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A Study of Fluzone® High-Dose Vaccine Compared With Fluzone® Vaccine In Elderly Adults

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ClinicalTrials.gov Identifier: NCT01427309
Recruitment Status : Completed
First Posted : September 1, 2011
Results First Posted : August 6, 2014
Last Update Posted : April 20, 2015
Sponsor:
Information provided by (Responsible Party):
Sanofi ( Sanofi Pasteur, a Sanofi Company )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Prevention
Condition Influenza
Interventions Biological: High Dose Trivalent Inactivated Influenza Vaccine
Biological: Trivalent Inactivated Influenza Vaccine
Enrollment 31989
Recruitment Details The study participants were enrolled from 06 September through 09 October 2011 for Year 1; and 09 through 21 October 2012 for Year 2 at 126 sites in the United States and Canada.
Pre-assignment Details A total of 31,989 participants were enrolled 31,983 were randomized and vaccinated in this study.
Arm/Group Title Fluzone® High Dose Vaccine (Year 1) Fluzone® Vaccine (Year 1) Fluzone® High Dose Vaccine (Year 2) Fluzone® Vaccine (Year 2)
Hide Arm/Group Description Adults ≥65 years of age received one dose of Fluzone High Dose vaccine Adults ≥65 years of age received one dose of Fluzone vaccine Adults ≥65 years of age received one dose of Fluzone High Dose vaccine Adults ≥65 years of age received one dose of Fluzone vaccine
Period Title: Overall Study
Started 7253 7244 8737 8749
Completed 6881 6837 8376 8373
Not Completed 372 407 361 376
Reason Not Completed
Lost to Follow-up             130             145             122             135
Protocol Violation             42             69             125             124
Adverse Event             0             0             3             1
Serious adverse event             52             45             50             61
Withdrawal by Subject             148             148             61             55
Arm/Group Title Fluzone® High Dose Vaccine (Year 1) Fluzone® Vaccine (Year 1) Fluzone® High Dose Vaccine (Year 2) Fluzone® Vaccine (Year 2) Total
Hide Arm/Group Description Adults ≥65 years of age received one dose of Fluzone High Dose vaccine Adults ≥65 years of age received one dose of Fluzone vaccine Adults ≥65 years of age received one dose of Fluzone High Dose vaccine Adults ≥65 years of age received one dose of Fluzone vaccine Total of all reporting groups
Overall Number of Baseline Participants 7253 7244 8737 8749 31983
Hide Baseline Analysis Population Description
The Full Analysis Set (FAS) as randomized, groups the participants according to the vaccine they were randomized to receive in the study.
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 7253 participants 7244 participants 8737 participants 8749 participants 31983 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
>=65 years
7253
 100.0%
7244
 100.0%
8737
 100.0%
8749
 100.0%
31983
 100.0%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 7253 participants 7244 participants 8737 participants 8749 participants 31983 participants
73.3  (5.88) 73.2  (5.82) 73.3  (5.74) 73.4  (5.85) 73.3  (5.82)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 7253 participants 7244 participants 8737 participants 8749 participants 31983 participants
Female
4085
  56.3%
4041
  55.8%
5046
  57.8%
4922
  56.3%
18094
  56.6%
Male
3168
  43.7%
3203
  44.2%
3691
  42.2%
3827
  43.7%
13889
  43.4%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
 Number Analyzed 7253 participants 7244 participants 8737 participants 8749 participants 31983 participants
United States 6953 6944 8315 8326 30538
Canada 300 300 422 423 1445
1.Primary Outcome
Title Occurrences of Culture- or Polymerase Chain Reaction (PCR)-Confirmed Influenza Caused by Any Influenza Viral Types/Subtypes, in Association With a Protocol-defined Influenza-like Illness (ILI).
Hide Description

Influenza positive cultures were confirmed using direct immunofluorescence techniques with influenza type-specific antibodies. 3 culture methods were utilized for each NP sample (Classic Flu A and B culture using Madin Darby Canine Kidney cells, Classic Flu A and B culture using Rhesus Monkey Kidney cells, and R Mix Flu A and B culture). The initial molecular test (PCR) was the validated ProFlu+™ assay by Prodesse, Inc., Waukesha, WI, which had been approved by the Food and Drug Administration through a 510K evaluation for specific detection of Influenza A, B or Respiratory Syncytial Virus.

A protocol-defined influenza-like illness was determined by the occurrence of at least 1 of the following respiratory symptoms: sore throat, cough, sputum production, wheezing, or difficulty breathing; concurrently with at least one of the following systemic symptoms: fever (defined as temperature > 99.0°F [> 37.2°C]), chills (shivering), tiredness (fatigue), headache, or myalgia (muscle aches).
Time Frame ≥14 days post-vaccination
Hide Outcome Measure Data
Hide Analysis Population Description
Clinical efficacy was assessed in subjects who met all eligibility criteria, received the vaccine they were randomized to, had successful surveillance contact, did not received additional influenza vaccinations and did not have protocol deviations likely to impact their responses for the primary and secondary endpoints (Per-protocol analysis set).
Arm/Group Title Fluzone® High Dose Vaccine (Year 1) Fluzone® Vaccine (Year 1) Fluzone® High Dose Vaccine (Year 2) Fluzone® Vaccine (Year 2)
Hide Arm/Group Description:
Adults ≥65 years of age received one dose of Fluzone High Dose vaccine
Adults ≥65 years of age received one dose of Fluzone vaccine
Adults ≥65 years of age received one dose of Fluzone High Dose vaccine
Adults ≥65 years of age received one dose of Fluzone vaccine
Overall Number of Participants Analyzed 7209 7207 8683 8704
Measure Type: Number
Unit of Measure: Participants
23 42 204 258
2.Secondary Outcome
Title Occurrences of Culture-confirmed Influenza Caused by Influenza Viral Types/Subtypes That Are Antigenically Similar to Those Contained in the Vaccine Formulations, in Association With a Protocol-defined Influenza-like Illness (ILI)
Hide Description Influenza positive cultures were confirmed by using direct immunofluorescence techniques with influenza type-specific (i.e., for Influenza A and Influenza B) antibodies. For culture confirmation of influenza, 3 different culture methods were utilized for each NP sample (Classic Flu A and B culture using Madin Darby Canine Kidney [MDCK] cells, Classic Flu A and B culture using Rhesus Monkey Kidney [RhMK] cells, and R Mix Flu A and B culture. For antigenic similarity determinations, a standard hemagglutination inhibition test using a panel of ferret antisera (ferret antigenicity testing) was used.
Time Frame ≥14 days post-vaccination
Hide Outcome Measure Data
Hide Analysis Population Description
Clinical efficacy was assessed in subjects who met all eligibility criteria, received the vaccine they were randomized to, had successful surveillance contact, did not received additional influenza vaccinations and did not have protocol deviations likely to impact their responses for the primary and secondary endpoints (Per-protocol analysis set).
Arm/Group Title Fluzone® High Dose Vaccine (Year 1) Fluzone® Vaccine (Year 1) Fluzone® High Dose Vaccine (Year 2) Fluzone® Vaccine (Year 2)
Hide Arm/Group Description:
Adults ≥65 years of age received one dose of Fluzone High Dose vaccine
Adults ≥65 years of age received one dose of Fluzone vaccine
Adults ≥65 years of age received one dose of Fluzone High Dose vaccine
Adults ≥65 years of age received one dose of Fluzone vaccine
Overall Number of Participants Analyzed 7209 7207 8683 8704
Measure Type: Number
Unit of Measure: Participants
2 7 61 85
3.Secondary Outcome
Title Occurrences of Culture-confirmed Influenza Caused by Any Influenza Viral Types/Subtypes, in Association With a Protocol-defined Influenza-like Illness
Hide Description

For culture confirmation of influenza, 3 different culture methods were utilized for each NP sample (Classic Flu A and B culture using Madin Darby Canine Kidney [MDCK] cells, Classic Flu A and B culture using Rhesus Monkey Kidney [RhMK] cells, and R Mix Flu A and B culture).

A protocol-defined influenza-like illness (ILI) was determined by the occurrence of at least one of the following respiratory symptoms: sore throat, cough, sputum production, wheezing, or difficulty breathing; concurrently with at least one of the following systemic symptoms: fever (defined as temperature > 99.0°F [> 37.2°C]), chills (shivering), tiredness (fatigue), headache, or myalgia (muscle aches).
Time Frame ≥14 days post-vaccination
Hide Outcome Measure Data
Hide Analysis Population Description
Occurrences of culture-confirmed influenza caused by any influenza viral types/subtypes, in association with a protocol-defined influenza-like illness was assessed in the Per-Protocol Analysis Set.
Arm/Group Title Fluzone® High Dose Vaccine (Year 1) Fluzone® Vaccine (Year 1) Fluzone® High Dose Vaccine (Year 2) Fluzone® Vaccine (Year 2)
Hide Arm/Group Description:
Adults ≥65 years of age received one dose of Fluzone High Dose vaccine
Adults ≥65 years of age received one dose of Fluzone vaccine
Adults ≥65 years of age received one dose of Fluzone High Dose vaccine
Adults ≥65 years of age received one dose of Fluzone vaccine
Overall Number of Participants Analyzed 7209 7207 8683 8704
Measure Type: Number
Unit of Measure: Participants
20 33 185 234
4.Secondary Outcome
Title Occurrences of Culture-confirmed Influenza Caused by Influenza Viral Types/Subtypes That Are Antigenically Similar to Those Contained in the Vaccine Formulations, in Association With a Modified CDC-defined Influenza-like Illness.
Hide Description

Influenza positive cultures were confirmed by using direct immunofluorescence techniques with influenza type-specific antibodies. For culture confirmation of influenza, 3 different culture methods were utilized for each NP sample (Classic Flu A and B culture using Madin Darby Canine Kidney cells, Classic Flu A and B culture using Rhesus Monkey Kidney cells, and R Mix Flu A and B culture). For antigenic similarity determinations, a standard hemagglutination inhibition test using a panel of ferret antisera (ferret antigenicity testing) was used.

The modified Centers for Disease Control and Prevention-defined influenza-like illness is the occurrence of fever (defined as temperature > 99.0°F [> 37.2°C]) with cough or sore throat.
Time Frame ≥14 days post-vaccination
Hide Outcome Measure Data
Hide Analysis Population Description
Occurrences of culture-confirmed influenza caused by influenza viral types/subtypes that are antigenically similar to those contained in the vaccine formulations, in association with a modified CDC-defined influenza-like illness were assessed in the Per-Protocol Analysis Set.
Arm/Group Title Fluzone® High Dose Vaccine (Year 1) Fluzone® Vaccine (Year 1) Fluzone® High Dose Vaccine (Year 2) Fluzone® Vaccine (Year 2)
Hide Arm/Group Description:
Adults ≥65 years of age received one dose of Fluzone High Dose vaccine
Adults ≥65 years of age received one dose of Fluzone vaccine
Adults ≥65 years of age received one dose of Fluzone High Dose vaccine
Adults ≥65 years of age received one dose of Fluzone vaccine
Overall Number of Participants Analyzed 7209 7207 8683 8704
Measure Type: Number
Unit of Measure: Participants
0 3 22 42
5.Secondary Outcome
Title Occurrences of Culture-confirmed Influenza Caused by Any Influenza Viral Types/Subtypes, in Association With a Modified CDC-defined Influenza-like Illness
Hide Description

Influenza positive cultures were confirmed by using direct immunofluorescence techniques with influenza type-specific antibodies. For culture confirmation of influenza, 3 different culture methods were utilized for each NP sample (Classic Flu A and B culture using Madin Darby Canine Kidney cells, Classic Flu A and B culture using Rhesus Monkey Kidney cells, and R Mix Flu A and B culture). For antigenic similarity determinations, a standard hemagglutination inhibition test using a panel of ferret antisera (ferret antigenicity testing) was used.

The modified Centers for Disease Control and Prevention-defined influenza-like illness is the occurrence of fever (defined as temperature > 99.0°F [> 37.2°C]) with cough or sore throat.
Time Frame ≥14 days post-vaccination
Hide Outcome Measure Data
Hide Analysis Population Description
Occurrences of culture-confirmed influenza caused by any influenza viral types/subtypes, in association with a modified CDC-defined influenza-like illness were assessed in the Per-Protocol Analysis Set.
Arm/Group Title Fluzone® High Dose Vaccine (Year 1) Fluzone® Vaccine (Year 1) Fluzone® High Dose Vaccine (Year 2) Fluzone® Vaccine (Year 2)
Hide Arm/Group Description:
Adults ≥65 years of age received one dose of Fluzone High Dose vaccine
Adults ≥65 years of age received one dose of Fluzone vaccine
Adults ≥65 years of age received one dose of Fluzone High Dose vaccine
Adults ≥65 years of age received one dose of Fluzone vaccine
Overall Number of Participants Analyzed 7209 7207 8683 8704
Measure Type: Number
Unit of Measure: Participants
7 7 77 103
6.Secondary Outcome
Title Occurrences of Culture-confirmed Influenza Caused by Influenza Viral Types/Subtypes That Are Antigenically Similar to Those Contained in the Vaccine Formulations, in Association With a Respiratory Illness
Hide Description

Influenza positive cultures were confirmed by using direct immunofluorescence techniques with influenza type-specific antibodies. For culture confirmation of influenza, 3 different culture methods were utilized for each NP sample (Classic Flu A and B culture using Madin Darby Canine Kidney cells, Classic Flu A and B culture using Rhesus Monkey Kidney cells, and R Mix Flu A and B culture). For antigenic similarity determinations, a standard hemagglutination inhibition test using a panel of ferret antisera (ferret antigenicity testing) was used.

Respiratory illness was defined as the occurrence of a new onset (or exacerbation of a pre-existing condition/symptom) of one or more of the following symptoms (that persist for or reoccur after a period of at least 12 hours): sneezing, stuffy or runny nose (nasal congestion), sore throat, cough, sputum production, wheezing, or difficulty breathing.
Time Frame ≥14 days post-vaccination
Hide Outcome Measure Data
Hide Analysis Population Description
Occurrences of culture-confirmed influenza caused by influenza viral types/subtypes that are antigenically similar to those contained in the vaccine formulations, in association with a respiratory illness were assessed in the Per-Protocol Analysis Set.
Arm/Group Title Fluzone® High Dose Vaccine (Year 1) Fluzone® Vaccine (Year 1) Fluzone® High Dose Vaccine (Year 2) Fluzone® Vaccine (Year 2)
Hide Arm/Group Description:
Adults ≥65 years of age received one dose of Fluzone High Dose vaccine
Adults ≥65 years of age received one dose of Fluzone vaccine
Adults ≥65 years of age received one dose of Fluzone High Dose vaccine
Adults ≥65 years of age received one dose of Fluzone vaccine
Overall Number of Participants Analyzed 7209 7207 8683 8704
Measure Type: Number
Unit of Measure: Participants
7 9 78 109
7.Secondary Outcome
Title Occurrences of Culture-confirmed Influenza Caused by Any Influenza Viral Types/Subtypes, in Association With a Respiratory Illness
Hide Description

Influenza positive cultures were confirmed by using direct immunofluorescence techniques with influenza type-specific (i.e., for Influenza A and Influenza B) antibodies. For culture confirmation of influenza, 3 different culture methods were utilized for each NP sample (Classic Flu A and B culture using Madin Darby Canine Kidney cells, Classic Flu A and B culture using Rhesus Monkey Kidney cells, and R Mix Flu A and B culture).

Respiratory illness is defined as the occurrence of a new onset (or exacerbation of a pre-existing condition/symptom) of one or more of the following symptoms (that persist for or reoccur after a period of at least 12 hours): sneezing, stuffy or runny nose (nasal congestion), sore throat, cough, sputum production, wheezing, or difficulty breathing.
Time Frame ≥14 days post-vaccination
Hide Outcome Measure Data
Hide Analysis Population Description
Occurrences of culture-confirmed influenza caused by any influenza viral types/subtypes, in association with a respiratory illness were assessed in the Per-Protocol Analysis Set.
Arm/Group Title Fluzone® High Dose Vaccine (Year 1) Fluzone® Vaccine (Year 1) Fluzone® High Dose Vaccine (Year 2) Fluzone® Vaccine (Year 2)
Hide Arm/Group Description:
Adults ≥65 years of age received one dose of Fluzone High Dose vaccine
Adults ≥65 years of age received one dose of Fluzone vaccine
Adults ≥65 years of age received one dose of Fluzone High Dose vaccine
Adults ≥65 years of age received one dose of Fluzone vaccine
Overall Number of Participants Analyzed 7209 7207 8683 8704
Measure Type: Number
Unit of Measure: Participants
38 44 238 294
8.Other Pre-specified Outcome
Title Safety Overview After Injection With Either Fluzone High Dose or Fluzone Vaccine Through the End of Surveillance Period
Hide Description All serious adverse events, including deaths and adverse events (AEs) of special interest (Guillain Barre Syndrome, Bell's Palsy, encephalitis/myelitis, optic neuritis, Stevens Johnson Syndrome, and toxic epidermal necrolysis) were collected.
Time Frame Day 0 up to Day 240 post-vaccination
Hide Outcome Measure Data
Hide Analysis Population Description
Safety was assessed in the Full Analysis Set.
Arm/Group Title Fluzone® High Dose Vaccine (Year 1) Fluzone® Vaccine (Year 1) Fluzone® High Dose Vaccine (Year 2) Fluzone® Vaccine (Year 2)
Hide Arm/Group Description:
Adults ≥65 years of age received one dose of Fluzone High Dose vaccine
Adults ≥65 years of age received one dose of Fluzone vaccine
Adults ≥65 years of age received one dose of Fluzone High Dose vaccine
Adults ≥65 years of age received one dose of Fluzone vaccine
Overall Number of Participants Analyzed 7254 7243 8738 8748
Measure Type: Number
Unit of Measure: Participants
Serious adverse events (SAE) 680 704 643 738
Death 48 40 35 44
Adverse events of special interest 2 2 1 4
Guillain Barré Syndrome 0 0 0 1
Bell's palsy 0 2 1 3
Encephalitis/myelitis 1 0 0 0
Optic neuritis 0 0 0 0
Stevens Johnson syndrome 1 0 0 0
Toxic epidermal necrolysis 0 0 0 0
SAE leading to study discontinuation 52 45 47 58
Related SAE 1 0 2 0
Related SAE leading to study discontinuation 0 0 0 0
Time Frame All serious adverse events, including deaths and adverse events (AEs) of special interest were collected from Day 0 (post-vaccination) up to Day 240 post-vaccination.
Adverse Event Reporting Description The total number (N) data for the serious adverse events were presented for each study year according to the study vaccine actually recieved by the participants - the Full (as treated) Analysis Set.
 
Arm/Group Title Fluzone® High Dose Vaccine (Year 1) Fluzone® Vaccine (Year 1) Fluzone® High Dose Vaccine (Year 2) Fluzone® Vaccine (Year 2)
Hide Arm/Group Description Adults ≥65 years of age received one dose of Fluzone High Dose vaccine Adults ≥65 years of age received one dose of Fluzone vaccine Adults ≥65 years of age received one dose of Fluzone High Dose vaccine Adults ≥65 years of age received one dose of Fluzone vaccine
All-Cause Mortality
Fluzone® High Dose Vaccine (Year 1) Fluzone® Vaccine (Year 1) Fluzone® High Dose Vaccine (Year 2) Fluzone® Vaccine (Year 2)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/-- 
Hide Serious Adverse Events
Fluzone® High Dose Vaccine (Year 1) Fluzone® Vaccine (Year 1) Fluzone® High Dose Vaccine (Year 2) Fluzone® Vaccine (Year 2)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   680/7254 (9.37%)   704/7243 (9.72%)   643/8738 (7.36%)   738/8748 (8.44%) 
Blood and lymphatic system disorders         
Anaemia * 1  8/7254 (0.11%)  4/7243 (0.06%)  9/8738 (0.10%)  7/8748 (0.08%) 
Anaemia macrocytic * 1  0/7254 (0.00%)  0/7243 (0.00%)  1/8738 (0.01%)  0/8748 (0.00%) 
Anaemia of chronic disease * 1  1/7254 (0.01%)  0/7243 (0.00%)  0/8738 (0.00%)  0/8748 (0.00%) 
Bone marrow failure * 1  0/7254 (0.00%)  1/7243 (0.01%)  0/8738 (0.00%)  0/8748 (0.00%) 
Coagulopathy * 1  0/7254 (0.00%)  0/7243 (0.00%)  1/8738 (0.01%)  0/8748 (0.00%) 
Haemorrhagic anaemia * 1  0/7254 (0.00%)  3/7243 (0.04%)  0/8738 (0.00%)  0/8748 (0.00%) 
Idiopathic thrombocytopenic purpura * 1  1/7254 (0.01%)  0/7243 (0.00%)  0/8738 (0.00%)  0/8748 (0.00%) 
Iron deficiency anaemia * 1  1/7254 (0.01%)  2/7243 (0.03%)  2/8738 (0.02%)  0/8748 (0.00%) 
Leukocytosis * 1  0/7254 (0.00%)  1/7243 (0.01%)  0/8738 (0.00%)  1/8748 (0.01%) 
Microcytic anaemia * 1  1/7254 (0.01%)  0/7243 (0.00%)  0/8738 (0.00%)  0/8748 (0.00%) 
Splenic lesion * 1  0/7254 (0.00%)  1/7243 (0.01%)  0/8738 (0.00%)  0/8748 (0.00%) 
Thrombocytopenia * 1  0/7254 (0.00%)  2/7243 (0.03%)  1/8738 (0.01%)  1/8748 (0.01%) 
Cardiac disorders         
Acute coronary syndrome * 1  4/7254 (0.06%)  1/7243 (0.01%)  3/8738 (0.03%)  2/8748 (0.02%) 
Acute myocardial infarction * 1  2/7254 (0.03%)  7/7243 (0.10%)  11/8738 (0.13%)  9/8748 (0.10%) 
Angina pectoris * 1  2/7254 (0.03%)  8/7243 (0.11%)  5/8738 (0.06%)  5/8748 (0.06%) 
Angina unstable * 1  2/7254 (0.03%)  9/7243 (0.12%)  8/8738 (0.09%)  5/8748 (0.06%) 
Aortic valve disease mixed * 1  0/7254 (0.00%)  0/7243 (0.00%)  1/8738 (0.01%)  0/8748 (0.00%) 
Aortic valve stenosis * 1  1/7254 (0.01%)  0/7243 (0.00%)  1/8738 (0.01%)  2/8748 (0.02%) 
Arrhythmia * 1  4/7254 (0.06%)  2/7243 (0.03%)  2/8738 (0.02%)  0/8748 (0.00%) 
Arteriosclerosis coronary artery * 1  2/7254 (0.03%)  1/7243 (0.01%)  0/8738 (0.00%)  0/8748 (0.00%) 
Arteriospasm coronary * 1  0/7254 (0.00%)  0/7243 (0.00%)  1/8738 (0.01%)  0/8748 (0.00%) 
Atrial fibrillation * 1  28/7254 (0.39%)  29/7243 (0.40%)  23/8738 (0.26%)  38/8748 (0.43%) 
Atrial flutter * 1  3/7254 (0.04%)  2/7243 (0.03%)  4/8738 (0.05%)  1/8748 (0.01%) 
Atrial tachycardia * 1  0/7254 (0.00%)  1/7243 (0.01%)  0/8738 (0.00%)  0/8748 (0.00%) 
Atrial thrombosis * 1  1/7254 (0.01%)  2/7243 (0.03%)  0/8738 (0.00%)  0/8748 (0.00%) 
Atrioventricular block * 1  0/7254 (0.00%)  1/7243 (0.01%)  1/8738 (0.01%)  0/8748 (0.00%) 
Atrioventricular block complete * 1  1/7254 (0.01%)  1/7243 (0.01%)  0/8738 (0.00%)  2/8748 (0.02%) 
Atrioventricular block second degree * 1  0/7254 (0.00%)  1/7243 (0.01%)  1/8738 (0.01%)  2/8748 (0.02%) 
Bradyarrhythmia * 1  0/7254 (0.00%)  0/7243 (0.00%)  1/8738 (0.01%)  0/8748 (0.00%) 
Bradycardia * 1  5/7254 (0.07%)  4/7243 (0.06%)  2/8738 (0.02%)  2/8748 (0.02%) 
Bundle branch block left * 1  0/7254 (0.00%)  0/7243 (0.00%)  1/8738 (0.01%)  0/8748 (0.00%) 
Cardiac arrest * 1  6/7254 (0.08%)  1/7243 (0.01%)  0/8738 (0.00%)  5/8748 (0.06%) 
Cardiac disorder * 1  1/7254 (0.01%)  0/7243 (0.00%)  1/8738 (0.01%)  0/8748 (0.00%) 
Cardiac failure * 1  2/7254 (0.03%)  0/7243 (0.00%)  2/8738 (0.02%)  4/8748 (0.05%) 
Cardiac failure acute * 1  1/7254 (0.01%)  0/7243 (0.00%)  2/8738 (0.02%)  0/8748 (0.00%) 
Cardiac failure chronic * 1  0/7254 (0.00%)  1/7243 (0.01%)  0/8738 (0.00%)  0/8748 (0.00%) 
Cardiac failure congestive * 1  15/7254 (0.21%)  22/7243 (0.30%)  19/8738 (0.22%)  29/8748 (0.33%) 
Cardiac valve disease * 1  0/7254 (0.00%)  0/7243 (0.00%)  2/8738 (0.02%)  0/8748 (0.00%) 
Cardio-respiratory arrest * 1  3/7254 (0.04%)  1/7243 (0.01%)  1/8738 (0.01%)  0/8748 (0.00%) 
Cardiomegaly * 1  1/7254 (0.01%)  0/7243 (0.00%)  0/8738 (0.00%)  0/8748 (0.00%) 
Cardiomyopathy * 1  1/7254 (0.01%)  0/7243 (0.00%)  2/8738 (0.02%)  3/8748 (0.03%) 
Cardiopulmonary failure * 1  0/7254 (0.00%)  0/7243 (0.00%)  0/8738 (0.00%)  1/8748 (0.01%) 
Cardiovascular disorder * 1  0/7254 (0.00%)  0/7243 (0.00%)  0/8738 (0.00%)  1/8748 (0.01%) 
Congestive cardiomyopathy * 1  0/7254 (0.00%)  1/7243 (0.01%)  0/8738 (0.00%)  0/8748 (0.00%) 
Coronary artery disease * 1  14/7254 (0.19%)  18/7243 (0.25%)  16/8738 (0.18%)  18/8748 (0.21%) 
Coronary artery insufficiency * 1  0/7254 (0.00%)  0/7243 (0.00%)  1/8738 (0.01%)  0/8748 (0.00%) 
Coronary artery occlusion * 1  4/7254 (0.06%)  2/7243 (0.03%)  3/8738 (0.03%)  1/8748 (0.01%) 
Coronary artery stenosis * 1  1/7254 (0.01%)  0/7243 (0.00%)  2/8738 (0.02%)  2/8748 (0.02%) 
Heart valve incompetence * 1  1/7254 (0.01%)  0/7243 (0.00%)  0/8738 (0.00%)  0/8748 (0.00%) 
Ischaemic cardiomyopathy * 1  1/7254 (0.01%)  0/7243 (0.00%)  1/8738 (0.01%)  2/8748 (0.02%) 
Mitral valve disease * 1  0/7254 (0.00%)  0/7243 (0.00%)  0/8738 (0.00%)  1/8748 (0.01%) 
Mitral valve incompetence * 1  1/7254 (0.01%)  1/7243 (0.01%)  1/8738 (0.01%)  0/8748 (0.00%) 
Mitral valve stenosis * 1  2/7254 (0.03%)  0/7243 (0.00%)  0/8738 (0.00%)  0/8748 (0.00%) 
Myocardial infarction * 1  21/7254 (0.29%)  21/7243 (0.29%)  14/8738 (0.16%)  10/8748 (0.11%) 
Myocardial ischaemia * 1  0/7254 (0.00%)  1/7243 (0.01%)  0/8738 (0.00%)  0/8748 (0.00%) 
Palpitations * 1  0/7254 (0.00%)  0/7243 (0.00%)  0/8738 (0.00%)  1/8748 (0.01%) 
Pericardial effusion * 1  0/7254 (0.00%)  1/7243 (0.01%)  0/8738 (0.00%)  2/8748 (0.02%) 
Pericarditis * 1  1/7254 (0.01%)  0/7243 (0.00%)  1/8738 (0.01%)  0/8748 (0.00%) 
Sick sinus syndrome * 1  1/7254 (0.01%)  0/7243 (0.00%)  3/8738 (0.03%)  4/8748 (0.05%) 
Sinus arrhythmia * 1  1/7254 (0.01%)  0/7243 (0.00%)  0/8738 (0.00%)  1/8748 (0.01%) 
Sinus bradycardia * 1  0/7254 (0.00%)  2/7243 (0.03%)  0/8738 (0.00%)  0/8748 (0.00%) 
Stress cardiomyopathy * 1  0/7254 (0.00%)  1/7243 (0.01%)  1/8738 (0.01%)  0/8748 (0.00%) 
Supraventricular tachycardia * 1  3/7254 (0.04%)  3/7243 (0.04%)  1/8738 (0.01%)  3/8748 (0.03%) 
Tachycardia * 1  2/7254 (0.03%)  1/7243 (0.01%)  2/8738 (0.02%)  0/8748 (0.00%) 
Ventricular extrasystoles * 1  0/7254 (0.00%)  1/7243 (0.01%)  0/8738 (0.00%)  1/8748 (0.01%) 
Ventricular fibrillation * 1  0/7254 (0.00%)  0/7243 (0.00%)  1/8738 (0.01%)  0/8748 (0.00%) 
Ventricular tachycardia * 1  1/7254 (0.01%)  2/7243 (0.03%)  1/8738 (0.01%)  2/8748 (0.02%) 
Congenital, familial and genetic disorders         
Arteriovenous malformation * 1  0/7254 (0.00%)  0/7243 (0.00%)  1/8738 (0.01%)  0/8748 (0.00%) 
Gastrointestinal arteriovenous malformation * 1  0/7254 (0.00%)  0/7243 (0.00%)  0/8738 (0.00%)  1/8748 (0.01%) 
Ear and labyrinth disorders         
Vertigo * 1  2/7254 (0.03%)  5/7243 (0.07%)  2/8738 (0.02%)  7/8748 (0.08%) 
Endocrine disorders         
Adrenocortical insufficiency acute * 1  0/7254 (0.00%)  0/7243 (0.00%)  0/8738 (0.00%)  1/8748 (0.01%) 
Goitre * 1  1/7254 (0.01%)  0/7243 (0.00%)  0/8738 (0.00%)  2/8748 (0.02%) 
Hyperparathyroidism * 1  0/7254 (0.00%)  1/7243 (0.01%)  0/8738 (0.00%)  0/8748 (0.00%) 
Hyperthyroidism * 1  0/7254 (0.00%)  1/7243 (0.01%)  1/8738 (0.01%)  0/8748 (0.00%) 
Thyroid mass * 1  1/7254 (0.01%)  0/7243 (0.00%)  0/8738 (0.00%)  0/8748 (0.00%) 
Eye disorders         
Cataract * 1  1/7254 (0.01%)  0/7243 (0.00%)  0/8738 (0.00%)  0/8748 (0.00%) 
Periorbital oedema * 1  0/7254 (0.00%)  0/7243 (0.00%)  1/8738 (0.01%)  0/8748 (0.00%) 
Retinal artery occlusion * 1  1/7254 (0.01%)  0/7243 (0.00%)  0/8738 (0.00%)  0/8748 (0.00%) 
Retinal detachment * 1  0/7254 (0.00%)  0/7243 (0.00%)  0/8738 (0.00%)  1/8748 (0.01%) 
Gastrointestinal disorders         
Abdominal hernia * 1  1/7254 (0.01%)  0/7243 (0.00%)  0/8738 (0.00%)  3/8748 (0.03%) 
Abdominal mass * 1  1/7254 (0.01%)  0/7243 (0.00%)  0/8738 (0.00%)  0/8748 (0.00%) 
Abdominal pain * 1  1/7254 (0.01%)  3/7243 (0.04%)  5/8738 (0.06%)  4/8748 (0.05%) 
Abdominal pain lower * 1  1/7254 (0.01%)  0/7243 (0.00%)  0/8738 (0.00%)  0/8748 (0.00%) 
Abdominal pain upper * 1  0/7254 (0.00%)  1/7243 (0.01%)  0/8738 (0.00%)  1/8748 (0.01%) 
Abdominal wall haematoma * 1  0/7254 (0.00%)  0/7243 (0.00%)  0/8738 (0.00%)  1/8748 (0.01%) 
Abdominal wall haemorrhage * 1  0/7254 (0.00%)  1/7243 (0.01%)  0/8738 (0.00%)  0/8748 (0.00%) 
Alcoholic pancreatitis * 1  1/7254 (0.01%)  1/7243 (0.01%)  0/8738 (0.00%)  0/8748 (0.00%) 
Anal fistula * 1  0/7254 (0.00%)  1/7243 (0.01%)  0/8738 (0.00%)  0/8748 (0.00%) 
Colitis * 1  2/7254 (0.03%)  6/7243 (0.08%)  1/8738 (0.01%)  1/8748 (0.01%) 
Colitis ischaemic * 1  2/7254 (0.03%)  2/7243 (0.03%)  3/8738 (0.03%)  4/8748 (0.05%) 
Colonic polyp * 1  0/7254 (0.00%)  1/7243 (0.01%)  0/8738 (0.00%)  2/8748 (0.02%) 
Colonic stenosis * 1  1/7254 (0.01%)  0/7243 (0.00%)  0/8738 (0.00%)  0/8748 (0.00%) 
Constipation * 1  0/7254 (0.00%)  0/7243 (0.00%)  3/8738 (0.03%)  0/8748 (0.00%) 
Crohn's disease * 1  0/7254 (0.00%)  0/7243 (0.00%)  0/8738 (0.00%)  1/8748 (0.01%) 
Diaphragmatic hernia * 1  0/7254 (0.00%)  0/7243 (0.00%)  0/8738 (0.00%)  1/8748 (0.01%) 
Diarrhoea * 1  0/7254 (0.00%)  0/7243 (0.00%)  0/8738 (0.00%)  2/8748 (0.02%) 
Dieulafoy's vascular malformation * 1  0/7254 (0.00%)  0/7243 (0.00%)  0/8738 (0.00%)  1/8748 (0.01%) 
Diverticular perforation * 1  2/7254 (0.03%)  1/7243 (0.01%)  0/8738 (0.00%)  1/8748 (0.01%) 
Diverticulum * 1  0/7254 (0.00%)  5/7243 (0.07%)  0/8738 (0.00%)  1/8748 (0.01%) 
Diverticulum intestinal * 1  0/7254 (0.00%)  1/7243 (0.01%)  0/8738 (0.00%)  0/8748 (0.00%) 
Diverticulum intestinal haemorrhagic * 1  1/7254 (0.01%)  1/7243 (0.01%)  0/8738 (0.00%)  0/8748 (0.00%) 
Duodenal stenosis * 1  1/7254 (0.01%)  0/7243 (0.00%)  0/8738 (0.00%)  0/8748 (0.00%) 
Duodenal ulcer * 1  1/7254 (0.01%)  1/7243 (0.01%)  0/8738 (0.00%)  2/8748 (0.02%) 
Duodenal ulcer haemorrhage * 1  1/7254 (0.01%)  0/7243 (0.00%)  0/8738 (0.00%)  0/8748 (0.00%) 
Dysphagia * 1  1/7254 (0.01%)  0/7243 (0.00%)  0/8738 (0.00%)  0/8748 (0.00%) 
Erosive oesophagitis * 1  1/7254 (0.01%)  0/7243 (0.00%)  0/8738 (0.00%)  0/8748 (0.00%) 
Faecaloma * 1  1/7254 (0.01%)  0/7243 (0.00%)  0/8738 (0.00%)  0/8748 (0.00%) 
Food poisoning * 1  0/7254 (0.00%)  1/7243 (0.01%)  2/8738 (0.02%)  0/8748 (0.00%) 
Gastric antral vascular ectasia * 1  0/7254 (0.00%)  0/7243 (0.00%)  0/8738 (0.00%)  1/8748 (0.01%) 
Gastric ulcer * 1  0/7254 (0.00%)  0/7243 (0.00%)  0/8738 (0.00%)  1/8748 (0.01%) 
Gastric ulcer haemorrhage * 1  0/7254 (0.00%)  0/7243 (0.00%)  0/8738 (0.00%)  3/8748 (0.03%) 
Gastritis * 1  1/7254 (0.01%)  4/7243 (0.06%)  0/8738 (0.00%)  0/8748 (0.00%) 
Gastritis erosive * 1  0/7254 (0.00%)  0/7243 (0.00%)  0/8738 (0.00%)  1/8748 (0.01%) 
Gastroduodenitis * 1  1/7254 (0.01%)  0/7243 (0.00%)  0/8738 (0.00%)  0/8748 (0.00%) 
Gastrointestinal disorder * 1  0/7254 (0.00%)  0/7243 (0.00%)  1/8738 (0.01%)  1/8748 (0.01%) 
Gastrointestinal haemorrhage * 1  6/7254 (0.08%)  7/7243 (0.10%)  5/8738 (0.06%)  9/8748 (0.10%) 
Gastrooesophageal reflux disease * 1  1/7254 (0.01%)  2/7243 (0.03%)  1/8738 (0.01%)  1/8748 (0.01%) 
Gastrooesophagitis * 1  0/7254 (0.00%)  0/7243 (0.00%)  0/8738 (0.00%)  1/8748 (0.01%) 
Haematemesis * 1  0/7254 (0.00%)  2/7243 (0.03%)  0/8738 (0.00%)  0/8748 (0.00%) 
Haematochezia * 1  1/7254 (0.01%)  0/7243 (0.00%)  0/8738 (0.00%)  1/8748 (0.01%) 
Haemorrhagic erosive gastritis * 1  1/7254 (0.01%)  0/7243 (0.00%)  0/8738 (0.00%)  0/8748 (0.00%) 
Hiatus hernia * 1  2/7254 (0.03%)  2/7243 (0.03%)  1/8738 (0.01%)  1/8748 (0.01%) 
Ileus * 1  1/7254 (0.01%)  0/7243 (0.00%)  1/8738 (0.01%)  0/8748 (0.00%) 
Impaired gastric emptying * 1  0/7254 (0.00%)  1/7243 (0.01%)  0/8738 (0.00%)  0/8748 (0.00%) 
Inguinal hernia * 1  1/7254 (0.01%)  1/7243 (0.01%)  0/8738 (0.00%)  4/8748 (0.05%) 
Intestinal ischaemia * 1  0/7254 (0.00%)  0/7243 (0.00%)  2/8738 (0.02%)  0/8748 (0.00%) 
Intestinal obstruction * 1  0/7254 (0.00%)  1/7243 (0.01%)  3/8738 (0.03%)  3/8748 (0.03%) 
Intestinal perforation * 1  0/7254 (0.00%)  1/7243 (0.01%)  1/8738 (0.01%)  2/8748 (0.02%) 
Intestinal polyp haemorrhage * 1  0/7254 (0.00%)  0/7243 (0.00%)  0/8738 (0.00%)  1/8748 (0.01%) 
Large intestine perforation * 1  1/7254 (0.01%)  1/7243 (0.01%)  0/8738 (0.00%)  2/8748 (0.02%) 
Lower gastrointestinal haemorrhage * 1  0/7254 (0.00%)  1/7243 (0.01%)  1/8738 (0.01%)  2/8748 (0.02%) 
Lumbar hernia * 1  1/7254 (0.01%)  1/7243 (0.01%)  0/8738 (0.00%)  0/8748 (0.00%) 
Mallory-Weiss syndrome * 1  0/7254 (0.00%)  1/7243 (0.01%)  0/8738 (0.00%)  1/8748 (0.01%) 
Nausea * 1  1/7254 (0.01%)  0/7243 (0.00%)  1/8738 (0.01%)  0/8748 (0.00%) 
Obstruction gastric * 1  0/7254 (0.00%)  1/7243 (0.01%)  0/8738 (0.00%)  0/8748 (0.00%) 
Oesophageal obstruction * 1  0/7254 (0.00%)  2/7243 (0.03%)  0/8738 (0.00%)  0/8748 (0.00%) 
Oesophageal spasm * 1  0/7254 (0.00%)  1/7243 (0.01%)  0/8738 (0.00%)  1/8748 (0.01%) 
Oesophageal varices haemorrhage * 1  0/7254 (0.00%)  1/7243 (0.01%)  0/8738 (0.00%)  0/8748 (0.00%) 
Pancreatitis * 1  5/7254 (0.07%)  2/7243 (0.03%)  1/8738 (0.01%)  0/8748 (0.00%) 
Pancreatitis acute * 1  3/7254 (0.04%)  2/7243 (0.03%)  0/8738 (0.00%)  5/8748 (0.06%) 
Pancreatitis necrotising * 1  0/7254 (0.00%)  0/7243 (0.00%)  0/8738 (0.00%)  1/8748 (0.01%) 
Pancreatitis relapsing * 1  1/7254 (0.01%)  0/7243 (0.00%)  0/8738 (0.00%)  0/8748 (0.00%) 
Peptic ulcer * 1  0/7254 (0.00%)  0/7243 (0.00%)  1/8738 (0.01%)  0/8748 (0.00%) 
Peptic ulcer haemorrhage * 1  1/7254 (0.01%)  0/7243 (0.00%)  0/8738 (0.00%)  0/8748 (0.00%) 
Pharyngoesophageal diverticulum * 1  0/7254 (0.00%)  0/7243 (0.00%)  1/8738 (0.01%)  0/8748 (0.00%) 
Proctitis * 1  0/7254 (0.00%)  0/7243 (0.00%)  1/8738 (0.01%)  0/8748 (0.00%) 
Rectal haemorrhage * 1  1/7254 (0.01%)  4/7243 (0.06%)  5/8738 (0.06%)  1/8748 (0.01%) 
Retroperitoneal haematoma * 1  2/7254 (0.03%)  0/7243 (0.00%)  0/8738 (0.00%)  0/8748 (0.00%) 
Small intestinal obstruction * 1  5/7254 (0.07%)  10/7243 (0.14%)  4/8738 (0.05%)  3/8748 (0.03%) 
Spigelian hernia * 1  0/7254 (0.00%)  0/7243 (0.00%)  1/8738 (0.01%)  0/8748 (0.00%) 
Tongue oedema * 1  0/7254 (0.00%)  0/7243 (0.00%)  0/8738 (0.00%)  1/8748 (0.01%) 
Umbilical hernia, obstructive * 1  0/7254 (0.00%)  2/7243 (0.03%)  0/8738 (0.00%)  1/8748 (0.01%) 
Upper gastrointestinal haemorrhage * 1  4/7254 (0.06%)  3/7243 (0.04%)  1/8738 (0.01%)  2/8748 (0.02%) 
Volvulus * 1  0/7254 (0.00%)  0/7243 (0.00%)  0/8738 (0.00%)  1/8748 (0.01%) 
Vomiting * 1  1/7254 (0.01%)  1/7243 (0.01%)  2/8738 (0.02%)  1/8748 (0.01%) 
General disorders         
Adverse drug reaction * 1  0/7254 (0.00%)  1/7243 (0.01%)  0/8738 (0.00%)  0/8748 (0.00%) 
Asthenia * 1  1/7254 (0.01%)  1/7243 (0.01%)  1/8738 (0.01%)  2/8748 (0.02%) 
Chest discomfort * 1  1/7254 (0.01%)  2/7243 (0.03%)  1/8738 (0.01%)  2/8748 (0.02%) 
Chest pain * 1  42/7254 (0.58%)  27/7243 (0.37%)  18/8738 (0.21%)  16/8748 (0.18%) 
Death * 1  0/7254 (0.00%)  3/7243 (0.04%)  0/8738 (0.00%)  2/8748 (0.02%) 
Device dislocation * 1  0/7254 (0.00%)  0/7243 (0.00%)  0/8738 (0.00%)  2/8748 (0.02%) 
Device failure * 1  0/7254 (0.00%)  0/7243 (0.00%)  0/8738 (0.00%)  1/8748 (0.01%) 
Device lead damage * 1  0/7254 (0.00%)  0/7243 (0.00%)  0/8738 (0.00%)  1/8748 (0.01%) 
Device malfunction * 1  0/7254 (0.00%)  2/7243 (0.03%)  1/8738 (0.01%)  0/8748 (0.00%) 
Device occlusion * 1  0/7254 (0.00%)  1/7243 (0.01%)  0/8738 (0.00%)  0/8748 (0.00%) 
Fatigue * 1  0/7254 (0.00%)  1/7243 (0.01%)  0/8738 (0.00%)  0/8748 (0.00%) 
Genaralized oedema * 1  0/7254 (0.00%)  0/7243 (0.00%)  1/8738 (0.01%)  0/8748 (0.00%) 
Hernia * 1  1/7254 (0.01%)  0/7243 (0.00%)  0/8738 (0.00%)  1/8748 (0.01%) 
Hernia obstructive * 1  0/7254 (0.00%)  0/7243 (0.00%)  0/8738 (0.00%)  1/8748 (0.01%) 
Impaired healing * 1  1/7254 (0.01%)  0/7243 (0.00%)  0/8738 (0.00%)  0/8748 (0.00%) 
Implant site inflammation * 1  0/7254 (0.00%)  0/7243 (0.00%)  0/8738 (0.00%)  1/8748 (0.01%) 
Influenza like illness * 1  0/7254 (0.00%)  1/7243 (0.01%)  1/8738 (0.01%)  0/8748 (0.00%) 
Ischaemic ulcer * 1  0/7254 (0.00%)  1/7243 (0.01%)  0/8738 (0.00%)  0/8748 (0.00%) 
Non-cardiac chest pain * 1  6/7254 (0.08%)  3/7243 (0.04%)  2/8738 (0.02%)  4/8748 (0.05%) 
Oedema peripheral * 1  2/7254 (0.03%)  1/7243 (0.01%)  1/8738 (0.01%)  1/8748 (0.01%) 
Pelvic mass * 1  0/7254 (0.00%)  0/7243 (0.00%)  0/8738 (0.00%)  1/8748 (0.01%) 
Pneumatosis * 1  0/7254 (0.00%)  1/7243 (0.01%)  0/8738 (0.00%)  0/8748 (0.00%) 
Pyrexia * 1  1/7254 (0.01%)  1/7243 (0.01%)  0/8738 (0.00%)  0/8748 (0.00%) 
Sudden cardiac death * 1  0/7254 (0.00%)  0/7243 (0.00%)  1/8738 (0.01%)  0/8748 (0.00%) 
Surgical failure * 1  0/7254 (0.00%)  0/7243 (0.00%)  1/8738 (0.01%)  0/8748 (0.00%) 
Hepatobiliary disorders         
Bile duct obstruction * 1  0/7254 (0.00%)  1/7243 (0.01%)  0/8738 (0.00%)  0/8748 (0.00%) 
Cholangitis * 1  0/7254 (0.00%)  0/7243 (0.00%)  1/8738 (0.01%)  1/8748 (0.01%) 
Cholangitis acute * 1  1/7254 (0.01%)  0/7243 (0.00%)  0/8738 (0.00%)  0/8748 (0.00%) 
Cholecystitis * 1  1/7254 (0.01%)  3/7243 (0.04%)  8/8738 (0.09%)  3/8748 (0.03%) 
Cholecystitis acute * 1  3/7254 (0.04%)  2/7243 (0.03%)  3/8738 (0.03%)  4/8748 (0.05%) 
Cholecystitis chronic * 1  1/7254 (0.01%)  1/7243 (0.01%)  0/8738 (0.00%)  0/8748 (0.00%) 
Cholelithiasis * 1  0/7254 (0.00%)  7/7243 (0.10%)  5/8738 (0.06%)  1/8748 (0.01%) 
Chronic hepatic failure * 1  1/7254 (0.01%)  0/7243 (0.00%)  0/8738 (0.00%)  0/8748 (0.00%) 
Gallbladder pain * 1  0/7254 (0.00%)  0/7243 (0.00%)  0/8738 (0.00%)  2/8748 (0.02%) 
Gallbladder perforation * 1  0/7254 (0.00%)  0/7243 (0.00%)  0/8738 (0.00%)  1/8748 (0.01%) 
Hepatitis * 1  1/7254 (0.01%)  0/7243 (0.00%)  0/8738 (0.00%)  0/8748 (0.00%) 
Hepatorenal syndrome * 1  0/7254 (0.00%)  0/7243 (0.00%)  1/8738 (0.01%)  0/8748 (0.00%) 
Immune system disorders         
Drug hypersensitivity * 1  2/7254 (0.03%)  1/7243 (0.01%)  0/8738 (0.00%)  0/8748 (0.00%) 
Hypersensitivity * 1  2/7254 (0.03%)  1/7243 (0.01%)  0/8738 (0.00%)  0/8748 (0.00%) 
Infections and infestations         
Abdominal abscess * 1  1/7254 (0.01%)  1/7243 (0.01%)  0/8738 (0.00%)  1/8748 (0.01%) 
Abdominal sepsis * 1  0/7254 (0.00%)  0/7243 (0.00%)  1/8738 (0.01%)  0/8748 (0.00%) 
Abdominal wall abscess * 1  0/7254 (0.00%)  0/7243 (0.00%)  0/8738 (0.00%)  1/8748 (0.01%) 
Abscess * 1  0/7254 (0.00%)  0/7243 (0.00%)  0/8738 (0.00%)  1/8748 (0.01%) 
Abscess limb * 1  1/7254 (0.01%)  0/7243 (0.00%)  0/8738 (0.00%)  0/8748 (0.00%) 
Acute sinusitis * 1  0/7254 (0.00%)  0/7243 (0.00%)  0/8738 (0.00%)  1/8748 (0.01%) 
Appendicitis * 1  2/7254 (0.03%)  4/7243 (0.06%)  3/8738 (0.03%)  4/8748 (0.05%) 
Arthritis bacterial * 1  1/7254 (0.01%)  0/7243 (0.00%)  1/8738 (0.01%)  0/8748 (0.00%) 
Arthritis infective * 1  1/7254 (0.01%)  0/7243 (0.00%)  1/8738 (0.01%)  0/8748 (0.00%) 
Atypical myocobacterial pneumonia * 1  0/7254 (0.00%)  0/7243 (0.00%)  0/8738 (0.00%)  1/8748 (0.01%) 
Bronchitis * 1  5/7254 (0.07%)  4/7243 (0.06%)  9/8738 (0.10%)  5/8748 (0.06%) 
Bronchopneumonia * 1  0/7254 (0.00%)  1/7243 (0.01%)  0/8738 (0.00%)  1/8748 (0.01%) 
Bursitis infective * 1  0/7254 (0.00%)  0/7243 (0.00%)  0/8738 (0.00%)  1/8748 (0.01%) 
Cellulitis * 1  12/7254 (0.17%)  9/7243 (0.12%)  8/8738 (0.09%)  12/8748 (0.14%) 
Cholecystitis infective * 1  0/7254 (0.00%)  1/7243 (0.01%)  0/8738 (0.00%)  0/8748 (0.00%) 
Clostridium difficile colitis * 1  1/7254 (0.01%)  3/7243 (0.04%)  1/8738 (0.01%)  0/8748 (0.00%) 
Cystitis * 1  0/7254 (0.00%)  1/7243 (0.01%)  0/8738 (0.00%)  1/8748 (0.01%) 
Device related infection * 1  1/7254 (0.01%)  1/7243 (0.01%)  0/8738 (0.00%)  1/8748 (0.01%) 
Diabetic foot infection * 1  0/7254 (0.00%)  0/7243 (0.00%)  1/8738 (0.01%)  1/8748 (0.01%) 
Diabetic gangrene * 1  1/7254 (0.01%)  0/7243 (0.00%)  0/8738 (0.00%)  0/8748 (0.00%) 
Diverticulitis * 1  8/7254 (0.11%)  5/7243 (0.07%)  5/8738 (0.06%)  11/8748 (0.13%) 
Endocarditis bacterial * 1  1/7254 (0.01%)  0/7243 (0.00%)  0/8738 (0.00%)  0/8748 (0.00%) 
Enterocolitis infectious * 1  0/7254 (0.00%)  1/7243 (0.01%)  0/8738 (0.00%)  1/8748 (0.01%) 
Enterocolitis viral * 1  1/7254 (0.01%)  0/7243 (0.00%)  0/8738 (0.00%)  0/8748 (0.00%) 
Escherichia bacteraemia * 1  0/7254 (0.00%)  1/7243 (0.01%)  1/8738 (0.01%)  1/8748 (0.01%) 
Escherichia urinary tract infection * 1  0/7254 (0.00%)  0/7243 (0.00%)  1/8738 (0.01%)  1/8748 (0.01%) 
Gangrene * 1  0/7254 (0.00%)  0/7243 (0.00%)  1/8738 (0.01%)  0/8748 (0.00%) 
Gastric ulcer helicobacter * 1  0/7254 (0.00%)  0/7243 (0.00%)  1/8738 (0.01%)  0/8748 (0.00%) 
Gastroenteritis * 1  5/7254 (0.07%)  6/7243 (0.08%)  5/8738 (0.06%)  9/8748 (0.10%) 
Gastroenteritis bacterial * 1  0/7254 (0.00%)  0/7243 (0.00%)  0/8738 (0.00%)  1/8748 (0.01%) 
Gastroenteritis salmonella * 1  2/7254 (0.03%)  0/7243 (0.00%)  0/8738 (0.00%)  0/8748 (0.00%) 
Gastroenteritis viral * 1  2/7254 (0.03%)  1/7243 (0.01%)  2/8738 (0.02%)  1/8748 (0.01%) 
Gastrointestinal infection * 1  0/7254 (0.00%)  1/7243 (0.01%)  0/8738 (0.00%)  0/8748 (0.00%) 
Groin infection * 1  1/7254 (0.01%)  0/7243 (0.00%)  0/8738 (0.00%)  0/8748 (0.00%) 
Herpes zoster * 1  0/7254 (0.00%)  1/7243 (0.01%)  1/8738 (0.01%)  0/8748 (0.00%) 
Infected cyst * 1  0/7254 (0.00%)  0/7243 (0.00%)  1/8738 (0.01%)  0/8748 (0.00%) 
Infective exacerbation of bronchiectasis * 1  0/7254 (0.00%)  0/7243 (0.00%)  0/8738 (0.00%)  1/8748 (0.01%) 
Influenza * 1  1/7254 (0.01%)  0/7243 (0.00%)  3/8738 (0.03%)  6/8748 (0.07%) 
Kidney infection * 1  0/7254 (0.00%)  1/7243 (0.01%)  1/8738 (0.01%)  2/8748 (0.02%) 
Laryngitis * 1  0/7254 (0.00%)  0/7243 (0.00%)  1/8738 (0.01%)  0/8748 (0.00%) 
Liver abscess * 1  0/7254 (0.00%)  0/7243 (0.00%)  1/8738 (0.01%)  1/8748 (0.01%) 
Lobar pneumonia * 1  0/7254 (0.00%)  1/7243 (0.01%)  2/8738 (0.02%)  6/8748 (0.07%) 
Localised infection * 1  2/7254 (0.03%)  2/7243 (0.03%)  1/8738 (0.01%)  0/8748 (0.00%) 
Lung infection * 1  0/7254 (0.00%)  0/7243 (0.00%)  1/8738 (0.01%)  0/8748 (0.00%) 
Nocardiosis * 1  0/7254 (0.00%)  0/7243 (0.00%)  1/8738 (0.01%)  0/8748 (0.00%) 
Osteomyelitis * 1  0/7254 (0.00%)  1/7243 (0.01%)  0/8738 (0.00%)  1/8748 (0.01%) 
Peridiverticular abscess * 1  0/7254 (0.00%)  0/7243 (0.00%)  0/8738 (0.00%)  1/8748 (0.01%) 
Perineal abscess * 1  0/7254 (0.00%)  0/7243 (0.00%)  1/8738 (0.01%)  0/8748 (0.00%) 
Periorbital cellulitis * 1  0/7254 (0.00%)  1/7243 (0.01%)  0/8738 (0.00%)  0/8748 (0.00%) 
Perirectal abscess * 1  0/7254 (0.00%)  0/7243 (0.00%)  1/8738 (0.01%)  0/8748 (0.00%) 
Peritonitis * 1  0/7254 (0.00%)  0/7243 (0.00%)  0/8738 (0.00%)  1/8748 (0.01%) 
Pneumonia * 1  28/7254 (0.39%)  44/7243 (0.61%)  35/8738 (0.40%)  44/8748 (0.50%) 
Pneumonia bacterial * 1  0/7254 (0.00%)  0/7243 (0.00%)  1/8738 (0.01%)  2/8748 (0.02%) 
Pneumonia pneumococcal * 1  0/7254 (0.00%)  0/7243 (0.00%)  0/8738 (0.00%)  2/8748 (0.02%) 
Pneumonia primary atypical * 1  0/7254 (0.00%)  1/7243 (0.01%)  0/8738 (0.00%)  0/8748 (0.00%) 
Pneumonia staphylococcal * 1  0/7254 (0.00%)  1/7243 (0.01%)  0/8738 (0.00%)  2/8748 (0.02%) 
Pneumonia viral * 1  0/7254 (0.00%)  1/7243 (0.01%)  0/8738 (0.00%)  1/8748 (0.01%) 
Postoperative wound infection * 1  2/7254 (0.03%)  1/7243 (0.01%)  0/8738 (0.00%)  0/8748 (0.00%) 
Pseudomonas infection * 1  0/7254 (0.00%)  0/7243 (0.00%)  0/8738 (0.00%)  1/8748 (0.01%) 
Pyelonephritis * 1  1/7254 (0.01%)  3/7243 (0.04%)  0/8738 (0.00%)  3/8748 (0.03%) 
Pyelonephritis acute * 1  0/7254 (0.00%)  1/7243 (0.01%)  1/8738 (0.01%)  0/8748 (0.00%) 
Respiratory syncytial virus infection * 1  0/7254 (0.00%)  0/7243 (0.00%)  1/8738 (0.01%)  0/8748 (0.00%) 
Sepsis * 1  4/7254 (0.06%)  3/7243 (0.04%)  5/8738 (0.06%)  5/8748 (0.06%) 
Septic shock * 1  0/7254 (0.00%)  1/7243 (0.01%)  0/8738 (0.00%)  1/8748 (0.01%) 
Sinusitis * 1  1/7254 (0.01%)  1/7243 (0.01%)  0/8738 (0.00%)  1/8748 (0.01%) 
Staphylococcal infection * 1  1/7254 (0.01%)  0/7243 (0.00%)  1/8738 (0.01%)  3/8748 (0.03%) 
Tracheobronchitis * 1  2/7254 (0.03%)  0/7243 (0.00%)  1/8738 (0.01%)  0/8748 (0.00%) 
Upper respiratory tract infection * 1  0/7254 (0.00%)  0/7243 (0.00%)  1/8738 (0.01%)  0/8748 (0.00%) 
Urethritis * 1  0/7254 (0.00%)  1/7243 (0.01%)  0/8738 (0.00%)  0/8748 (0.00%) 
Urinary tract infection * 1  9/7254 (0.12%)  8/7243 (0.11%)  5/8738 (0.06%)  16/8748 (0.18%) 
Urosepsis * 1  5/7254 (0.07%)  3/7243 (0.04%)  0/8738 (0.00%)  4/8748 (0.05%) 
Vestibular neuronitis * 1  0/7254 (0.00%)  1/7243 (0.01%)  0/8738 (0.00%)  0/8748 (0.00%) 
Viral diarrhoea * 1  1/7254 (0.01%)  0/7243 (0.00%)  0/8738 (0.00%)  0/8748 (0.00%) 
Viral infection * 1  0/7254 (0.00%)  0/7243 (0.00%)  0/8738 (0.00%)  4/8748 (0.05%) 
Viral labyrinthitis * 1  0/7254 (0.00%)  0/7243 (0.00%)  2/8738 (0.02%)  0/8748 (0.00%) 
Viral pericarditis * 1  1/7254 (0.01%)  0/7243 (0.00%)  0/8738 (0.00%)  0/8748 (0.00%) 
Clostridial infection * 1  0/7254 (0.00%)  1/7243 (0.01%)  0/8738 (0.00%)  0/8748 (0.00%) 
Bacteraemia * 1  0/7254 (0.00%)  0/7243 (0.00%)  1/8738 (0.01%)  1/8748 (0.01%) 
Bacterial infection * 1  0/7254 (0.00%)  0/7243 (0.00%)  1/8738 (0.01%)  0/8748 (0.00%) 
Urinary tract infection bacterial * 1  0/7254 (0.00%)  0/7243 (0.00%)  1/8738 (0.01%)  0/8748 (0.00%) 
Appendicitis perforated * 1  0/7254 (0.00%)  0/7243 (0.00%)  0/8738 (0.00%)  1/8748 (0.01%) 
Injury, poisoning and procedural complications         
Accident * 1  0/7254 (0.00%)  1/7243 (0.01%)  0/8738 (0.00%)  0/8748 (0.00%) 
Accidental overdose * 1  0/7254 (0.00%)  0/7243 (0.00%)  0/8738 (0.00%)  1/8748 (0.01%) 
Alcohol poisoning * 1  0/7254 (0.00%)  0/7243 (0.00%)  0/8738 (0.00%)  1/8748 (0.01%) 
Ankle fracture * 1  1/7254 (0.01%)  5/7243 (0.07%)  5/8738 (0.06%)  3/8748 (0.03%) 
Arteriovenous fistula site complication * 1  0/7254 (0.00%)  0/7243 (0.00%)  0/8738 (0.00%)  1/8748 (0.01%) 
Burns second degree * 1  0/7254 (0.00%)  1/7243 (0.01%)  0/8738 (0.00%)  1/8748 (0.01%) 
Carbon monoxide poisoning * 1  0/7254 (0.00%)  1/7243 (0.01%)  0/8738 (0.00%)  1/8748 (0.01%) 
Cervical vertebral fracture * 1  1/7254 (0.01%)  1/7243 (0.01%)  2/8738 (0.02%)  0/8748 (0.00%) 
Compression fracture * 1  1/7254 (0.01%)  0/7243 (0.00%)  0/8738 (0.00%)  0/8748 (0.00%) 
Concussion * 1  0/7254 (0.00%)  1/7243 (0.01%)  0/8738 (0.00%)  0/8748 (0.00%) 
Contusion * 1  1/7254 (0.01%)  0/7243 (0.00%)  0/8738 (0.00%)  3/8748 (0.03%) 
Craniocerebral injury * 1  0/7254 (0.00%)  0/7243 (0.00%)  0/8738 (0.00%)  2/8748 (0.02%) 
Ear injury * 1  1/7254 (0.01%)  0/7243 (0.00%)  0/8738 (0.00%)  0/8748 (0.00%) 
Fall * 1  0/7254 (0.00%)  0/7243 (0.00%)  4/8738 (0.05%)  0/8748 (0.00%) 
Femoral neck fracture * 1  1/7254 (0.01%)  5/7243 (0.07%)  1/8738 (0.01%)  0/8748 (0.00%) 
Femur fracture * 1  6/7254 (0.08%)  5/7243 (0.07%)  2/8738 (0.02%)  2/8748 (0.02%) 
Foot fracture * 1  0/7254 (0.00%)  0/7243 (0.00%)  1/8738 (0.01%)  0/8748 (0.00%) 
Forearm fracture * 1  0/7254 (0.00%)  1/7243 (0.01%)  0/8738 (0.00%)  0/8748 (0.00%) 
Fractured sacrum * 1  1/7254 (0.01%)  0/7243 (0.00%)  0/8738 (0.00%)  0/8748 (0.00%) 
Gastrointestinal stoma complication * 1  0/7254 (0.00%)  0/7243 (0.00%)  0/8738 (0.00%)  1/8748 (0.01%) 
Graft complication * 1  0/7254 (0.00%)  1/7243 (0.01%)  0/8738 (0.00%)  0/8748 (0.00%) 
Graft thrombosis * 1  1/7254 (0.01%)  0/7243 (0.00%)  0/8738 (0.00%)  0/8748 (0.00%) 
Head injury * 1  1/7254 (0.01%)  0/7243 (0.00%)  1/8738 (0.01%)  0/8748 (0.00%) 
Hip fracture * 1  8/7254 (0.11%)  4/7243 (0.06%)  5/8738 (0.06%)  11/8748 (0.13%) 
Humerus fracture * 1  3/7254 (0.04%)  2/7243 (0.03%)  4/8738 (0.05%)  1/8748 (0.01%) 
Incisional hernia * 1  2/7254 (0.03%)  2/7243 (0.03%)  0/8738 (0.00%)  2/8748 (0.02%) 
Injury * 1  2/7254 (0.03%)  2/7243 (0.03%)  2/8738 (0.02%)  0/8748 (0.00%) 
Intentional overdose * 1  0/7254 (0.00%)  0/7243 (0.00%)  1/8738 (0.01%)  0/8748 (0.00%) 
Joint dislocation * 1  2/7254 (0.03%)  1/7243 (0.01%)  1/8738 (0.01%)  3/8748 (0.03%) 
Joint injury * 1  0/7254 (0.00%)  1/7243 (0.01%)  1/8738 (0.01%)  1/8748 (0.01%) 
Joint sprain * 1  0/7254 (0.00%)  1/7243 (0.01%)  0/8738 (0.00%)  0/8748 (0.00%) 
Laceration * 1  1/7254 (0.01%)  0/7243 (0.00%)  1/8738 (0.01%)  1/8748 (0.01%) 
Ligament sprain * 1  0/7254 (0.00%)  1/7243 (0.01%)  0/8738 (0.00%)  0/8748 (0.00%) 
Meniscus lesion * 1  0/7254 (0.00%)  1/7243 (0.01%)  0/8738 (0.00%)  0/8748 (0.00%) 
Multiple fractures * 1  3/7254 (0.04%)  3/7243 (0.04%)  2/8738 (0.02%)  0/8748 (0.00%) 
Multiple injuries * 1  0/7254 (0.00%)  1/7243 (0.01%)  1/8738 (0.01%)  0/8748 (0.00%) 
Open fracture * 1  0/7254 (0.00%)  0/7243 (0.00%)  1/8738 (0.01%)  0/8748 (0.00%) 
Patella fracture * 1  2/7254 (0.03%)  1/7243 (0.01%)  0/8738 (0.00%)  2/8748 (0.02%) 
Pelvic fracture * 1  3/7254 (0.04%)  1/7243 (0.01%)  1/8738 (0.01%)  3/8748 (0.03%) 
Periprosthetic fracture * 1  0/7254 (0.00%)  1/7243 (0.01%)  0/8738 (0.00%)  1/8748 (0.01%) 
Post laminectomy syndrome * 1  0/7254 (0.00%)  1/7243 (0.01%)  0/8738 (0.00%)  0/8748 (0.00%) 
Post procedural complication * 1  1/7254 (0.01%)  0/7243 (0.00%)  1/8738 (0.01%)  2/8748 (0.02%) 
Post procedural haemorrhage * 1  1/7254 (0.01%)  0/7243 (0.00%)  0/8738 (0.00%)  0/8748 (0.00%) 
Postoperative fever * 1  0/7254 (0.00%)  1/7243 (0.01%)  0/8738 (0.00%)  0/8748 (0.00%) 
Postoperative respiratory distress * 1  0/7254 (0.00%)  0/7243 (0.00%)  0/8738 (0.00%)  1/8748 (0.01%) 
Procedural pain * 1  1/7254 (0.01%)  0/7243 (0.00%)  0/8738 (0.00%)  0/8748 (0.00%) 
Pubis fracture * 1  0/7254 (0.00%)  1/7243 (0.01%)  0/8738 (0.00%)  0/8748 (0.00%) 
Radius fracture * 1  0/7254 (0.00%)  0/7243 (0.00%)  0/8738 (0.00%)  1/8748 (0.01%) 
Respiratory fume inhalation disorder * 1  1/7254 (0.01%)  0/7243 (0.00%)  1/8738 (0.01%)  0/8748 (0.00%) 
Rib fracture * 1  2/7254 (0.03%)  3/7243 (0.04%)  0/8738 (0.00%)  3/8748 (0.03%) 
Road traffic accident * 1  0/7254 (0.00%)  2/7243 (0.03%)  3/8738 (0.03%)  0/8748 (0.00%) 
Skull fracture * 1  1/7254 (0.01%)  0/7243 (0.00%)  0/8738 (0.00%)  0/8748 (0.00%) 
Skull fractured base * 1  0/7254 (0.00%)  2/7243 (0.03%)  0/8738 (0.00%)  0/8748 (0.00%) 
Spinal compression fracture * 1  0/7254 (0.00%)  0/7243 (0.00%)  1/8738 (0.01%)  0/8748 (0.00%) 
Spinal fracture * 1  0/7254 (0.00%)  1/7243 (0.01%)  1/8738 (0.01%)  1/8748 (0.01%) 
Splenic rupture * 1  0/7254 (0.00%)  0/7243 (0.00%)  0/8738 (0.00%)  1/8748 (0.01%) 
Sternal fracture * 1  0/7254 (0.00%)  0/7243 (0.00%)  0/8738 (0.00%)  1/8748 (0.01%) 
Subdural haematoma * 1  5/7254 (0.07%)  3/7243 (0.04%)  1/8738 (0.01%)  2/8748 (0.02%) 
Tendon rupture * 1  0/7254 (0.00%)  0/7243 (0.00%)  0/8738 (0.00%)  1/8748 (0.01%) 
Tibia fracture * 1  1/7254 (0.01%)  0/7243 (0.00%)  0/8738 (0.00%)  1/8748 (0.01%) 
Toxicity to various agents * 1  1/7254 (0.01%)  1/7243 (0.01%)  0/8738 (0.00%)  0/8748 (0.00%) 
Traumatic fracture * 1  1/7254 (0.01%)  0/7243 (0.00%)  0/8738 (0.00%)  0/8748 (0.00%) 
Upper limb fracture * 1  2/7254 (0.03%)  0/7243 (0.00%)  1/8738 (0.01%)  1/8748 (0.01%) 
Vascular graft complication * 1  0/7254 (0.00%)  0/7243 (0.00%)  1/8738 (0.01%)  0/8748 (0.00%) 
Wound * 1  0/7254 (0.00%)  1/7243 (0.01%)  0/8738 (0.00%)  0/8748 (0.00%) 
Wound dehiscence * 1  0/7254 (0.00%)  0/7243 (0.00%)  0/8738 (0.00%)  1/8748 (0.01%) 
Wrist fracture * 1  1/7254 (0.01%)  0/7243 (0.00%)  3/8738 (0.03%)  0/8748 (0.00%) 
Extradural haematoma * 1  0/7254 (0.00%)  0/7243 (0.00%)  0/8738 (0.00%)  1/8748 (0.01%) 
Investigations         
Blood pressure increased * 1  0/7254 (0.00%)  0/7243 (0.00%)  0/8738 (0.00%)  1/8748 (0.01%) 
Cardiac stress test abnormal * 1  0/7254 (0.00%)  1/7243 (0.01%)  0/8738 (0.00%)  0/8748 (0.00%) 
Prostatic specific antigen increased * 1  0/7254 (0.00%)  1/7243 (0.01%)  0/8738 (0.00%)  0/8748 (0.00%) 
Metabolism and nutrition disorders         
Dehydration * 1  3/7254 (0.04%)  4/7243 (0.06%)  4/8738 (0.05%)  5/8748 (0.06%) 
Diabetic ketoacidosis * 1  0/7254 (0.00%)  1/7243 (0.01%)  0/8738 (0.00%)  1/8748 (0.01%) 
Diabetes mellitus inadequate control * 1  0/7254 (0.00%)  0/7243 (0.00%)  0/8738 (0.00%)  1/8748 (0.01%) 
Failure to thrive * 1  0/7254 (0.00%)  0/7243 (0.00%)  0/8738 (0.00%)  1/8748 (0.01%) 
Fluid overload * 1  0/7254 (0.00%)  1/7243 (0.01%)  0/8738 (0.00%)  0/8748 (0.00%) 
Fluid retention * 1  0/7254 (0.00%)  1/7243 (0.01%)  0/8738 (0.00%)  0/8748 (0.00%) 
Gout * 1  1/7254 (0.01%)  0/7243 (0.00%)  0/8738 (0.00%)  0/8748 (0.00%) 
Hypercalcaemia * 1  0/7254 (0.00%)  0/7243 (0.00%)  1/8738 (0.01%)  0/8748 (0.00%) 
Hyperglycaemia * 1  1/7254 (0.01%)  0/7243 (0.00%)  2/8738 (0.02%)  1/8748 (0.01%) 
Hypoglycaemia * 1  2/7254 (0.03%)  3/7243 (0.04%)  2/8738 (0.02%)  5/8748 (0.06%) 
Hypokalaemia * 1  3/7254 (0.04%)  2/7243 (0.03%)  0/8738 (0.00%)  1/8748 (0.01%) 
Hyponatraemia * 1  1/7254 (0.01%)  1/7243 (0.01%)  3/8738 (0.03%)  3/8748 (0.03%) 
Malnutrition * 1  0/7254 (0.00%)  1/7243 (0.01%)  0/8738 (0.00%)  0/8748 (0.00%) 
Type 2 diabetes mellitus * 1  0/7254 (0.00%)  1/7243 (0.01%)  0/8738 (0.00%)  1/8748 (0.01%) 
Hypocalcaemia * 1  1/7254 (0.01%)  0/7243 (0.00%)  0/8738 (0.00%)  0/8748 (0.00%) 
Musculoskeletal and connective tissue disorders         
Arthralgia * 1  6/7254 (0.08%)  4/7243 (0.06%)  6/8738 (0.07%)  1/8748 (0.01%) 
Arthritis * 1  4/7254 (0.06%)  1/7243 (0.01%)  4/8738 (0.05%)  1/8748 (0.01%) 
Arthropathy * 1  0/7254 (0.00%)  0/7243 (0.00%)  1/8738 (0.01%)  0/8748 (0.00%) 
Back pain * 1  4/7254 (0.06%)  1/7243 (0.01%)  2/8738 (0.02%)  6/8748 (0.07%) 
Bursitis * 1  0/7254 (0.00%)  0/7243 (0.00%)  0/8738 (0.00%)  1/8748 (0.01%) 
Cervical spinal stenosis * 1  1/7254 (0.01%)  3/7243 (0.04%)  1/8738 (0.01%)  5/8748 (0.06%) 
Chondrocalcinosis pyrophosphate * 1  0/7254 (0.00%)  1/7243 (0.01%)  0/8738 (0.00%)  0/8748 (0.00%) 
Costochondritis * 1  0/7254 (0.00%)  1/7243 (0.01%)  0/8738 (0.00%)  1/8748 (0.01%) 
Exostosis * 1  0/7254 (0.00%)  0/7243 (0.00%)  1/8738 (0.01%)  1/8748 (0.01%) 
Foot deformity * 1  2/7254 (0.03%)  2/7243 (0.03%)  1/8738 (0.01%)  0/8748 (0.00%) 
Fracture malunion * 1  0/7254 (0.00%)  0/7243 (0.00%)  0/8738 (0.00%)  1/8748 (0.01%) 
Gouty tophus * 1  1/7254 (0.01%)  0/7243 (0.00%)  0/8738 (0.00%)  0/8748 (0.00%) 
Groin pain * 1  0/7254 (0.00%)  0/7243 (0.00%)  3/8738 (0.03%)  0/8748 (0.00%) 
Intervertebral disc degeneration * 1  3/7254 (0.04%)  2/7243 (0.03%)  1/8738 (0.01%)  2/8748 (0.02%) 
Intervertebral disc displacement * 1  0/7254 (0.00%)  0/7243 (0.00%)  1/8738 (0.01%)  0/8748 (0.00%) 
Intervertebral disc protrusion * 1  2/7254 (0.03%)  5/7243 (0.07%)  2/8738 (0.02%)  1/8748 (0.01%) 
Knee deformity * 1  0/7254 (0.00%)  1/7243 (0.01%)  1/8738 (0.01%)  0/8748 (0.00%) 
Kyphosis * 1  0/7254 (0.00%)  1/7243 (0.01%)  0/8738 (0.00%)  0/8748 (0.00%) 
Lumbar spinal stenosis * 1  6/7254 (0.08%)  7/7243 (0.10%)  7/8738 (0.08%)  4/8748 (0.05%) 
Monarthritis * 1  1/7254 (0.01%)  0/7243 (0.00%)  0/8738 (0.00%)  0/8748 (0.00%) 
Muscle atrophy * 1  1/7254 (0.01%)  0/7243 (0.00%)  0/8738 (0.00%)  0/8748 (0.00%) 
Muscle spasms * 1  0/7254 (0.00%)  0/7243 (0.00%)  0/8738 (0.00%)  1/8748 (0.01%) 
Muscular weakness * 1  1/7254 (0.01%)  1/7243 (0.01%)  0/8738 (0.00%)  1/8748 (0.01%) 
Musculoskeletal chest pain * 1  1/7254 (0.01%)  1/7243 (0.01%)  0/8738 (0.00%)  3/8748 (0.03%) 
Musculoskeletal pain * 1  3/7254 (0.04%)  1/7243 (0.01%)  0/8738 (0.00%)  0/8748 (0.00%) 
Neck pain * 1  0/7254 (0.00%)  3/7243 (0.04%)  0/8738 (0.00%)  0/8748 (0.00%) 
Osteoarthritis * 1  48/7254 (0.66%)  29/7243 (0.40%)  50/8738 (0.57%)  35/8748 (0.40%) 
Osteonecrosis * 1  2/7254 (0.03%)  0/7243 (0.00%)  1/8738 (0.01%)  0/8748 (0.00%) 
Osteoporosis * 1  0/7254 (0.00%)  1/7243 (0.01%)  0/8738 (0.00%)  0/8748 (0.00%) 
Osteoporotic fracture * 1  0/7254 (0.00%)  1/7243 (0.01%)  0/8738 (0.00%)  0/8748 (0.00%) 
Pain in extremity * 1  1/7254 (0.01%)  0/7243 (0.00%)  1/8738 (0.01%)  0/8748 (0.00%) 
Periarthritis * 1  0/7254 (0.00%)  1/7243 (0.01%)  0/8738 (0.00%)  0/8748 (0.00%) 
Polymyalgia rheumatica * 1  1/7254 (0.01%)  0/7243 (0.00%)  0/8738 (0.00%)  0/8748 (0.00%) 
Rhabdomyolysis * 1  0/7254 (0.00%)  0/7243 (0.00%)  1/8738 (0.01%)  0/8748 (0.00%) 
Rheumatoid arthritis * 1  1/7254 (0.01%)  0/7243 (0.00%)  0/8738 (0.00%)  1/8748 (0.01%) 
Rotator cuff syndrome * 1  3/7254 (0.04%)  2/7243 (0.03%)  2/8738 (0.02%)  1/8748 (0.01%) 
Spinal column stenosis * 1  1/7254 (0.01%)  0/7243 (0.00%)  4/8738 (0.05%)  2/8748 (0.02%) 
Spinal osteoarthritis * 1  1/7254 (0.01%)  0/7243 (0.00%)  1/8738 (0.01%)  0/8748 (0.00%) 
Spondylolisthesis * 1  0/7254 (0.00%)  2/7243 (0.03%)  4/8738 (0.05%)  2/8748 (0.02%) 
Synovial cyst * 1  0/7254 (0.00%)  0/7243 (0.00%)  1/8738 (0.01%)  0/8748 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)         
Acute leukaemia * 1  0/7254 (0.00%)  0/7243 (0.00%)  1/8738 (0.01%)  0/8748 (0.00%) 
Acute myeloid leukaemia * 1  0/7254 (0.00%)  0/7243 (0.00%)  0/8738 (0.00%)  1/8748 (0.01%) 
Acute promyelocytic leukaemia * 1  1/7254 (0.01%)  0/7243 (0.00%)  0/8738 (0.00%)  0/8748 (0.00%) 
Adenocarcinoma * 1  0/7254 (0.00%)  0/7243 (0.00%)  0/8738 (0.00%)  1/8748 (0.01%) 
Adenocarcinoma pancreas * 1  0/7254 (0.00%)  0/7243 (0.00%)  1/8738 (0.01%)  1/8748 (0.01%) 
Adenoid cystic carcinoma * 1  0/7254 (0.00%)  0/7243 (0.00%)  0/8738 (0.00%)  1/8748 (0.01%) 
B-cell small lymphocytic lymphoma * 1  0/7254 (0.00%)  0/7243 (0.00%)  1/8738 (0.01%)  0/8748 (0.00%) 
Basal cell carcinoma * 1  0/7254 (0.00%)  1/7243 (0.01%)  1/8738 (0.01%)  0/8748 (0.00%) 
Benign neoplasm * 1  0/7254 (0.00%)  0/7243 (0.00%)  2/8738 (0.02%)  1/8748 (0.01%) 
Benign renal neoplasm * 1  0/7254 (0.00%)  0/7243 (0.00%)  1/8738 (0.01%)  0/8748 (0.00%) 
Bile duct cancer * 1  0/7254 (0.00%)  0/7243 (0.00%)  1/8738 (0.01%)  0/8748 (0.00%) 
Bladder cancer * 1  5/7254 (0.07%)  3/7243 (0.04%)  0/8738 (0.00%)  3/8748 (0.03%) 
Bladder cancer recurrent * 1  0/7254 (0.00%)  1/7243 (0.01%)  0/8738 (0.00%)  1/8748 (0.01%) 
Bladder neoplasm * 1  0/7254 (0.00%)  1/7243 (0.01%)  0/8738 (0.00%)  0/8748 (0.00%) 
Bladder transitional cell carcinoma * 1  0/7254 (0.00%)  1/7243 (0.01%)  1/8738 (0.01%)  0/8748 (0.00%) 
Bone cancer metastatic * 1  0/7254 (0.00%)  1/7243 (0.01%)  0/8738 (0.00%)  0/8748 (0.00%) 
Bone neoplasm * 1  0/7254 (0.00%)  0/7243 (0.00%)  0/8738 (0.00%)  1/8748 (0.01%) 
Bone neoplasm malignant * 1  0/7254 (0.00%)  1/7243 (0.01%)  0/8738 (0.00%)  0/8748 (0.00%) 
Brain neoplasm * 1  1/7254 (0.01%)  0/7243 (0.00%)  0/8738 (0.00%)  2/8748 (0.02%) 
Brain neoplasm malignant * 1  0/7254 (0.00%)  1/7243 (0.01%)  0/8738 (0.00%)  0/8748 (0.00%) 
Breast cancer * 1  7/7254 (0.10%)  11/7243 (0.15%)  7/8738 (0.08%)  7/8748 (0.08%) 
Breast cancer in situ * 1  1/7254 (0.01%)  2/7243 (0.03%)  2/8738 (0.02%)  0/8748 (0.00%) 
Breast cancer metastatic * 1  1/7254 (0.01%)  0/7243 (0.00%)  1/8738 (0.01%)  2/8748 (0.02%) 
Breast cancer recurrent * 1  1/7254 (0.01%)  0/7243 (0.00%)  0/8738 (0.00%)  0/8748 (0.00%) 
Breast cancer stage I * 1  1/7254 (0.01%)  0/7243 (0.00%)  1/8738 (0.01%)  0/8748 (0.00%) 
Bronchial carcinoma * 1  1/7254 (0.01%)  0/7243 (0.00%)  0/8738 (0.00%)  0/8748 (0.00%) 
Chronic lymphocytic leukaemia * 1  0/7254 (0.00%)  0/7243 (0.00%)  0/8738 (0.00%)  1/8748 (0.01%) 
Colon adenoma * 1  0/7254 (0.00%)  0/7243 (0.00%)  0/8738 (0.00%)  1/8748 (0.01%) 
Colon cancer * 1  0/7254 (0.00%)  3/7243 (0.04%)  4/8738 (0.05%)  5/8748 (0.06%) 
Colon cancer metastatic * 1  0/7254 (0.00%)  0/7243 (0.00%)  1/8738 (0.01%)  0/8748 (0.00%) 
Colon cancer stage II * 1  1/7254 (0.01%)  0/7243 (0.00%)  0/8738 (0.00%)  0/8748 (0.00%) 
Colorectal cancer * 1  0/7254 (0.00%)  0/7243 (0.00%)  0/8738 (0.00%)  1/8748 (0.01%) 
Duodenal neoplasm * 1  1/7254 (0.01%)  0/7243 (0.00%)  0/8738 (0.00%)  0/8748 (0.00%) 
Endometrial cancer * 1  1/7254 (0.01%)  1/7243 (0.01%)  2/8738 (0.02%)  0/8748 (0.00%) 
Endometrial cancer stage II * 1  1/7254 (0.01%)  0/7243 (0.00%)  0/8738 (0.00%)  0/8748 (0.00%) 
Gastric cancer * 1  1/7254 (0.01%)  0/7243 (0.00%)  0/8738 (0.00%)  2/8748 (0.02%) 
Gastric cancer recurrent * 1  0/7254 (0.00%)  0/7243 (0.00%)  1/8738 (0.01%)  0/8748 (0.00%) 
Gastric cancer stage I * 1  1/7254 (0.01%)  0/7243 (0.00%)  0/8738 (0.00%)  0/8748 (0.00%) 
Gastrinoma * 1  0/7254 (0.00%)  0/7243 (0.00%)  1/8738 (0.01%)  0/8748 (0.00%) 
Gastrointestinal stromal tumour * 1  1/7254 (0.01%)  0/7243 (0.00%)  0/8738 (0.00%)  0/8748 (0.00%) 
Glottis carcinoma * 1  0/7254 (0.00%)  0/7243 (0.00%)  0/8738 (0.00%)  1/8748 (0.01%) 
Head and neck cancer * 1  0/7254 (0.00%)  0/7243 (0.00%)  1/8738 (0.01%)  0/8748 (0.00%) 
Hepatic cancer metastatic * 1  2/7254 (0.03%)  0/7243 (0.00%)  0/8738 (0.00%)  0/8748 (0.00%) 
Hepatic neoplasm malignant * 1  1/7254 (0.01%)  2/7243 (0.03%)  2/8738 (0.02%)  0/8748 (0.00%) 
Hodgkin's disease * 1  0/7254 (0.00%)  0/7243 (0.00%)  0/8738 (0.00%)  1/8748 (0.01%) 
Intracranial meningioma malignant * 1  1/7254 (0.01%)  0/7243 (0.00%)  0/8738 (0.00%)  0/8748 (0.00%) 
Laryngeal cancer * 1  1/7254 (0.01%)  1/7243 (0.01%)  0/8738 (0.00%)  0/8748 (0.00%) 
Laryngeal cancer stage I * 1  0/7254 (0.00%)  0/7243 (0.00%)  0/8738 (0.00%)  1/8748 (0.01%) 
Lentigo maligna stage unspecified * 1  0/7254 (0.00%)  0/7243 (0.00%)  1/8738 (0.01%)  0/8748 (0.00%) 
Leukaemia * 1  0/7254 (0.00%)  1/7243 (0.01%)  0/8738 (0.00%)  1/8748 (0.01%) 
Liposarcoma * 1  0/7254 (0.00%)  0/7243 (0.00%)  0/8738 (0.00%)  1/8748 (0.01%) 
Lung adenocarcinoma * 1  1/7254 (0.01%)  1/7243 (0.01%)  0/8738 (0.00%)  0/8748 (0.00%) 
Lung cancer metastatic * 1  0/7254 (0.00%)  1/7243 (0.01%)  0/8738 (0.00%)  0/8748 (0.00%) 
Lung carcinoma cell type unspecified stage I * 1  0/7254 (0.00%)  1/7243 (0.01%)  0/8738 (0.00%)  0/8748 (0.00%) 
Lung carcinoma cell type unspecified stage 0 * 1  0/7254 (0.00%)  0/7243 (0.00%)  0/8738 (0.00%)  1/8748 (0.01%) 
Lung neoplasm * 1  1/7254 (0.01%)  0/7243 (0.00%)  0/8738 (0.00%)  0/8748 (0.00%) 
Lung neoplasm malignant * 1  4/7254 (0.06%)  11/7243 (0.15%)  6/8738 (0.07%)  3/8748 (0.03%) 
Lung squamous cell carcinoma stage unspecified * 1  0/7254 (0.00%)  0/7243 (0.00%)  1/8738 (0.01%)  2/8748 (0.02%) 
Lymphoma * 1  0/7254 (0.00%)  0/7243 (0.00%)  1/8738 (0.01%)  0/8748 (0.00%) 
Malignant melanoma * 1  1/7254 (0.01%)  1/7243 (0.01%)  2/8738 (0.02%)  1/8748 (0.01%) 
Meningioma * 1  1/7254 (0.01%)  1/7243 (0.01%)  1/8738 (0.01%)  0/8748 (0.00%) 
Meningioma benign * 1  0/7254 (0.00%)  1/7243 (0.01%)  0/8738 (0.00%)  0/8748 (0.00%) 
Metastases to bone * 1  0/7254 (0.00%)  1/7243 (0.01%)  1/8738 (0.01%)  0/8748 (0.00%) 
Metastases to central nervous system * 1  1/7254 (0.01%)  0/7243 (0.00%)  0/8738 (0.00%)  0/8748 (0.00%) 
Metastases to lung * 1  2/7254 (0.03%)  0/7243 (0.00%)  0/8738 (0.00%)  0/8748 (0.00%) 
Metastatic carcinoid tumour * 1  0/7254 (0.00%)  0/7243 (0.00%)  0/8738 (0.00%)  1/8748 (0.01%) 
Metastatic malignant melanoma * 1  1/7254 (0.01%)  0/7243 (0.00%)  0/8738 (0.00%)  0/8748 (0.00%) 
Metastatic neoplasm * 1  0/7254 (0.00%)  0/7243 (0.00%)  1/8738 (0.01%)  0/8748 (0.00%) 
Metastatic squamous cell carcinoma * 1  0/7254 (0.00%)  0/7243 (0.00%)  0/8738 (0.00%)  1/8748 (0.01%) 
Multiple myeloma * 1  1/7254 (0.01%)  2/7243 (0.03%)  2/8738 (0.02%)  0/8748 (0.00%) 
Myelodysplastic syndrome * 1  1/7254 (0.01%)  0/7243 (0.00%)  0/8738 (0.00%)  1/8748 (0.01%) 
Myeloid leukaemia * 1  0/7254 (0.00%)  0/7243 (0.00%)  1/8738 (0.01%)  0/8748 (0.00%) 
Myeloma recurrence * 1  0/7254 (0.00%)  1/7243 (0.01%)  0/8738 (0.00%)  0/8748 (0.00%) 
Neoplasm malignant * 1  0/7254 (0.00%)  2/7243 (0.03%)  0/8738 (0.00%)  1/8748 (0.01%) 
Neuroendocrine tumour * 1  0/7254 (0.00%)  0/7243 (0.00%)  1/8738 (0.01%)  0/8748 (0.00%) 
Non-Hodgkin's lymphoma * 1  1/7254 (0.01%)  0/7243 (0.00%)  0/8738 (0.00%)  1/8748 (0.01%) 
Non-small cell lung cancer * 1  1/7254 (0.01%)  0/7243 (0.00%)  1/8738 (0.01%)  0/8748 (0.00%) 
Non-small cell lung cancer metastatic * 1  0/7254 (0.00%)  1/7243 (0.01%)  0/8738 (0.00%)  0/8748 (0.00%) 
Oesophageal adenocarcinoma * 1  0/7254 (0.00%)  0/7243 (0.00%)  0/8738 (0.00%)  1/8748 (0.01%) 
Oesophageal carcinoma * 1  1/7254 (0.01%)  0/7243 (0.00%)  0/8738 (0.00%)  1/8748 (0.01%) 
Ovarian cancer metastatic * 1  1/7254 (0.01%)  0/7243 (0.00%)  0/8738 (0.00%)  0/8748 (0.00%) 
Pancreatic carcinoma * 1  1/7254 (0.01%)  3/7243 (0.04%)  1/8738 (0.01%)  0/8748 (0.00%) 
Pancreatic carcinoma metastatic * 1  1/7254 (0.01%)  0/7243 (0.00%)  2/8738 (0.02%)  0/8748 (0.00%) 
Paraproteinaemia * 1  1/7254 (0.01%)  0/7243 (0.00%)  0/8738 (0.00%)  0/8748 (0.00%) 
Penis carcinoma * 1  0/7254 (0.00%)  0/7243 (0.00%)  1/8738 (0.01%)  0/8748 (0.00%) 
Pituitary tumour * 1  1/7254 (0.01%)  0/7243 (0.00%)  0/8738 (0.00%)  0/8748 (0.00%) 
Pituitary tumour benign * 1  1/7254 (0.01%)  0/7243 (0.00%)  0/8738 (0.00%)  0/8748 (0.00%) 
Pleural neoplasm * 1  1/7254 (0.01%)  0/7243 (0.00%)  0/8738 (0.00%)  0/8748 (0.00%) 
Prostate cancer * 1  9/7254 (0.12%)  2/7243 (0.03%)  3/8738 (0.03%)  4/8748 (0.05%) 
Prostate cancer metastatic * 1  0/7254 (0.00%)  0/7243 (0.00%)  0/8738 (0.00%)  1/8748 (0.01%) 
Rectal cancer * 1  1/7254 (0.01%)  3/7243 (0.04%)  0/8738 (0.00%)  0/8748 (0.00%) 
Renal cancer * 1  1/7254 (0.01%)  0/7243 (0.00%)  0/8738 (0.00%)  0/8748 (0.00%) 
Renal cell carcinoma * 1  3/7254 (0.04%)  1/7243 (0.01%)  0/8738 (0.00%)  2/8748 (0.02%) 
Retroperitoneal neoplasm * 1  0/7254 (0.00%)  0/7243 (0.00%)  0/8738 (0.00%)  1/8748 (0.01%) 
Salivary gland cancer * 1  1/7254 (0.01%)  0/7243 (0.00%)  0/8738 (0.00%)  0/8748 (0.00%) 
Sarcoma * 1  0/7254 (0.00%)  1/7243 (0.01%)  1/8738 (0.01%)  0/8748 (0.00%) 
Skin cancer * 1  1/7254 (0.01%)  2/7243 (0.03%)  0/8738 (0.00%)  0/8748 (0.00%) 
Small cell lung cancer extensive stage * 1  0/7254 (0.00%)  0/7243 (0.00%)  1/8738 (0.01%)  0/8748 (0.00%) 
Small cell lung cancer stage unspecified * 1  1/7254 (0.01%)  0/7243 (0.00%)  2/8738 (0.02%)  1/8748 (0.01%) 
Small intestine carcinoma * 1  1/7254 (0.01%)  0/7243 (0.00%)  0/8738 (0.00%)  0/8748 (0.00%) 
Squamous cell carcinoma * 1  0/7254 (0.00%)  5/7243 (0.07%)  2/8738 (0.02%)  0/8748 (0.00%) 
Squamous cell carcinoma of skin * 1  0/7254 (0.00%)  0/7243 (0.00%)  0/8738 (0.00%)  1/8748 (0.01%) 
Throat cancer * 1  0/7254 (0.00%)  0/7243 (0.00%)  1/8738 (0.01%)  0/8748 (0.00%) 
Thyroid cancer * 1  0/7254 (0.00%)  4/7243 (0.06%)  0/8738 (0.00%)  1/8748 (0.01%) 
Thyroid neoplasm * 1  0/7254 (0.00%)  0/7243 (0.00%)  0/8738 (0.00%)  1/8748 (0.01%) 
Tongue neoplasm malignant stage unspecified * 1  1/7254 (0.01%)  0/7243 (0.00%)  0/8738 (0.00%)  0/8748 (0.00%) 
Tonsil cancer * 1  0/7254 (0.00%)  0/7243 (0.00%)  0/8738 (0.00%)  1/8748 (0.01%) 
Transitional cell carcinoma * 1  0/7254 (0.00%)  2/7243 (0.03%)  0/8738 (0.00%)  0/8748 (0.00%) 
Uterine cancer * 1  0/7254 (0.00%)  0/7243 (0.00%)  3/8738 (0.03%)  0/8748 (0.00%) 
Malignant melanoma in situ * 1  1/7254 (0.01%)  0/7243 (0.00%)  0/8738 (0.00%)  0/8748 (0.00%) 
Nervous system disorders         
Acute disseminated encephalomyelitis * 1  1/7254 (0.01%)  0/7243 (0.00%)  0/8738 (0.00%)  0/8748 (0.00%) 
Amnesia * 1  0/7254 (0.00%)  0/7243 (0.00%)  1/8738 (0.01%)  0/8748 (0.00%) 
Ataxia * 1  1/7254 (0.01%)  0/7243 (0.00%)  2/8738 (0.02%)  0/8748 (0.00%) 
Autonomic nervous system imbalance * 1  0/7254 (0.00%)  1/7243 (0.01%)  0/8738 (0.00%)  0/8748 (0.00%) 
Basal ganglia infarction * 1  0/7254 (0.00%)  0/7243 (0.00%)  1/8738 (0.01%)  0/8748 (0.00%) 
Carotid artery occlusion * 1  0/7254 (0.00%)  1/7243 (0.01%)  0/8738 (0.00%)  0/8748 (0.00%) 
Carotid artery stenosis * 1  3/7254 (0.04%)  2/7243 (0.03%)  4/8738 (0.05%)  0/8748 (0.00%) 
Cerebral amyloid angiopathy * 1  0/7254 (0.00%)  0/7243 (0.00%)  0/8738 (0.00%)  1/8748 (0.01%) 
Cerebral cyst * 1  0/7254 (0.00%)  0/7243 (0.00%)  1/8738 (0.01%)  0/8748 (0.00%) 
Cerebral haemorrhage * 1  1/7254 (0.01%)  1/7243 (0.01%)  2/8738 (0.02%)  0/8748 (0.00%) 
Cerebral infarction * 1  2/7254 (0.03%)  1/7243 (0.01%)  0/8738 (0.00%)  2/8748 (0.02%) 
Cerebral Ischaemia * 1  1/7254 (0.01%)  0/7243 (0.00%)  0/8738 (0.00%)  0/8748 (0.00%) 
Cerebrovascular accident * 1  20/7254 (0.28%)  19/7243 (0.26%)  13/8738 (0.15%)  21/8748 (0.24%) 
Cervicobrachial syndrome * 1  1/7254 (0.01%)  0/7243 (0.00%)  0/8738 (0.00%)  0/8748 (0.00%) 
Cervical myelopathy * 1  0/7254 (0.00%)  0/7243 (0.00%)  0/8738 (0.00%)  1/8748 (0.01%) 
Cognitive disorder * 1  0/7254 (0.00%)  0/7243 (0.00%)  1/8738 (0.01%)  0/8748 (0.00%) 
Complex partial seizures * 1  1/7254 (0.01%)  0/7243 (0.00%)  0/8738 (0.00%)  0/8748 (0.00%) 
Convulsion * 1  3/7254 (0.04%)  3/7243 (0.04%)  1/8738 (0.01%)  2/8748 (0.02%) 
Dementia Alzheimer's type * 1  0/7254 (0.00%)  0/7243 (0.00%)  1/8738 (0.01%)  0/8748 (0.00%) 
Dementia with Lewy bodies * 1  0/7254 (0.00%)  0/7243 (0.00%)  0/8738 (0.00%)  1/8748 (0.01%) 
Depressed level of consciousness * 1  0/7254 (0.00%)  1/7243 (0.01%)  0/8738 (0.00%)  0/8748 (0.00%) 
Dizziness * 1  2/7254 (0.03%)  2/7243 (0.03%)  1/8738 (0.01%)  0/8748 (0.00%) 
Dizziness postural * 1  1/7254 (0.01%)  0/7243 (0.00%)  0/8738 (0.00%)  0/8748 (0.00%) 
Dyskinesia * 1  0/7254 (0.00%)  1/7243 (0.01%)  0/8738 (0.00%)  0/8748 (0.00%) 
Encephalopathy * 1  2/7254 (0.03%)  1/7243 (0.01%)  2/8738 (0.02%)  1/8748 (0.01%) 
Epilepsy * 1  0/7254 (0.00%)  0/7243 (0.00%)  0/8738 (0.00%)  1/8748 (0.01%) 
Guillain-Barre syndrome * 1  0/7254 (0.00%)  0/7243 (0.00%)  0/8738 (0.00%)  1/8748 (0.01%) 
Haemorrhage intracranial * 1  0/7254 (0.00%)  2/7243 (0.03%)  1/8738 (0.01%)  2/8748 (0.02%) 
Haemorrhagic stroke * 1  0/7254 (0.00%)  1/7243 (0.01%)  1/8738 (0.01%)  0/8748 (0.00%) 
Headache * 1  2/7254 (0.03%)  0/7243 (0.00%)  0/8738 (0.00%)  0/8748 (0.00%) 
Hemiparesis * 1  0/7254 (0.00%)  0/7243 (0.00%)  0/8738 (0.00%)  1/8748 (0.01%) 
Hydrocephalus * 1  0/7254 (0.00%)  0/7243 (0.00%)  0/8738 (0.00%)  1/8748 (0.01%) 
Hypertensive encephalopathy * 1  0/7254 (0.00%)  0/7243 (0.00%)  1/8738 (0.01%)  0/8748 (0.00%) 
Intracranial aneurysm * 1  0/7254 (0.00%)  1/7243 (0.01%)  0/8738 (0.00%)  1/8748 (0.01%) 
Intraventricular haemorrhage * 1  1/7254 (0.01%)  0/7243 (0.00%)  0/8738 (0.00%)  0/8748 (0.00%) 
Ischaemic stroke * 1  1/7254 (0.01%)  0/7243 (0.00%)  1/8738 (0.01%)  0/8748 (0.00%) 
Lacunar infarction * 1  2/7254 (0.03%)  0/7243 (0.00%)  0/8738 (0.00%)  0/8748 (0.00%) 
Lethargy * 1  1/7254 (0.01%)  0/7243 (0.00%)  0/8738 (0.00%)  0/8748 (0.00%) 
Loss of consciousness * 1  0/7254 (0.00%)  0/7243 (0.00%)  1/8738 (0.01%)  0/8748 (0.00%) 
Lumbar radiculopathy * 1  3/7254 (0.04%)  0/7243 (0.00%)  1/8738 (0.01%)  0/8748 (0.00%) 
Metabolic encephalopathy * 1  0/7254 (0.00%)  0/7243 (0.00%)  1/8738 (0.01%)  0/8748 (0.00%) 
Migraine * 1  0/7254 (0.00%)  0/7243 (0.00%)  0/8738 (0.00%)  1/8748 (0.01%) 
Myasthenia gravis * 1  1/7254 (0.01%)  0/7243 (0.00%)  0/8738 (0.00%)  0/8748 (0.00%) 
Myelopathy * 1  0/7254 (0.00%)  0/7243 (0.00%)  1/8738 (0.01%)  1/8748 (0.01%) 
Normal pressure hydrocephalus * 1  3/7254 (0.04%)  0/7243 (0.00%)  0/8738 (0.00%)  0/8748 (0.00%) 
Paraesthesia * 1  0/7254 (0.00%)  1/7243 (0.01%)  0/8738 (0.00%)  0/8748 (0.00%) 
Parkinson's disease * 1  0/7254 (0.00%)  0/7243 (0.00%)  0/8738 (0.00%)  1/8748 (0.01%) 
Presyncope * 1  1/7254 (0.01%)  3/7243 (0.04%)  3/8738 (0.03%)  2/8748 (0.02%) 
Radiculopathy * 1  1/7254 (0.01%)  1/7243 (0.01%)  1/8738 (0.01%)  0/8748 (0.00%) 
Sciatica * 1  0/7254 (0.00%)  1/7243 (0.01%)  0/8738 (0.00%)  1/8748 (0.01%) 
Spondylitic myelopathy * 1  0/7254 (0.00%)  0/7243 (0.00%)  0/8738 (0.00%)  2/8748 (0.02%) 
Subarachnoid haemorrhage * 1  0/7254 (0.00%)  4/7243 (0.06%)  1/8738 (0.01%)  1/8748 (0.01%) 
Syncope * 1  18/7254 (0.25%)  19/7243 (0.26%)  15/8738 (0.17%)  16/8748 (0.18%) 
Thrombotic cerebral infarction * 1  1/7254 (0.01%)  1/7243 (0.01%)  0/8738 (0.00%)  0/8748 (0.00%) 
Toxic encephalopathy * 1  0/7254 (0.00%)  0/7243 (0.00%)  1/8738 (0.01%)  1/8748 (0.01%) 
Transient global amnesia * 1  1/7254 (0.01%)  1/7243 (0.01%)  0/8738 (0.00%)  0/8748 (0.00%) 
Transient ischaemic attack * 1  12/7254 (0.17%)  15/7243 (0.21%)  9/8738 (0.10%)  12/8748 (0.14%) 
VIIth nerve paralysis * 1  0/7254 (0.00%)  2/7243 (0.03%)  1/8738 (0.01%)  3/8748 (0.03%) 
VIth nerve paralysis * 1  0/7254 (0.00%)  0/7243 (0.00%)  1/8738 (0.01%)  1/8748 (0.01%) 
Basal ganglia haemorrhage * 1  0/7254 (0.00%)  1/7243 (0.01%)  0/8738 (0.00%)  0/8748 (0.00%) 
Psychiatric disorders         
Affective disorder * 1  0/7254 (0.00%)  0/7243 (0.00%)  0/8738 (0.00%)  1/8748 (0.01%) 
Alcohol withdrawal syndrome * 1  1/7254 (0.01%)  1/7243 (0.01%)  0/8738 (0.00%)  0/8748 (0.00%) 
Bipolar disorder * 1  1/7254 (0.01%)  0/7243 (0.00%)  0/8738 (0.00%)  0/8748 (0.00%) 
Bipolar I disorder * 1  0/7254 (0.00%)  0/7243 (0.00%)  1/8738 (0.01%)  0/8748 (0.00%) 
Completed suicide * 1  0/7254 (0.00%)  0/7243 (0.00%)  0/8738 (0.00%)  1/8748 (0.01%) 
Delirium * 1  1/7254 (0.01%)  0/7243 (0.00%)  0/8738 (0.00%)  1/8748 (0.01%) 
Depression * 1  1/7254 (0.01%)  2/7243 (0.03%)  1/8738 (0.01%)  0/8748 (0.00%) 
Hallucination, visual * 1  0/7254 (0.00%)  0/7243 (0.00%)  0/8738 (0.00%)  1/8748 (0.01%) 
Major depression * 1  1/7254 (0.01%)  1/7243 (0.01%)  1/8738 (0.01%)  1/8748 (0.01%) 
Mental status changes * 1  1/7254 (0.01%)  2/7243 (0.03%)  5/8738 (0.06%)  4/8748 (0.05%) 
Panic attack * 1  0/7254 (0.00%)  0/7243 (0.00%)  1/8738 (0.01%)  0/8748 (0.00%) 
Psychotic disorder * 1  0/7254 (0.00%)  0/7243 (0.00%)  0/8738 (0.00%)  1/8748 (0.01%) 
Suicidal ideation * 1  0/7254 (0.00%)  0/7243 (0.00%)  0/8738 (0.00%)  1/8748 (0.01%) 
Renal and urinary disorders         
Bladder fibrosis * 1  0/7254 (0.00%)  0/7243 (0.00%)  0/8738 (0.00%)  1/8748 (0.01%) 
Bladder prolapse * 1  0/7254 (0.00%)  0/7243 (0.00%)  2/8738 (0.02%)  0/8748 (0.00%) 
Calculus bladder * 1  0/7254 (0.00%)  0/7243 (0.00%)  0/8738 (0.00%)  1/8748 (0.01%) 
Calculus ureteric * 1  1/7254 (0.01%)  2/7243 (0.03%)  0/8738 (0.00%)  2/8748 (0.02%) 
Calculus urinary * 1  0/7254 (0.00%)  0/7243 (0.00%)  0/8738 (0.00%)  1/8748 (0.01%) 
Dysuria * 1  1/7254 (0.01%)  0/7243 (0.00%)  0/8738 (0.00%)  0/8748 (0.00%) 
Haematuria * 1  1/7254 (0.01%)  0/7243 (0.00%)  1/8738 (0.01%)  0/8748 (0.00%) 
Hydronephrosis * 1  0/7254 (0.00%)  0/7243 (0.00%)  2/8738 (0.02%)  0/8748 (0.00%) 
Nephrolithiasis * 1  3/7254 (0.04%)  5/7243 (0.07%)  2/8738 (0.02%)  1/8748 (0.01%) 
Obstructive uropathy * 1  0/7254 (0.00%)  0/7243 (0.00%)  1/8738 (0.01%)  0/8748 (0.00%) 
Renal artery stenosis * 1  1/7254 (0.01%)  1/7243 (0.01%)  1/8738 (0.01%)  1/8748 (0.01%) 
Renal colic * 1  0/7254 (0.00%)  0/7243 (0.00%)  0/8738 (0.00%)  1/8748 (0.01%) 
Renal failure * 1  2/7254 (0.03%)  1/7243 (0.01%)  1/8738 (0.01%)  4/8748 (0.05%) 
Renal failure acute * 1  8/7254 (0.11%)  5/7243 (0.07%)  11/8738 (0.13%)  14/8748 (0.16%) 
Renal failure chronic * 1  4/7254 (0.06%)  2/7243 (0.03%)  1/8738 (0.01%)  3/8748 (0.03%) 
Renal mass * 1  0/7254 (0.00%)  0/7243 (0.00%)  1/8738 (0.01%)  0/8748 (0.00%) 
Stress urinary incontinence * 1  0/7254 (0.00%)  0/7243 (0.00%)  0/8738 (0.00%)  1/8748 (0.01%) 
Urethral stenosis * 1  0/7254 (0.00%)  0/7243 (0.00%)  0/8738 (0.00%)  1/8748 (0.01%) 
Urinary incontinence * 1  1/7254 (0.01%)  1/7243 (0.01%)  0/8738 (0.00%)  0/8748 (0.00%) 
Urinary retention * 1  0/7254 (0.00%)  0/7243 (0.00%)  2/8738 (0.02%)  1/8748 (0.01%) 
Reproductive system and breast disorders         
Benign prostatic hyperplasia * 1  1/7254 (0.01%)  3/7243 (0.04%)  2/8738 (0.02%)  0/8748 (0.00%) 
Cystocele * 1  1/7254 (0.01%)  0/7243 (0.00%)  1/8738 (0.01%)  0/8748 (0.00%) 
Endometrial hyperplasia * 1  0/7254 (0.00%)  0/7243 (0.00%)  1/8738 (0.01%)  0/8748 (0.00%) 
Erectile dysfunction * 1  1/7254 (0.01%)  0/7243 (0.00%)  0/8738 (0.00%)  0/8748 (0.00%) 
Genital prolapse * 1  0/7254 (0.00%)  1/7243 (0.01%)  0/8738 (0.00%)  0/8748 (0.00%) 
Ovarian cyst * 1  0/7254 (0.00%)  0/7243 (0.00%)  0/8738 (0.00%)  1/8748 (0.01%) 
Ovarian mass * 1  1/7254 (0.01%)  0/7243 (0.00%)  0/8738 (0.00%)  0/8748 (0.00%) 
Pelvic pain * 1  0/7254 (0.00%)  0/7243 (0.00%)  0/8738 (0.00%)  1/8748 (0.01%) 
Pelvic prolapse * 1  1/7254 (0.01%)  0/7243 (0.00%)  1/8738 (0.01%)  0/8748 (0.00%) 
Prostatitis * 1  0/7254 (0.00%)  1/7243 (0.01%)  0/8738 (0.00%)  0/8748 (0.00%) 
Prostatomegaly * 1  0/7254 (0.00%)  0/7243 (0.00%)  1/8738 (0.01%)  1/8748 (0.01%) 
Uterine prolapse * 1  1/7254 (0.01%)  1/7243 (0.01%)  0/8738 (0.00%)  0/8748 (0.00%) 
Uterovaginal prolapse * 1  0/7254 (0.00%)  1/7243 (0.01%)  0/8738 (0.00%)  0/8748 (0.00%) 
Vaginal haematoma * 1  1/7254 (0.01%)  0/7243 (0.00%)  0/8738 (0.00%)  0/8748 (0.00%) 
Respiratory, thoracic and mediastinal disorders         
Acute respiratory failure * 1  1/7254 (0.01%)  6/7243 (0.08%)  6/8738 (0.07%)  7/8748 (0.08%) 
Alveolitis allergic * 1  0/7254 (0.00%)  0/7243 (0.00%)  0/8738 (0.00%)  1/8748 (0.01%) 
Asthma * 1  4/7254 (0.06%)  2/7243 (0.03%)  3/8738 (0.03%)  5/8748 (0.06%) 
Bronchitis chronic * 1  0/7254 (0.00%)  0/7243 (0.00%)  0/8738 (0.00%)  1/8748 (0.01%) 
Chronic obstructive pulmonary disease * 1  21/7254 (0.29%)  13/7243 (0.18%)  15/8738 (0.17%)  36/8748 (0.41%) 
Chronic respiratory failure * 1  0/7254 (0.00%)  1/7243 (0.01%)  0/8738 (0.00%)  0/8748 (0.00%) 
Dyspnoea * 1  5/7254 (0.07%)  6/7243 (0.08%)  3/8738 (0.03%)  8/8748 (0.09%) 
Dyspnoea exertional * 1  0/7254 (0.00%)  1/7243 (0.01%)  1/8738 (0.01%)  2/8748 (0.02%) 
Emphysema * 1  0/7254 (0.00%)  0/7243 (0.00%)  0/8738 (0.00%)  1/8748 (0.01%) 
Eosinophilic pneumonia * 1  0/7254 (0.00%)  1/7243 (0.01%)  0/8738 (0.00%)  0/8748 (0.00%) 
Epistaxis * 1  3/7254 (0.04%)  1/7243 (0.01%)  2/8738 (0.02%)  0/8748 (0.00%) 
Haemoptysis * 1  0/7254 (0.00%)  0/7243 (0.00%)  1/8738 (0.01%)  0/8748 (0.00%) 
Haemothorax * 1  0/7254 (0.00%)  0/7243 (0.00%)  0/8738 (0.00%)  1/8748 (0.01%) 
Hypoxia * 1  1/7254 (0.01%)  2/7243 (0.03%)  0/8738 (0.00%)  0/8748 (0.00%) 
Interstitial lung disease * 1  0/7254 (0.00%)  1/7243 (0.01%)  0/8738 (0.00%)  0/8748 (0.00%) 
Nasal septum deviation * 1  0/7254 (0.00%)  0/7243 (0.00%)  1/8738 (0.01%)  0/8748 (0.00%) 
Pleural effusion * 1  1/7254 (0.01%)  1/7243 (0.01%)  1/8738 (0.01%)  0/8748 (0.00%) 
Pleural haemorrhage * 1  1/7254 (0.01%)  0/7243 (0.00%)  0/8738 (0.00%)  0/8748 (0.00%) 
Pleurisy * 1  0/7254 (0.00%)  0/7243 (0.00%)  0/8738 (0.00%)  1/8748 (0.01%) 
Pleuritic pain * 1  0/7254 (0.00%)  0/7243 (0.00%)  0/8738 (0.00%)  1/8748 (0.01%) 
Pneumonia aspiration * 1  0/7254 (0.00%)  3/7243 (0.04%)  2/8738 (0.02%)  1/8748 (0.01%) 
Pneumonitis * 1  0/7254 (0.00%)  1/7243 (0.01%)  0/8738 (0.00%)  0/8748 (0.00%) 
Pneumothorax * 1  2/7254 (0.03%)  2/7243 (0.03%)  4/8738 (0.05%)  2/8748 (0.02%) 
Pulmonary embolism * 1  5/7254 (0.07%)  7/7243 (0.10%)  6/8738 (0.07%)  13/8748 (0.15%) 
Pulmonary fibrosis * 1  0/7254 (0.00%)  1/7243 (0.01%)  0/8738 (0.00%)  0/8748 (0.00%) 
Pulmonary hypertension * 1  0/7254 (0.00%)  2/7243 (0.03%)  0/8738 (0.00%)  0/8748 (0.00%) 
Pulmonary oedema * 1  1/7254 (0.01%)  0/7243 (0.00%)  1/8738 (0.01%)  0/8748 (0.00%) 
Respiratory arrest * 1  0/7254 (0.00%)  1/7243 (0.01%)  0/8738 (0.00%)  0/8748 (0.00%) 
Respiratory failure * 1  5/7254 (0.07%)  5/7243 (0.07%)  4/8738 (0.05%)  5/8748 (0.06%) 
Sleep apnoea syndrome * 1  0/7254 (0.00%)  1/7243 (0.01%)  0/8738 (0.00%)  0/8748 (0.00%) 
Skin and subcutaneous tissue disorders         
Angioedema * 1  1/7254 (0.01%)  0/7243 (0.00%)  2/8738 (0.02%)  0/8748 (0.00%) 
Capillaritis * 1  0/7254 (0.00%)  0/7243 (0.00%)  0/8738 (0.00%)  1/8748 (0.01%) 
Decubitus ulcer * 1  0/7254 (0.00%)  0/7243 (0.00%)  0/8738 (0.00%)  1/8748 (0.01%) 
Diabetic foot * 1  0/7254 (0.00%)  0/7243 (0.00%)  1/8738 (0.01%)  0/8748 (0.00%) 
Hypoaesthesia facial * 1  0/7254 (0.00%)  1/7243 (0.01%)  0/8738 (0.00%)  0/8748 (0.00%) 
Panniculitis * 1  1/7254 (0.01%)  0/7243 (0.00%)  0/8738 (0.00%)  0/8748 (0.00%) 
Rash * 1  0/7254 (0.00%)  0/7243 (0.00%)  1/8738 (0.01%)  0/8748 (0.00%) 
Stevens-Johnson syndrome * 1  1/7254 (0.01%)  0/7243 (0.00%)  0/8738 (0.00%)  0/8748 (0.00%) 
Skin hypertrophy * 1  0/7254 (0.00%)  0/7243 (0.00%)  0/8738 (0.00%)  1/8748 (0.01%) 
Social circumstances         
Activities of daily living impaired * 1  1/7254 (0.01%)  0/7243 (0.00%)  0/8738 (0.00%)  0/8748 (0.00%) 
Surgical and medical procedures         
Colostomy * 1  1/7254 (0.01%)  0/7243 (0.00%)  0/8738 (0.00%)  1/8748 (0.01%) 
Face lift * 1  0/7254 (0.00%)  1/7243 (0.01%)  0/8738 (0.00%)  0/8748 (0.00%) 
Implantable defibrillator removal * 1  1/7254 (0.01%)  0/7243 (0.00%)  0/8738 (0.00%)  0/8748 (0.00%) 
Intraocular lens implant * 1  0/7254 (0.00%)  0/7243 (0.00%)  0/8738 (0.00%)  1/8748 (0.01%) 
Renal surgery * 1  0/7254 (0.00%)  0/7243 (0.00%)  0/8738 (0.00%)  1/8748 (0.01%) 
Surgery * 1  0/7254 (0.00%)  0/7243 (0.00%)  0/8738 (0.00%)  1/8748 (0.01%) 
Vascular disorders         
Accelerated hypertension * 1  0/7254 (0.00%)  1/7243 (0.01%)  0/8738 (0.00%)  2/8748 (0.02%) 
Aneurysm ruptured * 1  0/7254 (0.00%)  1/7243 (0.01%)  0/8738 (0.00%)  0/8748 (0.00%) 
Aortic aneurysm * 1  5/7254 (0.07%)  3/7243 (0.04%)  5/8738 (0.06%)  6/8748 (0.07%) 
Aortic aneurysm rupture * 1  0/7254 (0.00%)  0/7243 (0.00%)  2/8738 (0.02%)  0/8748 (0.00%) 
Aortic dissection * 1  0/7254 (0.00%)  0/7243 (0.00%)  2/8738 (0.02%)  0/8748 (0.00%) 
Aortic rupture * 1  1/7254 (0.01%)  0/7243 (0.00%)  0/8738 (0.00%)  0/8748 (0.00%) 
Aortic stenosis * 1  2/7254 (0.03%)  2/7243 (0.03%)  2/8738 (0.02%)  2/8748 (0.02%) 
Arterial occlusive disease * 1  1/7254 (0.01%)  0/7243 (0.00%)  0/8738 (0.00%)  0/8748 (0.00%) 
Arterial stenosis limb * 1  1/7254 (0.01%)  0/7243 (0.00%)  0/8738 (0.00%)  0/8748 (0.00%) 
Arterial thrombosis limb * 1  0/7254 (0.00%)  0/7243 (0.00%)  1/8738 (0.01%)  0/8748 (0.00%) 
Arteriosclerosis * 1  1/7254 (0.01%)  1/7243 (0.01%)  0/8738 (0.00%)  3/8748 (0.03%) 
Arteriovenous fistula * 1  0/7254 (0.00%)  1/7243 (0.01%)  0/8738 (0.00%)  1/8748 (0.01%) 
Deep vein thrombosis * 1  5/7254 (0.07%)  5/7243 (0.07%)  1/8738 (0.01%)  6/8748 (0.07%) 
Embolism venous * 1  0/7254 (0.00%)  0/7243 (0.00%)  1/8738 (0.01%)  0/8748 (0.00%) 
Femoral artery occlusion * 1  1/7254 (0.01%)  0/7243 (0.00%)  0/8738 (0.00%)  0/8748 (0.00%) 
Haematoma * 1  4/7254 (0.06%)  2/7243 (0.03%)  1/8738 (0.01%)  0/8748 (0.00%) 
Hypertension * 1  8/7254 (0.11%)  4/7243 (0.06%)  4/8738 (0.05%)  3/8748 (0.03%) 
Hypertensive crisis * 1  0/7254 (0.00%)  0/7243 (0.00%)  1/8738 (0.01%)  0/8748 (0.00%) 
Hypertensive emergency * 1  1/7254 (0.01%)  0/7243 (0.00%)  0/8738 (0.00%)  0/8748 (0.00%) 
Hypotension * 1  8/7254 (0.11%)  4/7243 (0.06%)  2/8738 (0.02%)  2/8748 (0.02%) 
Hypovolaemic shock * 1  0/7254 (0.00%)  0/7243 (0.00%)  1/8738 (0.01%)  0/8748 (0.00%) 
Infarction * 1  0/7254 (0.00%)  1/7243 (0.01%)  0/8738 (0.00%)  0/8748 (0.00%) 
Intermittent claudication * 1  1/7254 (0.01%)  1/7243 (0.01%)  0/8738 (0.00%)  0/8748 (0.00%) 
Intra-abdominal haematoma * 1  0/7254 (0.00%)  1/7243 (0.01%)  0/8738 (0.00%)  0/8748 (0.00%) 
Ischaemia * 1  0/7254 (0.00%)  1/7243 (0.01%)  0/8738 (0.00%)  0/8748 (0.00%) 
Malignant hypertension * 1  1/7254 (0.01%)  0/7243 (0.00%)  0/8738 (0.00%)  0/8748 (0.00%) 
Orthostatic hypertension * 1  0/7254 (0.00%)  0/7243 (0.00%)  0/8738 (0.00%)  1/8748 (0.01%) 
Orthostatic hypotension * 1  1/7254 (0.01%)  5/7243 (0.07%)  0/8738 (0.00%)  1/8748 (0.01%) 
Peripheral arterial occlusive disease * 1  1/7254 (0.01%)  0/7243 (0.00%)  2/8738 (0.02%)  1/8748 (0.01%) 
Peripheral artery aneurysm * 1  0/7254 (0.00%)  0/7243 (0.00%)  1/8738 (0.01%)  0/8748 (0.00%) 
Peripheral ischaemia * 1  0/7254 (0.00%)  0/7243 (0.00%)  3/8738 (0.03%)  0/8748 (0.00%) 
Peripheral vascular disorder * 1  1/7254 (0.01%)  1/7243 (0.01%)  1/8738 (0.01%)  2/8748 (0.02%) 
Shock * 1  0/7254 (0.00%)  0/7243 (0.00%)  1/8738 (0.01%)  0/8748 (0.00%) 
Steal syndrome * 1  0/7254 (0.00%)  0/7243 (0.00%)  0/8738 (0.00%)  1/8748 (0.01%) 
Thrombosis * 1  1/7254 (0.01%)  1/7243 (0.01%)  0/8738 (0.00%)  0/8748 (0.00%) 
Venous insufficiency * 1  0/7254 (0.00%)  1/7243 (0.01%)  0/8738 (0.00%)  0/8748 (0.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA version 15.0
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5.00%
Fluzone® High Dose Vaccine (Year 1) Fluzone® Vaccine (Year 1) Fluzone® High Dose Vaccine (Year 2) Fluzone® Vaccine (Year 2)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/7254 (0.00%)   0/7243 (0.00%)   0/8738 (0.00%)   0/8748 (0.00%) 
[Not Specified]
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Medical Director
Organization: Sanofi Pasteur Inc.
EMail: RegistryContactUs@sanofipasteur.com
Publications of Results:
DiazGranados CA, Dunning AJ, Kimmel M, Kirby D, Treanor J, Collins A, Pollak R, Christoff J, Earl J, Landolfi V, Martin E, Gurunathan S, Nathan R, Greenberg DP, Tornieporth NG, Decker MD, Talbot HK. Efficacy of high-dose versus standard-dose influenza vaccine in older adults. N Engl J Med. 2014 Aug 14;371(7):635-45. doi: 10.1056/NEJMoa1315727.
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Sanofi ( Sanofi Pasteur, a Sanofi Company )
ClinicalTrials.gov Identifier: NCT01427309    
Other Study ID Numbers: FIM12
U1111-1120-1300 ( Other Identifier: WHO )
First Submitted: August 30, 2011
First Posted: September 1, 2011
Results First Submitted: July 8, 2014
Results First Posted: August 6, 2014
Last Update Posted: April 20, 2015