.3)
Toxin B TNA: Day 60 Number Analyzed 30 participants 16 participants
53.0
(18.3 to 153)
13.1
(8.11 to 21.0)
11.Secondary Outcome
Title Percentage of Participants Reporting Solicited Injection Site and Systemic Reactions
Hide Description Solicited injection site reactions: pain, erythema, and swelling. Pain: Grade 1: no interference with activity, Grade 2: some interference with activity, Grade 3: significant; prevents daily activity; Erythema and swelling: Grade 1: >= 25 to <=50 mm, Grade 2: >51 to <=100 mm, Grade 3: >100 mm. Solicited systemic reactions: fever, headache, malaise, myalgia, and arthralgia. Fever: Grade 1: >= 38.0°C to <=38.4°C or >= 100.4° Fahrenheit (F) to <=101.1°F, Grade 2: >=38.5°C to <= 38.9°C or >=101.2°F to <=102.0°F, Grade 3: >=39.0°C or >=102.1°F. Headache, malaise, and myalgia: Grade 1: no interference with activity, Grade 2: some interference with activity, Grade 3: significant; prevents daily activity; Arthralgia: Grade 1: free range of motion but complains of pain or discomfort, Grade 2: decreased range of motion due to pain or discomfort, Grade 3: unwilling to move due to pain.
Time Frame Day 0 to Day 6 after any vaccination
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Hide Analysis Population Description
Analysis was performed on all participants who received vaccine and were evaluable for reactogenicity. Here, 'number analyzed' = participants with available data for each specified category.
Arm/Group Title C. Difficile Vaccine Group Placebo Group
Hide Arm/Group Description:
Participants received 1 injection of 0.5 mL C. difficile toxoid vaccine at Days 0 (Injection 1), 7 (Injection 2), and 30 (Injection 3).
Participants received 1 injection of 0.5 mL placebo matched to vaccine at Days 0 (Injection 1), 7 (Injection 2), and 30 (Injection 3).
Overall Number of Participants Analyzed 1227 608
Measure Type: Number
Unit of Measure: percentage of participants
Injection site Pain Number Analyzed 1199 participants 586 participants
38.6 13.5
Injection site Erythema Number Analyzed 1196 participants 587 participants
4.2 0.0
Injection site Swelling Number Analyzed 1197 participants 587 participants
3.8 0.3
Fever Number Analyzed 1173 participants 577 participants
4.8 5.7
Headache Number Analyzed 1196 participants 586 participants
25.3 22.5
Malaise Number Analyzed 1196 participants 586 participants
23.9 19.6
Myalgia Number Analyzed 1196 participants 586 participants
26.6 21.2
Arthralgia Number Analyzed 1196 participants 586 participants
19.5 16.7
Time Frame Adverse events data was collected throughout the study (up to 3 years).
Adverse Event Reporting Description Safety Analysis Set included all participants who received at least one study or control vaccine and were analyzed according to the vaccine received. Solicited reaction(SR) was an adverse event (AE) that was prelisted (i.e.,solicited) in the electronic case report form (eCRF) and considered to be related to vaccination. An unsolicited AE was an observed AE that did not fulfill the conditions prelisted (i.e.,solicited) in the eCRF in terms of symptom and/or onset post-vaccination.
 
Arm/Group Title C. Difficile Vaccine Group Placebo Group
Hide Arm/Group Description Participants received 1 injection of 0.5 mL C. difficile toxoid vaccine at Days 0 (Injection 1), 7 (Injection 2), and 30 (Injection 3). Participants received 1 injection of 0.5 mL placebo matched to vaccine at Days 0 (Injection 1), 7 (Injection 2), and 30 (Injection 3).
All-Cause Mortality
C. Difficile Vaccine Group Placebo Group
Affected / at Risk (%) Affected / at Risk (%)
Total   255/6113 (4.17%)      127/3057 (4.15%)    
Hide Serious Adverse Events
C. Difficile Vaccine Group Placebo Group
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1662/6113 (27.19%)      851/3057 (27.84%)    
Blood and lymphatic system disorders     
Anaemia † 1  19/6113 (0.31%)  20 11/3057 (0.36%)  13
Antiphospholipid Syndrome † 1  0/6113 (0.00%)  0 1/3057 (0.03%)  1
Coagulopathy † 1  4/6113 (0.07%)  4 0/3057 (0.00%)  0
Haemolytic Anaemia † 1  0/6113 (0.00%)  0 1/3057 (0.03%)  1
Haemorrhagic Anaemia † 1  2/6113 (0.03%)  2 5/3057 (0.16%)  5
Iron Deficiency Anaemia † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Microcytic Anaemia † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Nephrogenic Anaemia † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Normochromic Normocytic Anaemia † 1  0/6113 (0.00%)  0 1/3057 (0.03%)  1
Thrombocytosis † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Cardiac disorders     
Acute Coronary Syndrome † 1  13/6113 (0.21%)  15 2/3057 (0.07%)  2
Acute Myocardial Infarction † 1  56/6113 (0.92%)  59 22/3057 (0.72%)  24
Angina Pectoris † 1  19/6113 (0.31%)  20 10/3057 (0.33%)  10
Angina Unstable † 1  27/6113 (0.44%)  32 9/3057 (0.29%)  15
Aortic Valve Incompetence † 1  0/6113 (0.00%)  0 1/3057 (0.03%)  1
Aortic Valve Stenosis † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Arrhythmia † 1  9/6113 (0.15%)  9 2/3057 (0.07%)  2
Arrhythmia Supraventricular † 1  2/6113 (0.03%)  2 0/3057 (0.00%)  0
Arteriosclerosis Coronary Artery † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Atrial Fibrillation † 1  42/6113 (0.69%)  53 14/3057 (0.46%)  15
Atrial Flutter † 1  3/6113 (0.05%)  3 2/3057 (0.07%)  2
Atrial Tachycardia † 1  1/6113 (0.02%)  1 1/3057 (0.03%)  1
Atrial Thrombosis † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Atrioventricular Block † 1  1/6113 (0.02%)  1 1/3057 (0.03%)  1
Atrioventricular Block Complete † 1  0/6113 (0.00%)  0 2/3057 (0.07%)  2
Bradyarrhythmia † 1  0/6113 (0.00%)  0 1/3057 (0.03%)  1
Bradycardia † 1  5/6113 (0.08%)  6 5/3057 (0.16%)  5
Bundle Branch Block Left † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Cardiac Arrest † 1  10/6113 (0.16%)  11 8/3057 (0.26%)  8
Cardiac Disorder † 1  2/6113 (0.03%)  2 0/3057 (0.00%)  0
Cardiac Failure † 1  34/6113 (0.56%)  40 16/3057 (0.52%)  36
Cardiac Failure Acute † 1  16/6113 (0.26%)  22 6/3057 (0.20%)  7
Cardiac Failure Chronic † 1  3/6113 (0.05%)  5 0/3057 (0.00%)  0
Cardiac Failure Congestive † 1  69/6113 (1.13%)  102 29/3057 (0.95%)  37
Cardiac Tamponade † 1  6/6113 (0.10%)  6 2/3057 (0.07%)  2
Cardiac Valve Disease † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Cardio-Respiratory Arrest † 1  10/6113 (0.16%)  11 3/3057 (0.10%)  3
Cardiogenic Shock † 1  8/6113 (0.13%)  9 5/3057 (0.16%)  5
Cardiomyopathy † 1  5/6113 (0.08%)  6 1/3057 (0.03%)  1
Cardiopulmonary Failure † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Cardiorenal Syndrome † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Cor Pulmonale † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Coronary Artery Disease † 1  22/6113 (0.36%)  23 7/3057 (0.23%)  7
Coronary Artery Occlusion † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Coronary Artery Stenosis † 1  7/6113 (0.11%)  8 2/3057 (0.07%)  2
Coronary Artery Thrombosis † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Heart Valve Incompetence † 1  1/6113 (0.02%)  1 1/3057 (0.03%)  1
Hypertensive Heart Disease † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Intracardiac Thrombus † 1  1/6113 (0.02%)  1 2/3057 (0.07%)  2
Ischaemic Cardiomyopathy † 1  1/6113 (0.02%)  1 2/3057 (0.07%)  2
Left Ventricular Failure † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Mitral Valve Incompetence † 1  3/6113 (0.05%)  3 1/3057 (0.03%)  1
Myocardial Infarction † 1  27/6113 (0.44%)  27 16/3057 (0.52%)  16
Myocardial Ischaemia † 1  8/6113 (0.13%)  8 3/3057 (0.10%)  3
Palpitations † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Pericardial Effusion † 1  5/6113 (0.08%)  5 0/3057 (0.00%)  0
Pericarditis † 1  1/6113 (0.02%)  1 2/3057 (0.07%)  2
Prinzmetal Angina † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Pulseless Electrical Activity † 1  0/6113 (0.00%)  0 1/3057 (0.03%)  1
Reperfusion Arrhythmia † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Right Ventricular Failure † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Sick Sinus Syndrome † 1  2/6113 (0.03%)  2 3/3057 (0.10%)  3
Sinoatrial Block † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Sinus Bradycardia † 1  1/6113 (0.02%)  1 1/3057 (0.03%)  1
Stress Cardiomyopathy † 1  0/6113 (0.00%)  0 1/3057 (0.03%)  1
Supraventricular Tachyarrhythmia † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Supraventricular Tachycardia † 1  1/6113 (0.02%)  1 1/3057 (0.03%)  1
Tachyarrhythmia † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Tachycardia † 1  0/6113 (0.00%)  0 2/3057 (0.07%)  2
Tricuspid Valve Incompetence † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Ventricle Rupture † 1  0/6113 (0.00%)  0 1/3057 (0.03%)  1
Ventricular Arrhythmia † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Ventricular Fibrillation † 1  3/6113 (0.05%)  3 1/3057 (0.03%)  1
Ventricular Tachycardia † 1  5/6113 (0.08%)  5 4/3057 (0.13%)  4
Congenital, familial and genetic disorders     
Anophthalmos † 1  0/6113 (0.00%)  0 1/3057 (0.03%)  1
Cardiac Septal Defect † 1  0/6113 (0.00%)  0 1/3057 (0.03%)  1
Ectopic Ureter † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Hydrocele † 1  0/6113 (0.00%)  0 1/3057 (0.03%)  1
Ear and labyrinth disorders     
Deafness Neurosensory † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Meniere's Disease † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Sudden Hearing Loss † 1  0/6113 (0.00%)  0 1/3057 (0.03%)  1
Vertigo † 1  2/6113 (0.03%)  2 1/3057 (0.03%)  1
Vertigo Positional † 1  4/6113 (0.07%)  4 0/3057 (0.00%)  0
Endocrine disorders     
Adrenal Insufficiency † 1  0/6113 (0.00%)  0 1/3057 (0.03%)  1
Goitre † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Hyperparathyroidism † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Hyperparathyroidism Primary † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Thyroid Mass † 1  2/6113 (0.03%)  2 1/3057 (0.03%)  1
Eye disorders     
Amaurosis † 1  1/6113 (0.02%)  1 1/3057 (0.03%)  1
Amaurosis Fugax † 1  2/6113 (0.03%)  2 0/3057 (0.00%)  0
Aphakia † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Cataract † 1  2/6113 (0.03%)  2 2/3057 (0.07%)  3
Conjunctivochalasis † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Eyelid Ptosis † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Glaucoma † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Phacolytic Glaucoma † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Pterygium † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Retinal Detachment † 1  0/6113 (0.00%)  0 1/3057 (0.03%)  1
Retinal Vein Occlusion † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Vitreous Haemorrhage † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Gastrointestinal disorders     
Abdominal Adhesions † 1  2/6113 (0.03%)  2 0/3057 (0.00%)  0
Abdominal Hernia † 1  3/6113 (0.05%)  3 1/3057 (0.03%)  1
Abdominal Pain † 1  14/6113 (0.23%)  14 11/3057 (0.36%)  15
Abdominal Pain Lower † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Abdominal Pain Upper † 1  2/6113 (0.03%)  2 2/3057 (0.07%)  2
Abdominal Wall Haematoma † 1  2/6113 (0.03%)  2 0/3057 (0.00%)  0
Anal Fissure † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Anal Fistula † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Ascites † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Change Of Bowel Habit † 1  0/6113 (0.00%)  0 1/3057 (0.03%)  1
Colitis † 1  5/6113 (0.08%)  5 0/3057 (0.00%)  0
Colitis Ischaemic † 1  1/6113 (0.02%)  1 2/3057 (0.07%)  2
Colitis Microscopic † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Colonic Pseudo-Obstruction † 1  0/6113 (0.00%)  0 1/3057 (0.03%)  1
Colonic Stenosis † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Constipation † 1  9/6113 (0.15%)  9 2/3057 (0.07%)  2
Crohn's Disease † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Dental Pulp Disorder † 1  0/6113 (0.00%)  0 1/3057 (0.03%)  1
Diabetic Gastroparesis † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Diaphragmatic Hernia † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Diarrhoea † 1  8/6113 (0.13%)  8 2/3057 (0.07%)  2
Diverticular Perforation † 1  2/6113 (0.03%)  2 0/3057 (0.00%)  0
Diverticulum † 1  4/6113 (0.07%)  5 1/3057 (0.03%)  1
Duodenal Ulcer † 1  2/6113 (0.03%)  2 1/3057 (0.03%)  1
Duodenal Ulcer Haemorrhage † 1  2/6113 (0.03%)  2 0/3057 (0.00%)  0
Dyspepsia † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Enterovesical Fistula † 1  1/6113 (0.02%)  2 1/3057 (0.03%)  1
Erosive Duodenitis † 1  0/6113 (0.00%)  0 1/3057 (0.03%)  1
Erosive Oesophagitis † 1  0/6113 (0.00%)  0 1/3057 (0.03%)  1
Faecaloma † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Food Poisoning † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Gastric Disorder † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Gastric Haemorrhage † 1  0/6113 (0.00%)  0 2/3057 (0.07%)  2
Gastric Ulcer † 1  1/6113 (0.02%)  1 2/3057 (0.07%)  2
Gastric Ulcer Haemorrhage † 1  2/6113 (0.03%)  2 0/3057 (0.00%)  0
Gastric Ulcer Perforation † 1  2/6113 (0.03%)  2 0/3057 (0.00%)  0
Gastritis † 1  8/6113 (0.13%)  8 4/3057 (0.13%)  5
Gastritis Erosive † 1  0/6113 (0.00%)  0 1/3057 (0.03%)  1
Gastritis Haemorrhagic † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Gastroduodenal Ulcer † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Gastrointestinal Amyloidosis † 1  0/6113 (0.00%)  0 1/3057 (0.03%)  1
Gastrointestinal Haemorrhage † 1  13/6113 (0.21%)  13 6/3057 (0.20%)  6
Gastrointestinal Hypomotility † 1  1/6113 (0.02%)  1 1/3057 (0.03%)  1
Gastrointestinal Obstruction † 1  0/6113 (0.00%)  0 1/3057 (0.03%)  1
Gastrooesophageal Reflux Disease † 1  2/6113 (0.03%)  2 0/3057 (0.00%)  0
Haematemesis † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Haemorrhoids † 1  2/6113 (0.03%)  2 0/3057 (0.00%)  0
Hernial Eventration † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Hiatus Hernia † 1  2/6113 (0.03%)  2 0/3057 (0.00%)  0
Ileal Stenosis † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Ileus † 1  6/6113 (0.10%)  6 2/3057 (0.07%)  2
Ileus Paralytic † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Impaired Gastric Emptying † 1  1/6113 (0.02%)  5 0/3057 (0.00%)  0
Inguinal Hernia † 1  4/6113 (0.07%)  4 3/3057 (0.10%)  3
Inguinal Hernia, Obstructive † 1  0/6113 (0.00%)  0 1/3057 (0.03%)  1
Intestinal Haemorrhage † 1  1/6113 (0.02%)  1 1/3057 (0.03%)  1
Intestinal Obstruction † 1  6/6113 (0.10%)  7 1/3057 (0.03%)  1
Intestinal Perforation † 1  0/6113 (0.00%)  0 1/3057 (0.03%)  1
Intra-Abdominal Haemorrhage † 1  0/6113 (0.00%)  0 1/3057 (0.03%)  1
Large Intestinal Obstruction † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Large Intestine Polyp † 1  5/6113 (0.08%)  5 0/3057 (0.00%)  0
Lower Gastrointestinal Haemorrhage † 1  4/6113 (0.07%)  4 0/3057 (0.00%)  0
Melaena † 1  1/6113 (0.02%)  1 2/3057 (0.07%)  2
Mesenteric Artery Thrombosis † 1  0/6113 (0.00%)  0 1/3057 (0.03%)  2
Mesenteric Vein Thrombosis † 1  0/6113 (0.00%)  0 1/3057 (0.03%)  1
Nausea † 1  2/6113 (0.03%)  2 1/3057 (0.03%)  1
Oesophageal Obstruction † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Oesophageal Stenosis † 1  0/6113 (0.00%)  0 1/3057 (0.03%)  1
Oesophageal Varices Haemorrhage † 1  2/6113 (0.03%)  3 0/3057 (0.00%)  0
Oesophagitis † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Oral Disorder † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Pancreatic Pseudocyst † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Pancreatitis † 1  6/6113 (0.10%)  7 3/3057 (0.10%)  3
Pancreatitis Acute † 1  4/6113 (0.07%)  5 6/3057 (0.20%)  6
Pancreatitis Chronic † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Pancreatitis Relapsing † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Peptic Ulcer † 1  1/6113 (0.02%)  1 2/3057 (0.07%)  2
Periodontal Disease † 1  0/6113 (0.00%)  0 1/3057 (0.03%)  1
Peritoneal Adhesions † 1  0/6113 (0.00%)  0 1/3057 (0.03%)  1
Peritoneal Haemorrhage † 1  0/6113 (0.00%)  0 1/3057 (0.03%)  1
Proctalgia † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Rectal Haemorrhage † 1  4/6113 (0.07%)  4 2/3057 (0.07%)  2
Rectal Prolapse † 1  2/6113 (0.03%)  2 0/3057 (0.00%)  0
Small Intestinal Obstruction † 1  5/6113 (0.08%)  5 2/3057 (0.07%)  2
Spigelian Hernia † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Subileus † 1  0/6113 (0.00%)  0 1/3057 (0.03%)  1
Thrombosis Mesenteric Vessel † 1  0/6113 (0.00%)  0 1/3057 (0.03%)  1
Umbilical Hernia † 1  2/6113 (0.03%)  2 1/3057 (0.03%)  1
Umbilical Hernia, Obstructive † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Upper Gastrointestinal Haemorrhage † 1  5/6113 (0.08%)  5 2/3057 (0.07%)  2
Varices Oesophageal † 1  2/6113 (0.03%)  2 0/3057 (0.00%)  0
Volvulus † 1  0/6113 (0.00%)  0 1/3057 (0.03%)  1
Vomiting † 1  4/6113 (0.07%)  4 2/3057 (0.07%)  2
General disorders     
Asthenia † 1  4/6113 (0.07%)  4 2/3057 (0.07%)  2
Catheter Site Haemorrhage † 1  2/6113 (0.03%)  2 0/3057 (0.00%)  0
Chest Discomfort † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Chest Pain † 1  50/6113 (0.82%)  56 19/3057 (0.62%)  27
Death † 1  8/6113 (0.13%)  8 6/3057 (0.20%)  6
Device Dislocation † 1  9/6113 (0.15%)  9 1/3057 (0.03%)  1
Device Failure † 1  3/6113 (0.05%)  3 2/3057 (0.07%)  2
Device Issue † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Device Leakage † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Device Malfunction † 1  1/6113 (0.02%)  1 1/3057 (0.03%)  1
Device Occlusion † 1  2/6113 (0.03%)  2 1/3057 (0.03%)  1
Drug Interaction † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Fatigue † 1  1/6113 (0.02%)  1 1/3057 (0.03%)  1
General Physical Health Deterioration † 1  1/6113 (0.02%)  1 1/3057 (0.03%)  1
General Symptom † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Generalised Oedema † 1  0/6113 (0.00%)  0 1/3057 (0.03%)  1
Hernia Obstructive † 1  0/6113 (0.00%)  0 1/3057 (0.03%)  1
Hyperthermia † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Impaired Healing † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Implant Site Haematoma † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Inflammation † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Malaise † 1  1/6113 (0.02%)  1 1/3057 (0.03%)  1
Medical Device Complication † 1  7/6113 (0.11%)  8 4/3057 (0.13%)  4
Multi-Organ Failure † 1  4/6113 (0.07%)  4 3/3057 (0.10%)  3
Non-Cardiac Chest Pain † 1  2/6113 (0.03%)  2 2/3057 (0.07%)  2
Oedema † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Oedema Peripheral † 1  3/6113 (0.05%)  3 1/3057 (0.03%)  1
Pain † 1  2/6113 (0.03%)  2 3/3057 (0.10%)  3
Patient-Device Incompatibility † 1  0/6113 (0.00%)  0 1/3057 (0.03%)  1
Perforated Ulcer † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Polyp † 1  0/6113 (0.00%)  0 1/3057 (0.03%)  1
Pyrexia † 1  5/6113 (0.08%)  5 3/3057 (0.10%)  3
Spinal Pain † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Stent-Graft Endoleak † 1  1/6113 (0.02%)  1 1/3057 (0.03%)  1
Sudden Cardiac Death † 1  2/6113 (0.03%)  2 1/3057 (0.03%)  1
Sudden Death † 1  2/6113 (0.03%)  2 1/3057 (0.03%)  1
Surgical Failure † 1  0/6113 (0.00%)  0 1/3057 (0.03%)  1
Systemic Inflammatory Response Syndrome † 1  1/6113 (0.02%)  1 2/3057 (0.07%)  2
Hepatobiliary disorders     
Bile Duct Obstruction † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Bile Duct Stenosis † 1  1/6113 (0.02%)  2 0/3057 (0.00%)  0
Bile Duct Stone † 1  3/6113 (0.05%)  3 3/3057 (0.10%)  3
Cholangitis † 1  2/6113 (0.03%)  2 3/3057 (0.10%)  3
Cholangitis Acute † 1  0/6113 (0.00%)  0 1/3057 (0.03%)  1
Cholecystitis † 1  7/6113 (0.11%)  7 1/3057 (0.03%)  1
Cholecystitis Acute † 1  2/6113 (0.03%)  2 7/3057 (0.23%)  7
Cholecystitis Chronic † 1  1/6113 (0.02%)  1 1/3057 (0.03%)  1
Cholelithiasis † 1  7/6113 (0.11%)  7 6/3057 (0.20%)  6
Cirrhosis Alcoholic † 1  2/6113 (0.03%)  2 1/3057 (0.03%)  2
Gallbladder Polyp † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Hepatic Cirrhosis † 1  2/6113 (0.03%)  2 1/3057 (0.03%)  1
Hepatic Cyst † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Hepatic Failure † 1  1/6113 (0.02%)  1 1/3057 (0.03%)  1
Hepatitis † 1  0/6113 (0.00%)  0 1/3057 (0.03%)  1
Hepatitis Acute † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Hepatorenal Syndrome † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Hydrocholecystis † 1  0/6113 (0.00%)  0 1/3057 (0.03%)  1
Immune system disorders     
Anaphylactic Reaction † 1  2/6113 (0.03%)  2 0/3057 (0.00%)  0
Anaphylactic Shock † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Device Allergy † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Food Allergy † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Secondary Immunodeficiency † 1  0/6113 (0.00%)  0 1/3057 (0.03%)  1
Infections and infestations     
Abdominal Hernia Gangrenous † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Abdominal Infection † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Abdominal Sepsis † 1  2/6113 (0.03%)  2 3/3057 (0.10%)  3
Abdominal Wall Abscess † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Abscess † 1  4/6113 (0.07%)  5 0/3057 (0.00%)  0
Abscess Limb † 1  4/6113 (0.07%)  4 2/3057 (0.07%)  2
Anal Abscess † 1  2/6113 (0.03%)  2 1/3057 (0.03%)  1
Appendicitis † 1  5/6113 (0.08%)  5 2/3057 (0.07%)  2
Appendicitis Perforated † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Arteriovenous Graft Site Abscess † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Arthritis Bacterial † 1  11/6113 (0.18%)  11 3/3057 (0.10%)  3
Arthritis Infective † 1  8/6113 (0.13%)  9 3/3057 (0.10%)  4
Asymptomatic Bacteriuria † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Atypical Mycobacterial Infection † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Bacteraemia † 1  8/6113 (0.13%)  9 2/3057 (0.07%)  2
Bacterial Infection † 1  1/6113 (0.02%)  1 1/3057 (0.03%)  1
Bacterial Sepsis † 1  4/6113 (0.07%)  4 0/3057 (0.00%)  0
Bacterial Tracheitis † 1  0/6113 (0.00%)  0 1/3057 (0.03%)  1
Beta Haemolytic Streptococcal Infection † 1  1/6113 (0.02%)  1 1/3057 (0.03%)  1
Biliary Sepsis † 1  0/6113 (0.00%)  0 1/3057 (0.03%)  1
Breast Abscess † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Breast Cellulitis † 1  0/6113 (0.00%)  0 1/3057 (0.03%)  1
Bronchitis † 1  11/6113 (0.18%)  11 3/3057 (0.10%)  3
Bronchopneumonia † 1  3/6113 (0.05%)  3 0/3057 (0.00%)  0
Bursitis Infective † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Candida Sepsis † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Cellulitis † 1  63/6113 (1.03%)  78 36/3057 (1.18%)  41
Chronic Hepatitis C † 1  0/6113 (0.00%)  0 1/3057 (0.03%)  1
Clostridium Difficile Colitis † 1  3/6113 (0.05%)  3 0/3057 (0.00%)  0
Clostridium Difficile Infection † 1  3/6113 (0.05%)  3 1/3057 (0.03%)  1
Dengue Fever † 1  2/6113 (0.03%)  2 2/3057 (0.07%)  2
Dermo-Hypodermitis † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Device Related Infection † 1  18/6113 (0.29%)  22 12/3057 (0.39%)  14
Diabetic Foot Infection † 1  26/6113 (0.43%)  30 9/3057 (0.29%)  9
Diabetic Gangrene † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Diarrhoea Infectious † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Disseminated Tuberculosis † 1  0/6113 (0.00%)  0 1/3057 (0.03%)  1
Diverticulitis † 1  4/6113 (0.07%)  4 2/3057 (0.07%)  2
Empyema † 1  0/6113 (0.00%)  0 2/3057 (0.07%)  2
Endocarditis † 1  0/6113 (0.00%)  0 1/3057 (0.03%)  1
Endocarditis Bacterial † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Enterobacter Pneumonia † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Enterocolitis Bacterial † 1  0/6113 (0.00%)  0 1/3057 (0.03%)  1
Enterocolitis Infectious † 1  0/6113 (0.00%)  0 1/3057 (0.03%)  1
Erysipelas † 1  3/6113 (0.05%)  3 1/3057 (0.03%)  1
Escherichia Bacteraemia † 1  2/6113 (0.03%)  2 0/3057 (0.00%)  0
Escherichia Sepsis † 1  0/6113 (0.00%)  0 1/3057 (0.03%)  1
Escherichia Urinary Tract Infection † 1  2/6113 (0.03%)  2 0/3057 (0.00%)  0
Gangrene † 1  2/6113 (0.03%)  2 1/3057 (0.03%)  3
Gastric Infection † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Gastroenteritis † 1  10/6113 (0.16%)  10 6/3057 (0.20%)  6
Gastroenteritis Viral † 1  3/6113 (0.05%)  3 0/3057 (0.00%)  0
Genital Herpes † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Graft Infection † 1  2/6113 (0.03%)  2 0/3057 (0.00%)  0
Groin Abscess † 1  3/6113 (0.05%)  3 0/3057 (0.00%)  0
Haematoma Infection † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Hepatic Cyst Infection † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Herpes Virus Infection † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Herpes Zoster † 1  3/6113 (0.05%)  3 1/3057 (0.03%)  1
Implant Site Infection † 1  2/6113 (0.03%)  2 0/3057 (0.00%)  0
Incision Site Infection † 1  0/6113 (0.00%)  0 1/3057 (0.03%)  1
Infected Skin Ulcer † 1  2/6113 (0.03%)  3 2/3057 (0.07%)  2
Infection † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Infection In An Immunocompromised Host † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Infective Exacerbation Of Bronchiectasis † 1  2/6113 (0.03%)  6 0/3057 (0.00%)  0
Infective Exacerbation Of Chronic Obstructive Airways Disease † 1  2/6113 (0.03%)  2 1/3057 (0.03%)  1
Infective Spondylitis † 1  0/6113 (0.00%)  0 1/3057 (0.03%)  1
Influenza † 1  5/6113 (0.08%)  5 2/3057 (0.07%)  2
Intervertebral Discitis † 1  3/6113 (0.05%)  3 0/3057 (0.00%)  0
Joint Abscess † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Kidney Infection † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Liver Abscess † 1  1/6113 (0.02%)  1 1/3057 (0.03%)  1
Lobar Pneumonia † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Localised Infection † 1  4/6113 (0.07%)  4 4/3057 (0.13%)  5
Lower Respiratory Tract Infection † 1  7/6113 (0.11%)  7 2/3057 (0.07%)  2
Lower Respiratory Tract Infection Viral † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Lung Infection † 1  1/6113 (0.02%)  1 1/3057 (0.03%)  1
Mediastinitis † 1  4/6113 (0.07%)  4 2/3057 (0.07%)  2
Meningitis † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Mumps † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Mycobacterium Avium Complex Infection † 1  0/6113 (0.00%)  0 1/3057 (0.03%)  1
Nail Infection † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Neurological Infection † 1  0/6113 (0.00%)  0 1/3057 (0.03%)  1
Neurosyphilis † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Orchitis † 1  6/6113 (0.10%)  6 1/3057 (0.03%)  2
Osteomyelitis † 1  27/6113 (0.44%)  29 11/3057 (0.36%)  16
Osteomyelitis Acute † 1  2/6113 (0.03%)  2 0/3057 (0.00%)  0
Osteomyelitis Chronic † 1  2/6113 (0.03%)  2 2/3057 (0.07%)  2
Otitis Externa † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Paraspinal Abscess † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Paronychia † 1  0/6113 (0.00%)  0 1/3057 (0.03%)  1
Perihepatic Abscess † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Perineal Abscess † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Periodontitis † 1  2/6113 (0.03%)  2 0/3057 (0.00%)  0
Peritonitis † 1  2/6113 (0.03%)  2 0/3057 (0.00%)  0
Peritonsillar Abscess † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Pneumonia † 1  107/6113 (1.75%)  122 67/3057 (2.19%)  84
Pneumonia Bacterial † 1  5/6113 (0.08%)  9 2/3057 (0.07%)  2
Pneumonia Necrotising † 1  0/6113 (0.00%)  0 1/3057 (0.03%)  1
Pneumonia Pneumococcal † 1  1/6113 (0.02%)  1 1/3057 (0.03%)  1
Pneumonia Staphylococcal † 1  0/6113 (0.00%)  0 1/3057 (0.03%)  1
Poliomyelitis † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Post Procedural Cellulitis † 1  1/6113 (0.02%)  1 1/3057 (0.03%)  2
Post Procedural Infection † 1  7/6113 (0.11%)  7 1/3057 (0.03%)  1
Post Procedural Pneumonia † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Post Procedural Sepsis † 1  1/6113 (0.02%)  1 1/3057 (0.03%)  1
Postoperative Wound Infection † 1  28/6113 (0.46%)  30 15/3057 (0.49%)  15
Prostatic Abscess † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Psoas Abscess † 1  0/6113 (0.00%)  0 2/3057 (0.07%)  2
Pulmonary Sepsis † 1  1/6113 (0.02%)  2 2/3057 (0.07%)  2
Pulmonary Tuberculosis † 1  2/6113 (0.03%)  2 0/3057 (0.00%)  0
Pyelonephritis † 1  5/6113 (0.08%)  5 2/3057 (0.07%)  2
Pyelonephritis Acute † 1  7/6113 (0.11%)  8 1/3057 (0.03%)  1
Renal Abscess † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Respiratory Tract Infection † 1  7/6113 (0.11%)  8 4/3057 (0.13%)  6
Scrotal Abscess † 1  0/6113 (0.00%)  0 1/3057 (0.03%)  1
Sepsis † 1  34/6113 (0.56%)  38 18/3057 (0.59%)  18
Septic Arthritis Staphylococcal † 1  2/6113 (0.03%)  2 0/3057 (0.00%)  0
Septic Shock † 1  26/6113 (0.43%)  27 13/3057 (0.43%)  13
Sinusitis Bacterial † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Skin Bacterial Infection † 1  3/6113 (0.05%)  4 0/3057 (0.00%)  0
Skin Infection † 1  2/6113 (0.03%)  2 2/3057 (0.07%)  2
Soft Tissue Infection † 1  3/6113 (0.05%)  3 4/3057 (0.13%)  4
Staphylococcal Bacteraemia † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Staphylococcal Infection † 1  4/6113 (0.07%)  4 3/3057 (0.10%)  3
Staphylococcal Osteomyelitis † 1  1/6113 (0.02%)  1 2/3057 (0.07%)  2
Staphylococcal Sepsis † 1  1/6113 (0.02%)  1 1/3057 (0.03%)  1
Subcutaneous Abscess † 1  0/6113 (0.00%)  0 2/3057 (0.07%)  2
Tracheitis † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Tracheobronchitis † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Tuberculosis † 1  2/6113 (0.03%)  2 0/3057 (0.00%)  0
Upper Respiratory Tract Infection † 1  1/6113 (0.02%)  1 1/3057 (0.03%)  1
Urinary Bladder Abscess † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Urinary Tract Infection † 1  91/6113 (1.49%)  116 38/3057 (1.24%)  47
Urinary Tract Infection Bacterial † 1  3/6113 (0.05%)  3 1/3057 (0.03%)  1
Urinary Tract Infection Pseudomonal † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Urosepsis † 1  11/6113 (0.18%)  12 6/3057 (0.20%)  6
Viral Infection † 1  0/6113 (0.00%)  0 1/3057 (0.03%)  1
Viral Upper Respiratory Tract Infection † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Wound Infection † 1  5/6113 (0.08%)  5 1/3057 (0.03%)  1
Wound Infection Bacterial † 1  0/6113 (0.00%)  0 1/3057 (0.03%)  1
Injury, poisoning and procedural complications     
Abdominal Wound Dehiscence † 1  2/6113 (0.03%)  2 0/3057 (0.00%)  0
Accidental Overdose † 1  1/6113 (0.02%)  1 1/3057 (0.03%)  1
Alcohol Poisoning † 1  2/6113 (0.03%)  2 2/3057 (0.07%)  2
Anaemia Postoperative † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Animal Bite † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Ankle Fracture † 1  4/6113 (0.07%)  4 4/3057 (0.13%)  4
Arterial Injury † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Bladder Injury † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Bone Fissure † 1  0/6113 (0.00%)  0 1/3057 (0.03%)  1
Cardiac Procedure Complication † 1  0/6113 (0.00%)  0 1/3057 (0.03%)  1
Cervical Vertebral Fracture † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Chemical Poisoning † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Concussion † 1  0/6113 (0.00%)  0 1/3057 (0.03%)  1
Contusion † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Coronary Artery Restenosis † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Craniocerebral Injury † 1  1/6113 (0.02%)  1 1/3057 (0.03%)  1
Dislocation Of Vertebra † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Dural Tear † 1  0/6113 (0.00%)  0 1/3057 (0.03%)  1
Exposure To Toxic Agent † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Extradural Haematoma † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Facial Bones Fracture † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Fall † 1  17/6113 (0.28%)  18 7/3057 (0.23%)  7
Fat Embolism † 1  1/6113 (0.02%)  1 1/3057 (0.03%)  1
Femoral Neck Fracture † 1  5/6113 (0.08%)  5 2/3057 (0.07%)  2
Femur Fracture † 1  11/6113 (0.18%)  12 4/3057 (0.13%)  4
Foot Fracture † 1  2/6113 (0.03%)  2 0/3057 (0.00%)  0
Forearm Fracture † 1  1/6113 (0.02%)  1 1/3057 (0.03%)  1
Head Injury † 1  0/6113 (0.00%)  0 1/3057 (0.03%)  1
Heat Exhaustion † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Heat Stroke † 1  0/6113 (0.00%)  0 1/3057 (0.03%)  1
Hip Fracture † 1  8/6113 (0.13%)  8 6/3057 (0.20%)  7
Humerus Fracture † 1  4/6113 (0.07%)  4 1/3057 (0.03%)  1
Incisional Hernia † 1  0/6113 (0.00%)  0 1/3057 (0.03%)  1
Joint Dislocation † 1  12/6113 (0.20%)  16 0/3057 (0.00%)  0
Joint Dislocation Postoperative † 1  4/6113 (0.07%)  5 0/3057 (0.00%)  0
Joint Injury † 1  0/6113 (0.00%)  0 1/3057 (0.03%)  1
Laceration † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Ligament Injury † 1  2/6113 (0.03%)  3 1/3057 (0.03%)  1
Ligament Rupture † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Ligament Sprain † 1  4/6113 (0.07%)  4 0/3057 (0.00%)  0
Limb Injury † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Lower Limb Fracture † 1  3/6113 (0.05%)  3 2/3057 (0.07%)  2
Mechanical Ventilation Complication † 1  0/6113 (0.00%)  0 1/3057 (0.03%)  1
Meniscus Injury † 1  0/6113 (0.00%)  0 5/3057 (0.16%)  6
Multiple Fractures † 1  0/6113 (0.00%)  0 3/3057 (0.10%)  3
Multiple Injuries † 1  2/6113 (0.03%)  2 0/3057 (0.00%)  0
Muscle Rupture † 1  0/6113 (0.00%)  0 1/3057 (0.03%)  1
Muscle Strain † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Overdose † 1  4/6113 (0.07%)  4 0/3057 (0.00%)  0
Patella Fracture † 1  2/6113 (0.03%)  2 0/3057 (0.00%)  0
Pelvic Fracture † 1  1/6113 (0.02%)  1 2/3057 (0.07%)  2
Periprosthetic Fracture † 1  6/6113 (0.10%)  7 5/3057 (0.16%)  6
Pneumothorax Traumatic † 1  2/6113 (0.03%)  2 0/3057 (0.00%)  0
Post Concussion Syndrome † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Post Procedural Complication † 1  18/6113 (0.29%)  18 11/3057 (0.36%)  13
Post Procedural Discharge † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Post Procedural Haematoma † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Post Procedural Haematuria † 1  0/6113 (0.00%)  0 1/3057 (0.03%)  1
Post Procedural Haemorrhage † 1  3/6113 (0.05%)  3 3/3057 (0.10%)  3
Post Procedural Swelling † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Postoperative Fever † 1  2/6113 (0.03%)  2 0/3057 (0.00%)  0
Postoperative Ileus † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Postoperative Respiratory Failure † 1  0/6113 (0.00%)  0 1/3057 (0.03%)  1
Postoperative Thoracic Procedure Complication † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Postoperative Wound Complication † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Procedural Haemorrhage † 1  4/6113 (0.07%)  5 0/3057 (0.00%)  0
Procedural Hypotension † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Procedural Nausea † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Procedural Pain † 1  2/6113 (0.03%)  2 1/3057 (0.03%)  1
Pubis Fracture † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Radius Fracture † 1  0/6113 (0.00%)  0 1/3057 (0.03%)  1
Rectal Laceration Postoperative † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Renal Haematoma † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Rib Fracture † 1  2/6113 (0.03%)  2 3/3057 (0.10%)  3
Road Traffic Accident † 1  2/6113 (0.03%)  2 5/3057 (0.16%)  5
Scrotal Haematoma † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Seroma † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Skin Injury † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Spinal Compression Fracture † 1  1/6113 (0.02%)  1 1/3057 (0.03%)  1
Spinal Fracture † 1  1/6113 (0.02%)  1 1/3057 (0.03%)  1
Stab Wound † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Stress Fracture † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Subdural Haematoma † 1  6/6113 (0.10%)  6 3/3057 (0.10%)  3
Subdural Haemorrhage † 1  0/6113 (0.00%)  0 1/3057 (0.03%)  1
Tendon Rupture † 1  0/6113 (0.00%)  0 1/3057 (0.03%)  1
Thermal Burn † 1  1/6113 (0.02%)  1 1/3057 (0.03%)  1
Thoracic Vertebral Fracture † 1  2/6113 (0.03%)  2 0/3057 (0.00%)  0
Tibia Fracture † 1  4/6113 (0.07%)  4 1/3057 (0.03%)  1
Toxicity To Various Agents † 1  4/6113 (0.07%)  4 1/3057 (0.03%)  1
Tracheostomy Malfunction † 1  1/6113 (0.02%)  1 1/3057 (0.03%)  1
Traumatic Arthritis † 1  0/6113 (0.00%)  0 1/3057 (0.03%)  1
Traumatic Intracranial Haemorrhage † 1  0/6113 (0.00%)  0 1/3057 (0.03%)  1
Upper Limb Fracture † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Urethral Injury † 1  0/6113 (0.00%)  0 1/3057 (0.03%)  1
Urethral Stricture Postoperative † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Vascular Bypass Dysfunction † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Vascular Graft Occlusion † 1  1/6113 (0.02%)  1 1/3057 (0.03%)  1
Vascular Graft Thrombosis † 1  2/6113 (0.03%)  2 0/3057 (0.00%)  0
Vascular Pseudoaneurysm † 1  1/6113 (0.02%)  1 1/3057 (0.03%)  1
Wound † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Wound Dehiscence † 1  3/6113 (0.05%)  5 2/3057 (0.07%)  2
Wrist Fracture † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Investigations     
Anticoagulation Drug Level Above Therapeutic † 1  0/6113 (0.00%)  0 1/3057 (0.03%)  1
Aspiration Bronchial † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Blood Creatinine Increased † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Blood Potassium Decreased † 1  0/6113 (0.00%)  0 1/3057 (0.03%)  1
Carbon Dioxide Abnormal † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Cardiac Pacemaker Evaluation † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Coagulation Time Prolonged † 1  0/6113 (0.00%)  0 1/3057 (0.03%)  1
Electrocardiogram St Segment Elevation † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Influenza A Virus Test Positive † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
International Normalised Ratio Increased † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Oxygen Saturation Decreased † 1  0/6113 (0.00%)  0 1/3057 (0.03%)  1
Prothrombin Time Abnormal † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Transaminases Increased † 1  0/6113 (0.00%)  0 1/3057 (0.03%)  1
Urine Output Decreased † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Metabolism and nutrition disorders     
Cachexia † 1  0/6113 (0.00%)  0 1/3057 (0.03%)  1
Central Obesity † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Decreased Appetite † 1  0/6113 (0.00%)  0 1/3057 (0.03%)  1
Dehydration † 1  5/6113 (0.08%)  5 0/3057 (0.00%)  0
Diabetes Mellitus † 1  12/6113 (0.20%)  15 2/3057 (0.07%)  2
Diabetes Mellitus Inadequate Control † 1  8/6113 (0.13%)  11 2/3057 (0.07%)  2
Diabetic Complication † 1  2/6113 (0.03%)  2 2/3057 (0.07%)  2
Diabetic Ketoacidosis † 1  3/6113 (0.05%)  4 2/3057 (0.07%)  2
Electrolyte Imbalance † 1  2/6113 (0.03%)  2 3/3057 (0.10%)  3
Fluid Overload † 1  4/6113 (0.07%)  6 5/3057 (0.16%)  13
Gout † 1  5/6113 (0.08%)  6 0/3057 (0.00%)  0
Hyperamylasaemia † 1  0/6113 (0.00%)  0 1/3057 (0.03%)  1
Hypercalcaemia † 1  1/6113 (0.02%)  1 2/3057 (0.07%)  2
Hyperglycaemia † 1  10/6113 (0.16%)  12 6/3057 (0.20%)  6
Hyperglycaemic Hyperosmolar Nonketotic Syndrome † 1  3/6113 (0.05%)  3 0/3057 (0.00%)  0
Hyperkalaemia † 1  5/6113 (0.08%)  6 4/3057 (0.13%)  4
Hyperuricaemia † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Hypervolaemia † 1  0/6113 (0.00%)  0 1/3057 (0.03%)  1
Hypoglycaemia † 1  11/6113 (0.18%)  11 6/3057 (0.20%)  7
Hypokalaemia † 1  2/6113 (0.03%)  2 1/3057 (0.03%)  2
Hyponatraemia † 1  6/6113 (0.10%)  6 1/3057 (0.03%)  1
Hypovolaemia † 1  0/6113 (0.00%)  0 1/3057 (0.03%)  1
Malnutrition † 1  0/6113 (0.00%)  0 2/3057 (0.07%)  2
Metabolic Acidosis † 1  0/6113 (0.00%)  0 3/3057 (0.10%)  3
Obesity † 1  2/6113 (0.03%)  2 0/3057 (0.00%)  0
Type 1 Diabetes Mellitus † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Type 2 Diabetes Mellitus † 1  1/6113 (0.02%)  1 2/3057 (0.07%)  2
Musculoskeletal and connective tissue disorders     
Ankylosing Spondylitis † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Arthralgia † 1  10/6113 (0.16%)  10 4/3057 (0.13%)  4
Arthritis † 1  2/6113 (0.03%)  2 1/3057 (0.03%)  1
Arthrofibrosis † 1  0/6113 (0.00%)  0 1/3057 (0.03%)  1
Arthropathy † 1  0/6113 (0.00%)  0 1/3057 (0.03%)  1
Back Pain † 1  8/6113 (0.13%)  9 8/3057 (0.26%)  10
Bursitis † 1  3/6113 (0.05%)  3 2/3057 (0.07%)  2
Cervical Spinal Stenosis † 1  2/6113 (0.03%)  2 0/3057 (0.00%)  0
Chondropathy † 1  0/6113 (0.00%)  0 1/3057 (0.03%)  1
Chronic Recurrent Multifocal Osteomyelitis † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Collagen Disorder † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Costochondritis † 1  2/6113 (0.03%)  2 0/3057 (0.00%)  0
Exostosis † 1  0/6113 (0.00%)  0 1/3057 (0.03%)  1
Fistula † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Foot Deformity † 1  0/6113 (0.00%)  0 1/3057 (0.03%)  1
Fracture Nonunion † 1  2/6113 (0.03%)  2 0/3057 (0.00%)  0
Gouty Arthritis † 1  1/6113 (0.02%)  1 1/3057 (0.03%)  1
Intervertebral Disc Degeneration † 1  3/6113 (0.05%)  3 1/3057 (0.03%)  1
Intervertebral Disc Disorder † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Intervertebral Disc Protrusion † 1  4/6113 (0.07%)  4 3/3057 (0.10%)  3
Joint Instability † 1  1/6113 (0.02%)  1 1/3057 (0.03%)  1
Joint Swelling † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Lumbar Spinal Stenosis † 1  4/6113 (0.07%)  4 2/3057 (0.07%)  2
Mobility Decreased † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Muscle Necrosis † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Muscle Spasms † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Musculoskeletal Chest Pain † 1  5/6113 (0.08%)  5 1/3057 (0.03%)  1
Musculoskeletal Pain † 1  2/6113 (0.03%)  2 1/3057 (0.03%)  1
Myalgia † 1  0/6113 (0.00%)  0 1/3057 (0.03%)  1
Neck Pain † 1  1/6113 (0.02%)  1 2/3057 (0.07%)  2
Osteitis † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Osteoarthritis † 1  47/6113 (0.77%)  51 19/3057 (0.62%)  19
Pain In Extremity † 1  3/6113 (0.05%)  3 0/3057 (0.00%)  0
Pseudarthrosis † 1  1/6113 (0.02%)  1 1/3057 (0.03%)  1
Psoriatic Arthropathy † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Rhabdomyolysis † 1  1/6113 (0.02%)  1 1/3057 (0.03%)  1
Rotator Cuff Syndrome † 1  4/6113 (0.07%)  4 2/3057 (0.07%)  3
Scoliosis † 1  0/6113 (0.00%)  0 2/3057 (0.07%)  2
Spinal Column Stenosis † 1  2/6113 (0.03%)  2 2/3057 (0.07%)  2
Spinal Osteoarthritis † 1  2/6113 (0.03%)  2 1/3057 (0.03%)  1
Spondylitis † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Spondylolisthesis † 1  1/6113 (0.02%)  1 1/3057 (0.03%)  1
Tendonitis † 1  1/6113 (0.02%)  1 1/3057 (0.03%)  1
Tenosynovitis † 1  0/6113 (0.00%)  0 1/3057 (0.03%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Abdominal Neoplasm † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Adenocarcinoma † 1  1/6113 (0.02%)  1 1/3057 (0.03%)  1
Adenocarcinoma Gastric † 1  2/6113 (0.03%)  2 0/3057 (0.00%)  0
Adenocarcinoma Of Colon † 1  0/6113 (0.00%)  0 1/3057 (0.03%)  1
Adenocarcinoma Pancreas † 1  0/6113 (0.00%)  0 1/3057 (0.03%)  1
Adrenal Adenoma † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Basal Cell Carcinoma † 1  2/6113 (0.03%)  2 2/3057 (0.07%)  2
Benign Bone Neoplasm † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Bladder Cancer † 1  3/6113 (0.05%)  3 1/3057 (0.03%)  1
Bladder Neoplasm † 1  3/6113 (0.05%)  3 0/3057 (0.00%)  0
Bladder Transitional Cell Carcinoma Recurrent † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Bladder Transitional Cell Carcinoma Stage Ii † 1  0/6113 (0.00%)  0 1/3057 (0.03%)  1
Bone Cancer † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Brain Cancer Metastatic † 1  0/6113 (0.00%)  0 1/3057 (0.03%)  1
Brain Neoplasm † 1  2/6113 (0.03%)  2 0/3057 (0.00%)  0
Brain Neoplasm Malignant † 1  0/6113 (0.00%)  0 1/3057 (0.03%)  1
Breast Cancer † 1  4/6113 (0.07%)  4 2/3057 (0.07%)  2
Breast Cancer Metastatic † 1  0/6113 (0.00%)  0 1/3057 (0.03%)  2
Breast Cancer Stage Ii † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Breast Neoplasm † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Bronchial Carcinoma † 1  1/6113 (0.02%)  1 1/3057 (0.03%)  1
Burkitt's Lymphoma † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Carcinoid Tumour Of The Duodenum † 1  0/6113 (0.00%)  0 1/3057 (0.03%)  1
Cervix Carcinoma † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Cervix Carcinoma Recurrent † 1  1/6113 (0.02%)  3 0/3057 (0.00%)  0
Cervix Carcinoma Stage I † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Chronic Lymphocytic Leukaemia † 1  2/6113 (0.03%)  2 0/3057 (0.00%)  0
Clear Cell Renal Cell Carcinoma † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Colon Adenoma † 1  1/6113 (0.02%)  1 1/3057 (0.03%)  1
Colon Cancer † 1  2/6113 (0.03%)  3 1/3057 (0.03%)  1
Colon Neoplasm † 1  1/6113 (0.02%)  1 1/3057 (0.03%)  1
Diffuse Large B-Cell Lymphoma † 1  1/6113 (0.02%)  1 1/3057 (0.03%)  1
Endometrial Adenocarcinoma † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Endometrial Cancer † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Eyelid Tumour † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Gallbladder Adenocarcinoma † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Gastric Adenoma † 1  1/6113 (0.02%)  1 1/3057 (0.03%)  1
Gastric Neoplasm † 1  0/6113 (0.00%)  0 1/3057 (0.03%)  1
Gastrointestinal Carcinoma † 1  0/6113 (0.00%)  0 1/3057 (0.03%)  1
Gastrointestinal Neoplasm † 1  0/6113 (0.00%)  0 1/3057 (0.03%)  1
Gastrointestinal Stromal Tumour † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Glioblastoma Multiforme † 1  0/6113 (0.00%)  0 1/3057 (0.03%)  1
Hepatic Cancer † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Hepatocellular Carcinoma † 1  2/6113 (0.03%)  2 1/3057 (0.03%)  1
Intraductal Papillary Mucinous Neoplasm † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Kaposi's Sarcoma † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Leiomyosarcoma † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Leukaemia † 1  1/6113 (0.02%)  3 0/3057 (0.00%)  0
Lipoma † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Lung Adenocarcinoma † 1  2/6113 (0.03%)  2 0/3057 (0.00%)  0
Lung Cancer Metastatic † 1  1/6113 (0.02%)  1 1/3057 (0.03%)  1
Lung Carcinoma Cell Type Unspecified Recurrent † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Lung Carcinoma Cell Type Unspecified Stage Iv † 1  0/6113 (0.00%)  0 1/3057 (0.03%)  1
Lung Neoplasm † 1  1/6113 (0.02%)  2 0/3057 (0.00%)  0
Lung Neoplasm Malignant † 1  3/6113 (0.05%)  3 1/3057 (0.03%)  1
Lymphoma † 1  2/6113 (0.03%)  2 2/3057 (0.07%)  2
Malignant Melanoma † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Malignant Neoplasm Of Eye † 1  0/6113 (0.00%)  0 1/3057 (0.03%)  1
Malignant Neoplasm Of Renal Pelvis † 1  0/6113 (0.00%)  0 1/3057 (0.03%)  1
Malignant Pleural Effusion † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Malignant Respiratory Tract Neoplasm † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Mantle Cell Lymphoma † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Mediastinum Neoplasm † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Meningioma † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Mesothelioma † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Metastases To Central Nervous System † 1  0/6113 (0.00%)  0 1/3057 (0.03%)  1
Metastases To Lung † 1  0/6113 (0.00%)  0 1/3057 (0.03%)  1
Metastatic Carcinoma Of The Bladder † 1  2/6113 (0.03%)  4 0/3057 (0.00%)  0
Metastatic Neoplasm † 1  1/6113 (0.02%)  1 1/3057 (0.03%)  1
Neoplasm Malignant † 1  2/6113 (0.03%)  2 0/3057 (0.00%)  0
Neoplasm Of Thymus † 1  0/6113 (0.00%)  0 1/3057 (0.03%)  1
Neoplasm Prostate † 1  0/6113 (0.00%)  0 1/3057 (0.03%)  1
Neuroendocrine Tumour † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Nodal Marginal Zone B-Cell Lymphoma † 1  0/6113 (0.00%)  0 1/3057 (0.03%)  1
Non-Small Cell Lung Cancer † 1  1/6113 (0.02%)  1 1/3057 (0.03%)  1
Non-Small Cell Lung Cancer Recurrent † 1  1/6113 (0.02%)  4 0/3057 (0.00%)  0
Oesophageal Carcinoma † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Ovarian Cancer † 1  0/6113 (0.00%)  0 2/3057 (0.07%)  2
Ovarian Epithelial Cancer † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Pancreatic Carcinoma † 1  2/6113 (0.03%)  2 0/3057 (0.00%)  0
Pancreatic Carcinoma Metastatic † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Pancreatic Neuroendocrine Tumour † 1  0/6113 (0.00%)  0 1/3057 (0.03%)  1
Papillary Thyroid Cancer † 1  0/6113 (0.00%)  0 1/3057 (0.03%)  1
Parathyroid Tumour Benign † 1  1/6113 (0.02%)  1 1/3057 (0.03%)  1
Plasma Cell Myeloma † 1  2/6113 (0.03%)  2 2/3057 (0.07%)  2
Prostate Cancer † 1  17/6113 (0.28%)  17 3/3057 (0.10%)  3
Prostate Cancer Metastatic † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Rectal Adenocarcinoma † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Rectal Cancer † 1  0/6113 (0.00%)  0 1/3057 (0.03%)  1
Renal Cell Carcinoma † 1  1/6113 (0.02%)  1 1/3057 (0.03%)  1
Renal Neoplasm † 1  1/6113 (0.02%)  1 1/3057 (0.03%)  1
Retroperitoneal Cancer † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Salivary Gland Adenoma † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Salivary Gland Cancer † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Small Cell Lung Cancer † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Small Intestine Carcinoma † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Squamous Cell Carcinoma † 1  2/6113 (0.03%)  2 0/3057 (0.00%)  0
Superficial Spreading Melanoma Stage Unspecified † 1  0/6113 (0.00%)  0 1/3057 (0.03%)  1
Testicular Neoplasm † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Transitional Cell Carcinoma † 1  3/6113 (0.05%)  3 1/3057 (0.03%)  1
Uterine Cancer † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Nervous system disorders     
Altered State Of Consciousness † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Apallic Syndrome † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Arachnoid Cyst † 1  1/6113 (0.02%)  1 1/3057 (0.03%)  1
Ataxia † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Brain Stem Stroke † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Carotid Arteriosclerosis † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Carotid Artery Stenosis † 1  2/6113 (0.03%)  2 1/3057 (0.03%)  1
Carpal Tunnel Syndrome † 1  0/6113 (0.00%)  0 2/3057 (0.07%)  2
Cerebral Artery Stenosis † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Cerebral Haemorrhage † 1  4/6113 (0.07%)  4 2/3057 (0.07%)  2
Cerebral Infarction † 1  5/6113 (0.08%)  5 7/3057 (0.23%)  7
Cerebral Ischaemia † 1  1/6113 (0.02%)  1 1/3057 (0.03%)  1
Cerebral Thrombosis † 1  1/6113 (0.02%)  1 0/3057 (0.00%)  0
Cerebrovascular Accident † 1  19/6113 (0.31%)  20 8/3057 (0.26%)  8
Cerebrovascular Disorder † 1  3/6113 (0.05%)  3 3/3057 (0.10%)  3
Cervical Myelopathy † 1  0/6113 (0.00%)  0 1/3057 (0.03%)  1
Cervicobrachial Syndrome † 1  0/6113 (0.00%)  0 2/3057 (0.07%)  2
Chronic Inflammatory Demyelinating Polyradiculoneuropathy † 1  0/6113 (0.00%)  0 1/3057 (0.03%)  1
Convulsion † 1  11/6113 (0.18%)  15 9/3057 (0.29%)  22