Study of a Candidate Clostridium Difficile Toxoid Vaccine in Subjects at Risk for C. Difficile Infection

Sponsor
Sanofi Pasteur, a Sanofi Company (Industry)
Overall Status
Terminated
CT.gov ID
NCT01887912
Collaborator
(none)
9,302
335
2
58.4
27.8
0.5

Study Details

Study Description

Brief Summary

The aim of this study was to evaluate the efficacy of the Clostridium difficile vaccine to prevent primary symptomatic C. difficile infection (CDI) in participants at risk for CDI where there is a substantial unmet medical need.

Primary objective:
  • To assess the efficacy of the C. difficile vaccine in preventing the onset of symptomatic primary CDI confirmed by polymerase chain reaction (PCR) in adult participants aged >= 50 years who are at risk for CDI and have received at least 1 injection.
Secondary Objectives:
Efficacy:
  • To assess prevention of symptomatic PCR-confirmed primary CDI cases after 3 injections administered at 0, 7, and 30 days.

  • To assess prevention of symptomatic PCR-confirmed primary CDI cases after completion of at least 2 injections.

Immunogenicity:
  • To describe the immunogenicity to toxin A and toxin B at specific time points in a subset of participant and in participants with CDI at Day 0 and Day 60.
Safety:
  • To describe the safety profile of all participants who received at least 1 injection.
Condition or Disease Intervention/Treatment Phase
  • Biological: C. difficile Toxoid Vaccine
  • Biological: Placebo: 0.9% normal saline
Phase 3

Detailed Description

The study was designed as an event-driven group sequential protocol with 4 interim analyses at defined information milestones and a final analysis when a specific number of clinical endpoints are reached. Analyses of trial futility (non-efficacy) were to be performed at the first 2 interim analyses, and the study was to be stopped if either of those analyses provided robust and compelling evidence that meaningful levels of vaccine efficacy (VE) would not be demonstrated.

Following completion of the first interim analysis (50 cases of confirmed CDI observed), the futility criterion was met and in accordance with IDMC recommendation, enrollment and further vaccination ceased in November 2017.

Due to the early termination of the study, some of the planned secondary efficacy endpoints could not be analyzed as all planned data were not collected.

Participants were randomized to receive either the candidate vaccine or a placebo that was to be administered in a 3-dose schedule. At the time of group assignment, 928 participants (10% of total enrollment) were randomized to an immunogenicity subset; and 1859 participants (20% of total enrollment) were randomized to a reactogenicity subset.

Safety was assessed in all participants in terms of unsolicited adverse events from Day 0 to Day 60, as well as serious adverse events (SAEs) throughout the study. Solicited adverse reactions were collected for 6 days following each injection in the reactogenicity subset.

Study Design

Study Type:
Interventional
Actual Enrollment :
9302 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Intervention Model Description:
This study was observer-blind. The vaccine preparer and administrator may have been unblinded to treatment assignment due to the steps necessary for vaccine preparation. However, the participant, the Investigator, and study staff members who collected the safety data and laboratory personnel who analyzed the blood and stool samples were all blinded to the group assignment.This study was observer-blind. The vaccine preparer and administrator may have been unblinded to treatment assignment due to the steps necessary for vaccine preparation. However, the participant, the Investigator, and study staff members who collected the safety data and laboratory personnel who analyzed the blood and stool samples were all blinded to the group assignment.
Masking:
Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose:
Prevention
Official Title:
Efficacy, Immunogenicity, and Safety Study of Clostridium Difficile Toxoid Vaccine in Subjects at Risk for C. Difficile Infection (Cdiffense™)
Actual Study Start Date :
Jul 30, 2013
Actual Primary Completion Date :
Jun 12, 2018
Actual Study Completion Date :
Jun 12, 2018

Arms and Interventions

Arm Intervention/Treatment
Experimental: C. difficile Vaccine Group

Participants received 1 injection of 0.5 mL C. difficile toxoid vaccine at Days 0 (Injection 1), 7 (Injection 2), and 30 (Injection 3).

Biological: C. difficile Toxoid Vaccine
0.5 mL, Intramuscular

Placebo Comparator: Placebo Group

Participants received 1 injection of 0.5 mL placebo matched to vaccine at Days 0 (Injection 1), 7 (Injection 2), and 30 (Injection 3).

Biological: Placebo: 0.9% normal saline
0.5 mL, Intramuscular

Outcome Measures

Primary Outcome Measures

  1. Number of Participants With Symptomatic Polymerase Chain Reaction (PCR)-Confirmed Primary C. Difficile Infection (CDI) Cases [Up to 3 years post injection 1]

    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.

Secondary Outcome Measures

  1. Number of Participants With Severe PCR-Confirmed Primary CDI Cases [Up to 3 years post injection 1]

    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.

  2. Number of Participants With Loose Stool Episodes [Up to 3 years post injection 1]

    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.

  3. Number of Participants With Symptomatic PCR Confirmed CDI Cases: Per-Protocol Population [Up to 3 years post injection 1]

    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).

  4. Serum Antibody Concentrations Against Toxins A and B Measured by Enzyme-Linked Immunosorbent Assay (ELISA) [Day 0, Day 14, Day 30, Day 60, Day 210, Day 390, Day 570, Day 750, Day 930, and Day 1110]

    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).

  5. Percentage of Participants With >= 2 and 4-Fold Rise in Serum Antibody Concentrations From Baseline Against Toxins A and B Measured by ELISA [Day 60]

    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.

  6. Serum Antibody Concentrations Against Toxins A and B Measured by ELISA in Participants With CDI [Day 0 and Day 60]

    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.

  7. Serum Antibody Concentrations Against Toxins A and B Measured by Toxin Neutralization Assay (TNA) [Day 0, Day 14, Day 30, Day 60, Day 210, Day 390, Day 570, Day 750, Day 930, and Day 1110]

    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.

  8. Percentage of Participants With >= 2 and 4-Fold Rise in Serum Antibody Concentrations From Baseline Against Toxins A and B Measured by TNA [Day 60]

    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.

  9. Serum Antibody Concentrations Against Toxins A and B Measured by TNA in Participants With CDI [Day 0 and Day 60]

    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.

  10. Percentage of Participants Reporting Solicited Injection Site and Systemic Reactions [Day 0 to Day 6 after any vaccination]

    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.

Eligibility Criteria

Criteria

Ages Eligible for Study:
50 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
Yes
Inclusion Criteria:
  • Aged >= 50 years on the day of inclusion

  • Informed consent form had been signed and dated.

  • Attended all scheduled visits and complied with all trial procedures.

  • Covered by health insurance (if required).

  • Must fulfill at least 1 of the following criteria

Risk Stratum 1:
  • Had at least 2 hospital stays, each lasting at least >= 24 hours, in the 12 months before enrollment, and

  • Had received systemic (not topical) antibiotics in the 12 months before enrollment, or

Risk Stratum 2:
  • Was anticipated to have an in-patient hospitalization for a planned surgical procedure within 60 days of enrollment. The impending hospital stay was planned to be >= 72 hours for a surgery involving 1 of the following:

  • Kidney/bladder/urinary system

  • Musculoskeletal system

  • Respiratory system

  • Circulatory system

  • Central nervous system.

Exclusion Criteria:
  • Participant was pregnant, or lactating, or of childbearing potential (to be considered of non-childbearing potential, a female must be post-menopausal for at least 1 year, surgically sterile, or using an effective method of contraception or abstinence from at least 4 weeks prior to the first vaccination and until at least 4 weeks after the last vaccination).

  • Participation in the 4 weeks preceding the first trial vaccination or participation during the present trial period in another clinical trial investigating a vaccine, drug, medical device, or medical procedure.

  • Receipt of any vaccine in the 4 weeks preceding the first trial vaccination except for influenza (seasonal or pandemic) and pneumococcal vaccines. This exception includes monovalent pandemic influenza vaccines and multivalent influenza vaccines.

  • Previous vaccination against C. difficile with either the trial vaccine, another vaccine, or monoclonal antibodies.

  • Diarrhea on day of enrollment.

  • Self-reported current or prior CDI episode.

  • Anticipated or current receipt of kidney dialysis treatment.

  • History of gastrointestinal surgery for gastrointestinal malignancy (Note: Colonoscopy, polypectomy, and appendectomy are not exclusion criteria).

  • History of inflammatory bowel disease, irritable bowel syndrome (must include diarrhea as a symptom), colostomy, or small or large intestine bowel surgery where resection was performed.

  • Receiving enteral feeding (e.g., nasogastric, gastrostomy, and jejunostomy tube feeding).

  • Known or suspected congenital or acquired immunodeficiency; or receipt of immunosuppressive therapy, such as anti-cancer chemotherapy or radiation therapy, within the preceding 6 months; or long-term systemic corticosteroid therapy (prednisone or equivalent for more than 2 consecutive weeks within the past 3 months).

  • Known systemic hypersensitivity to any of the vaccine components, or history of a life-threatening reaction to the vaccine used in the trial or to a vaccine containing any of the same substances.

  • Self-reported thrombocytopenia, contraindicating intramuscular vaccination.

  • Deprived of freedom by an administrative or court order, or in an emergency setting, or hospitalized involuntarily.

  • Current alcohol abuse or drug addiction that might interfere with the ability to comply with trial procedures in the opinion of the Investigator.

  • Chronic illness that, in the opinion of the investigator, is at a stage where it might interfere with trial conduct or completion.

  • Moderate or severe acute illness/infection (according to investigator judgment) on the day of vaccination or febrile illness (temperature >= 38.0 degree Celsius [>= 100.4°Fahrenheit]). A prospective participant should not be included in the study until the condition has resolved or the febrile event has subsided.

  • Identified as an Investigator or employee of the Investigator or study center with direct involvement in the proposed study, or identified as an immediate family member (i.e., parent, spouse, natural or adopted child) of the Investigator or employee with direct involvement in the proposed study.

Contacts and Locations

Locations

Site City State Country Postal Code
1 Huntsville Alabama United States 35803
2 Investigational Site 104 Mobile Alabama United States 36608
3 Flagstaff Arizona United States 86001
4 Investigational Site 194 Phoenix Arizona United States 85018
5 Investigational Site 503 Surprise Arizona United States 85374
6 Little Rock Arkansas United States 72205
7 Bakersfield California United States 93301
8 Banning California United States 92220
9 Garden Grove California United States 92844
10 La Mesa California United States 91942
11 Investigational Site 534 Los Angeles California United States 90022
12 Investigational Site 051 Los Angeles California United States 90027
13 Modesto California United States 95350
14 Redding California United States 96001
15 Sacramento California United States 95817
16 Investigational Site 504 Simi Valley California United States 93065
17 Investigational Site 057 Stanford California United States 94305
18 Investigational Site 176 Upland California United States 91786
19 Ventura California United States 93003
20 Investigational Site 546 Wheat Ridge Colorado United States 90033
21 Bristol Connecticut United States 06010
22 Danbury Connecticut United States 06810
23 Investigational Site 143 Bradenton Florida United States 34209
24 Investigational Site 187 Brandon Florida United States 33511
25 Investigational Site 075 Clearwater Florida United States 33756
26 Investigational Site 517 Clearwater Florida United States 33765
27 Investigational Site 055 Crystal River Florida United States 34429
28 DeLand Florida United States 32720
29 Investigational Site 506 Gainesville Florida United States 32607
30 Investigational Site 099 Hialeah Florida United States 33012
31 Investigational Site 009 Jacksonville Florida United States 32216
32 Lauderdale Lakes Florida United States 33319
33 Miami Florida United States 33165
34 Orange Park Florida United States 32073
35 Investigational Site 112 Pensacola Florida United States 32504
36 Port Saint Lucie Florida United States 34987
37 Investigational Site 040 Saint Petersburg Florida United States 33709
38 Investigational Site 114 Saint Petersburg Florida United States 33713
39 Investigational Site 088 Sarasota Florida United States 34239
40 Tamarac Florida United States 33321
41 Tampa Florida United States 33612
42 West Palm Beach Florida United States 33401
43 Investigational Site 149 Augusta Georgia United States 30912
44 Investigational Site 529 Decatur Georgia United States 30030
45 Macon Georgia United States 31201
46 Investigational Site 010 Savannah Georgia United States 31406
47 Investigational Site 049 Idaho Falls Idaho United States 83494
48 Investigational Site 543 Pocatello Idaho United States 83201
49 Evanston Illinois United States 60201
50 Peoria Illinois United States 61602
51 Peoria Illinois United States 61614
52 Anderson Indiana United States 46011
53 Investigational Site 101 Iowa City Iowa United States 52242
54 Topeka Kansas United States 66606
55 Louisville Kentucky United States 40202
56 Investigational Site 091 Metairie Louisiana United States 70006
57 Investigational Site 084 New Orleans Louisiana United States 70121
58 Opelousas Louisiana United States 70570
59 Investigational Site 077 Shreveport Louisiana United States 71101
60 Auburn Maine United States 04210
61 Baltimore Maryland United States 21224
62 Investigational Site 002 Boston Massachusetts United States 02215
63 Investigational Site 035 West Roxbury Massachusetts United States 02132
64 Investigational Site 190 Ann Arbor Michigan United States 48106
65 Investigational Site 175 Detroit Michigan United States 48202
66 Investigational Site 183 Flint Michigan United States 48504
67 Grosse Pointe Woods Michigan United States 48236
68 Kalamazoo Michigan United States 49007
69 Livonia Michigan United States 48152
70 Investigational Site 069 Royal Oak Michigan United States 48073
71 Stevensville Michigan United States 49127
72 Troy Michigan United States 48098
73 Butte Montana United States 59701
74 Investigational Site 189 Hillsborough New Jersey United States 8844
75 Investigational Site 044 Neptune New Jersey United States 07753
76 Teaneck New Jersey United States 07666
77 Albuquerque New Mexico United States 27103
78 Albuquerque New Mexico United States 87102
79 Bronx New York United States 10467
80 Investigational Site 013 Bronx New York United States 10468
81 Investigational Site 022 Endwell New York United States 13760
82 Rochester New York United States 14621
83 Rochester New York United States 14642
84 Syracuse New York United States 13210
85 Investigational Site 146 Asheville North Carolina United States 28805
86 Cary North Carolina United States 27518
87 Charlotte North Carolina United States 28209
88 Hickory North Carolina United States 28602
89 Raleigh North Carolina United States 27612
90 Raleigh North Carolina United States 48202
91 Statesville North Carolina United States 28625
92 Wilmington North Carolina United States 28401
93 Winston-Salem North Carolina United States 27103
94 Investigational Site 031 Fargo North Dakota United States 58104
95 Fargo North Dakota United States 58122
96 Investigational Site 523 Canton Ohio United States 44710
97 Cincinnati Ohio United States 45219
98 Cleveland Ohio United States 44106
99 Investigational Site 129 Cleveland Ohio United States 44109
100 Cleveland Ohio United States 44118
101 Investigational Site 003 Columbus Ohio United States 43215
102 Investigational Site 061 Dayton Ohio United States 45419
103 Dayton Ohio United States 45428
104 Kettering Ohio United States 45429
105 Marion Ohio United States 43302
106 Investigational Site 095 Middletown Ohio United States 45005
107 Bend Oregon United States 97701
108 Investigational Site 528 Camp Hill Pennsylvania United States 17011
109 Hershey Pennsylvania United States 17033
110 Philadelphia Pennsylvania United States 19140
111 Pittsburgh Pennsylvania United States 15212
112 Pittsburgh Pennsylvania United States 15240
113 Investigational Site 083 Uniontown Pennsylvania United States 15401
114 West Reading Pennsylvania United States 19611
115 Investigational Site 020 Wilkes-Barre Pennsylvania United States 18711
116 Investigational Site 050 Pawtucket Rhode Island United States 02860
117 Providence Rhode Island United States 02906
118 Providence Rhode Island United States 02908
119 Investigational Site 540 Charleston South Carolina United States 29407
120 Investigational Site 047 Mount Pleasant South Carolina United States 29464
121 Investigational Site 180 Spartanburg South Carolina United States 29303
122 Investigational Site 086 Rapid City South Dakota United States 57701
123 Franklin Tennessee United States 37067
124 Jackson Tennessee United States 38305
125 Nashville Tennessee United States 37082
126 Nashville Tennessee United States 37203
127 Investigational Site 544 Austin Texas United States 78726
128 Corpus Christi Texas United States 78413
129 Investigational Site 006 Dallas Texas United States 75216
130 Investigational Site 119 Fort Worth Texas United States 76104
131 Groesbeck Texas United States 76642
132 Investigational Site 193 San Antonio Texas United States 78229
133 Tomball Texas United States 77375
134 Investigational Site 135 Orem Utah United States 84058
135 Investigational Site 080 Salt Lake City Utah United States 84124
136 Investigational Site 012 Lynchburg Virginia United States 24501
137 Williamsburg Virginia United States 23185
138 Investigational Site 196 Winchester Virginia United States 22601
139 Spokane Washington United States 99202
140 Tacoma Washington United States 98405
141 Investigational Site 030 Marshfield Wisconsin United States 54449
142 Weston Wisconsin United States 54476
143 Westmead New South Wales Australia 2145
144 Investigational Site 401 Cairns Queensland Australia 4870
145 Woolloongabba Queensland Australia 4102
146 Investigational Site 404 Bedford Park South Australia Australia 5042
147 Investigational Site 403 Clayton Victoria Australia 3168
148 Nedlands Western Australia Australia 6009
149 Subiaco Western Australia Australia 6008
150 Salvador BA Brazil 40420-000
151 Salvador BA Brazil 41253-190
152 Aparecida de Goiânia GO Brazil 74935-530
153 Belo Horizonte MG Brazil 30150-221
154 Belo Horizonte MG Brazil 30190-130
155 Juiz De Fora MG Brazil 36010-570
156 Recife PE Brazil 52020-010
157 Curitiba PR Brazil 80810-040
158 Nova Iguaçu RJ Brazil 26030-380
159 Rio de Janeiro RJ Brazil 22271-100
160 Natal RN Brazil 59025-600
161 Canoas RS Brazil 92425-900
162 Porto Alegre RS Brazil 90035-003
163 Santo Andre SP Brazil 09060-650
164 Campinas Brazil 13020431
165 New Westminster British Columbia Canada V3L 3W7
166 Investigational Site 156 Surrey British Columbia Canada V3V 1Z2
167 Investigational Site 158 Vancouver British Columbia Canada V5Z IM9
168 Winnipeg Manitoba Canada R3A IR9
169 Halifax Nova Scotia Canada B3K 6R8
170 Investigational Site 163 Truro Nova Scotia Canada B2N 1L2
171 Guelph Ontario Canada N1H 1B1
172 Toronto Ontario Canada M5G 1X5
173 Montreal Quebec Canada H3T 1E2
174 Pierrefonds Quebec Canada H9H 4Y6
175 Investigational Site 152 Québec Quebec Canada G1E 7G9
176 Investigational Site 151 Sherbrooke Quebec Canada J1H5N4
177 Investigational Site 161 Trois-Rivières Quebec Canada G8Z 3R9
178 Barranquilla Alantico Colombia
179 Medellin Antioquia Colombia
180 Bogota Ditrito Capital Colombia
181 Bogota Ditrito Colombia
182 Armenia Quindio Colombia
183 Bucaramanga Santander Colombia
184 Floridablanca Santander Colombia
185 Yopal Colombia
186 San José Costa Rica 250-1000
187 Investigational Site 215 Aarhus Denmark 8200
188 Investigational Site 347 Santo Domingo Dominican Republic
189 Espoo Finland FIN-02100
190 Helsinki Finland FIN-00100
191 Helsinki Finland FIN-00930
192 Investigational Site 203 Järvenpää Finland FIN-04400
193 Kokkola Finland 67100
194 Oulu Finland FIN-90220
195 Pori Finland 28100
196 Seinajoki Finland 60100
197 Investigational Site 201 Tampere Finland FIN-33100
198 Investigational Site 202 Turku Finland FIN-20520
199 Vantaa Finland FIN-01300
200 Investigational Site 230 Dijon France 21079
201 Lille France 49100
202 Limoges France 87042
203 Lyon France 69004
204 Montpellier France 34295
205 Orleans France 45100
206 Investigational Site 221 Paris France 75014
207 Investigational Site 229 Pringy France 21079
208 Saint Etienne France 42055
209 Investigational Site 223 St Priest en Jarez France 42270
210 Tourcoing France 59208
211 Investigational Site 232 Tours France 37044
212 Munich Bavaria Germany 81675
213 Investigational Site 242 Wurzburg Bayern Germany 97074
214 Investigational Site 244 Deggingen BW Germany 73326
215 Cologne NRW Germany 50937
216 Leipzig Sachsen Germany 04109
217 Jena Thuringia Germany 07747
218 Berlin Germany 10629
219 Berlin Germany 13347
220 Essen Germany 45355
221 Goch Germany 47574
222 Investigational Site 247 Hamburg Germany 20359
223 Investigational Site 245 Hamburg Germany 22143
224 Leipzig Germany 97074
225 Guatemala Guatemala 1001
226 Investigational Site 450 Aichi Japan 491-8551
227 Investigational Site 468 Chiba Japan 278-0004
228 Investigational Site 467 Fukui Japan 910-0067
229 Investigational Site 464 Fukuoka Japan 800-0344
230 Investigational Site 465 Fukuoka Japan 814-8525
231 Investigational Site 466 Fukuoka Japan 838-0069
232 Investigational Site 457 Gunma Japan 371-0014
233 Investigational Site 455 Hyōgo Japan 666-0125
234 Investigational Site 453 Ibaraki Japan 300-0028
235 Investigational Site 460 Kyoto Japan 611-0041
236 Investigational Site 454 Kyoto Japan 613-0034
237 Investigational Site 456 Nagano Japan 382-0091
238 Investigational Site 452 Nagano Japan 390-8601
239 Investigational Site 458 Nagano Japan 392-8510
240 Investigational Site 469 Okinawa Japan 904-2293
241 Investigational Site 459 Saitama Japan 348-0044
242 Investigational Site 467 Shimonoseki Japan 750-8520
243 Investigational Site 451 Tokyo Japan 171-0014
244 Investigational Site 463 Yamaguchi Japan 750-8520
245 Investigational Site 461 Ōsaka Japan 596-8522
246 Seoul Gangnam-gu Korea, Republic of 135-710
247 Investigational Site 407 Wŏnju Gangwon-do Korea, Republic of 26427
248 Investigational Site 413 Ansan Gyeonggi-do Korea, Republic of 15355
249 Daegu Jung-Gu Korea, Republic of 700-721
250 Investigational Site 427 Incheon Namdong-gu Korea, Republic of 22332
251 Seoul Seocho-gu Korea, Republic of 137-701
252 Seoul Seodaemun-gu Korea, Republic of 120-752
253 Seoul Seongbuk-gu Korea, Republic of 136-705
254 Seoul Seongdong-gu Korea, Republic of 132-792
255 Seoul Songpa-gu Korea, Republic of 138-736
256 Investigational Site 446 Busan Korea, Republic of 49201
257 Cheongju Korea, Republic of 361-711
258 Investigational Site 439 Gyeonggi-do Korea, Republic of 16247
259 Gyeonggi-do Korea, Republic of 443-380
260 Investigational Site 412 Incheon Korea, Republic of 21565
261 Investigational Site 409 Seoul Korea, Republic of 2841
262 Investigational Site 408 Seoul Korea, Republic of 3722
263 Investigational Site 415 Seoul Korea, Republic of 5355
264 Investigational Site 418 Seoul Korea, Republic of 5505
265 Investigational Site 411 Seoul Korea, Republic of 6351
266 Investigational Site 437 Seoul Korea, Republic of 7441
267 Investigational Site 438 Seoul Korea, Republic of 8308
268 Aguascalientes AGS Mexico 20230
269 Tijuana Baja California Mexico 22320
270 Investigational Site 325 Mexico City D.f. Mexico 14000
271 Investigational Site 329 Mexico City D.f. Mexico 14080
272 Investigational Site 352 Ecatepec Estado De Mexico Mexico 55076
273 Investigational Site 324 Guadalajara Jalisco Mexico 44280
274 Investigational Site 351 Cuernavaca Morelos Mexico 62290
275 Monterrey NL Mexico 64460
276 San Luis Potosi SLP Mexico 78240
277 Investigational Site 363 Ciudad Victoria Tamaulipas Mexico
278 Investigational Site 326 Durango Mexico 34000
279 Morelos Mexico
280 San Luis Potosi Mexico 78240
281 Investigational Site 354 Panama City Panama
282 Investigational Site 364 Trujillo La Libertad Peru 130101
283 Investigational Site 332 Jesus Maria Lima Peru lima 11
284 Lima Cercado Lima Peru
285 Investigational Site 334 San Martín de Porres Lima Peru lima 31
286 Surquillo Lima Peru
287 Investigational Site 356 Lima Peru callao 2
288 Investigational Site 355 Lima Peru lima 1
289 Lima Peru
290 Investigational Site 365 Piura Peru 200101
291 Alabang Philippines 1770
292 Dasmarinas Philippines 4114
293 Manila Philippines 1000
294 Manila Philippines 1004
295 Pasig City Philippines 1600
296 Quezon City Philippines 1100
297 Quezon City Philippines 1101
298 Investigational Site 284 Bydgoszcz Poland 85-863
299 Investigational Site 283 Nowy Duninów Poland 09-505
300 Investigational Site 171 Bayamon Puerto Rico 00960
301 Bayamon Puerto Rico 00961
302 Singapore Singapore 119074
303 Investigational Site 419 Singapore Singapore 119228
304 Singapore Singapore 169608
305 Investigational Site 428 Singapore Singapore 308433
306 Investigational Site 445 Singapore Singapore 768828
307 Investigational Site 294 Cordoba Spain 14004
308 Investigational Site 293 Santander Spain 39008
309 Investigational Site 292 Terrassa Spain 08221
310 Investigational Site 295 Vigo Spain 36312
311 Göthenburg SWE Sweden 41685
312 Stockholm Sweden 11157
313 Umea Sweden 90185
314 Kaohsiung Taiwan 813
315 Investigational Site 426 New Taipei City Taiwan 22056
316 New Taipei City Taiwan 23156
317 Investigational Site 429 Taichung City Taiwan 40201
318 Investigational Site 421 Tainan Taiwan 71004
319 Investigational Site 425 Taipei Taiwan 10002
320 Tiachung Taiwan 404
321 Investigational Site 443 Bangkok Thailand 10330
322 Investigational Site 442 Bangkok Thailand 10400
323 Investigational Site 441 Khon Kaen Thailand 40002
324 Investigational Site 276 Blackpool United Kingdom FY3 7EN
325 Blackpool United Kingdom FY3 8NR
326 Investigational Site 277 Coventry United Kingdom CV2 2DX
327 Harrow United Kingdom HA1 3UJ
328 Investigational Site 281 Leeds United Kingdom LS9 7TF
329 Liverpool United Kingdom L78XP
330 Investigational Site 271 London United Kingdom SW17 0RE
331 Manchester United Kingdom M8 5RB
332 Middlesex United Kingdom HA1 3UJ
333 North Shields United Kingdom NE29 8NH
334 Investigational Site 275 Penzance United Kingdom TR19 7HX
335 Stoke on Trent United Kingdom SR53SY

Sponsors and Collaborators

  • Sanofi Pasteur, a Sanofi Company

Investigators

  • Study Director: Medical Director, Sanofi Pasteur Inc.

Study Documents (Full-Text)

More Information

Publications

None provided.
Responsible Party:
Sanofi Pasteur, a Sanofi Company
ClinicalTrials.gov Identifier:
NCT01887912
Other Study ID Numbers:
  • H-030-014
  • 2013-000775-32
  • U1111-1127-7162
First Posted:
Jun 27, 2013
Last Update Posted:
Mar 28, 2022
Last Verified:
Mar 1, 2022
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Sanofi Pasteur, a Sanofi Company
Additional relevant MeSH terms:

Study Results

Participant Flow

Recruitment Details Study participants were enrolled in the study from 30 July 2013 to 17 November 2017.
Pre-assignment Detail A total of 9302 participants were enrolled and randomized in the study.
Arm/Group Title C. Difficile Vaccine Group Placebo Group
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 6113 3057
COMPLETED 4809 2370
NOT COMPLETED 1392 731

Baseline Characteristics

Arm/Group Title C. Difficile Vaccine Group Placebo Group Total
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 Participants 6201 3101 9302
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]
65.9
(8.86)
65.8
(8.87)
65.8
(8.86)
Sex: Female, Male (Count of Participants)
Female
2629
42.4%
1294
41.7%
3923
42.2%
Male
3572
57.6%
1807
58.3%
5379
57.8%
Ethnicity (NIH/OMB) (Count of 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) (Count of 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%
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%

Outcome Measures

1. Primary Outcome
Title Number of Participants With Symptomatic Polymerase Chain Reaction (PCR)-Confirmed Primary C. Difficile Infection (CDI) Cases
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

Outcome Measure Data

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
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).
Measure Participants 6173 3085
Count of Participants [Participants]
34
0.5%
16
0.5%
2. Secondary Outcome
Title Number of Participants With Severe PCR-Confirmed Primary CDI Cases
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

Outcome Measure Data

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
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).
Measure Participants 34 16
Count of Participants [Participants]
9
0.1%
6
0.2%
3. Secondary Outcome
Title Number of Participants With Loose Stool Episodes
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

Outcome Measure Data

Analysis Population Description
Analysis was performed on participants with protocol-defined PCR confirmed CDI cases.
Arm/Group Title C. Difficile Vaccine Group Placebo Group
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).
Measure Participants 34 16
<3
0
0%
0
0%
3 to 6
7
0.1%
4
0.1%
7 to 10
7
0.1%
2
0.1%
11 to 15
7
0.1%
4
0.1%
>15
13
0.2%
6
0.2%
4. Secondary Outcome
Title Number of Participants With Symptomatic PCR Confirmed CDI Cases: Per-Protocol Population
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

Outcome Measure Data

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
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).
Measure Participants 4786 2378
Count of Participants [Participants]
23
0.4%
13
0.4%
5. Secondary Outcome
Title Serum Antibody Concentrations Against Toxins A and B Measured by Enzyme-Linked Immunosorbent Assay (ELISA)
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

Outcome Measure Data

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
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).
Measure Participants 471 236
Toxin A ImunnoglobulinG (IgG): Day 0
0.957
0.999
Toxin A IgG: Day 14
3.19
0.913
Toxin A IgG: Day 30
12.2
0.959
Toxin A IgG: Day 60
43.7
0.933
Toxin A IgG: Day 210
12.0
0.944
Toxin A IgG: Day 390
6.02
0.955
Toxin A IgG: Day 570
4.50
0.908
Toxin A IgG: Day 750
4.02
0.856
Toxin A IgG: Day 930
3.83
0.902
Toxin A IgG: Day 1110
3.75
1.09
Toxin B IgG: Day 0
1.40
1.49
Toxin B IgG: Day 14
4.36
1.56
Toxin B IgG: Day 30
10.0
1.46
Toxin B IgG: Day 60
24.8
1.42
Toxin B IgG: Day 210
6.62
1.31
Toxin B IgG: Day 390
3.98
1.24
Toxin B IgG: Day 570
3.37
1.15
Toxin B IgG: Day 750
2.86
1.11
Toxin B IgG: Day 930
2.42
1.13
Toxin B IgG: Day 1110
3.46
0.966
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
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

Outcome Measure Data

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
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).
Measure Participants 436 220
Toxin A IgG: >=2
93.3
1.5%
0.9
0%
Toxin A IgG: >=4
88.9
1.4%
0.0
0%
Toxin B IgG: >=2
82.2
1.3%
4.6
0.1%
Toxin B IgG: >=4
73.2
1.2%
0.5
0%
7. Secondary Outcome
Title Serum Antibody Concentrations Against Toxins A and B Measured by ELISA in Participants With CDI
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

Outcome Measure Data

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
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).
Measure Participants 34 16
Toxin A IgG: Day 0
1.15
1.04
Toxin A IgG: Day 60
42.1
1.06
Toxin B IgG: Day 0
1.41
1.05
Toxin B IgG: Day 60
19.3
1.13
8. Secondary Outcome
Title Serum Antibody Concentrations Against Toxins A and B Measured by Toxin Neutralization Assay (TNA)
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

Outcome Measure Data

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
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).
Measure Participants 471 236
Toxin A TNA: Day 0
9.86
10.1
Toxin A TNA: Day 14
28.5
9.86
Toxin A TNA: Day 30
50.5
9.97
Toxin A TNA: Day 60
269
9.82
Toxin A TNA: Day 210
269
10.3
Toxin A TNA: Day 390
217
10.1
Toxin A TNA: Day 570
184
9.86
Toxin A TNA: Day 750
186
10.2
Toxin A TNA: Day 930
173
10.7
Toxin A TNA: Day 1110
212
10.2
Toxin B TNA: Day 0
12.3
13.2
Toxin B TNA: Day 14
32.7
13.3
Toxin B TNA: Day 30
37.8
13.4
Toxin B TNA: Day 60
43.9
14.3
Toxin B TNA: Day 210
41.4
13.2
Toxin B TNA: Day 390
38.4
13.5
Toxin B TNA: Day 570
35.7
13.7
Toxin B TNA: Day 750
34.3
14.6
Toxin B TNA: Day 930
31.0
17.0
Toxin B TNA: Day 1110
46.8
14.0
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
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

Outcome Measure Data

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
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).
Measure Participants 436 220
Toxin A TNA: >=2
85.6
1.4%
0.5
0%
Toxin A TNA: >=4
78.2
1.3%
0.5
0%
Toxin B TNA: >=2
30.9
0.5%
2.8
0.1%
Toxin B TNA: >=4
27.4
0.4%
1.8
0.1%
10. Secondary Outcome
Title Serum Antibody Concentrations Against Toxins A and B Measured by TNA in Participants With CDI
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

Outcome Measure Data

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
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).
Measure Participants 34 16
Toxin A TNA: Day 0
12.4
12.0
Toxin A TNA: Day 60
176
10.7
Toxin B TNA: Day 0
16.7
11.1
Toxin B TNA: Day 60
53.0
13.1
11. Secondary Outcome
Title Percentage of Participants Reporting Solicited Injection Site and Systemic Reactions
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

Outcome Measure Data

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
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).
Measure Participants 1227 608
Injection site Pain
38.6
0.6%
13.5
0.4%
Injection site Erythema
4.2
0.1%
0.0
0%
Injection site Swelling
3.8
0.1%
0.3
0%
Fever
4.8
0.1%
5.7
0.2%
Headache
25.3
0.4%
22.5
0.7%
Malaise
23.9
0.4%
19.6
0.6%
Myalgia
26.6
0.4%
21.2
0.7%
Arthralgia
19.5
0.3%
16.7
0.5%

Adverse Events

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
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 (%) # Events Affected / at Risk (%) # Events
Total 255/6113 (4.2%) 127/3057 (4.2%)
Serious Adverse Events
C. Difficile Vaccine Group Placebo Group
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 1662/6113 (27.2%) 851/3057 (27.8%)
Blood and lymphatic system disorders
Anaemia 19/6113 (0.3%) 20 11/3057 (0.4%) 13
Antiphospholipid Syndrome 0/6113 (0%) 0 1/3057 (0%) 1
Coagulopathy 4/6113 (0.1%) 4 0/3057 (0%) 0
Haemolytic Anaemia 0/6113 (0%) 0 1/3057 (0%) 1
Haemorrhagic Anaemia 2/6113 (0%) 2 5/3057 (0.2%) 5
Iron Deficiency Anaemia 1/6113 (0%) 1 0/3057 (0%) 0
Microcytic Anaemia 1/6113 (0%) 1 0/3057 (0%) 0
Nephrogenic Anaemia 1/6113 (0%) 1 0/3057 (0%) 0
Normochromic Normocytic Anaemia 0/6113 (0%) 0 1/3057 (0%) 1
Thrombocytosis 1/6113 (0%) 1 0/3057 (0%) 0
Cardiac disorders
Acute Coronary Syndrome 13/6113 (0.2%) 15 2/3057 (0.1%) 2
Acute Myocardial Infarction 56/6113 (0.9%) 59 22/3057 (0.7%) 24
Angina Pectoris 19/6113 (0.3%) 20 10/3057 (0.3%) 10
Angina Unstable 27/6113 (0.4%) 32 9/3057 (0.3%) 15
Aortic Valve Incompetence 0/6113 (0%) 0 1/3057 (0%) 1
Aortic Valve Stenosis 1/6113 (0%) 1 0/3057 (0%) 0
Arrhythmia 9/6113 (0.1%) 9 2/3057 (0.1%) 2
Arrhythmia Supraventricular 2/6113 (0%) 2 0/3057 (0%) 0
Arteriosclerosis Coronary Artery 1/6113 (0%) 1 0/3057 (0%) 0
Atrial Fibrillation 42/6113 (0.7%) 53 14/3057 (0.5%) 15
Atrial Flutter 3/6113 (0%) 3 2/3057 (0.1%) 2
Atrial Tachycardia 1/6113 (0%) 1 1/3057 (0%) 1
Atrial Thrombosis 1/6113 (0%) 1 0/3057 (0%) 0
Atrioventricular Block 1/6113 (0%) 1 1/3057 (0%) 1
Atrioventricular Block Complete 0/6113 (0%) 0 2/3057 (0.1%) 2
Bradyarrhythmia 0/6113 (0%) 0 1/3057 (0%) 1
Bradycardia 5/6113 (0.1%) 6 5/3057 (0.2%) 5
Bundle Branch Block Left 1/6113 (0%) 1 0/3057 (0%) 0
Cardiac Arrest 10/6113 (0.2%) 11 8/3057 (0.3%) 8
Cardiac Disorder 2/6113 (0%) 2 0/3057 (0%) 0
Cardiac Failure 34/6113 (0.6%) 40 16/3057 (0.5%) 36
Cardiac Failure Acute 16/6113 (0.3%) 22 6/3057 (0.2%) 7
Cardiac Failure Chronic 3/6113 (0%) 5 0/3057 (0%) 0
Cardiac Failure Congestive 69/6113 (1.1%) 102 29/3057 (0.9%) 37
Cardiac Tamponade 6/6113 (0.1%) 6 2/3057 (0.1%) 2
Cardiac Valve Disease 1/6113 (0%) 1 0/3057 (0%) 0
Cardio-Respiratory Arrest 10/6113 (0.2%) 11 3/3057 (0.1%) 3
Cardiogenic Shock 8/6113 (0.1%) 9 5/3057 (0.2%) 5
Cardiomyopathy 5/6113 (0.1%) 6 1/3057 (0%) 1
Cardiopulmonary Failure 1/6113 (0%) 1 0/3057 (0%) 0
Cardiorenal Syndrome 1/6113 (0%) 1 0/3057 (0%) 0
Cor Pulmonale 1/6113 (0%) 1 0/3057 (0%) 0
Coronary Artery Disease 22/6113 (0.4%) 23 7/3057 (0.2%) 7
Coronary Artery Occlusion 1/6113 (0%) 1 0/3057 (0%) 0
Coronary Artery Stenosis 7/6113 (0.1%) 8 2/3057 (0.1%) 2
Coronary Artery Thrombosis 1/6113 (0%) 1 0/3057 (0%) 0
Heart Valve Incompetence 1/6113 (0%) 1 1/3057 (0%) 1
Hypertensive Heart Disease 1/6113 (0%) 1 0/3057 (0%) 0
Intracardiac Thrombus 1/6113 (0%) 1 2/3057 (0.1%) 2
Ischaemic Cardiomyopathy 1/6113 (0%) 1 2/3057 (0.1%) 2
Left Ventricular Failure 1/6113 (0%) 1 0/3057 (0%) 0
Mitral Valve Incompetence 3/6113 (0%) 3 1/3057 (0%) 1
Myocardial Infarction 27/6113 (0.4%) 27 16/3057 (0.5%) 16
Myocardial Ischaemia 8/6113 (0.1%) 8 3/3057 (0.1%) 3
Palpitations 1/6113 (0%) 1 0/3057 (0%) 0
Pericardial Effusion 5/6113 (0.1%) 5 0/3057 (0%) 0
Pericarditis 1/6113 (0%) 1 2/3057 (0.1%) 2
Prinzmetal Angina 1/6113 (0%) 1 0/3057 (0%) 0
Pulseless Electrical Activity 0/6113 (0%) 0 1/3057 (0%) 1
Reperfusion Arrhythmia 1/6113 (0%) 1 0/3057 (0%) 0
Right Ventricular Failure 1/6113 (0%) 1 0/3057 (0%) 0
Sick Sinus Syndrome 2/6113 (0%) 2 3/3057 (0.1%) 3
Sinoatrial Block 1/6113 (0%) 1 0/3057 (0%) 0
Sinus Bradycardia 1/6113 (0%) 1 1/3057 (0%) 1
Stress Cardiomyopathy 0/6113 (0%) 0 1/3057 (0%) 1
Supraventricular Tachyarrhythmia 1/6113 (0%) 1 0/3057 (0%) 0
Supraventricular Tachycardia 1/6113 (0%) 1 1/3057 (0%) 1
Tachyarrhythmia 1/6113 (0%) 1 0/3057 (0%) 0
Tachycardia 0/6113 (0%) 0 2/3057 (0.1%) 2
Tricuspid Valve Incompetence 1/6113 (0%) 1 0/3057 (0%) 0
Ventricle Rupture 0/6113 (0%) 0 1/3057 (0%) 1
Ventricular Arrhythmia 1/6113 (0%) 1 0/3057 (0%) 0
Ventricular Fibrillation 3/6113 (0%) 3 1/3057 (0%) 1
Ventricular Tachycardia 5/6113 (0.1%) 5 4/3057 (0.1%) 4
Congenital, familial and genetic disorders
Anophthalmos 0/6113 (0%) 0 1/3057 (0%) 1
Cardiac Septal Defect 0/6113 (0%) 0 1/3057 (0%) 1
Ectopic Ureter 1/6113 (0%) 1 0/3057 (0%) 0
Hydrocele 0/6113 (0%) 0 1/3057 (0%) 1
Ear and labyrinth disorders
Deafness Neurosensory 1/6113 (0%) 1 0/3057 (0%) 0
Meniere's Disease 1/6113 (0%) 1 0/3057 (0%) 0
Sudden Hearing Loss 0/6113 (0%) 0 1/3057 (0%) 1
Vertigo 2/6113 (0%) 2 1/3057 (0%) 1
Vertigo Positional 4/6113 (0.1%) 4 0/3057 (0%) 0
Endocrine disorders
Adrenal Insufficiency 0/6113 (0%) 0 1/3057 (0%) 1
Goitre 1/6113 (0%) 1 0/3057 (0%) 0
Hyperparathyroidism 1/6113 (0%) 1 0/3057 (0%) 0
Hyperparathyroidism Primary 1/6113 (0%) 1 0/3057 (0%) 0
Thyroid Mass 2/6113 (0%) 2 1/3057 (0%) 1
Eye disorders
Amaurosis 1/6113 (0%) 1 1/3057 (0%) 1
Amaurosis Fugax 2/6113 (0%) 2 0/3057 (0%) 0
Aphakia 1/6113 (0%) 1 0/3057 (0%) 0
Cataract 2/6113 (0%) 2 2/3057 (0.1%) 3
Conjunctivochalasis 1/6113 (0%) 1 0/3057 (0%) 0
Eyelid Ptosis 1/6113 (0%) 1 0/3057 (0%) 0
Glaucoma 1/6113 (0%) 1 0/3057 (0%) 0
Phacolytic Glaucoma 1/6113 (0%) 1 0/3057 (0%) 0
Pterygium 1/6113 (0%) 1 0/3057 (0%) 0
Retinal Detachment 0/6113 (0%) 0 1/3057 (0%) 1
Retinal Vein Occlusion 1/6113 (0%) 1 0/3057 (0%) 0
Vitreous Haemorrhage 1/6113 (0%) 1 0/3057 (0%) 0
Gastrointestinal disorders
Abdominal Adhesions 2/6113 (0%) 2 0/3057 (0%) 0
Abdominal Hernia 3/6113 (0%) 3 1/3057 (0%) 1
Abdominal Pain 14/6113 (0.2%) 14 11/3057 (0.4%) 15
Abdominal Pain Lower 1/6113 (0%) 1 0/3057 (0%) 0
Abdominal Pain Upper 2/6113 (0%) 2 2/3057 (0.1%) 2
Abdominal Wall Haematoma 2/6113 (0%) 2 0/3057 (0%) 0
Anal Fissure 1/6113 (0%) 1 0/3057 (0%) 0
Anal Fistula 1/6113 (0%) 1 0/3057 (0%) 0
Ascites 1/6113 (0%) 1 0/3057 (0%) 0
Change Of Bowel Habit 0/6113 (0%) 0 1/3057 (0%) 1
Colitis 5/6113 (0.1%) 5 0/3057 (0%) 0
Colitis Ischaemic 1/6113 (0%) 1 2/3057 (0.1%) 2
Colitis Microscopic 1/6113 (0%) 1 0/3057 (0%) 0
Colonic Pseudo-Obstruction 0/6113 (0%) 0 1/3057 (0%) 1
Colonic Stenosis 1/6113 (0%) 1 0/3057 (0%) 0
Constipation 9/6113 (0.1%) 9 2/3057 (0.1%) 2
Crohn's Disease 1/6113 (0%) 1 0/3057 (0%) 0
Dental Pulp Disorder 0/6113 (0%) 0 1/3057 (0%) 1
Diabetic Gastroparesis 1/6113 (0%) 1 0/3057 (0%) 0
Diaphragmatic Hernia 1/6113 (0%) 1 0/3057 (0%) 0
Diarrhoea 8/6113 (0.1%) 8 2/3057 (0.1%) 2
Diverticular Perforation 2/6113 (0%) 2 0/3057 (0%) 0
Diverticulum 4/6113 (0.1%) 5 1/3057 (0%) 1
Duodenal Ulcer 2/6113 (0%) 2 1/3057 (0%) 1
Duodenal Ulcer Haemorrhage 2/6113 (0%) 2 0/3057 (0%) 0
Dyspepsia 1/6113 (0%) 1 0/3057 (0%) 0
Enterovesical Fistula 1/6113 (0%) 2 1/3057 (0%) 1
Erosive Duodenitis 0/6113 (0%) 0 1/3057 (0%) 1
Erosive Oesophagitis 0/6113 (0%) 0 1/3057 (0%) 1
Faecaloma 1/6113 (0%) 1 0/3057 (0%) 0
Food Poisoning 1/6113 (0%) 1 0/3057 (0%) 0
Gastric Disorder 1/6113 (0%) 1 0/3057 (0%) 0
Gastric Haemorrhage 0/6113 (0%) 0 2/3057 (0.1%) 2
Gastric Ulcer 1/6113 (0%) 1 2/3057 (0.1%) 2
Gastric Ulcer Haemorrhage 2/6113 (0%) 2 0/3057 (0%) 0
Gastric Ulcer Perforation 2/6113 (0%) 2 0/3057 (0%) 0
Gastritis 8/6113 (0.1%) 8 4/3057 (0.1%) 5
Gastritis Erosive 0/6113 (0%) 0 1/3057 (0%) 1
Gastritis Haemorrhagic 1/6113 (0%) 1 0/3057 (0%) 0
Gastroduodenal Ulcer 1/6113 (0%) 1 0/3057 (0%) 0
Gastrointestinal Amyloidosis 0/6113 (0%) 0 1/3057 (0%) 1
Gastrointestinal Haemorrhage 13/6113 (0.2%) 13 6/3057 (0.2%) 6
Gastrointestinal Hypomotility 1/6113 (0%) 1 1/3057 (0%) 1
Gastrointestinal Obstruction 0/6113 (0%) 0 1/3057 (0%) 1
Gastrooesophageal Reflux Disease 2/6113 (0%) 2 0/3057 (0%) 0
Haematemesis 1/6113 (0%) 1 0/3057 (0%) 0
Haemorrhoids 2/6113 (0%) 2 0/3057 (0%) 0
Hernial Eventration 1/6113 (0%) 1 0/3057 (0%) 0
Hiatus Hernia 2/6113 (0%) 2 0/3057 (0%) 0
Ileal Stenosis 1/6113 (0%) 1 0/3057 (0%) 0
Ileus 6/6113 (0.1%) 6 2/3057 (0.1%) 2
Ileus Paralytic 1/6113 (0%) 1 0/3057 (0%) 0
Impaired Gastric Emptying 1/6113 (0%) 5 0/3057 (0%) 0
Inguinal Hernia 4/6113 (0.1%) 4 3/3057 (0.1%) 3
Inguinal Hernia, Obstructive 0/6113 (0%) 0 1/3057 (0%) 1
Intestinal Haemorrhage 1/6113 (0%) 1 1/3057 (0%) 1
Intestinal Obstruction 6/6113 (0.1%) 7 1/3057 (0%) 1
Intestinal Perforation 0/6113 (0%) 0 1/3057 (0%) 1
Intra-Abdominal Haemorrhage 0/6113 (0%) 0 1/3057 (0%) 1
Large Intestinal Obstruction 1/6113 (0%) 1 0/3057 (0%) 0
Large Intestine Polyp 5/6113 (0.1%) 5 0/3057 (0%) 0
Lower Gastrointestinal Haemorrhage 4/6113 (0.1%) 4 0/3057 (0%) 0
Melaena 1/6113 (0%) 1 2/3057 (0.1%) 2
Mesenteric Artery Thrombosis 0/6113 (0%) 0 1/3057 (0%) 2
Mesenteric Vein Thrombosis 0/6113 (0%) 0 1/3057 (0%) 1
Nausea 2/6113 (0%) 2 1/3057 (0%) 1
Oesophageal Obstruction 1/6113 (0%) 1 0/3057 (0%) 0
Oesophageal Stenosis 0/6113 (0%) 0 1/3057 (0%) 1
Oesophageal Varices Haemorrhage 2/6113 (0%) 3 0/3057 (0%) 0
Oesophagitis 1/6113 (0%) 1 0/3057 (0%) 0
Oral Disorder 1/6113 (0%) 1 0/3057 (0%) 0
Pancreatic Pseudocyst 1/6113 (0%) 1 0/3057 (0%) 0
Pancreatitis 6/6113 (0.1%) 7 3/3057 (0.1%) 3
Pancreatitis Acute 4/6113 (0.1%) 5 6/3057 (0.2%) 6
Pancreatitis Chronic 1/6113 (0%) 1 0/3057 (0%) 0
Pancreatitis Relapsing 1/6113 (0%) 1 0/3057 (0%) 0
Peptic Ulcer 1/6113 (0%) 1 2/3057 (0.1%) 2
Periodontal Disease 0/6113 (0%) 0 1/3057 (0%) 1
Peritoneal Adhesions 0/6113 (0%) 0 1/3057 (0%) 1
Peritoneal Haemorrhage 0/6113 (0%) 0 1/3057 (0%) 1
Proctalgia 1/6113 (0%) 1 0/3057 (0%) 0
Rectal Haemorrhage 4/6113 (0.1%) 4 2/3057 (0.1%) 2
Rectal Prolapse 2/6113 (0%) 2 0/3057 (0%) 0
Small Intestinal Obstruction 5/6113 (0.1%) 5 2/3057 (0.1%) 2
Spigelian Hernia 1/6113 (0%) 1 0/3057 (0%) 0
Subileus 0/6113 (0%) 0 1/3057 (0%) 1
Thrombosis Mesenteric Vessel 0/6113 (0%) 0 1/3057 (0%) 1
Umbilical Hernia 2/6113 (0%) 2 1/3057 (0%) 1
Umbilical Hernia, Obstructive 1/6113 (0%) 1 0/3057 (0%) 0
Upper Gastrointestinal Haemorrhage 5/6113 (0.1%) 5 2/3057 (0.1%) 2
Varices Oesophageal 2/6113 (0%) 2 0/3057 (0%) 0
Volvulus 0/6113 (0%) 0 1/3057 (0%) 1
Vomiting 4/6113 (0.1%) 4 2/3057 (0.1%) 2
General disorders
Asthenia 4/6113 (0.1%) 4 2/3057 (0.1%) 2
Catheter Site Haemorrhage 2/6113 (0%) 2 0/3057 (0%) 0
Chest Discomfort 1/6113 (0%) 1 0/3057 (0%) 0
Chest Pain 50/6113 (0.8%) 56 19/3057 (0.6%) 27
Death 8/6113 (0.1%) 8 6/3057 (0.2%) 6
Device Dislocation 9/6113 (0.1%) 9 1/3057 (0%) 1
Device Failure 3/6113 (0%) 3 2/3057 (0.1%) 2
Device Issue 1/6113 (0%) 1 0/3057 (0%) 0
Device Leakage 1/6113 (0%) 1 0/3057 (0%) 0
Device Malfunction 1/6113 (0%) 1 1/3057 (0%) 1
Device Occlusion 2/6113 (0%) 2 1/3057 (0%) 1
Drug Interaction 1/6113 (0%) 1 0/3057 (0%) 0
Fatigue 1/6113 (0%) 1 1/3057 (0%) 1
General Physical Health Deterioration 1/6113 (0%) 1 1/3057 (0%) 1
General Symptom 1/6113 (0%) 1 0/3057 (0%) 0
Generalised Oedema 0/6113 (0%) 0 1/3057 (0%) 1
Hernia Obstructive 0/6113 (0%) 0 1/3057 (0%) 1
Hyperthermia 1/6113 (0%) 1 0/3057 (0%) 0
Impaired Healing 1/6113 (0%) 1 0/3057 (0%) 0
Implant Site Haematoma 1/6113 (0%) 1 0/3057 (0%) 0
Inflammation 1/6113 (0%) 1 0/3057 (0%) 0
Malaise 1/6113 (0%) 1 1/3057 (0%) 1
Medical Device Complication 7/6113 (0.1%) 8 4/3057 (0.1%) 4
Multi-Organ Failure 4/6113 (0.1%) 4 3/3057 (0.1%) 3
Non-Cardiac Chest Pain 2/6113 (0%) 2 2/3057 (0.1%) 2
Oedema 1/6113 (0%) 1 0/3057 (0%) 0
Oedema Peripheral 3/6113 (0%) 3 1/3057 (0%) 1
Pain 2/6113 (0%) 2 3/3057 (0.1%) 3
Patient-Device Incompatibility 0/6113 (0%) 0 1/3057 (0%) 1
Perforated Ulcer 1/6113 (0%) 1 0/3057 (0%) 0
Polyp 0/6113 (0%) 0 1/3057 (0%) 1
Pyrexia 5/6113 (0.1%) 5 3/3057 (0.1%) 3
Spinal Pain 1/6113 (0%) 1 0/3057 (0%) 0
Stent-Graft Endoleak 1/6113 (0%) 1 1/3057 (0%) 1
Sudden Cardiac Death 2/6113 (0%) 2 1/3057 (0%) 1
Sudden Death 2/6113 (0%) 2 1/3057 (0%) 1
Surgical Failure 0/6113 (0%) 0 1/3057 (0%) 1
Systemic Inflammatory Response Syndrome 1/6113 (0%) 1 2/3057 (0.1%) 2
Hepatobiliary disorders
Bile Duct Obstruction 1/6113 (0%) 1 0/3057 (0%) 0
Bile Duct Stenosis 1/6113 (0%) 2 0/3057 (0%) 0
Bile Duct Stone 3/6113 (0%) 3 3/3057 (0.1%) 3
Cholangitis 2/6113 (0%) 2 3/3057 (0.1%) 3
Cholangitis Acute 0/6113 (0%) 0 1/3057 (0%) 1
Cholecystitis 7/6113 (0.1%) 7 1/3057 (0%) 1
Cholecystitis Acute 2/6113 (0%) 2 7/3057 (0.2%) 7
Cholecystitis Chronic 1/6113 (0%) 1 1/3057 (0%) 1
Cholelithiasis 7/6113 (0.1%) 7 6/3057 (0.2%) 6
Cirrhosis Alcoholic 2/6113 (0%) 2 1/3057 (0%) 2
Gallbladder Polyp 1/6113 (0%) 1 0/3057 (0%) 0
Hepatic Cirrhosis 2/6113 (0%) 2 1/3057 (0%) 1
Hepatic Cyst 1/6113 (0%) 1 0/3057 (0%) 0
Hepatic Failure 1/6113 (0%) 1 1/3057 (0%) 1
Hepatitis 0/6113 (0%) 0 1/3057 (0%) 1
Hepatitis Acute 1/6113 (0%) 1 0/3057 (0%) 0
Hepatorenal Syndrome 1/6113 (0%) 1 0/3057 (0%) 0
Hydrocholecystis 0/6113 (0%) 0 1/3057 (0%) 1
Immune system disorders
Anaphylactic Reaction 2/6113 (0%) 2 0/3057 (0%) 0
Anaphylactic Shock 1/6113 (0%) 1 0/3057 (0%) 0
Device Allergy 1/6113 (0%) 1 0/3057 (0%) 0
Food Allergy 1/6113 (0%) 1 0/3057 (0%) 0
Secondary Immunodeficiency 0/6113 (0%) 0 1/3057 (0%) 1
Infections and infestations
Abdominal Hernia Gangrenous 1/6113 (0%) 1 0/3057 (0%) 0
Abdominal Infection 1/6113 (0%) 1 0/3057 (0%) 0
Abdominal Sepsis 2/6113 (0%) 2 3/3057 (0.1%) 3
Abdominal Wall Abscess 1/6113 (0%) 1 0/3057 (0%) 0
Abscess 4/6113 (0.1%) 5 0/3057 (0%) 0
Abscess Limb 4/6113 (0.1%) 4 2/3057 (0.1%) 2
Anal Abscess 2/6113 (0%) 2 1/3057 (0%) 1
Appendicitis 5/6113 (0.1%) 5 2/3057 (0.1%) 2
Appendicitis Perforated 1/6113 (0%) 1 0/3057 (0%) 0
Arteriovenous Graft Site Abscess 1/6113 (0%) 1 0/3057 (0%) 0
Arthritis Bacterial 11/6113 (0.2%) 11 3/3057 (0.1%) 3
Arthritis Infective 8/6113 (0.1%) 9 3/3057 (0.1%) 4
Asymptomatic Bacteriuria 1/6113 (0%) 1 0/3057 (0%) 0
Atypical Mycobacterial Infection 1/6113 (0%) 1 0/3057 (0%) 0
Bacteraemia 8/6113 (0.1%) 9 2/3057 (0.1%) 2
Bacterial Infection 1/6113 (0%) 1 1/3057 (0%) 1
Bacterial Sepsis 4/6113 (0.1%) 4 0/3057 (0%) 0
Bacterial Tracheitis 0/6113 (0%) 0 1/3057 (0%) 1
Beta Haemolytic Streptococcal Infection 1/6113 (0%) 1 1/3057 (0%) 1
Biliary Sepsis 0/6113 (0%) 0 1/3057 (0%) 1
Breast Abscess 1/6113 (0%) 1 0/3057 (0%) 0
Breast Cellulitis 0/6113 (0%) 0 1/3057 (0%) 1
Bronchitis 11/6113 (0.2%) 11 3/3057 (0.1%) 3
Bronchopneumonia 3/6113 (0%) 3 0/3057 (0%) 0
Bursitis Infective 1/6113 (0%) 1 0/3057 (0%) 0
Candida Sepsis 1/6113 (0%) 1 0/3057 (0%) 0
Cellulitis 63/6113 (1%) 78 36/3057 (1.2%) 41
Chronic Hepatitis C 0/6113 (0%) 0 1/3057 (0%) 1
Clostridium Difficile Colitis 3/6113 (0%) 3 0/3057 (0%) 0
Clostridium Difficile Infection 3/6113 (0%) 3 1/3057 (0%) 1
Dengue Fever 2/6113 (0%) 2 2/3057 (0.1%) 2
Dermo-Hypodermitis 1/6113 (0%) 1 0/3057 (0%) 0
Device Related Infection 18/6113 (0.3%) 22 12/3057 (0.4%) 14
Diabetic Foot Infection 26/6113 (0.4%) 30 9/3057 (0.3%) 9
Diabetic Gangrene 1/6113 (0%) 1 0/3057 (0%) 0
Diarrhoea Infectious 1/6113 (0%) 1 0/3057 (0%) 0
Disseminated Tuberculosis 0/6113 (0%) 0 1/3057 (0%) 1
Diverticulitis 4/6113 (0.1%) 4 2/3057 (0.1%) 2
Empyema 0/6113 (0%) 0 2/3057 (0.1%) 2
Endocarditis 0/6113 (0%) 0 1/3057 (0%) 1
Endocarditis Bacterial 1/6113 (0%) 1 0/3057 (0%) 0
Enterobacter Pneumonia 1/6113 (0%) 1 0/3057 (0%) 0
Enterocolitis Bacterial 0/6113 (0%) 0 1/3057 (0%) 1
Enterocolitis Infectious 0/6113 (0%) 0 1/3057 (0%) 1
Erysipelas 3/6113 (0%) 3 1/3057 (0%) 1
Escherichia Bacteraemia 2/6113 (0%) 2 0/3057 (0%) 0
Escherichia Sepsis 0/6113 (0%) 0 1/3057 (0%) 1
Escherichia Urinary Tract Infection 2/6113 (0%) 2 0/3057 (0%) 0
Gangrene 2/6113 (0%) 2 1/3057 (0%) 3
Gastric Infection 1/6113 (0%) 1 0/3057 (0%) 0
Gastroenteritis 10/6113 (0.2%) 10 6/3057 (0.2%) 6
Gastroenteritis Viral 3/6113 (0%) 3 0/3057 (0%) 0
Genital Herpes 1/6113 (0%) 1 0/3057 (0%) 0
Graft Infection 2/6113 (0%) 2 0/3057 (0%) 0
Groin Abscess 3/6113 (0%) 3 0/3057 (0%) 0
Haematoma Infection 1/6113 (0%) 1 0/3057 (0%) 0
Hepatic Cyst Infection 1/6113 (0%) 1 0/3057 (0%) 0
Herpes Virus Infection 1/6113 (0%) 1 0/3057 (0%) 0
Herpes Zoster 3/6113 (0%) 3 1/3057 (0%) 1
Implant Site Infection 2/6113 (0%) 2 0/3057 (0%) 0
Incision Site Infection 0/6113 (0%) 0 1/3057 (0%) 1
Infected Skin Ulcer 2/6113 (0%) 3 2/3057 (0.1%) 2
Infection 1/6113 (0%) 1 0/3057 (0%) 0
Infection In An Immunocompromised Host 1/6113 (0%) 1 0/3057 (0%) 0
Infective Exacerbation Of Bronchiectasis 2/6113 (0%) 6 0/3057 (0%) 0
Infective Exacerbation Of Chronic Obstructive Airways Disease 2/6113 (0%) 2 1/3057 (0%) 1
Infective Spondylitis 0/6113 (0%) 0 1/3057 (0%) 1
Influenza 5/6113 (0.1%) 5 2/3057 (0.1%) 2
Intervertebral Discitis 3/6113 (0%) 3 0/3057 (0%) 0
Joint Abscess 1/6113 (0%) 1 0/3057 (0%) 0
Kidney Infection 1/6113 (0%) 1 0/3057 (0%) 0
Liver Abscess 1/6113 (0%) 1 1/3057 (0%) 1
Lobar Pneumonia 1/6113 (0%) 1 0/3057 (0%) 0
Localised Infection 4/6113 (0.1%) 4 4/3057 (0.1%) 5
Lower Respiratory Tract Infection 7/6113 (0.1%) 7 2/3057 (0.1%) 2
Lower Respiratory Tract Infection Viral 1/6113 (0%) 1 0/3057 (0%) 0
Lung Infection 1/6113 (0%) 1 1/3057 (0%) 1
Mediastinitis 4/6113 (0.1%) 4 2/3057 (0.1%) 2
Meningitis 1/6113 (0%) 1 0/3057 (0%) 0
Mumps 1/6113 (0%) 1 0/3057 (0%) 0
Mycobacterium Avium Complex Infection 0/6113 (0%) 0 1/3057 (0%) 1
Nail Infection 1/6113 (0%) 1 0/3057 (0%) 0
Neurological Infection 0/6113 (0%) 0 1/3057 (0%) 1
Neurosyphilis 1/6113 (0%) 1 0/3057 (0%) 0
Orchitis 6/6113 (0.1%) 6 1/3057 (0%) 2
Osteomyelitis 27/6113 (0.4%) 29 11/3057 (0.4%) 16
Osteomyelitis Acute 2/6113 (0%) 2 0/3057 (0%) 0
Osteomyelitis Chronic 2/6113 (0%) 2 2/3057 (0.1%) 2
Otitis Externa 1/6113 (0%) 1 0/3057 (0%) 0
Paraspinal Abscess 1/6113 (0%) 1 0/3057 (0%) 0
Paronychia 0/6113 (0%) 0 1/3057 (0%) 1
Perihepatic Abscess 1/6113 (0%) 1 0/3057 (0%) 0
Perineal Abscess 1/6113 (0%) 1 0/3057 (0%) 0
Periodontitis 2/6113 (0%) 2 0/3057 (0%) 0
Peritonitis 2/6113 (0%) 2 0/3057 (0%) 0
Peritonsillar Abscess 1/6113 (0%) 1 0/3057 (0%) 0
Pneumonia 107/6113 (1.8%) 122 67/3057 (2.2%) 84
Pneumonia Bacterial 5/6113 (0.1%) 9 2/3057 (0.1%) 2
Pneumonia Necrotising 0/6113 (0%) 0 1/3057 (0%) 1
Pneumonia Pneumococcal 1/6113 (0%) 1 1/3057 (0%) 1
Pneumonia Staphylococcal 0/6113 (0%) 0 1/3057 (0%) 1
Poliomyelitis 1/6113 (0%) 1 0/3057 (0%) 0
Post Procedural Cellulitis 1/6113 (0%) 1 1/3057 (0%) 2
Post Procedural Infection 7/6113 (0.1%) 7 1/3057 (0%) 1
Post Procedural Pneumonia 1/6113 (0%) 1 0/3057 (0%) 0
Post Procedural Sepsis 1/6113 (0%) 1 1/3057 (0%) 1
Postoperative Wound Infection 28/6113 (0.5%) 30 15/3057 (0.5%) 15
Prostatic Abscess 1/6113 (0%) 1 0/3057 (0%) 0
Psoas Abscess 0/6113 (0%) 0 2/3057 (0.1%) 2
Pulmonary Sepsis 1/6113 (0%) 2 2/3057 (0.1%) 2
Pulmonary Tuberculosis 2/6113 (0%) 2 0/3057 (0%) 0
Pyelonephritis 5/6113 (0.1%) 5 2/3057 (0.1%) 2
Pyelonephritis Acute 7/6113 (0.1%) 8 1/3057 (0%) 1
Renal Abscess 1/6113 (0%) 1 0/3057 (0%) 0
Respiratory Tract Infection 7/6113 (0.1%) 8 4/3057 (0.1%) 6
Scrotal Abscess 0/6113 (0%) 0 1/3057 (0%) 1
Sepsis 34/6113 (0.6%) 38 18/3057 (0.6%) 18
Septic Arthritis Staphylococcal 2/6113 (0%) 2 0/3057 (0%) 0
Septic Shock 26/6113 (0.4%) 27 13/3057 (0.4%) 13
Sinusitis Bacterial 1/6113 (0%) 1 0/3057 (0%) 0
Skin Bacterial Infection 3/6113 (0%) 4 0/3057 (0%) 0
Skin Infection 2/6113 (0%) 2 2/3057 (0.1%) 2
Soft Tissue Infection 3/6113 (0%) 3 4/3057 (0.1%) 4
Staphylococcal Bacteraemia 1/6113 (0%) 1 0/3057 (0%) 0
Staphylococcal Infection 4/6113 (0.1%) 4 3/3057 (0.1%) 3
Staphylococcal Osteomyelitis 1/6113 (0%) 1 2/3057 (0.1%) 2
Staphylococcal Sepsis 1/6113 (0%) 1 1/3057 (0%) 1
Subcutaneous Abscess 0/6113 (0%) 0 2/3057 (0.1%) 2
Tracheitis 1/6113 (0%) 1 0/3057 (0%) 0
Tracheobronchitis 1/6113 (0%) 1 0/3057 (0%) 0
Tuberculosis 2/6113 (0%) 2 0/3057 (0%) 0
Upper Respiratory Tract Infection 1/6113 (0%) 1 1/3057 (0%) 1
Urinary Bladder Abscess 1/6113 (0%) 1 0/3057 (0%) 0
Urinary Tract Infection 91/6113 (1.5%) 116 38/3057 (1.2%) 47
Urinary Tract Infection Bacterial 3/6113 (0%) 3 1/3057 (0%) 1
Urinary Tract Infection Pseudomonal 1/6113 (0%) 1 0/3057 (0%) 0
Urosepsis 11/6113 (0.2%) 12 6/3057 (0.2%) 6
Viral Infection 0/6113 (0%) 0 1/3057 (0%) 1
Viral Upper Respiratory Tract Infection 1/6113 (0%) 1 0/3057 (0%) 0
Wound Infection 5/6113 (0.1%) 5 1/3057 (0%) 1
Wound Infection Bacterial 0/6113 (0%) 0 1/3057 (0%) 1
Injury, poisoning and procedural complications
Abdominal Wound Dehiscence 2/6113 (0%) 2 0/3057 (0%) 0
Accidental Overdose 1/6113 (0%) 1 1/3057 (0%) 1
Alcohol Poisoning 2/6113 (0%) 2 2/3057 (0.1%) 2
Anaemia Postoperative 1/6113 (0%) 1 0/3057 (0%) 0
Animal Bite 1/6113 (0%) 1 0/3057 (0%) 0
Ankle Fracture 4/6113 (0.1%) 4 4/3057 (0.1%) 4
Arterial Injury 1/6113 (0%) 1 0/3057 (0%) 0
Bladder Injury 1/6113 (0%) 1 0/3057 (0%) 0
Bone Fissure 0/6113 (0%) 0 1/3057 (0%) 1
Cardiac Procedure Complication 0/6113 (0%) 0 1/3057 (0%) 1
Cervical Vertebral Fracture 1/6113 (0%) 1 0/3057 (0%) 0
Chemical Poisoning 1/6113 (0%) 1 0/3057 (0%) 0
Concussion 0/6113 (0%) 0 1/3057 (0%) 1
Contusion 1/6113 (0%) 1 0/3057 (0%) 0
Coronary Artery Restenosis 1/6113 (0%) 1 0/3057 (0%) 0
Craniocerebral Injury 1/6113 (0%) 1 1/3057 (0%) 1
Dislocation Of Vertebra 1/6113 (0%) 1 0/3057 (0%) 0
Dural Tear 0/6113 (0%) 0 1/3057 (0%) 1
Exposure To Toxic Agent 1/6113 (0%) 1 0/3057 (0%) 0
Extradural Haematoma 1/6113 (0%) 1 0/3057 (0%) 0
Facial Bones Fracture 1/6113 (0%) 1 0/3057 (0%) 0
Fall 17/6113 (0.3%) 18 7/3057 (0.2%) 7
Fat Embolism 1/6113 (0%) 1 1/3057 (0%) 1
Femoral Neck Fracture 5/6113 (0.1%) 5 2/3057 (0.1%) 2
Femur Fracture 11/6113 (0.2%) 12 4/3057 (0.1%) 4
Foot Fracture 2/6113 (0%) 2 0/3057 (0%) 0
Forearm Fracture 1/6113 (0%) 1 1/3057 (0%) 1
Head Injury 0/6113 (0%) 0 1/3057 (0%) 1
Heat Exhaustion 1/6113 (0%) 1 0/3057 (0%) 0
Heat Stroke 0/6113 (0%) 0 1/3057 (0%) 1
Hip Fracture 8/6113 (0.1%) 8 6/3057 (0.2%) 7
Humerus Fracture 4/6113 (0.1%) 4 1/3057 (0%) 1
Incisional Hernia 0/6113 (0%) 0 1/3057 (0%) 1
Joint Dislocation 12/6113 (0.2%) 16 0/3057 (0%) 0
Joint Dislocation Postoperative 4/6113 (0.1%) 5 0/3057 (0%) 0
Joint Injury 0/6113 (0%) 0 1/3057 (0%) 1
Laceration 1/6113 (0%) 1 0/3057 (0%) 0
Ligament Injury 2/6113 (0%) 3 1/3057 (0%) 1
Ligament Rupture 1/6113 (0%) 1 0/3057 (0%) 0
Ligament Sprain 4/6113 (0.1%) 4 0/3057 (0%) 0
Limb Injury 1/6113 (0%) 1 0/3057 (0%) 0
Lower Limb Fracture 3/6113 (0%) 3 2/3057 (0.1%) 2
Mechanical Ventilation Complication 0/6113 (0%) 0 1/3057 (0%) 1
Meniscus Injury 0/6113 (0%) 0 5/3057 (0.2%) 6
Multiple Fractures 0/6113 (0%) 0 3/3057 (0.1%) 3
Multiple Injuries 2/6113 (0%) 2 0/3057 (0%) 0
Muscle Rupture 0/6113 (0%) 0 1/3057 (0%) 1
Muscle Strain 1/6113 (0%) 1 0/3057 (0%) 0
Overdose 4/6113 (0.1%) 4 0/3057 (0%) 0
Patella Fracture 2/6113 (0%) 2 0/3057 (0%) 0
Pelvic Fracture 1/6113 (0%) 1 2/3057 (0.1%) 2
Periprosthetic Fracture 6/6113 (0.1%) 7 5/3057 (0.2%) 6
Pneumothorax Traumatic 2/6113 (0%) 2 0/3057 (0%) 0
Post Concussion Syndrome 1/6113 (0%) 1 0/3057 (0%) 0
Post Procedural Complication 18/6113 (0.3%) 18 11/3057 (0.4%) 13
Post Procedural Discharge 1/6113 (0%) 1 0/3057 (0%) 0
Post Procedural Haematoma 1/6113 (0%) 1 0/3057 (0%) 0
Post Procedural Haematuria 0/6113 (0%) 0 1/3057 (0%) 1
Post Procedural Haemorrhage 3/6113 (0%) 3 3/3057 (0.1%) 3
Post Procedural Swelling 1/6113 (0%) 1 0/3057 (0%) 0
Postoperative Fever 2/6113 (0%) 2 0/3057 (0%) 0
Postoperative Ileus 1/6113 (0%) 1 0/3057 (0%) 0
Postoperative Respiratory Failure 0/6113 (0%) 0 1/3057 (0%) 1
Postoperative Thoracic Procedure Complication 1/6113 (0%) 1 0/3057 (0%) 0
Postoperative Wound Complication 1/6113 (0%) 1 0/3057 (0%) 0
Procedural Haemorrhage 4/6113 (0.1%) 5 0/3057 (0%) 0
Procedural Hypotension 1/6113 (0%) 1 0/3057 (0%) 0
Procedural Nausea 1/6113 (0%) 1 0/3057 (0%) 0
Procedural Pain 2/6113 (0%) 2 1/3057 (0%) 1
Pubis Fracture 1/6113 (0%) 1 0/3057 (0%) 0
Radius Fracture 0/6113 (0%) 0 1/3057 (0%) 1
Rectal Laceration Postoperative 1/6113 (0%) 1 0/3057 (0%) 0
Renal Haematoma 1/6113 (0%) 1 0/3057 (0%) 0
Rib Fracture 2/6113 (0%) 2 3/3057 (0.1%) 3
Road Traffic Accident 2/6113 (0%) 2 5/3057 (0.2%) 5
Scrotal Haematoma 1/6113 (0%) 1 0/3057 (0%) 0
Seroma 1/6113 (0%) 1 0/3057 (0%) 0
Skin Injury 1/6113 (0%) 1 0/3057 (0%) 0
Spinal Compression Fracture 1/6113 (0%) 1 1/3057 (0%) 1
Spinal Fracture 1/6113 (0%) 1 1/3057 (0%) 1
Stab Wound 1/6113 (0%) 1 0/3057 (0%) 0
Stress Fracture 1/6113 (0%) 1 0/3057 (0%) 0
Subdural Haematoma 6/6113 (0.1%) 6 3/3057 (0.1%) 3
Subdural Haemorrhage 0/6113 (0%) 0 1/3057 (0%) 1
Tendon Rupture 0/6113 (0%) 0 1/3057 (0%) 1
Thermal Burn 1/6113 (0%) 1 1/3057 (0%) 1
Thoracic Vertebral Fracture 2/6113 (0%) 2 0/3057 (0%) 0
Tibia Fracture 4/6113 (0.1%) 4 1/3057 (0%) 1
Toxicity To Various Agents 4/6113 (0.1%) 4 1/3057 (0%) 1
Tracheostomy Malfunction 1/6113 (0%) 1 1/3057 (0%) 1
Traumatic Arthritis 0/6113 (0%) 0 1/3057 (0%) 1
Traumatic Intracranial Haemorrhage 0/6113 (0%) 0 1/3057 (0%) 1
Upper Limb Fracture 1/6113 (0%) 1 0/3057 (0%) 0
Urethral Injury 0/6113 (0%) 0 1/3057 (0%) 1
Urethral Stricture Postoperative 1/6113 (0%) 1 0/3057 (0%) 0
Vascular Bypass Dysfunction 1/6113 (0%) 1 0/3057 (0%) 0
Vascular Graft Occlusion 1/6113 (0%) 1 1/3057 (0%) 1
Vascular Graft Thrombosis 2/6113 (0%) 2 0/3057 (0%) 0
Vascular Pseudoaneurysm 1/6113 (0%) 1 1/3057 (0%) 1
Wound 1/6113 (0%) 1 0/3057 (0%) 0
Wound Dehiscence 3/6113 (0%) 5 2/3057 (0.1%) 2
Wrist Fracture 1/6113 (0%) 1 0/3057 (0%) 0
Investigations
Anticoagulation Drug Level Above Therapeutic 0/6113 (0%) 0 1/3057 (0%) 1
Aspiration Bronchial 1/6113 (0%) 1 0/3057 (0%) 0
Blood Creatinine Increased 1/6113 (0%) 1 0/3057 (0%) 0
Blood Potassium Decreased 0/6113 (0%) 0 1/3057 (0%) 1
Carbon Dioxide Abnormal 1/6113 (0%) 1 0/3057 (0%) 0
Cardiac Pacemaker Evaluation 1/6113 (0%) 1 0/3057 (0%) 0
Coagulation Time Prolonged 0/6113 (0%) 0 1/3057 (0%) 1
Electrocardiogram St Segment Elevation 1/6113 (0%) 1 0/3057 (0%) 0
Influenza A Virus Test Positive 1/6113 (0%) 1 0/3057 (0%) 0
International Normalised Ratio Increased 1/6113 (0%) 1 0/3057 (0%) 0
Oxygen Saturation Decreased 0/6113 (0%) 0 1/3057 (0%) 1
Prothrombin Time Abnormal 1/6113 (0%) 1 0/3057 (0%) 0
Transaminases Increased 0/6113 (0%) 0 1/3057 (0%) 1
Urine Output Decreased 1/6113 (0%) 1 0/3057 (0%) 0
Metabolism and nutrition disorders
Cachexia 0/6113 (0%) 0 1/3057 (0%) 1
Central Obesity 1/6113 (0%) 1 0/3057 (0%) 0
Decreased Appetite 0/6113 (0%) 0 1/3057 (0%) 1
Dehydration 5/6113 (0.1%) 5 0/3057 (0%) 0
Diabetes Mellitus 12/6113 (0.2%) 15 2/3057 (0.1%) 2
Diabetes Mellitus Inadequate Control 8/6113 (0.1%) 11 2/3057 (0.1%) 2
Diabetic Complication 2/6113 (0%) 2 2/3057 (0.1%) 2
Diabetic Ketoacidosis 3/6113 (0%) 4 2/3057 (0.1%) 2
Electrolyte Imbalance 2/6113 (0%) 2 3/3057 (0.1%) 3
Fluid Overload 4/6113 (0.1%) 6 5/3057 (0.2%) 13
Gout 5/6113 (0.1%) 6 0/3057 (0%) 0
Hyperamylasaemia 0/6113 (0%) 0 1/3057 (0%) 1
Hypercalcaemia 1/6113 (0%) 1 2/3057 (0.1%) 2
Hyperglycaemia 10/6113 (0.2%) 12 6/3057 (0.2%) 6
Hyperglycaemic Hyperosmolar Nonketotic Syndrome 3/6113 (0%) 3 0/3057 (0%) 0
Hyperkalaemia 5/6113 (0.1%) 6 4/3057 (0.1%) 4
Hyperuricaemia 1/6113 (0%) 1 0/3057 (0%) 0
Hypervolaemia 0/6113 (0%) 0 1/3057 (0%) 1
Hypoglycaemia 11/6113 (0.2%) 11 6/3057 (0.2%) 7
Hypokalaemia 2/6113 (0%) 2 1/3057 (0%) 2
Hyponatraemia 6/6113 (0.1%) 6 1/3057 (0%) 1
Hypovolaemia 0/6113 (0%) 0 1/3057 (0%) 1
Malnutrition 0/6113 (0%) 0 2/3057 (0.1%) 2
Metabolic Acidosis 0/6113 (0%) 0 3/3057 (0.1%) 3
Obesity 2/6113 (0%) 2 0/3057 (0%) 0
Type 1 Diabetes Mellitus 1/6113 (0%) 1 0/3057 (0%) 0
Type 2 Diabetes Mellitus 1/6113 (0%) 1 2/3057 (0.1%) 2
Musculoskeletal and connective tissue disorders
Ankylosing Spondylitis 1/6113 (0%) 1 0/3057 (0%) 0
Arthralgia 10/6113 (0.2%) 10 4/3057 (0.1%) 4
Arthritis 2/6113 (0%) 2 1/3057 (0%) 1
Arthrofibrosis 0/6113 (0%) 0 1/3057 (0%) 1
Arthropathy 0/6113 (0%) 0 1/3057 (0%) 1
Back Pain 8/6113 (0.1%) 9 8/3057 (0.3%) 10
Bursitis 3/6113 (0%) 3 2/3057 (0.1%) 2
Cervical Spinal Stenosis 2/6113 (0%) 2 0/3057 (0%) 0
Chondropathy 0/6113 (0%) 0 1/3057 (0%) 1
Chronic Recurrent Multifocal Osteomyelitis 1/6113 (0%) 1 0/3057 (0%) 0
Collagen Disorder 1/6113 (0%) 1 0/3057 (0%) 0
Costochondritis 2/6113 (0%) 2 0/3057 (0%) 0
Exostosis 0/6113 (0%) 0 1/3057 (0%) 1
Fistula 1/6113 (0%) 1 0/3057 (0%) 0
Foot Deformity 0/6113 (0%) 0 1/3057 (0%) 1
Fracture Nonunion 2/6113 (0%) 2 0/3057 (0%) 0
Gouty Arthritis 1/6113 (0%) 1 1/3057 (0%) 1
Intervertebral Disc Degeneration 3/6113 (0%) 3 1/3057 (0%) 1
Intervertebral Disc Disorder 1/6113 (0%) 1 0/3057 (0%) 0
Intervertebral Disc Protrusion 4/6113 (0.1%) 4 3/3057 (0.1%) 3
Joint Instability 1/6113 (0%) 1 1/3057 (0%) 1
Joint Swelling 1/6113 (0%) 1 0/3057 (0%) 0
Lumbar Spinal Stenosis 4/6113 (0.1%) 4 2/3057 (0.1%) 2
Mobility Decreased 1/6113 (0%) 1 0/3057 (0%) 0
Muscle Necrosis 1/6113 (0%) 1 0/3057 (0%) 0
Muscle Spasms 1/6113 (0%) 1 0/3057 (0%) 0
Musculoskeletal Chest Pain 5/6113 (0.1%) 5 1/3057 (0%) 1
Musculoskeletal Pain 2/6113 (0%) 2 1/3057 (0%) 1
Myalgia 0/6113 (0%) 0 1/3057 (0%) 1
Neck Pain 1/6113 (0%) 1 2/3057 (0.1%) 2
Osteitis 1/6113 (0%) 1 0/3057 (0%) 0
Osteoarthritis 47/6113 (0.8%) 51 19/3057 (0.6%) 19
Pain In Extremity 3/6113 (0%) 3 0/3057 (0%) 0
Pseudarthrosis 1/6113 (0%) 1 1/3057 (0%) 1
Psoriatic Arthropathy 1/6113 (0%) 1 0/3057 (0%) 0
Rhabdomyolysis 1/6113 (0%) 1 1/3057 (0%) 1
Rotator Cuff Syndrome 4/6113 (0.1%) 4 2/3057 (0.1%) 3
Scoliosis 0/6113 (0%) 0 2/3057 (0.1%) 2
Spinal Column Stenosis 2/6113 (0%) 2 2/3057 (0.1%) 2
Spinal Osteoarthritis 2/6113 (0%) 2 1/3057 (0%) 1
Spondylitis 1/6113 (0%) 1 0/3057 (0%) 0
Spondylolisthesis 1/6113 (0%) 1 1/3057 (0%) 1
Tendonitis 1/6113 (0%) 1 1/3057 (0%) 1
Tenosynovitis 0/6113 (0%) 0 1/3057 (0%) 1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Abdominal Neoplasm 1/6113 (0%) 1 0/3057 (0%) 0
Adenocarcinoma 1/6113 (0%) 1 1/3057 (0%) 1
Adenocarcinoma Gastric 2/6113 (0%) 2 0/3057 (0%) 0
Adenocarcinoma Of Colon 0/6113 (0%) 0 1/3057 (0%) 1
Adenocarcinoma Pancreas 0/6113 (0%) 0 1/3057 (0%) 1
Adrenal Adenoma 1/6113 (0%) 1 0/3057 (0%) 0
Basal Cell Carcinoma 2/6113 (0%) 2 2/3057 (0.1%) 2
Benign Bone Neoplasm 1/6113 (0%) 1 0/3057 (0%) 0
Bladder Cancer 3/6113 (0%) 3 1/3057 (0%) 1
Bladder Neoplasm 3/6113 (0%) 3 0/3057 (0%) 0
Bladder Transitional Cell Carcinoma Recurrent 1/6113 (0%) 1 0/3057 (0%) 0
Bladder Transitional Cell Carcinoma Stage Ii 0/6113 (0%) 0 1/3057 (0%) 1
Bone Cancer 1/6113 (0%) 1 0/3057 (0%) 0
Brain Cancer Metastatic 0/6113 (0%) 0 1/3057 (0%) 1
Brain Neoplasm 2/6113 (0%) 2 0/3057 (0%) 0
Brain Neoplasm Malignant 0/6113 (0%) 0 1/3057 (0%) 1
Breast Cancer 4/6113 (0.1%) 4 2/3057 (0.1%) 2
Breast Cancer Metastatic 0/6113 (0%) 0 1/3057 (0%) 2
Breast Cancer Stage Ii 1/6113 (0%) 1 0/3057 (0%) 0
Breast Neoplasm 1/6113 (0%) 1 0/3057 (0%) 0
Bronchial Carcinoma 1/6113 (0%) 1 1/3057 (0%) 1
Burkitt's Lymphoma 1/6113 (0%) 1 0/3057 (0%) 0
Carcinoid Tumour Of The Duodenum 0/6113 (0%) 0 1/3057 (0%) 1
Cervix Carcinoma 1/6113 (0%) 1 0/3057 (0%) 0
Cervix Carcinoma Recurrent 1/6113 (0%) 3 0/3057 (0%) 0
Cervix Carcinoma Stage I 1/6113 (0%) 1 0/3057 (0%) 0
Chronic Lymphocytic Leukaemia 2/6113 (0%) 2 0/3057 (0%) 0
Clear Cell Renal Cell Carcinoma 1/6113 (0%) 1 0/3057 (0%) 0
Colon Adenoma 1/6113 (0%) 1 1/3057 (0%) 1
Colon Cancer 2/6113 (0%) 3 1/3057 (0%) 1
Colon Neoplasm 1/6113 (0%) 1 1/3057 (0%) 1
Diffuse Large B-Cell Lymphoma 1/6113 (0%) 1 1/3057 (0%) 1
Endometrial Adenocarcinoma 1/6113 (0%) 1 0/3057 (0%) 0
Endometrial Cancer 1/6113 (0%) 1 0/3057 (0%) 0
Eyelid Tumour 1/6113 (0%) 1 0/3057 (0%) 0
Gallbladder Adenocarcinoma 1/6113 (0%) 1 0/3057 (0%) 0
Gastric Adenoma 1/6113 (0%) 1 1/3057 (0%) 1
Gastric Neoplasm 0/6113 (0%) 0 1/3057 (0%) 1
Gastrointestinal Carcinoma 0/6113 (0%) 0 1/3057 (0%) 1
Gastrointestinal Neoplasm 0/6113 (0%) 0 1/3057 (0%) 1
Gastrointestinal Stromal Tumour 1/6113 (0%) 1 0/3057 (0%) 0
Glioblastoma Multiforme 0/6113 (0%) 0 1/3057 (0%) 1
Hepatic Cancer 1/6113 (0%) 1 0/3057 (0%) 0
Hepatocellular Carcinoma 2/6113 (0%) 2 1/3057 (0%) 1
Intraductal Papillary Mucinous Neoplasm 1/6113 (0%) 1 0/3057 (0%) 0
Kaposi's Sarcoma 1/6113 (0%) 1 0/3057 (0%) 0
Leiomyosarcoma 1/6113 (0%) 1 0/3057 (0%) 0
Leukaemia 1/6113 (0%) 3 0/3057 (0%) 0
Lipoma 1/6113 (0%) 1 0/3057 (0%) 0
Lung Adenocarcinoma 2/6113 (0%) 2 0/3057 (0%) 0
Lung Cancer Metastatic 1/6113 (0%) 1 1/3057 (0%) 1
Lung Carcinoma Cell Type Unspecified Recurrent 1/6113 (0%) 1 0/3057 (0%) 0
Lung Carcinoma Cell Type Unspecified Stage Iv 0/6113 (0%) 0 1/3057 (0%) 1
Lung Neoplasm 1/6113 (0%) 2 0/3057 (0%) 0
Lung Neoplasm Malignant 3/6113 (0%) 3 1/3057 (0%) 1
Lymphoma 2/6113 (0%) 2 2/3057 (0.1%) 2
Malignant Melanoma 1/6113 (0%) 1 0/3057 (0%) 0
Malignant Neoplasm Of Eye 0/6113 (0%) 0 1/3057 (0%) 1
Malignant Neoplasm Of Renal Pelvis 0/6113 (0%) 0 1/3057 (0%) 1
Malignant Pleural Effusion 1/6113 (0%) 1 0/3057 (0%) 0
Malignant Respiratory Tract Neoplasm 1/6113 (0%) 1 0/3057 (0%) 0
Mantle Cell Lymphoma 1/6113 (0%) 1 0/3057 (0%) 0
Mediastinum Neoplasm 1/6113 (0%) 1 0/3057 (0%) 0
Meningioma 1/6113 (0%) 1 0/3057 (0%) 0
Mesothelioma 1/6113 (0%) 1 0/3057 (0%) 0
Metastases To Central Nervous System 0/6113 (0%) 0 1/3057 (0%) 1
Metastases To Lung 0/6113 (0%) 0 1/3057 (0%) 1
Metastatic Carcinoma Of The Bladder 2/6113 (0%) 4 0/3057 (0%) 0
Metastatic Neoplasm 1/6113 (0%) 1 1/3057 (0%) 1
Neoplasm Malignant 2/6113 (0%) 2 0/3057 (0%) 0
Neoplasm Of Thymus 0/6113 (0%) 0 1/3057 (0%) 1
Neoplasm Prostate 0/6113 (0%) 0 1/3057 (0%) 1
Neuroendocrine Tumour 1/6113 (0%) 1 0/3057 (0%) 0
Nodal Marginal Zone B-Cell Lymphoma 0/6113 (0%) 0 1/3057 (0%) 1
Non-Small Cell Lung Cancer 1/6113 (0%) 1 1/3057 (0%) 1
Non-Small Cell Lung Cancer Recurrent 1/6113 (0%) 4 0/3057 (0%) 0
Oesophageal Carcinoma 1/6113 (0%) 1 0/3057 (0%) 0
Ovarian Cancer 0/6113 (0%) 0 2/3057 (0.1%) 2
Ovarian Epithelial Cancer 1/6113 (0%) 1 0/3057 (0%) 0
Pancreatic Carcinoma 2/6113 (0%) 2 0/3057 (0%) 0
Pancreatic Carcinoma Metastatic 1/6113 (0%) 1 0/3057 (0%) 0
Pancreatic Neuroendocrine Tumour 0/6113 (0%) 0 1/3057 (0%) 1
Papillary Thyroid Cancer 0/6113 (0%) 0 1/3057 (0%) 1
Parathyroid Tumour Benign 1/6113 (0%) 1 1/3057 (0%) 1
Plasma Cell Myeloma 2/6113 (0%) 2 2/3057 (0.1%) 2
Prostate Cancer 17/6113 (0.3%) 17 3/3057 (0.1%) 3
Prostate Cancer Metastatic 1/6113 (0%) 1 0/3057 (0%) 0
Rectal Adenocarcinoma 1/6113 (0%) 1 0/3057 (0%) 0
Rectal Cancer 0/6113 (0%) 0 1/3057 (0%) 1
Renal Cell Carcinoma 1/6113 (0%) 1 1/3057 (0%) 1
Renal Neoplasm 1/6113 (0%) 1 1/3057 (0%) 1
Retroperitoneal Cancer 1/6113 (0%) 1 0/3057 (0%) 0
Salivary Gland Adenoma 1/6113 (0%) 1 0/3057 (0%) 0
Salivary Gland Cancer 1/6113 (0%) 1 0/3057 (0%) 0
Small Cell Lung Cancer 1/6113 (0%) 1 0/3057 (0%) 0
Small Intestine Carcinoma 1/6113 (0%) 1 0/3057 (0%) 0
Squamous Cell Carcinoma 2/6113 (0%) 2 0/3057 (0%) 0
Superficial Spreading Melanoma Stage Unspecified 0/6113 (0%) 0 1/3057 (0%) 1
Testicular Neoplasm 1/6113 (0%) 1 0/3057 (0%) 0
Transitional Cell Carcinoma 3/6113 (0%) 3 1/3057 (0%) 1
Uterine Cancer 1/6113 (0%) 1 0/3057 (0%) 0
Nervous system disorders
Altered State Of Consciousness 1/6113 (0%) 1 0/3057 (0%) 0
Apallic Syndrome 1/6113 (0%) 1 0/3057 (0%) 0
Arachnoid Cyst 1/6113 (0%) 1 1/3057 (0%) 1
Ataxia 1/6113 (0%) 1 0/3057 (0%) 0
Brain Stem Stroke 1/6113 (0%) 1 0/3057 (0%) 0
Carotid Arteriosclerosis 1/6113 (0%) 1 0/3057 (0%) 0
Carotid Artery Stenosis 2/6113 (0%) 2 1/3057 (0%) 1
Carpal Tunnel Syndrome 0/6113 (0%) 0 2/3057 (0.1%) 2
Cerebral Artery Stenosis 1/6113 (0%) 1 0/3057 (0%) 0
Cerebral Haemorrhage 4/6113 (0.1%) 4 2/3057 (0.1%) 2
Cerebral Infarction 5/6113 (0.1%) 5 7/3057 (0.2%) 7
Cerebral Ischaemia 1/6113 (0%) 1 1/3057 (0%) 1
Cerebral Thrombosis 1/6113 (0%) 1 0/3057 (0%) 0
Cerebrovascular Accident 19/6113 (0.3%) 20 8/3057 (0.3%) 8
Cerebrovascular Disorder 3/6113 (0%) 3 3/3057 (0.1%) 3
Cervical Myelopathy 0/6113 (0%) 0 1/3057 (0%) 1
Cervicobrachial Syndrome 0/6113 (0%) 0 2/3057 (0.1%) 2
Chronic Inflammatory Demyelinating Polyradiculoneuropathy 0/6113 (0%) 0 1/3057 (0%) 1
Convulsion 11/6113 (0.2%) 15 9/3057 (0.3%) 22
Critical Illness Polyneuropathy 1/6113 (0%) 1 0/3057 (0%) 0
Dementia 1/6113 (0%) 1 0/3057 (0%) 0
Dementia Alzheimer's Type 0/6113 (0%) 0 1/3057 (0%) 1
Dementia With Lewy Bodies 1/6113 (0%) 1 1/3057 (0%) 1
Diabetic Neuropathy 0/6113 (0%) 0 2/3057 (0.1%) 3
Dizziness 4/6113 (0.1%) 4 4/3057 (0.1%) 4
Dizziness Postural 1/6113 (0%) 1 0/3057 (0%) 0
Embolic Stroke 1/6113 (0%) 1 0/3057 (0%) 0
Encephalopathy 5/6113 (0.1%) 5 4/3057 (0.1%) 4
Epilepsy 2/6113 (0%) 3 1/3057 (0%) 3
Facial Paresis 1/6113 (0%) 1 0/3057 (0%) 0
Haemorrhage Intracranial 1/6113 (0%) 1 1/3057 (0%) 1
Haemorrhagic Stroke 2/6113 (0%) 2 0/3057 (0%) 0
Headache 3/6113 (0%) 3 2/3057 (0.1%) 2
Hemiplegic Migraine 0/6113 (0%) 0 1/3057 (0%) 1
Hepatic Encephalopathy 2/6113 (0%) 6 4/3057 (0.1%) 7
Hydrocephalus 1/6113 (0%) 1 1/3057 (0%) 2
Hypertensive Encephalopathy 1/6113 (0%) 1 0/3057 (0%) 0
Hypoaesthesia 1/6113 (0%) 1 0/3057 (0%) 0
Hypoglycaemic Encephalopathy 1/6113 (0%) 1 0/3057 (0%) 0
Hypoxic-Ischaemic Encephalopathy 3/6113 (0%) 3 1/3057 (0%) 1
Intercostal Neuralgia 0/6113 (0%) 0 1/3057 (0%) 1
Intracranial Aneurysm 1/6113 (0%) 1 2/3057 (0.1%) 2
Intracranial Pressure Increased 1/6113 (0%) 1 0/3057 (0%) 0
Ischaemic Cerebral Infarction 1/6113 (0%) 1 0/3057 (0%) 0
Ischaemic Stroke 11/6113 (0.2%) 13 5/3057 (0.2%) 5
Lacunar Infarction 1/6113 (0%) 1 0/3057 (0%) 0
Lumbar Radiculopathy 0/6113 (0%) 0 1/3057 (0%) 1
Metabolic Encephalopathy 1/6113 (0%) 1 0/3057 (0%) 0
Migraine 3/6113 (0%) 3 1/3057 (0%) 1
Neuropathy Peripheral 0/6113 (0%) 0 2/3057 (0.1%) 2
Normal Pressure Hydrocephalus 1/6113 (0%) 1 0/3057 (0%) 0
Paraesthesia 1/6113 (0%) 1 0/3057 (0%) 0
Partial Seizures 1/6113 (0%) 2 0/3057 (0%) 0
Pneumocephalus 0/6113 (0%) 0 1/3057 (0%) 1
Polyneuropathy 1/6113 (0%) 1 0/3057 (0%) 0
Post-Traumatic Headache 1/6113 (0%) 1 0/3057 (0%) 0
Presyncope 3/6113 (0%) 3 1/3057 (0%) 1
Radicular Pain 1/6113 (0%) 1 0/3057 (0%) 0
Radicular Syndrome 1/6113 (0%) 1 0/3057 (0%) 0
Spinal Cord Compression 0/6113 (0%) 0 1/3057 (0%) 1
Status Epilepticus 0/6113 (0%) 0 1/3057 (0%) 1
Subarachnoid Haemorrhage 3/6113 (0%) 3 0/3057 (0%) 0
Syncope 14/6113 (0.2%) 15 9/3057 (0.3%) 9
Tension Headache 0/6113 (0%) 0 1/3057 (0%) 1
Thalamus Haemorrhage 1/6113 (0%) 1 0/3057 (0%) 0
Toxic Encephalopathy 1/6113 (0%) 1 1/3057 (0%) 1
Transient Global Amnesia 1/6113 (0%) 1 0/3057 (0%) 0
Transient Ischaemic Attack 21/6113 (0.3%) 21 8/3057 (0.3%) 8
Tremor 1/6113 (0%) 1 0/3057 (0%) 0
Trigeminal Neuralgia 0/6113 (0%) 0 1/3057 (0%) 1
Vertebrobasilar Insufficiency 0/6113 (0%) 0 1/3057 (0%) 1
Vertigo Cns Origin 0/6113 (0%) 0 1/3057 (0%) 1
Vocal Cord Paralysis 0/6113 (0%) 0 1/3057 (0%) 1
Psychiatric disorders
Alcohol Abuse 1/6113 (0%) 1 0/3057 (0%) 0
Alcohol Withdrawal Syndrome 2/6113 (0%) 3 0/3057 (0%) 0
Completed Suicide 1/6113 (0%) 1 0/3057 (0%) 0
Conversion Disorder 1/6113 (0%) 1 1/3057 (0%) 1
Delirium 2/6113 (0%) 2 4/3057 (0.1%) 4
Depression 4/6113 (0.1%) 5 1/3057 (0%) 1
Drug Dependence 1/6113 (0%) 1 0/3057 (0%) 0
Impaired Self-Care 1/6113 (0%) 1 0/3057 (0%) 0
Major Depression 0/6113 (0%) 0 1/3057 (0%) 1
Mental Disorder 0/6113 (0%) 0 1/3057 (0%) 1
Mental Status Changes 4/6113 (0.1%) 4 5/3057 (0.2%) 5
Panic Attack 0/6113 (0%) 0 1/3057 (0%) 1
Psychotic Disorder 1/6113 (0%) 1 0/3057 (0%) 0
Schizoaffective Disorder 0/6113 (0%) 0 1/3057 (0%) 1
Schizophrenia 1/6113 (0%) 1 0/3057 (0%) 0
Suicidal Ideation 0/6113 (0%) 0 3/3057 (0.1%) 3
Suicide Attempt 1/6113 (0%) 1 1/3057 (0%) 1
Renal and urinary disorders
Azotaemia 2/6113 (0%) 2 0/3057 (0%) 0
Bladder Mass 1/6113 (0%) 1 0/3057 (0%) 0
Bladder Neck Obstruction 1/6113 (0%) 1 0/3057 (0%) 0
Bladder Outlet Obstruction 2/6113 (0%) 2 0/3057 (0%) 0
Calculus Ureteric 2/6113 (0%) 2 2/3057 (0.1%) 3
Calculus Urinary 2/6113 (0%) 2 0/3057 (0%) 0
Cystitis Interstitial 0/6113 (0%) 0 1/3057 (0%) 1
Diabetic Nephropathy 1/6113 (0%) 1 0/3057 (0%) 0
Haematuria 8/6113 (0.1%) 8 6/3057 (0.2%) 7
Hydronephrosis 4/6113 (0.1%) 4 0/3057 (0%) 0
Lupus Nephritis 0/6113 (0%) 0 1/3057 (0%) 1
Micturition Disorder 0/6113 (0%) 0 1/3057 (0%) 1
Nephrolithiasis 9/6113 (0.1%) 10 1/3057 (0%) 2
Nephrotic Syndrome 0/6113 (0%) 0 1/3057 (0%) 1
Obstructive Uropathy 2/6113 (0%) 2 0/3057 (0%) 0
Proteinuria 1/6113 (0%) 1 0/3057 (0%) 0
Renal Failure 7/6113 (0.1%) 8 3/3057 (0.1%) 3
Renal Failure Acute 31/6113 (0.5%) 35 8/3057 (0.3%) 9
Renal Failure Chronic 17/6113 (0.3%) 19 3/3057 (0.1%) 3
Renal Haemorrhage 1/6113 (0%) 1 0/3057 (0%) 0
Renal Impairment 1/6113 (0%) 1 1/3057 (0%) 1
Renal Injury 1/6113 (0%) 1 0/3057 (0%) 0
Renal Tubular Necrosis 0/6113 (0%) 0 1/3057 (0%) 1
Strangury 1/6113 (0%) 1 0/3057 (0%) 0
Stress Urinary Incontinence 1/6113 (0%) 1 0/3057 (0%) 0
Tubulointerstitial Nephritis 1/6113 (0%) 1 0/3057 (0%) 0
Ureteric Stenosis 1/6113 (0%) 1 0/3057 (0%) 0
Urethral Stenosis 7/6113 (0.1%) 8 6/3057 (0.2%) 9
Urinary Incontinence 3/6113 (0%) 5 1/3057 (0%) 1
Urinary Retention 5/6113 (0.1%) 8 2/3057 (0.1%) 2
Urinoma 0/6113 (0%) 0 1/3057 (0%) 1
Vesicocutaneous Fistula 0/6113 (0%) 0 1/3057 (0%) 2
Reproductive system and breast disorders
Benign Prostatic Hyperplasia 8/6113 (0.1%) 8 5/3057 (0.2%) 5
Breast Enlargement 0/6113 (0%) 0 1/3057 (0%) 1
Epididymitis 2/6113 (0%) 2 0/3057 (0%) 0
Female Genital Tract Fistula 1/6113 (0%) 1 0/3057 (0%) 0
Genital Prolapse 0/6113 (0%) 0 1/3057 (0%) 1
Ovarian Cyst 1/6113 (0%) 1 0/3057 (0%) 0
Postmenopausal Haemorrhage 0/6113 (0%) 0 1/3057 (0%) 1
Prostatitis 0/6113 (0%) 0 2/3057 (0.1%) 2
Prostatomegaly 1/6113 (0%) 1 0/3057 (0%) 0
Uterine Haemorrhage 2/6113 (0%) 2 0/3057 (0%) 0
Vaginal Haemorrhage 0/6113 (0%) 0 1/3057 (0%) 1
Vaginal Prolapse 1/6113 (0%) 1 0/3057 (0%) 0
Respiratory, thoracic and mediastinal disorders
Acute Pulmonary Oedema 3/6113 (0%) 3 1/3057 (0%) 1
Acute Respiratory Distress Syndrome 4/6113 (0.1%) 4 0/3057 (0%) 0
Acute Respiratory Failure 23/6113 (0.4%) 29 10/3057 (0.3%) 12
Alveolitis Allergic 1/6113 (0%) 1 0/3057 (0%) 0
Apnoea 1/6113 (0%) 1 0/3057 (0%) 0
Aspiration 1/6113 (0%) 1 0/3057 (0%) 0
Asthma 18/6113 (0.3%) 23 3/3057 (0.1%) 4
Atelectasis 3/6113 (0%) 3 1/3057 (0%) 1
Bronchiectasis 0/6113 (0%) 0 1/3057 (0%) 1
Bronchitis Chronic 0/6113 (0%) 0 2/3057 (0.1%) 2
Bronchospasm 2/6113 (0%) 2 1/3057 (0%) 1
Chronic Obstructive Pulmonary Disease 84/6113 (1.4%) 121 51/3057 (1.7%) 71
Chronic Respiratory Failure 2/6113 (0%) 2 1/3057 (0%) 1
Dyspnoea 12/6113 (0.2%) 15 15/3057 (0.5%) 15
Dyspnoea Exertional 1/6113 (0%) 1 0/3057 (0%) 0
Emphysema 1/6113 (0%) 1 0/3057 (0%) 0
Epistaxis 1/6113 (0%) 1 2/3057 (0.1%) 5
Haemoptysis 1/6113 (0%) 1 1/3057 (0%) 1
Hydropneumothorax 1/6113 (0%) 1 0/3057 (0%) 0
Hypoxia 1/6113 (0%) 1 0/3057 (0%) 0
Idiopathic Pulmonary Fibrosis 1/6113 (0%) 1 1/3057 (0%) 1
Interstitial Lung Disease 6/6113 (0.1%) 8 1/3057 (0%) 1
Lung Disorder 1/6113 (0%) 1 0/3057 (0%) 0
Lung Hernia 1/6113 (0%) 1 0/3057 (0%) 0
Mediastinal Disorder 0/6113 (0%) 0 1/3057 (0%) 1
Mediastinal Haemorrhage 1/6113 (0%) 1 0/3057 (0%) 0
Obstructive Airways Disorder 1/6113 (0%) 1 0/3057 (0%) 0
Pleural Effusion 21/6113 (0.3%) 22 10/3057 (0.3%) 11
Pleuritic Pain 0/6113 (0%) 0 1/3057 (0%) 1
Pneumonia Aspiration 4/6113 (0.1%) 4 3/3057 (0.1%) 5
Pneumonitis 1/6113 (0%) 1 0/3057 (0%) 0
Pneumothorax 5/6113 (0.1%) 6 1/3057 (0%) 1
Pulmonary Congestion 2/6113 (0%) 2 1/3057 (0%) 1
Pulmonary Embolism 23/6113 (0.4%) 23 17/3057 (0.6%) 17
Pulmonary Fibrosis 1/6113 (0%) 1 0/3057 (0%) 0
Pulmonary Hypertension 1/6113 (0%) 1 1/3057 (0%) 1
Pulmonary Microemboli 1/6113 (0%) 1 0/3057 (0%) 0
Pulmonary Oedema 6/6113 (0.1%) 6 3/3057 (0.1%) 3
Respiratory Acidosis 1/6113 (0%) 1 0/3057 (0%) 0
Respiratory Arrest 1/6113 (0%) 1 1/3057 (0%) 1
Respiratory Disorder 0/6113 (0%) 0 1/3057 (0%) 1
Respiratory Distress 3/6113 (0%) 4 0/3057 (0%) 0
Respiratory Failure 16/6113 (0.3%) 18 12/3057 (0.4%) 15
Sinus Polyp 1/6113 (0%) 1 0/3057 (0%) 0
Sleep Apnoea Syndrome 4/6113 (0.1%) 5 3/3057 (0.1%) 3
Status Asthmaticus 1/6113 (0%) 1 0/3057 (0%) 0
Tracheal Stenosis 0/6113 (0%) 0 1/3057 (0%) 3
Skin and subcutaneous tissue disorders
Angioedema 0/6113 (0%) 0 1/3057 (0%) 1
Decubitus Ulcer 4/6113 (0.1%) 4 0/3057 (0%) 0
Dermatitis Contact 1/6113 (0%) 1 0/3057 (0%) 0
Diabetic Foot 24/6113 (0.4%) 25 13/3057 (0.4%) 14
Diabetic Ulcer 1/6113 (0%) 1 0/3057 (0%) 0
Ecchymosis 0/6113 (0%) 0 1/3057 (0%) 1
Eczema 1/6113 (0%) 1 0/3057 (0%) 0
Hidradenitis 2/6113 (0%) 2 0/3057 (0%) 0
Rash 1/6113 (0%) 1 0/3057 (0%) 0
Rash Erythematous 1/6113 (0%) 1 0/3057 (0%) 0
Skin Necrosis 1/6113 (0%) 1 0/3057 (0%) 0
Skin Ulcer 11/6113 (0.2%) 12 7/3057 (0.2%) 9
Stevens-Johnson Syndrome 0/6113 (0%) 0 1/3057 (0%) 1
Surgical and medical procedures
Artificial Urinary Sphincter Implant 1/6113 (0%) 1 0/3057 (0%) 0
Cardiac Pacemaker Battery Replacement 1/6113 (0%) 1 0/3057 (0%) 0
Cardioversion 0/6113 (0%) 0 1/3057 (0%) 1
Cerebrospinal Fluid Drainage 0/6113 (0%) 0 1/3057 (0%) 1
Hip Arthroplasty 1/6113 (0%) 1 1/3057 (0%) 1
Incisional Drainage 0/6113 (0%) 0 1/3057 (0%) 1
Knee Arthroplasty 1/6113 (0%) 1 0/3057 (0%) 0
Knee Operation 0/6113 (0%) 0 1/3057 (0%) 1
Leg Amputation 0/6113 (0%) 0 1/3057 (0%) 1
Metatarsal Excision 1/6113 (0%) 1 0/3057 (0%) 0
Parathyroidectomy 1/6113 (0%) 1 0/3057 (0%) 0
Rehabilitation Therapy 2/6113 (0%) 2 0/3057 (0%) 0
Tooth Extraction 1/6113 (0%) 1 0/3057 (0%) 0
Vascular disorders
Aneurysm 0/6113 (0%) 0 1/3057 (0%) 2
Aneurysm Ruptured 1/6113 (0%) 1 0/3057 (0%) 0
Aortic Aneurysm 1/6113 (0%) 1 3/3057 (0.1%) 3
Aortic Aneurysm Rupture 0/6113 (0%) 0 1/3057 (0%) 1
Aortic Stenosis 2/6113 (0%) 2 2/3057 (0.1%) 2
Aortic Thrombosis 0/6113 (0%) 0 1/3057 (0%) 1
Arterial Occlusive Disease 2/6113 (0%) 2 1/3057 (0%) 1
Arterial Stenosis 2/6113 (0%) 2 0/3057 (0%) 0
Arteriosclerosis 4/6113 (0.1%) 4 0/3057 (0%) 0
Circulatory Collapse 1/6113 (0%) 2 0/3057 (0%) 0
Deep Vein Thrombosis 12/6113 (0.2%) 12 5/3057 (0.2%) 5
Essential Hypertension 0/6113 (0%) 0 2/3057 (0.1%) 2
Extremity Necrosis 2/6113 (0%) 2 0/3057 (0%) 0
Femoral Artery Occlusion 0/6113 (0%) 0 1/3057 (0%) 1
Haematoma 4/6113 (0.1%) 4 2/3057 (0.1%) 2
Hypertension 7/6113 (0.1%) 7 2/3057 (0.1%) 2
Hypertensive Crisis 9/6113 (0.1%) 9 1/3057 (0%) 1
Hypertensive Emergency 3/6113 (0%) 3 0/3057 (0%) 0
Hypotension 2/6113 (0%) 2 5/3057 (0.2%) 5
Hypovolaemic Shock 4/6113 (0.1%) 4 4/3057 (0.1%) 4
Infarction 0/6113 (0%) 0 1/3057 (0%) 1
Intra-Abdominal Haematoma 0/6113 (0%) 0 1/3057 (0%) 1
Lymphoedema 1/6113 (0%) 1 1/3057 (0%) 1
Orthostatic Hypotension 2/6113 (0%) 2 0/3057 (0%) 0
Peripheral Arterial Occlusive Disease 7/6113 (0.1%) 8 4/3057 (0.1%) 4
Peripheral Artery Aneurysm 0/6113 (0%) 0 1/3057 (0%) 2
Peripheral Artery Stenosis 4/6113 (0.1%) 5 0/3057 (0%) 0
Peripheral Artery Thrombosis 1/6113 (0%) 1 0/3057 (0%) 0
Peripheral Embolism 0/6113 (0%) 0 1/3057 (0%) 1
Peripheral Ischaemia 11/6113 (0.2%) 15 1/3057 (0%) 1
Peripheral Vascular Disorder 12/6113 (0.2%) 13 1/3057 (0%) 1
Phlebitis 1/6113 (0%) 1 1/3057 (0%) 1
Phlebitis Deep 0/6113 (0%) 0 1/3057 (0%) 1
Post Thrombotic Syndrome 1/6113 (0%) 2 0/3057 (0%) 0
Shock 1/6113 (0%) 1 1/3057 (0%) 1
Shock Haemorrhagic 5/6113 (0.1%) 5 1/3057 (0%) 1
Subclavian Artery Stenosis 0/6113 (0%) 0 1/3057 (0%) 1
Temporal Arteritis 1/6113 (0%) 1 0/3057 (0%) 0
Thromboangiitis Obliterans 1/6113 (0%) 2 0/3057 (0%) 0
Thrombophlebitis Superficial 1/6113 (0%) 2 0/3057 (0%) 0
Varicophlebitis 1/6113 (0%) 1 0/3057 (0%) 0
Varicose Ulceration 1/6113 (0%) 1 2/3057 (0.1%) 2
Vascular Insufficiency 1/6113 (0%) 1 0/3057 (0%) 0
Venous Thrombosis 2/6113 (0%) 2 0/3057 (0%) 0
Venous Thrombosis Limb 1/6113 (0%) 1 1/3057 (0%) 1
Other (Not Including Serious) Adverse Events
C. Difficile Vaccine Group Placebo Group
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 1347/6113 (22%) 401/3057 (13.1%)
General disorders
Injection Site Pain 855/6113 (14%) 1252 127/3057 (4.2%) 157
Malaise 325/6113 (5.3%) 456 135/3057 (4.4%) 195
Musculoskeletal and connective tissue disorders
Arthralgia 345/6113 (5.6%) 481 146/3057 (4.8%) 205
Myalgia 368/6113 (6%) 556 132/3057 (4.3%) 201
Nervous system disorders
Headache 531/6113 (8.7%) 758 229/3057 (7.5%) 327

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Sponsor must have the opportunity to review at least 60 days prior to submission for publication or presentation. If review indicates that potentially patentable subject matter would be disclosed, publication or public disclosure may be delayed for a maximum of an additional 60 days to allow for filing the necessary patent applications.

Results Point of Contact

Name/Title Medical Director
Organization Sanofi Pasteur
Phone 800-633-1610 ext 1#
Email Contact-US@sanofi.com
Responsible Party:
Sanofi Pasteur, a Sanofi Company
ClinicalTrials.gov Identifier:
NCT01887912
Other Study ID Numbers:
  • H-030-014
  • 2013-000775-32
  • U1111-1127-7162
First Posted:
Jun 27, 2013
Last Update Posted:
Mar 28, 2022
Last Verified:
Mar 1, 2022