Clincosm LogoSign in Get a demo

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

Sponsor
Sanofi Pasteur, a Sanofi Company (Industry)
Overall Status
Completed
CT.gov ID
NCT01427309
Collaborator
(none)
31,989
Enrollment
113
Locations
2
Arms
26
Duration (Months)
283.1
Patients Per Site
10.9
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The aim of this study is to determine the efficacy of Fluzone High-Dose compared to standard dose Fluzone for laboratory-confirmed or culture-confirmed influenza caused by influenza types/subtypes that are similar (for laboratory-confirmed) or antigenically similar (for culture-confirmed) to those contained in the respective annual vaccine formulations.

Primary Objective:
  • To compare the clinical efficacy of Fluzone High-Dose to that of Fluzone in elderly adults, with respect to laboratory-confirmed influenza caused by any influenza viral types/subtypes, associated with the occurrence of a protocol-defined influenza-like-illnesses (ILI).
Secondary Objectives:

  • To compare the clinical efficacy of Fluzone High-Dose to that of Fluzone in elderly adults, with respect to laboratory-confirmed influenza, caused by any influenza viral types/subtypes, associated with the occurrence of a protocol-defined ILI.

  • To compare the clinical efficacy of Fluzone High-Dose to that of Fluzone in elderly adults, with respect to culture-confirmed influenza, caused by any influenza viral types/subtypes, associated with the occurrence of a protocol-defined ILI.

  • To compare the clinical efficacy of Fluzone High-Dose to that of Fluzone in elderly adults, with respect to culture-confirmed influenza caused by viral types/subtypes antigenically similar to those contained in the respective annual vaccine formulations, associated with the occurrence of a modified Centers for Disease Control and Prevention (CDC)-defined ILI.

  • To compare the clinical efficacy of Fluzone High-Dose to that of Fluzone in elderly adults, with respect to culture-confirmed influenza caused by any influenza viral types/subtypes, associated with the occurrence of a modified CDC-defined ILI.

  • To compare the clinical efficacy of Fluzone High-Dose to that of Fluzone in elderly adults, with respect to culture-confirmed influenza caused by viral types/subtypes antigenically similar to those contained in the respective annual vaccine formulations, associated with the occurrence of a respiratory illness.

  • To compare the clinical efficacy of Fluzone High-Dose to that of Fluzone in elderly adults, with respect to culture-confirmed influenza caused by any influenza viral types/subtypes, associated with the occurrence of a respiratory illness.

Condition or Disease Intervention/Treatment Phase
  • Biological: High Dose Trivalent Inactivated Influenza Vaccine
  • Biological: Trivalent Inactivated Influenza Vaccine
 Phase 4

Detailed Description

The trial will span 2 influenza seasons. Each study year, participants will be randomized to receive one dose of either Fluzone® High-Dose or Fluzone® vaccine prior to the start of the influenza season and will be followed until the end of each season.

The duration of each participant's participation in the respective study year will be 6 to 8 months, depending on the time of enrollment.

Study Design

Study Type:
Interventional
Actual Enrollment :
31989 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Prevention
Official Title:
Efficacy Study of Fluzone® High-Dose Vaccine Compared With Fluzone® Vaccine In Elderly Adults
Study Start Date :
Sep 1, 2011
Actual Primary Completion Date :
May 1, 2013
Actual Study Completion Date :
Nov 1, 2013

Arms and Interventions

Arm Intervention/Treatment
Experimental: High Dose Trivalent Inactivated Influenza Vaccine

Participants will receive an injection of High Dose Trivalent Inactivated Influenza Vaccine

Biological: High Dose Trivalent Inactivated Influenza Vaccine
0.5 mL Intramuscular
Other Names:
  • Fluzone® High Dose

    		•
    Active Comparator: Trivalent Inactivated Influenza Vaccine

    Participants will receive an injection of the Trivalent Inactivated Influenza vaccine

    Biological: Trivalent Inactivated Influenza Vaccine
    0.5 mL, Intramuscular
    Other Names:
  • Fluzone®

    		•

    Outcome Measures

    Primary Outcome Measures

    1. 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). [≥14 days post-vaccination]

      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).

    Secondary Outcome Measures

    1. 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) [≥14 days post-vaccination]

      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.

    2. Occurrences of Culture-confirmed Influenza Caused by Any Influenza Viral Types/Subtypes, in Association With a Protocol-defined Influenza-like Illness [≥14 days post-vaccination]

      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).

    3. 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. [≥14 days post-vaccination]

      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.

    4. Occurrences of Culture-confirmed Influenza Caused by Any Influenza Viral Types/Subtypes, in Association With a Modified CDC-defined Influenza-like Illness [≥14 days post-vaccination]

      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.

    5. 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 [≥14 days post-vaccination]

      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.

    6. Occurrences of Culture-confirmed Influenza Caused by Any Influenza Viral Types/Subtypes, in Association With a Respiratory Illness [≥14 days post-vaccination]

      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.

    Other Outcome Measures

    1. Safety Overview After Injection With Either Fluzone High Dose or Fluzone Vaccine Through the End of Surveillance Period [Day 0 up to Day 240 post-vaccination]

      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.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    65 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    Yes
    Inclusion Criteria:

    • Aged ≥ 65 years on the day of vaccination

    • Informed consent form signed and dated

    • Able to attend all scheduled visits and to comply with all trial procedures.

    Exclusion Criteria:

    • Participation at the time of study enrollment (or in the 4 weeks preceding the trial vaccination), or planned participation during each year of the trial period, in another clinical trial investigating a vaccine, drug, medical device, or medical procedure (Note: Concomitant participation in an observational trial is acceptable)

    • Vaccination against influenza in the 6 months preceding the trial vaccination

    • Systemic hypersensitivity to eggs, chicken proteins, or any of the vaccine components, or a history of a life-threatening reaction to Fluzone High-Dose or Fluzone vaccine or to a vaccine containing any of the same substances

    • Personal history of Guillain-Barré Syndrome

    • Dementia or any other cognitive condition at a stage that could interfere with following the trial procedures

    • Thrombocytopenia contraindicating intramuscular (IM) vaccination, as judged by the investigator

    • Bleeding disorder or receipt of anticoagulants in the 3 weeks preceding inclusion, contraindicating intramuscular vaccination, as judged by the investigator

    • Current alcohol abuse or drug addiction

    • Subject deprived of freedom by an administrative or court order, or in an emergency setting, or hospitalized involuntarily

    • 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

    • Moderate or severe acute illness with or without fever (oral temperature > 99.0ºF [> 37.2ºC]). If this contraindication exists, vaccination will be deferred until the individual has been medically stable and/or afebrile (temperature ≤ 99.0 ºF [≤ 37.2ºC]) for at least 24 hours

    • Signs and symptoms of an acute infectious respiratory illness. If this exists, vaccination will be deferred until the symptoms resolve.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Mobile Alabama United States 36608
    2 Chandler Arizona United States 85224
    3 Glendale Arizona United States 85306
    4 Glendale Arizona United States 85308
    5 Mesa Arizona United States 85203
    6 Mesa Arizona United States 85213
    7 Phoenix Arizona United States 85020
    8 Phoenix Arizona United States 85028
    9 Phoenix Arizona United States 85050
    10 Scottsdale Arizona United States 85251
    11 Tempe Arizona United States 85283
    12 Harrisburg Arkansas United States 72432
    13 Anaheim California United States 92801
    14 La Mesa California United States 91942
    15 Oceanside California United States 92056
    16 Redding California United States 96001
    17 San Diego California United States 92103
    18 Santa Rosa California United States 95405
    19 Aurora Colorado United States 80045
    20 Colorado Springs Colorado United States 80907
    21 Colorado Springs Colorado United States 80922
    22 Milford Connecticut United States 01757
    23 Milford Connecticut United States 06460
    24 Brooksville Florida United States 34601
    25 Clearwater Florida United States 33756
    26 Clearwater Florida United States 33761
    27 Coral Gables Florida United States 33134
    28 Crystal River Florida United States 34429
    29 DeLand Florida United States 32720
    30 Jacksonville Florida United States 32216
    31 Melbourne Florida United States 32935
    32 Pembroke Pine Florida United States 33026
    33 Pinellas Park Florida United States 33781
    34 Sarasota Florida United States 34231
    35 Stockbridge Georgia United States 30281
    36 Boise Idaho United States 83642
    37 Chicago Illinois United States 60654
    38 Peoria Illinois United States 61602
    39 Mishawaka Indiana United States 46545
    40 Lenexa Kansas United States 66219
    41 Newton Kansas United States 67114
    42 Overland Park Kansas United States 66212
    43 Prairie Village Kansas United States 66206
    44 Wichita Kansas United States 67205
    45 Wichita Kansas United States 67207
    46 Bardstown Kentucky United States 40004
    47 Lexington Kentucky United States 40504
    48 Columbia Maryland United States 21045
    49 Elkridge Maryland United States 21075
    50 Rockville Maryland United States 20850
    51 Brockton Massachusetts United States 02301
    52 Haverhill Massachusetts United States 01830
    53 Edina Minnesota United States 55435
    54 Kansas City Missouri United States 64114
    55 St. Louis Missouri United States 63141
    56 Missoula Montana United States 59808
    57 Bellevue Nebraska United States 68005
    58 Omaha Nebraska United States 68114
    59 Las Vega Nevada United States 89104
    60 Newington New Hampshire United States 03801
    61 Edison New Jersey United States 08817
    62 Albuquerque New Mexico United States 87018
    63 Binghamton New York United States 13901
    64 Endwell New York United States 13760
    65 Rochester New York United States 14609
    66 Rochester New York United States 14642
    67 Cary North Carolina United States 27518
    68 Charlotte North Carolina United States 28209
    69 Hickory North Carolina United States 28602
    70 Raleigh North Carolina United States 27609
    71 Raleigh North Carolina United States 27612
    72 Salisbury North Carolina United States 28144
    73 Wilmington North Carolina United States 28401
    74 Winston Salem North Carolina United States 27103
    75 Fargo North Dakota United States 58104
    76 Idaho Falls North Dakota United States 83404
    77 Akron Ohio United States 44311
    78 Cincinnati Ohio United States 45227
    79 Cincinnati Ohio United States 45259
    80 Cleveland Ohio United States 44122
    81 Columbus Ohio United States 43213
    82 Norman Oklahoma United States 73069
    83 Erie Pennsylvania United States 16506
    84 Pittsburgh Pennsylvania United States 15241
    85 Scranton Pennsylvania United States 18510
    86 Warwick Rhode Island United States 02886
    87 Anderson South Carolina United States 29621
    88 Clinton South Carolina United States 29325
    89 Greer South Carolina United States 29650
    90 Mt. Pleasant South Carolina United States 29464
    91 Spartanburg South Carolina United States 29303
    92 Bristol Tennessee United States 37620
    93 Nashville Tennessee United States 37203
    94 Nashville Tennessee United States 37212
    95 Fort Worth Texas United States 76107
    96 San Antonio Texas United States 78229
    97 Tomball Texas United States 77375
    98 Salt Lake City Utah United States 84109
    99 Salt Lake City Utah United States 84121
    100 Salt Lake City Utah United States 84124
    101 South Jordan Utah United States 84095
    102 West Jordan Utah United States 84088
    103 Norfolk Virginia United States 23507
    104 Williamsburg Virginia United States 23185
    105 Winchester Virginia United States 22601
    106 Coquitlam British Columbia Canada V3K3P4
    107 Mount Pearl Newfoundland and Labrador Canada A1N1W7
    108 Truro Nova Scotia Canada B2N1L2
    109 Sudbury Ontario Canada P3E1H5
    110 Toronto Ontario Canada M9W4L6
    111 Sherbrooke Quebec Canada J1H4J6
    112 Bayamon Puerto Rico 00961
    113 San Juan Puerto Rico 00909

    Sponsors and Collaborators

    • Sanofi Pasteur, a Sanofi Company

    Investigators

    • Study Director: Medical Director, Sanofi Pasteur Inc.

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Sanofi Pasteur, a Sanofi Company
    ClinicalTrials.gov Identifier:
    NCT01427309
    Other Study ID Numbers:
    • FIM12
    • U1111-1120-1300
    First Posted:
    Sep 1, 2011
    Last Update Posted:
    Apr 20, 2015
    Last Verified:
    Mar 1, 2015
    Keywords provided by Sanofi Pasteur, a Sanofi Company
    Influenza
    Trivalent Inactivated Influenza Vaccine
    High-Dose Trivalent Inactivated Influenza Vaccine
    Fluzone® High-Dose
    Influenza vaccines
    Additional relevant MeSH terms:
    Influenza, Human
    Vaccines

    Study Results

    Participant Flow

    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 Detail 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)
    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

    Baseline Characteristics

    Arm/Group Title Fluzone® High Dose Vaccine (Year 1) Fluzone® Vaccine (Year 1) Fluzone® High Dose Vaccine (Year 2) Fluzone® Vaccine (Year 2) Total
    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 Participants 7253 7244 8737 8749 31983
    Age (Count of Participants)
    <=18 years
    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%
    >=65 years
    7253
    100%
    7244
    100%
    8737
    100%
    8749
    100%
    31983
    100%
    Age (Years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [Years]
    73.3
    (5.88)
    73.2
    (5.82)
    73.3
    (5.74)
    73.4
    (5.85)
    73.3
    (5.82)
    Sex: Female, Male (Count of 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 (Number) [Number]
    United States
    6953
    95.9%
    6944
    95.9%
    8315
    95.2%
    8326
    95.2%
    30538
    95.5%
    Canada
    300
    4.1%
    300
    4.1%
    422
    4.8%
    423
    4.8%
    1445
    4.5%

    Outcome Measures

    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).
    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

    Outcome Measure Data

    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)
    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
    Measure Participants 7209 7207 8683 8704
    Number [Participants]
    23
    0.3%
    42
    0.6%
    204
    2.3%
    258
    2.9%
    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)
    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

    Outcome Measure Data

    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)
    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
    Measure Participants 7209 7207 8683 8704
    Number [Participants]
    2
    0%
    7
    0.1%
    61
    0.7%
    85
    1%
    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
    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

    Outcome Measure Data

    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)
    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
    Measure Participants 7209 7207 8683 8704
    Number [Participants]
    20
    0.3%
    33
    0.5%
    185
    2.1%
    234
    2.7%
    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.
    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

    Outcome Measure Data

    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)
    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
    Measure Participants 7209 7207 8683 8704
    Number [Participants]
    0
    0%
    3
    0%
    22
    0.3%
    42
    0.5%
    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
    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

    Outcome Measure Data

    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)
    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
    Measure Participants 7209 7207 8683 8704
    Number [Participants]
    7
    0.1%
    7
    0.1%
    77
    0.9%
    103
    1.2%
    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
    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

    Outcome Measure Data

    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)
    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
    Measure Participants 7209 7207 8683 8704
    Number [Participants]
    7
    0.1%
    9
    0.1%
    78
    0.9%
    109
    1.2%
    7. Secondary Outcome
    Title Occurrences of Culture-confirmed Influenza Caused by Any Influenza Viral Types/Subtypes, in Association With a Respiratory Illness
    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

    Outcome Measure Data

    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)
    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
    Measure Participants 7209 7207 8683 8704
    Number [Participants]
    38
    0.5%
    44
    0.6%
    238
    2.7%
    294
    3.4%
    8. Other Pre-specified Outcome
    Title Safety Overview After Injection With Either Fluzone High Dose or Fluzone Vaccine Through the End of Surveillance Period
    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

    Outcome Measure Data

    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)
    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
    Measure Participants 7254 7243 8738 8748
    Serious adverse events (SAE)
    680
    9.4%
    704
    9.7%
    643
    7.4%
    738
    8.4%
    Death
    48
    0.7%
    40
    0.6%
    35
    0.4%
    44
    0.5%
    Adverse events of special interest
    2
    0%
    2
    0%
    1
    0%
    4
    0%
    Guillain Barré Syndrome
    0
    0%
    0
    0%
    0
    0%
    1
    0%
    Bell's palsy
    0
    0%
    2
    0%
    1
    0%
    3
    0%
    Encephalitis/myelitis
    1
    0%
    0
    0%
    0
    0%
    0
    0%
    Optic neuritis
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Stevens Johnson syndrome
    1
    0%
    0
    0%
    0
    0%
    0
    0%
    Toxic epidermal necrolysis
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    SAE leading to study discontinuation
    52
    0.7%
    45
    0.6%
    47
    0.5%
    58
    0.7%
    Related SAE
    1
    0%
    0
    0%
    2
    0%
    0
    0%
    Related SAE leading to study discontinuation
    0
    0%
    0
    0%
    0
    0%
    0
    0%

    Adverse Events

    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)
    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 (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN) / (NaN) / (NaN)
    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 (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 680/7254 (9.4%) 704/7243 (9.7%) 643/8738 (7.4%) 738/8748 (8.4%)
    Blood and lymphatic system disorders
    Anaemia 8/7254 (0.1%) 4/7243 (0.1%) 9/8738 (0.1%) 7/8748 (0.1%)
    Anaemia macrocytic 0/7254 (0%) 0/7243 (0%) 1/8738 (0%) 0/8748 (0%)
    Anaemia of chronic disease 1/7254 (0%) 0/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Bone marrow failure 0/7254 (0%) 1/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Coagulopathy 0/7254 (0%) 0/7243 (0%) 1/8738 (0%) 0/8748 (0%)
    Haemorrhagic anaemia 0/7254 (0%) 3/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Idiopathic thrombocytopenic purpura 1/7254 (0%) 0/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Iron deficiency anaemia 1/7254 (0%) 2/7243 (0%) 2/8738 (0%) 0/8748 (0%)
    Leukocytosis 0/7254 (0%) 1/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Microcytic anaemia 1/7254 (0%) 0/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Splenic lesion 0/7254 (0%) 1/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Thrombocytopenia 0/7254 (0%) 2/7243 (0%) 1/8738 (0%) 1/8748 (0%)
    Cardiac disorders
    Acute coronary syndrome 4/7254 (0.1%) 1/7243 (0%) 3/8738 (0%) 2/8748 (0%)
    Acute myocardial infarction 2/7254 (0%) 7/7243 (0.1%) 11/8738 (0.1%) 9/8748 (0.1%)
    Angina pectoris 2/7254 (0%) 8/7243 (0.1%) 5/8738 (0.1%) 5/8748 (0.1%)
    Angina unstable 2/7254 (0%) 9/7243 (0.1%) 8/8738 (0.1%) 5/8748 (0.1%)
    Aortic valve disease mixed 0/7254 (0%) 0/7243 (0%) 1/8738 (0%) 0/8748 (0%)
    Aortic valve stenosis 1/7254 (0%) 0/7243 (0%) 1/8738 (0%) 2/8748 (0%)
    Arrhythmia 4/7254 (0.1%) 2/7243 (0%) 2/8738 (0%) 0/8748 (0%)
    Arteriosclerosis coronary artery 2/7254 (0%) 1/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Arteriospasm coronary 0/7254 (0%) 0/7243 (0%) 1/8738 (0%) 0/8748 (0%)
    Atrial fibrillation 28/7254 (0.4%) 29/7243 (0.4%) 23/8738 (0.3%) 38/8748 (0.4%)
    Atrial flutter 3/7254 (0%) 2/7243 (0%) 4/8738 (0%) 1/8748 (0%)
    Atrial tachycardia 0/7254 (0%) 1/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Atrial thrombosis 1/7254 (0%) 2/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Atrioventricular block 0/7254 (0%) 1/7243 (0%) 1/8738 (0%) 0/8748 (0%)
    Atrioventricular block complete 1/7254 (0%) 1/7243 (0%) 0/8738 (0%) 2/8748 (0%)
    Atrioventricular block second degree 0/7254 (0%) 1/7243 (0%) 1/8738 (0%) 2/8748 (0%)
    Bradyarrhythmia 0/7254 (0%) 0/7243 (0%) 1/8738 (0%) 0/8748 (0%)
    Bradycardia 5/7254 (0.1%) 4/7243 (0.1%) 2/8738 (0%) 2/8748 (0%)
    Bundle branch block left 0/7254 (0%) 0/7243 (0%) 1/8738 (0%) 0/8748 (0%)
    Cardiac arrest 6/7254 (0.1%) 1/7243 (0%) 0/8738 (0%) 5/8748 (0.1%)
    Cardiac disorder 1/7254 (0%) 0/7243 (0%) 1/8738 (0%) 0/8748 (0%)
    Cardiac failure 2/7254 (0%) 0/7243 (0%) 2/8738 (0%) 4/8748 (0%)
    Cardiac failure acute 1/7254 (0%) 0/7243 (0%) 2/8738 (0%) 0/8748 (0%)
    Cardiac failure chronic 0/7254 (0%) 1/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Cardiac failure congestive 15/7254 (0.2%) 22/7243 (0.3%) 19/8738 (0.2%) 29/8748 (0.3%)
    Cardiac valve disease 0/7254 (0%) 0/7243 (0%) 2/8738 (0%) 0/8748 (0%)
    Cardio-respiratory arrest 3/7254 (0%) 1/7243 (0%) 1/8738 (0%) 0/8748 (0%)
    Cardiomegaly 1/7254 (0%) 0/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Cardiomyopathy 1/7254 (0%) 0/7243 (0%) 2/8738 (0%) 3/8748 (0%)
    Cardiopulmonary failure 0/7254 (0%) 0/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Cardiovascular disorder 0/7254 (0%) 0/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Congestive cardiomyopathy 0/7254 (0%) 1/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Coronary artery disease 14/7254 (0.2%) 18/7243 (0.2%) 16/8738 (0.2%) 18/8748 (0.2%)
    Coronary artery insufficiency 0/7254 (0%) 0/7243 (0%) 1/8738 (0%) 0/8748 (0%)
    Coronary artery occlusion 4/7254 (0.1%) 2/7243 (0%) 3/8738 (0%) 1/8748 (0%)
    Coronary artery stenosis 1/7254 (0%) 0/7243 (0%) 2/8738 (0%) 2/8748 (0%)
    Heart valve incompetence 1/7254 (0%) 0/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Ischaemic cardiomyopathy 1/7254 (0%) 0/7243 (0%) 1/8738 (0%) 2/8748 (0%)
    Mitral valve disease 0/7254 (0%) 0/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Mitral valve incompetence 1/7254 (0%) 1/7243 (0%) 1/8738 (0%) 0/8748 (0%)
    Mitral valve stenosis 2/7254 (0%) 0/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Myocardial infarction 21/7254 (0.3%) 21/7243 (0.3%) 14/8738 (0.2%) 10/8748 (0.1%)
    Myocardial ischaemia 0/7254 (0%) 1/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Palpitations 0/7254 (0%) 0/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Pericardial effusion 0/7254 (0%) 1/7243 (0%) 0/8738 (0%) 2/8748 (0%)
    Pericarditis 1/7254 (0%) 0/7243 (0%) 1/8738 (0%) 0/8748 (0%)
    Sick sinus syndrome 1/7254 (0%) 0/7243 (0%) 3/8738 (0%) 4/8748 (0%)
    Sinus arrhythmia 1/7254 (0%) 0/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Sinus bradycardia 0/7254 (0%) 2/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Stress cardiomyopathy 0/7254 (0%) 1/7243 (0%) 1/8738 (0%) 0/8748 (0%)
    Supraventricular tachycardia 3/7254 (0%) 3/7243 (0%) 1/8738 (0%) 3/8748 (0%)
    Tachycardia 2/7254 (0%) 1/7243 (0%) 2/8738 (0%) 0/8748 (0%)
    Ventricular extrasystoles 0/7254 (0%) 1/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Ventricular fibrillation 0/7254 (0%) 0/7243 (0%) 1/8738 (0%) 0/8748 (0%)
    Ventricular tachycardia 1/7254 (0%) 2/7243 (0%) 1/8738 (0%) 2/8748 (0%)
    Congenital, familial and genetic disorders
    Arteriovenous malformation 0/7254 (0%) 0/7243 (0%) 1/8738 (0%) 0/8748 (0%)
    Gastrointestinal arteriovenous malformation 0/7254 (0%) 0/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Ear and labyrinth disorders
    Vertigo 2/7254 (0%) 5/7243 (0.1%) 2/8738 (0%) 7/8748 (0.1%)
    Endocrine disorders
    Adrenocortical insufficiency acute 0/7254 (0%) 0/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Goitre 1/7254 (0%) 0/7243 (0%) 0/8738 (0%) 2/8748 (0%)
    Hyperparathyroidism 0/7254 (0%) 1/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Hyperthyroidism 0/7254 (0%) 1/7243 (0%) 1/8738 (0%) 0/8748 (0%)
    Thyroid mass 1/7254 (0%) 0/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Eye disorders
    Cataract 1/7254 (0%) 0/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Periorbital oedema 0/7254 (0%) 0/7243 (0%) 1/8738 (0%) 0/8748 (0%)
    Retinal artery occlusion 1/7254 (0%) 0/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Retinal detachment 0/7254 (0%) 0/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Gastrointestinal disorders
    Abdominal hernia 1/7254 (0%) 0/7243 (0%) 0/8738 (0%) 3/8748 (0%)
    Abdominal mass 1/7254 (0%) 0/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Abdominal pain 1/7254 (0%) 3/7243 (0%) 5/8738 (0.1%) 4/8748 (0%)
    Abdominal pain lower 1/7254 (0%) 0/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Abdominal pain upper 0/7254 (0%) 1/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Abdominal wall haematoma 0/7254 (0%) 0/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Abdominal wall haemorrhage 0/7254 (0%) 1/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Alcoholic pancreatitis 1/7254 (0%) 1/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Anal fistula 0/7254 (0%) 1/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Colitis 2/7254 (0%) 6/7243 (0.1%) 1/8738 (0%) 1/8748 (0%)
    Colitis ischaemic 2/7254 (0%) 2/7243 (0%) 3/8738 (0%) 4/8748 (0%)
    Colonic polyp 0/7254 (0%) 1/7243 (0%) 0/8738 (0%) 2/8748 (0%)
    Colonic stenosis 1/7254 (0%) 0/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Constipation 0/7254 (0%) 0/7243 (0%) 3/8738 (0%) 0/8748 (0%)
    Crohn's disease 0/7254 (0%) 0/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Diaphragmatic hernia 0/7254 (0%) 0/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Diarrhoea 0/7254 (0%) 0/7243 (0%) 0/8738 (0%) 2/8748 (0%)
    Dieulafoy's vascular malformation 0/7254 (0%) 0/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Diverticular perforation 2/7254 (0%) 1/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Diverticulum 0/7254 (0%) 5/7243 (0.1%) 0/8738 (0%) 1/8748 (0%)
    Diverticulum intestinal 0/7254 (0%) 1/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Diverticulum intestinal haemorrhagic 1/7254 (0%) 1/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Duodenal stenosis 1/7254 (0%) 0/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Duodenal ulcer 1/7254 (0%) 1/7243 (0%) 0/8738 (0%) 2/8748 (0%)
    Duodenal ulcer haemorrhage 1/7254 (0%) 0/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Dysphagia 1/7254 (0%) 0/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Erosive oesophagitis 1/7254 (0%) 0/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Faecaloma 1/7254 (0%) 0/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Food poisoning 0/7254 (0%) 1/7243 (0%) 2/8738 (0%) 0/8748 (0%)
    Gastric antral vascular ectasia 0/7254 (0%) 0/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Gastric ulcer 0/7254 (0%) 0/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Gastric ulcer haemorrhage 0/7254 (0%) 0/7243 (0%) 0/8738 (0%) 3/8748 (0%)
    Gastritis 1/7254 (0%) 4/7243 (0.1%) 0/8738 (0%) 0/8748 (0%)
    Gastritis erosive 0/7254 (0%) 0/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Gastroduodenitis 1/7254 (0%) 0/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Gastrointestinal disorder 0/7254 (0%) 0/7243 (0%) 1/8738 (0%) 1/8748 (0%)
    Gastrointestinal haemorrhage 6/7254 (0.1%) 7/7243 (0.1%) 5/8738 (0.1%) 9/8748 (0.1%)
    Gastrooesophageal reflux disease 1/7254 (0%) 2/7243 (0%) 1/8738 (0%) 1/8748 (0%)
    Gastrooesophagitis 0/7254 (0%) 0/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Haematemesis 0/7254 (0%) 2/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Haematochezia 1/7254 (0%) 0/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Haemorrhagic erosive gastritis 1/7254 (0%) 0/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Hiatus hernia 2/7254 (0%) 2/7243 (0%) 1/8738 (0%) 1/8748 (0%)
    Ileus 1/7254 (0%) 0/7243 (0%) 1/8738 (0%) 0/8748 (0%)
    Impaired gastric emptying 0/7254 (0%) 1/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Inguinal hernia 1/7254 (0%) 1/7243 (0%) 0/8738 (0%) 4/8748 (0%)
    Intestinal ischaemia 0/7254 (0%) 0/7243 (0%) 2/8738 (0%) 0/8748 (0%)
    Intestinal obstruction 0/7254 (0%) 1/7243 (0%) 3/8738 (0%) 3/8748 (0%)
    Intestinal perforation 0/7254 (0%) 1/7243 (0%) 1/8738 (0%) 2/8748 (0%)
    Intestinal polyp haemorrhage 0/7254 (0%) 0/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Large intestine perforation 1/7254 (0%) 1/7243 (0%) 0/8738 (0%) 2/8748 (0%)
    Lower gastrointestinal haemorrhage 0/7254 (0%) 1/7243 (0%) 1/8738 (0%) 2/8748 (0%)
    Lumbar hernia 1/7254 (0%) 1/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Mallory-Weiss syndrome 0/7254 (0%) 1/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Nausea 1/7254 (0%) 0/7243 (0%) 1/8738 (0%) 0/8748 (0%)
    Obstruction gastric 0/7254 (0%) 1/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Oesophageal obstruction 0/7254 (0%) 2/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Oesophageal spasm 0/7254 (0%) 1/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Oesophageal varices haemorrhage 0/7254 (0%) 1/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Pancreatitis 5/7254 (0.1%) 2/7243 (0%) 1/8738 (0%) 0/8748 (0%)
    Pancreatitis acute 3/7254 (0%) 2/7243 (0%) 0/8738 (0%) 5/8748 (0.1%)
    Pancreatitis necrotising 0/7254 (0%) 0/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Pancreatitis relapsing 1/7254 (0%) 0/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Peptic ulcer 0/7254 (0%) 0/7243 (0%) 1/8738 (0%) 0/8748 (0%)
    Peptic ulcer haemorrhage 1/7254 (0%) 0/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Pharyngoesophageal diverticulum 0/7254 (0%) 0/7243 (0%) 1/8738 (0%) 0/8748 (0%)
    Proctitis 0/7254 (0%) 0/7243 (0%) 1/8738 (0%) 0/8748 (0%)
    Rectal haemorrhage 1/7254 (0%) 4/7243 (0.1%) 5/8738 (0.1%) 1/8748 (0%)
    Retroperitoneal haematoma 2/7254 (0%) 0/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Small intestinal obstruction 5/7254 (0.1%) 10/7243 (0.1%) 4/8738 (0%) 3/8748 (0%)
    Spigelian hernia 0/7254 (0%) 0/7243 (0%) 1/8738 (0%) 0/8748 (0%)
    Tongue oedema 0/7254 (0%) 0/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Umbilical hernia, obstructive 0/7254 (0%) 2/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Upper gastrointestinal haemorrhage 4/7254 (0.1%) 3/7243 (0%) 1/8738 (0%) 2/8748 (0%)
    Volvulus 0/7254 (0%) 0/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Vomiting 1/7254 (0%) 1/7243 (0%) 2/8738 (0%) 1/8748 (0%)
    General disorders
    Adverse drug reaction 0/7254 (0%) 1/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Asthenia 1/7254 (0%) 1/7243 (0%) 1/8738 (0%) 2/8748 (0%)
    Chest discomfort 1/7254 (0%) 2/7243 (0%) 1/8738 (0%) 2/8748 (0%)
    Chest pain 42/7254 (0.6%) 27/7243 (0.4%) 18/8738 (0.2%) 16/8748 (0.2%)
    Death 0/7254 (0%) 3/7243 (0%) 0/8738 (0%) 2/8748 (0%)
    Device dislocation 0/7254 (0%) 0/7243 (0%) 0/8738 (0%) 2/8748 (0%)
    Device failure 0/7254 (0%) 0/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Device lead damage 0/7254 (0%) 0/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Device malfunction 0/7254 (0%) 2/7243 (0%) 1/8738 (0%) 0/8748 (0%)
    Device occlusion 0/7254 (0%) 1/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Fatigue 0/7254 (0%) 1/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Genaralized oedema 0/7254 (0%) 0/7243 (0%) 1/8738 (0%) 0/8748 (0%)
    Hernia 1/7254 (0%) 0/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Hernia obstructive 0/7254 (0%) 0/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Impaired healing 1/7254 (0%) 0/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Implant site inflammation 0/7254 (0%) 0/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Influenza like illness 0/7254 (0%) 1/7243 (0%) 1/8738 (0%) 0/8748 (0%)
    Ischaemic ulcer 0/7254 (0%) 1/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Non-cardiac chest pain 6/7254 (0.1%) 3/7243 (0%) 2/8738 (0%) 4/8748 (0%)
    Oedema peripheral 2/7254 (0%) 1/7243 (0%) 1/8738 (0%) 1/8748 (0%)
    Pelvic mass 0/7254 (0%) 0/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Pneumatosis 0/7254 (0%) 1/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Pyrexia 1/7254 (0%) 1/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Sudden cardiac death 0/7254 (0%) 0/7243 (0%) 1/8738 (0%) 0/8748 (0%)
    Surgical failure 0/7254 (0%) 0/7243 (0%) 1/8738 (0%) 0/8748 (0%)
    Hepatobiliary disorders
    Bile duct obstruction 0/7254 (0%) 1/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Cholangitis 0/7254 (0%) 0/7243 (0%) 1/8738 (0%) 1/8748 (0%)
    Cholangitis acute 1/7254 (0%) 0/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Cholecystitis 1/7254 (0%) 3/7243 (0%) 8/8738 (0.1%) 3/8748 (0%)
    Cholecystitis acute 3/7254 (0%) 2/7243 (0%) 3/8738 (0%) 4/8748 (0%)
    Cholecystitis chronic 1/7254 (0%) 1/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Cholelithiasis 0/7254 (0%) 7/7243 (0.1%) 5/8738 (0.1%) 1/8748 (0%)
    Chronic hepatic failure 1/7254 (0%) 0/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Gallbladder pain 0/7254 (0%) 0/7243 (0%) 0/8738 (0%) 2/8748 (0%)
    Gallbladder perforation 0/7254 (0%) 0/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Hepatitis 1/7254 (0%) 0/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Hepatorenal syndrome 0/7254 (0%) 0/7243 (0%) 1/8738 (0%) 0/8748 (0%)
    Immune system disorders
    Drug hypersensitivity 2/7254 (0%) 1/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Hypersensitivity 2/7254 (0%) 1/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Infections and infestations
    Abdominal abscess 1/7254 (0%) 1/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Abdominal sepsis 0/7254 (0%) 0/7243 (0%) 1/8738 (0%) 0/8748 (0%)
    Abdominal wall abscess 0/7254 (0%) 0/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Abscess 0/7254 (0%) 0/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Abscess limb 1/7254 (0%) 0/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Acute sinusitis 0/7254 (0%) 0/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Appendicitis 2/7254 (0%) 4/7243 (0.1%) 3/8738 (0%) 4/8748 (0%)
    Arthritis bacterial 1/7254 (0%) 0/7243 (0%) 1/8738 (0%) 0/8748 (0%)
    Arthritis infective 1/7254 (0%) 0/7243 (0%) 1/8738 (0%) 0/8748 (0%)
    Atypical myocobacterial pneumonia 0/7254 (0%) 0/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Bronchitis 5/7254 (0.1%) 4/7243 (0.1%) 9/8738 (0.1%) 5/8748 (0.1%)
    Bronchopneumonia 0/7254 (0%) 1/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Bursitis infective 0/7254 (0%) 0/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Cellulitis 12/7254 (0.2%) 9/7243 (0.1%) 8/8738 (0.1%) 12/8748 (0.1%)
    Cholecystitis infective 0/7254 (0%) 1/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Clostridium difficile colitis 1/7254 (0%) 3/7243 (0%) 1/8738 (0%) 0/8748 (0%)
    Cystitis 0/7254 (0%) 1/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Device related infection 1/7254 (0%) 1/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Diabetic foot infection 0/7254 (0%) 0/7243 (0%) 1/8738 (0%) 1/8748 (0%)
    Diabetic gangrene 1/7254 (0%) 0/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Diverticulitis 8/7254 (0.1%) 5/7243 (0.1%) 5/8738 (0.1%) 11/8748 (0.1%)
    Endocarditis bacterial 1/7254 (0%) 0/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Enterocolitis infectious 0/7254 (0%) 1/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Enterocolitis viral 1/7254 (0%) 0/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Escherichia bacteraemia 0/7254 (0%) 1/7243 (0%) 1/8738 (0%) 1/8748 (0%)
    Escherichia urinary tract infection 0/7254 (0%) 0/7243 (0%) 1/8738 (0%) 1/8748 (0%)
    Gangrene 0/7254 (0%) 0/7243 (0%) 1/8738 (0%) 0/8748 (0%)
    Gastric ulcer helicobacter 0/7254 (0%) 0/7243 (0%) 1/8738 (0%) 0/8748 (0%)
    Gastroenteritis 5/7254 (0.1%) 6/7243 (0.1%) 5/8738 (0.1%) 9/8748 (0.1%)
    Gastroenteritis bacterial 0/7254 (0%) 0/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Gastroenteritis salmonella 2/7254 (0%) 0/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Gastroenteritis viral 2/7254 (0%) 1/7243 (0%) 2/8738 (0%) 1/8748 (0%)
    Gastrointestinal infection 0/7254 (0%) 1/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Groin infection 1/7254 (0%) 0/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Herpes zoster 0/7254 (0%) 1/7243 (0%) 1/8738 (0%) 0/8748 (0%)
    Infected cyst 0/7254 (0%) 0/7243 (0%) 1/8738 (0%) 0/8748 (0%)
    Infective exacerbation of bronchiectasis 0/7254 (0%) 0/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Influenza 1/7254 (0%) 0/7243 (0%) 3/8738 (0%) 6/8748 (0.1%)
    Kidney infection 0/7254 (0%) 1/7243 (0%) 1/8738 (0%) 2/8748 (0%)
    Laryngitis 0/7254 (0%) 0/7243 (0%) 1/8738 (0%) 0/8748 (0%)
    Liver abscess 0/7254 (0%) 0/7243 (0%) 1/8738 (0%) 1/8748 (0%)
    Lobar pneumonia 0/7254 (0%) 1/7243 (0%) 2/8738 (0%) 6/8748 (0.1%)
    Localised infection 2/7254 (0%) 2/7243 (0%) 1/8738 (0%) 0/8748 (0%)
    Lung infection 0/7254 (0%) 0/7243 (0%) 1/8738 (0%) 0/8748 (0%)
    Nocardiosis 0/7254 (0%) 0/7243 (0%) 1/8738 (0%) 0/8748 (0%)
    Osteomyelitis 0/7254 (0%) 1/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Peridiverticular abscess 0/7254 (0%) 0/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Perineal abscess 0/7254 (0%) 0/7243 (0%) 1/8738 (0%) 0/8748 (0%)
    Periorbital cellulitis 0/7254 (0%) 1/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Perirectal abscess 0/7254 (0%) 0/7243 (0%) 1/8738 (0%) 0/8748 (0%)
    Peritonitis 0/7254 (0%) 0/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Pneumonia 28/7254 (0.4%) 44/7243 (0.6%) 35/8738 (0.4%) 44/8748 (0.5%)
    Pneumonia bacterial 0/7254 (0%) 0/7243 (0%) 1/8738 (0%) 2/8748 (0%)
    Pneumonia pneumococcal 0/7254 (0%) 0/7243 (0%) 0/8738 (0%) 2/8748 (0%)
    Pneumonia primary atypical 0/7254 (0%) 1/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Pneumonia staphylococcal 0/7254 (0%) 1/7243 (0%) 0/8738 (0%) 2/8748 (0%)
    Pneumonia viral 0/7254 (0%) 1/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Postoperative wound infection 2/7254 (0%) 1/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Pseudomonas infection 0/7254 (0%) 0/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Pyelonephritis 1/7254 (0%) 3/7243 (0%) 0/8738 (0%) 3/8748 (0%)
    Pyelonephritis acute 0/7254 (0%) 1/7243 (0%) 1/8738 (0%) 0/8748 (0%)
    Respiratory syncytial virus infection 0/7254 (0%) 0/7243 (0%) 1/8738 (0%) 0/8748 (0%)
    Sepsis 4/7254 (0.1%) 3/7243 (0%) 5/8738 (0.1%) 5/8748 (0.1%)
    Septic shock 0/7254 (0%) 1/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Sinusitis 1/7254 (0%) 1/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Staphylococcal infection 1/7254 (0%) 0/7243 (0%) 1/8738 (0%) 3/8748 (0%)
    Tracheobronchitis 2/7254 (0%) 0/7243 (0%) 1/8738 (0%) 0/8748 (0%)
    Upper respiratory tract infection 0/7254 (0%) 0/7243 (0%) 1/8738 (0%) 0/8748 (0%)
    Urethritis 0/7254 (0%) 1/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Urinary tract infection 9/7254 (0.1%) 8/7243 (0.1%) 5/8738 (0.1%) 16/8748 (0.2%)
    Urosepsis 5/7254 (0.1%) 3/7243 (0%) 0/8738 (0%) 4/8748 (0%)
    Vestibular neuronitis 0/7254 (0%) 1/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Viral diarrhoea 1/7254 (0%) 0/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Viral infection 0/7254 (0%) 0/7243 (0%) 0/8738 (0%) 4/8748 (0%)
    Viral labyrinthitis 0/7254 (0%) 0/7243 (0%) 2/8738 (0%) 0/8748 (0%)
    Viral pericarditis 1/7254 (0%) 0/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Clostridial infection 0/7254 (0%) 1/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Bacteraemia 0/7254 (0%) 0/7243 (0%) 1/8738 (0%) 1/8748 (0%)
    Bacterial infection 0/7254 (0%) 0/7243 (0%) 1/8738 (0%) 0/8748 (0%)
    Urinary tract infection bacterial 0/7254 (0%) 0/7243 (0%) 1/8738 (0%) 0/8748 (0%)
    Appendicitis perforated 0/7254 (0%) 0/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Injury, poisoning and procedural complications
    Accident 0/7254 (0%) 1/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Accidental overdose 0/7254 (0%) 0/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Alcohol poisoning 0/7254 (0%) 0/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Ankle fracture 1/7254 (0%) 5/7243 (0.1%) 5/8738 (0.1%) 3/8748 (0%)
    Arteriovenous fistula site complication 0/7254 (0%) 0/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Burns second degree 0/7254 (0%) 1/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Carbon monoxide poisoning 0/7254 (0%) 1/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Cervical vertebral fracture 1/7254 (0%) 1/7243 (0%) 2/8738 (0%) 0/8748 (0%)
    Compression fracture 1/7254 (0%) 0/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Concussion 0/7254 (0%) 1/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Contusion 1/7254 (0%) 0/7243 (0%) 0/8738 (0%) 3/8748 (0%)
    Craniocerebral injury 0/7254 (0%) 0/7243 (0%) 0/8738 (0%) 2/8748 (0%)
    Ear injury 1/7254 (0%) 0/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Fall 0/7254 (0%) 0/7243 (0%) 4/8738 (0%) 0/8748 (0%)
    Femoral neck fracture 1/7254 (0%) 5/7243 (0.1%) 1/8738 (0%) 0/8748 (0%)
    Femur fracture 6/7254 (0.1%) 5/7243 (0.1%) 2/8738 (0%) 2/8748 (0%)
    Foot fracture 0/7254 (0%) 0/7243 (0%) 1/8738 (0%) 0/8748 (0%)
    Forearm fracture 0/7254 (0%) 1/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Fractured sacrum 1/7254 (0%) 0/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Gastrointestinal stoma complication 0/7254 (0%) 0/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Graft complication 0/7254 (0%) 1/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Graft thrombosis 1/7254 (0%) 0/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Head injury 1/7254 (0%) 0/7243 (0%) 1/8738 (0%) 0/8748 (0%)
    Hip fracture 8/7254 (0.1%) 4/7243 (0.1%) 5/8738 (0.1%) 11/8748 (0.1%)
    Humerus fracture 3/7254 (0%) 2/7243 (0%) 4/8738 (0%) 1/8748 (0%)
    Incisional hernia 2/7254 (0%) 2/7243 (0%) 0/8738 (0%) 2/8748 (0%)
    Injury 2/7254 (0%) 2/7243 (0%) 2/8738 (0%) 0/8748 (0%)
    Intentional overdose 0/7254 (0%) 0/7243 (0%) 1/8738 (0%) 0/8748 (0%)
    Joint dislocation 2/7254 (0%) 1/7243 (0%) 1/8738 (0%) 3/8748 (0%)
    Joint injury 0/7254 (0%) 1/7243 (0%) 1/8738 (0%) 1/8748 (0%)
    Joint sprain 0/7254 (0%) 1/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Laceration 1/7254 (0%) 0/7243 (0%) 1/8738 (0%) 1/8748 (0%)
    Ligament sprain 0/7254 (0%) 1/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Meniscus lesion 0/7254 (0%) 1/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Multiple fractures 3/7254 (0%) 3/7243 (0%) 2/8738 (0%) 0/8748 (0%)
    Multiple injuries 0/7254 (0%) 1/7243 (0%) 1/8738 (0%) 0/8748 (0%)
    Open fracture 0/7254 (0%) 0/7243 (0%) 1/8738 (0%) 0/8748 (0%)
    Patella fracture 2/7254 (0%) 1/7243 (0%) 0/8738 (0%) 2/8748 (0%)
    Pelvic fracture 3/7254 (0%) 1/7243 (0%) 1/8738 (0%) 3/8748 (0%)
    Periprosthetic fracture 0/7254 (0%) 1/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Post laminectomy syndrome 0/7254 (0%) 1/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Post procedural complication 1/7254 (0%) 0/7243 (0%) 1/8738 (0%) 2/8748 (0%)
    Post procedural haemorrhage 1/7254 (0%) 0/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Postoperative fever 0/7254 (0%) 1/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Postoperative respiratory distress 0/7254 (0%) 0/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Procedural pain 1/7254 (0%) 0/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Pubis fracture 0/7254 (0%) 1/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Radius fracture 0/7254 (0%) 0/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Respiratory fume inhalation disorder 1/7254 (0%) 0/7243 (0%) 1/8738 (0%) 0/8748 (0%)
    Rib fracture 2/7254 (0%) 3/7243 (0%) 0/8738 (0%) 3/8748 (0%)
    Road traffic accident 0/7254 (0%) 2/7243 (0%) 3/8738 (0%) 0/8748 (0%)
    Skull fracture 1/7254 (0%) 0/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Skull fractured base 0/7254 (0%) 2/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Spinal compression fracture 0/7254 (0%) 0/7243 (0%) 1/8738 (0%) 0/8748 (0%)
    Spinal fracture 0/7254 (0%) 1/7243 (0%) 1/8738 (0%) 1/8748 (0%)
    Splenic rupture 0/7254 (0%) 0/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Sternal fracture 0/7254 (0%) 0/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Subdural haematoma 5/7254 (0.1%) 3/7243 (0%) 1/8738 (0%) 2/8748 (0%)
    Tendon rupture 0/7254 (0%) 0/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Tibia fracture 1/7254 (0%) 0/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Toxicity to various agents 1/7254 (0%) 1/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Traumatic fracture 1/7254 (0%) 0/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Upper limb fracture 2/7254 (0%) 0/7243 (0%) 1/8738 (0%) 1/8748 (0%)
    Vascular graft complication 0/7254 (0%) 0/7243 (0%) 1/8738 (0%) 0/8748 (0%)
    Wound 0/7254 (0%) 1/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Wound dehiscence 0/7254 (0%) 0/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Wrist fracture 1/7254 (0%) 0/7243 (0%) 3/8738 (0%) 0/8748 (0%)
    Extradural haematoma 0/7254 (0%) 0/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Investigations
    Blood pressure increased 0/7254 (0%) 0/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Cardiac stress test abnormal 0/7254 (0%) 1/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Prostatic specific antigen increased 0/7254 (0%) 1/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Metabolism and nutrition disorders
    Dehydration 3/7254 (0%) 4/7243 (0.1%) 4/8738 (0%) 5/8748 (0.1%)
    Diabetic ketoacidosis 0/7254 (0%) 1/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Diabetes mellitus inadequate control 0/7254 (0%) 0/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Failure to thrive 0/7254 (0%) 0/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Fluid overload 0/7254 (0%) 1/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Fluid retention 0/7254 (0%) 1/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Gout 1/7254 (0%) 0/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Hypercalcaemia 0/7254 (0%) 0/7243 (0%) 1/8738 (0%) 0/8748 (0%)
    Hyperglycaemia 1/7254 (0%) 0/7243 (0%) 2/8738 (0%) 1/8748 (0%)
    Hypoglycaemia 2/7254 (0%) 3/7243 (0%) 2/8738 (0%) 5/8748 (0.1%)
    Hypokalaemia 3/7254 (0%) 2/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Hyponatraemia 1/7254 (0%) 1/7243 (0%) 3/8738 (0%) 3/8748 (0%)
    Malnutrition 0/7254 (0%) 1/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Type 2 diabetes mellitus 0/7254 (0%) 1/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Hypocalcaemia 1/7254 (0%) 0/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 6/7254 (0.1%) 4/7243 (0.1%) 6/8738 (0.1%) 1/8748 (0%)
    Arthritis 4/7254 (0.1%) 1/7243 (0%) 4/8738 (0%) 1/8748 (0%)
    Arthropathy 0/7254 (0%) 0/7243 (0%) 1/8738 (0%) 0/8748 (0%)
    Back pain 4/7254 (0.1%) 1/7243 (0%) 2/8738 (0%) 6/8748 (0.1%)
    Bursitis 0/7254 (0%) 0/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Cervical spinal stenosis 1/7254 (0%) 3/7243 (0%) 1/8738 (0%) 5/8748 (0.1%)
    Chondrocalcinosis pyrophosphate 0/7254 (0%) 1/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Costochondritis 0/7254 (0%) 1/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Exostosis 0/7254 (0%) 0/7243 (0%) 1/8738 (0%) 1/8748 (0%)
    Foot deformity 2/7254 (0%) 2/7243 (0%) 1/8738 (0%) 0/8748 (0%)
    Fracture malunion 0/7254 (0%) 0/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Gouty tophus 1/7254 (0%) 0/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Groin pain 0/7254 (0%) 0/7243 (0%) 3/8738 (0%) 0/8748 (0%)
    Intervertebral disc degeneration 3/7254 (0%) 2/7243 (0%) 1/8738 (0%) 2/8748 (0%)
    Intervertebral disc displacement 0/7254 (0%) 0/7243 (0%) 1/8738 (0%) 0/8748 (0%)
    Intervertebral disc protrusion 2/7254 (0%) 5/7243 (0.1%) 2/8738 (0%) 1/8748 (0%)
    Knee deformity 0/7254 (0%) 1/7243 (0%) 1/8738 (0%) 0/8748 (0%)
    Kyphosis 0/7254 (0%) 1/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Lumbar spinal stenosis 6/7254 (0.1%) 7/7243 (0.1%) 7/8738 (0.1%) 4/8748 (0%)
    Monarthritis 1/7254 (0%) 0/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Muscle atrophy 1/7254 (0%) 0/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Muscle spasms 0/7254 (0%) 0/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Muscular weakness 1/7254 (0%) 1/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Musculoskeletal chest pain 1/7254 (0%) 1/7243 (0%) 0/8738 (0%) 3/8748 (0%)
    Musculoskeletal pain 3/7254 (0%) 1/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Neck pain 0/7254 (0%) 3/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Osteoarthritis 48/7254 (0.7%) 29/7243 (0.4%) 50/8738 (0.6%) 35/8748 (0.4%)
    Osteonecrosis 2/7254 (0%) 0/7243 (0%) 1/8738 (0%) 0/8748 (0%)
    Osteoporosis 0/7254 (0%) 1/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Osteoporotic fracture 0/7254 (0%) 1/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Pain in extremity 1/7254 (0%) 0/7243 (0%) 1/8738 (0%) 0/8748 (0%)
    Periarthritis 0/7254 (0%) 1/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Polymyalgia rheumatica 1/7254 (0%) 0/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Rhabdomyolysis 0/7254 (0%) 0/7243 (0%) 1/8738 (0%) 0/8748 (0%)
    Rheumatoid arthritis 1/7254 (0%) 0/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Rotator cuff syndrome 3/7254 (0%) 2/7243 (0%) 2/8738 (0%) 1/8748 (0%)
    Spinal column stenosis 1/7254 (0%) 0/7243 (0%) 4/8738 (0%) 2/8748 (0%)
    Spinal osteoarthritis 1/7254 (0%) 0/7243 (0%) 1/8738 (0%) 0/8748 (0%)
    Spondylolisthesis 0/7254 (0%) 2/7243 (0%) 4/8738 (0%) 2/8748 (0%)
    Synovial cyst 0/7254 (0%) 0/7243 (0%) 1/8738 (0%) 0/8748 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Acute leukaemia 0/7254 (0%) 0/7243 (0%) 1/8738 (0%) 0/8748 (0%)
    Acute myeloid leukaemia 0/7254 (0%) 0/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Acute promyelocytic leukaemia 1/7254 (0%) 0/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Adenocarcinoma 0/7254 (0%) 0/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Adenocarcinoma pancreas 0/7254 (0%) 0/7243 (0%) 1/8738 (0%) 1/8748 (0%)
    Adenoid cystic carcinoma 0/7254 (0%) 0/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    B-cell small lymphocytic lymphoma 0/7254 (0%) 0/7243 (0%) 1/8738 (0%) 0/8748 (0%)
    Basal cell carcinoma 0/7254 (0%) 1/7243 (0%) 1/8738 (0%) 0/8748 (0%)
    Benign neoplasm 0/7254 (0%) 0/7243 (0%) 2/8738 (0%) 1/8748 (0%)
    Benign renal neoplasm 0/7254 (0%) 0/7243 (0%) 1/8738 (0%) 0/8748 (0%)
    Bile duct cancer 0/7254 (0%) 0/7243 (0%) 1/8738 (0%) 0/8748 (0%)
    Bladder cancer 5/7254 (0.1%) 3/7243 (0%) 0/8738 (0%) 3/8748 (0%)
    Bladder cancer recurrent 0/7254 (0%) 1/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Bladder neoplasm 0/7254 (0%) 1/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Bladder transitional cell carcinoma 0/7254 (0%) 1/7243 (0%) 1/8738 (0%) 0/8748 (0%)
    Bone cancer metastatic 0/7254 (0%) 1/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Bone neoplasm 0/7254 (0%) 0/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Bone neoplasm malignant 0/7254 (0%) 1/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Brain neoplasm 1/7254 (0%) 0/7243 (0%) 0/8738 (0%) 2/8748 (0%)
    Brain neoplasm malignant 0/7254 (0%) 1/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Breast cancer 7/7254 (0.1%) 11/7243 (0.2%) 7/8738 (0.1%) 7/8748 (0.1%)
    Breast cancer in situ 1/7254 (0%) 2/7243 (0%) 2/8738 (0%) 0/8748 (0%)
    Breast cancer metastatic 1/7254 (0%) 0/7243 (0%) 1/8738 (0%) 2/8748 (0%)
    Breast cancer recurrent 1/7254 (0%) 0/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Breast cancer stage I 1/7254 (0%) 0/7243 (0%) 1/8738 (0%) 0/8748 (0%)
    Bronchial carcinoma 1/7254 (0%) 0/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Chronic lymphocytic leukaemia 0/7254 (0%) 0/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Colon adenoma 0/7254 (0%) 0/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Colon cancer 0/7254 (0%) 3/7243 (0%) 4/8738 (0%) 5/8748 (0.1%)
    Colon cancer metastatic 0/7254 (0%) 0/7243 (0%) 1/8738 (0%) 0/8748 (0%)
    Colon cancer stage II 1/7254 (0%) 0/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Colorectal cancer 0/7254 (0%) 0/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Duodenal neoplasm 1/7254 (0%) 0/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Endometrial cancer 1/7254 (0%) 1/7243 (0%) 2/8738 (0%) 0/8748 (0%)
    Endometrial cancer stage II 1/7254 (0%) 0/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Gastric cancer 1/7254 (0%) 0/7243 (0%) 0/8738 (0%) 2/8748 (0%)
    Gastric cancer recurrent 0/7254 (0%) 0/7243 (0%) 1/8738 (0%) 0/8748 (0%)
    Gastric cancer stage I 1/7254 (0%) 0/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Gastrinoma 0/7254 (0%) 0/7243 (0%) 1/8738 (0%) 0/8748 (0%)
    Gastrointestinal stromal tumour 1/7254 (0%) 0/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Glottis carcinoma 0/7254 (0%) 0/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Head and neck cancer 0/7254 (0%) 0/7243 (0%) 1/8738 (0%) 0/8748 (0%)
    Hepatic cancer metastatic 2/7254 (0%) 0/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Hepatic neoplasm malignant 1/7254 (0%) 2/7243 (0%) 2/8738 (0%) 0/8748 (0%)
    Hodgkin's disease 0/7254 (0%) 0/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Intracranial meningioma malignant 1/7254 (0%) 0/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Laryngeal cancer 1/7254 (0%) 1/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Laryngeal cancer stage I 0/7254 (0%) 0/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Lentigo maligna stage unspecified 0/7254 (0%) 0/7243 (0%) 1/8738 (0%) 0/8748 (0%)
    Leukaemia 0/7254 (0%) 1/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Liposarcoma 0/7254 (0%) 0/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Lung adenocarcinoma 1/7254 (0%) 1/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Lung cancer metastatic 0/7254 (0%) 1/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Lung carcinoma cell type unspecified stage I 0/7254 (0%) 1/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Lung carcinoma cell type unspecified stage 0 0/7254 (0%) 0/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Lung neoplasm 1/7254 (0%) 0/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Lung neoplasm malignant 4/7254 (0.1%) 11/7243 (0.2%) 6/8738 (0.1%) 3/8748 (0%)
    Lung squamous cell carcinoma stage unspecified 0/7254 (0%) 0/7243 (0%) 1/8738 (0%) 2/8748 (0%)
    Lymphoma 0/7254 (0%) 0/7243 (0%) 1/8738 (0%) 0/8748 (0%)
    Malignant melanoma 1/7254 (0%) 1/7243 (0%) 2/8738 (0%) 1/8748 (0%)
    Meningioma 1/7254 (0%) 1/7243 (0%) 1/8738 (0%) 0/8748 (0%)
    Meningioma benign 0/7254 (0%) 1/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Metastases to bone 0/7254 (0%) 1/7243 (0%) 1/8738 (0%) 0/8748 (0%)
    Metastases to central nervous system 1/7254 (0%) 0/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Metastases to lung 2/7254 (0%) 0/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Metastatic carcinoid tumour 0/7254 (0%) 0/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Metastatic malignant melanoma 1/7254 (0%) 0/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Metastatic neoplasm 0/7254 (0%) 0/7243 (0%) 1/8738 (0%) 0/8748 (0%)
    Metastatic squamous cell carcinoma 0/7254 (0%) 0/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Multiple myeloma 1/7254 (0%) 2/7243 (0%) 2/8738 (0%) 0/8748 (0%)
    Myelodysplastic syndrome 1/7254 (0%) 0/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Myeloid leukaemia 0/7254 (0%) 0/7243 (0%) 1/8738 (0%) 0/8748 (0%)
    Myeloma recurrence 0/7254 (0%) 1/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Neoplasm malignant 0/7254 (0%) 2/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Neuroendocrine tumour 0/7254 (0%) 0/7243 (0%) 1/8738 (0%) 0/8748 (0%)
    Non-Hodgkin's lymphoma 1/7254 (0%) 0/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Non-small cell lung cancer 1/7254 (0%) 0/7243 (0%) 1/8738 (0%) 0/8748 (0%)
    Non-small cell lung cancer metastatic 0/7254 (0%) 1/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Oesophageal adenocarcinoma 0/7254 (0%) 0/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Oesophageal carcinoma 1/7254 (0%) 0/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Ovarian cancer metastatic 1/7254 (0%) 0/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Pancreatic carcinoma 1/7254 (0%) 3/7243 (0%) 1/8738 (0%) 0/8748 (0%)
    Pancreatic carcinoma metastatic 1/7254 (0%) 0/7243 (0%) 2/8738 (0%) 0/8748 (0%)
    Paraproteinaemia 1/7254 (0%) 0/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Penis carcinoma 0/7254 (0%) 0/7243 (0%) 1/8738 (0%) 0/8748 (0%)
    Pituitary tumour 1/7254 (0%) 0/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Pituitary tumour benign 1/7254 (0%) 0/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Pleural neoplasm 1/7254 (0%) 0/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Prostate cancer 9/7254 (0.1%) 2/7243 (0%) 3/8738 (0%) 4/8748 (0%)
    Prostate cancer metastatic 0/7254 (0%) 0/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Rectal cancer 1/7254 (0%) 3/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Renal cancer 1/7254 (0%) 0/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Renal cell carcinoma 3/7254 (0%) 1/7243 (0%) 0/8738 (0%) 2/8748 (0%)
    Retroperitoneal neoplasm 0/7254 (0%) 0/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Salivary gland cancer 1/7254 (0%) 0/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Sarcoma 0/7254 (0%) 1/7243 (0%) 1/8738 (0%) 0/8748 (0%)
    Skin cancer 1/7254 (0%) 2/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Small cell lung cancer extensive stage 0/7254 (0%) 0/7243 (0%) 1/8738 (0%) 0/8748 (0%)
    Small cell lung cancer stage unspecified 1/7254 (0%) 0/7243 (0%) 2/8738 (0%) 1/8748 (0%)
    Small intestine carcinoma 1/7254 (0%) 0/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Squamous cell carcinoma 0/7254 (0%) 5/7243 (0.1%) 2/8738 (0%) 0/8748 (0%)
    Squamous cell carcinoma of skin 0/7254 (0%) 0/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Throat cancer 0/7254 (0%) 0/7243 (0%) 1/8738 (0%) 0/8748 (0%)
    Thyroid cancer 0/7254 (0%) 4/7243 (0.1%) 0/8738 (0%) 1/8748 (0%)
    Thyroid neoplasm 0/7254 (0%) 0/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Tongue neoplasm malignant stage unspecified 1/7254 (0%) 0/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Tonsil cancer 0/7254 (0%) 0/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Transitional cell carcinoma 0/7254 (0%) 2/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Uterine cancer 0/7254 (0%) 0/7243 (0%) 3/8738 (0%) 0/8748 (0%)
    Malignant melanoma in situ 1/7254 (0%) 0/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Nervous system disorders
    Acute disseminated encephalomyelitis 1/7254 (0%) 0/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Amnesia 0/7254 (0%) 0/7243 (0%) 1/8738 (0%) 0/8748 (0%)
    Ataxia 1/7254 (0%) 0/7243 (0%) 2/8738 (0%) 0/8748 (0%)
    Autonomic nervous system imbalance 0/7254 (0%) 1/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Basal ganglia infarction 0/7254 (0%) 0/7243 (0%) 1/8738 (0%) 0/8748 (0%)
    Carotid artery occlusion 0/7254 (0%) 1/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Carotid artery stenosis 3/7254 (0%) 2/7243 (0%) 4/8738 (0%) 0/8748 (0%)
    Cerebral amyloid angiopathy 0/7254 (0%) 0/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Cerebral cyst 0/7254 (0%) 0/7243 (0%) 1/8738 (0%) 0/8748 (0%)
    Cerebral haemorrhage 1/7254 (0%) 1/7243 (0%) 2/8738 (0%) 0/8748 (0%)
    Cerebral infarction 2/7254 (0%) 1/7243 (0%) 0/8738 (0%) 2/8748 (0%)
    Cerebral Ischaemia 1/7254 (0%) 0/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Cerebrovascular accident 20/7254 (0.3%) 19/7243 (0.3%) 13/8738 (0.1%) 21/8748 (0.2%)
    Cervicobrachial syndrome 1/7254 (0%) 0/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Cervical myelopathy 0/7254 (0%) 0/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Cognitive disorder 0/7254 (0%) 0/7243 (0%) 1/8738 (0%) 0/8748 (0%)
    Complex partial seizures 1/7254 (0%) 0/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Convulsion 3/7254 (0%) 3/7243 (0%) 1/8738 (0%) 2/8748 (0%)
    Dementia Alzheimer's type 0/7254 (0%) 0/7243 (0%) 1/8738 (0%) 0/8748 (0%)
    Dementia with Lewy bodies 0/7254 (0%) 0/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Depressed level of consciousness 0/7254 (0%) 1/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Dizziness 2/7254 (0%) 2/7243 (0%) 1/8738 (0%) 0/8748 (0%)
    Dizziness postural 1/7254 (0%) 0/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Dyskinesia 0/7254 (0%) 1/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Encephalopathy 2/7254 (0%) 1/7243 (0%) 2/8738 (0%) 1/8748 (0%)
    Epilepsy 0/7254 (0%) 0/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Guillain-Barre syndrome 0/7254 (0%) 0/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Haemorrhage intracranial 0/7254 (0%) 2/7243 (0%) 1/8738 (0%) 2/8748 (0%)
    Haemorrhagic stroke 0/7254 (0%) 1/7243 (0%) 1/8738 (0%) 0/8748 (0%)
    Headache 2/7254 (0%) 0/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Hemiparesis 0/7254 (0%) 0/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Hydrocephalus 0/7254 (0%) 0/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Hypertensive encephalopathy 0/7254 (0%) 0/7243 (0%) 1/8738 (0%) 0/8748 (0%)
    Intracranial aneurysm 0/7254 (0%) 1/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Intraventricular haemorrhage 1/7254 (0%) 0/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Ischaemic stroke 1/7254 (0%) 0/7243 (0%) 1/8738 (0%) 0/8748 (0%)
    Lacunar infarction 2/7254 (0%) 0/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Lethargy 1/7254 (0%) 0/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Loss of consciousness 0/7254 (0%) 0/7243 (0%) 1/8738 (0%) 0/8748 (0%)
    Lumbar radiculopathy 3/7254 (0%) 0/7243 (0%) 1/8738 (0%) 0/8748 (0%)
    Metabolic encephalopathy 0/7254 (0%) 0/7243 (0%) 1/8738 (0%) 0/8748 (0%)
    Migraine 0/7254 (0%) 0/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Myasthenia gravis 1/7254 (0%) 0/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Myelopathy 0/7254 (0%) 0/7243 (0%) 1/8738 (0%) 1/8748 (0%)
    Normal pressure hydrocephalus 3/7254 (0%) 0/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Paraesthesia 0/7254 (0%) 1/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Parkinson's disease 0/7254 (0%) 0/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Presyncope 1/7254 (0%) 3/7243 (0%) 3/8738 (0%) 2/8748 (0%)
    Radiculopathy 1/7254 (0%) 1/7243 (0%) 1/8738 (0%) 0/8748 (0%)
    Sciatica 0/7254 (0%) 1/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Spondylitic myelopathy 0/7254 (0%) 0/7243 (0%) 0/8738 (0%) 2/8748 (0%)
    Subarachnoid haemorrhage 0/7254 (0%) 4/7243 (0.1%) 1/8738 (0%) 1/8748 (0%)
    Syncope 18/7254 (0.2%) 19/7243 (0.3%) 15/8738 (0.2%) 16/8748 (0.2%)
    Thrombotic cerebral infarction 1/7254 (0%) 1/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Toxic encephalopathy 0/7254 (0%) 0/7243 (0%) 1/8738 (0%) 1/8748 (0%)
    Transient global amnesia 1/7254 (0%) 1/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Transient ischaemic attack 12/7254 (0.2%) 15/7243 (0.2%) 9/8738 (0.1%) 12/8748 (0.1%)
    VIIth nerve paralysis 0/7254 (0%) 2/7243 (0%) 1/8738 (0%) 3/8748 (0%)
    VIth nerve paralysis 0/7254 (0%) 0/7243 (0%) 1/8738 (0%) 1/8748 (0%)
    Basal ganglia haemorrhage 0/7254 (0%) 1/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Psychiatric disorders
    Affective disorder 0/7254 (0%) 0/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Alcohol withdrawal syndrome 1/7254 (0%) 1/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Bipolar disorder 1/7254 (0%) 0/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Bipolar I disorder 0/7254 (0%) 0/7243 (0%) 1/8738 (0%) 0/8748 (0%)
    Completed suicide 0/7254 (0%) 0/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Delirium 1/7254 (0%) 0/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Depression 1/7254 (0%) 2/7243 (0%) 1/8738 (0%) 0/8748 (0%)
    Hallucination, visual 0/7254 (0%) 0/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Major depression 1/7254 (0%) 1/7243 (0%) 1/8738 (0%) 1/8748 (0%)
    Mental status changes 1/7254 (0%) 2/7243 (0%) 5/8738 (0.1%) 4/8748 (0%)
    Panic attack 0/7254 (0%) 0/7243 (0%) 1/8738 (0%) 0/8748 (0%)
    Psychotic disorder 0/7254 (0%) 0/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Suicidal ideation 0/7254 (0%) 0/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Renal and urinary disorders
    Bladder fibrosis 0/7254 (0%) 0/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Bladder prolapse 0/7254 (0%) 0/7243 (0%) 2/8738 (0%) 0/8748 (0%)
    Calculus bladder 0/7254 (0%) 0/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Calculus ureteric 1/7254 (0%) 2/7243 (0%) 0/8738 (0%) 2/8748 (0%)
    Calculus urinary 0/7254 (0%) 0/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Dysuria 1/7254 (0%) 0/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Haematuria 1/7254 (0%) 0/7243 (0%) 1/8738 (0%) 0/8748 (0%)
    Hydronephrosis 0/7254 (0%) 0/7243 (0%) 2/8738 (0%) 0/8748 (0%)
    Nephrolithiasis 3/7254 (0%) 5/7243 (0.1%) 2/8738 (0%) 1/8748 (0%)
    Obstructive uropathy 0/7254 (0%) 0/7243 (0%) 1/8738 (0%) 0/8748 (0%)
    Renal artery stenosis 1/7254 (0%) 1/7243 (0%) 1/8738 (0%) 1/8748 (0%)
    Renal colic 0/7254 (0%) 0/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Renal failure 2/7254 (0%) 1/7243 (0%) 1/8738 (0%) 4/8748 (0%)
    Renal failure acute 8/7254 (0.1%) 5/7243 (0.1%) 11/8738 (0.1%) 14/8748 (0.2%)
    Renal failure chronic 4/7254 (0.1%) 2/7243 (0%) 1/8738 (0%) 3/8748 (0%)
    Renal mass 0/7254 (0%) 0/7243 (0%) 1/8738 (0%) 0/8748 (0%)
    Stress urinary incontinence 0/7254 (0%) 0/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Urethral stenosis 0/7254 (0%) 0/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Urinary incontinence 1/7254 (0%) 1/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Urinary retention 0/7254 (0%) 0/7243 (0%) 2/8738 (0%) 1/8748 (0%)
    Reproductive system and breast disorders
    Benign prostatic hyperplasia 1/7254 (0%) 3/7243 (0%) 2/8738 (0%) 0/8748 (0%)
    Cystocele 1/7254 (0%) 0/7243 (0%) 1/8738 (0%) 0/8748 (0%)
    Endometrial hyperplasia 0/7254 (0%) 0/7243 (0%) 1/8738 (0%) 0/8748 (0%)
    Erectile dysfunction 1/7254 (0%) 0/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Genital prolapse 0/7254 (0%) 1/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Ovarian cyst 0/7254 (0%) 0/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Ovarian mass 1/7254 (0%) 0/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Pelvic pain 0/7254 (0%) 0/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Pelvic prolapse 1/7254 (0%) 0/7243 (0%) 1/8738 (0%) 0/8748 (0%)
    Prostatitis 0/7254 (0%) 1/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Prostatomegaly 0/7254 (0%) 0/7243 (0%) 1/8738 (0%) 1/8748 (0%)
    Uterine prolapse 1/7254 (0%) 1/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Uterovaginal prolapse 0/7254 (0%) 1/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Vaginal haematoma 1/7254 (0%) 0/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Respiratory, thoracic and mediastinal disorders
    Acute respiratory failure 1/7254 (0%) 6/7243 (0.1%) 6/8738 (0.1%) 7/8748 (0.1%)
    Alveolitis allergic 0/7254 (0%) 0/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Asthma 4/7254 (0.1%) 2/7243 (0%) 3/8738 (0%) 5/8748 (0.1%)
    Bronchitis chronic 0/7254 (0%) 0/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Chronic obstructive pulmonary disease 21/7254 (0.3%) 13/7243 (0.2%) 15/8738 (0.2%) 36/8748 (0.4%)
    Chronic respiratory failure 0/7254 (0%) 1/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Dyspnoea 5/7254 (0.1%) 6/7243 (0.1%) 3/8738 (0%) 8/8748 (0.1%)
    Dyspnoea exertional 0/7254 (0%) 1/7243 (0%) 1/8738 (0%) 2/8748 (0%)
    Emphysema 0/7254 (0%) 0/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Eosinophilic pneumonia 0/7254 (0%) 1/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Epistaxis 3/7254 (0%) 1/7243 (0%) 2/8738 (0%) 0/8748 (0%)
    Haemoptysis 0/7254 (0%) 0/7243 (0%) 1/8738 (0%) 0/8748 (0%)
    Haemothorax 0/7254 (0%) 0/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Hypoxia 1/7254 (0%) 2/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Interstitial lung disease 0/7254 (0%) 1/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Nasal septum deviation 0/7254 (0%) 0/7243 (0%) 1/8738 (0%) 0/8748 (0%)
    Pleural effusion 1/7254 (0%) 1/7243 (0%) 1/8738 (0%) 0/8748 (0%)
    Pleural haemorrhage 1/7254 (0%) 0/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Pleurisy 0/7254 (0%) 0/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Pleuritic pain 0/7254 (0%) 0/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Pneumonia aspiration 0/7254 (0%) 3/7243 (0%) 2/8738 (0%) 1/8748 (0%)
    Pneumonitis 0/7254 (0%) 1/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Pneumothorax 2/7254 (0%) 2/7243 (0%) 4/8738 (0%) 2/8748 (0%)
    Pulmonary embolism 5/7254 (0.1%) 7/7243 (0.1%) 6/8738 (0.1%) 13/8748 (0.1%)
    Pulmonary fibrosis 0/7254 (0%) 1/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Pulmonary hypertension 0/7254 (0%) 2/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Pulmonary oedema 1/7254 (0%) 0/7243 (0%) 1/8738 (0%) 0/8748 (0%)
    Respiratory arrest 0/7254 (0%) 1/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Respiratory failure 5/7254 (0.1%) 5/7243 (0.1%) 4/8738 (0%) 5/8748 (0.1%)
    Sleep apnoea syndrome 0/7254 (0%) 1/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Skin and subcutaneous tissue disorders
    Angioedema 1/7254 (0%) 0/7243 (0%) 2/8738 (0%) 0/8748 (0%)
    Capillaritis 0/7254 (0%) 0/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Decubitus ulcer 0/7254 (0%) 0/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Diabetic foot 0/7254 (0%) 0/7243 (0%) 1/8738 (0%) 0/8748 (0%)
    Hypoaesthesia facial 0/7254 (0%) 1/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Panniculitis 1/7254 (0%) 0/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Rash 0/7254 (0%) 0/7243 (0%) 1/8738 (0%) 0/8748 (0%)
    Stevens-Johnson syndrome 1/7254 (0%) 0/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Skin hypertrophy 0/7254 (0%) 0/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Social circumstances
    Activities of daily living impaired 1/7254 (0%) 0/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Surgical and medical procedures
    Colostomy 1/7254 (0%) 0/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Face lift 0/7254 (0%) 1/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Implantable defibrillator removal 1/7254 (0%) 0/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Intraocular lens implant 0/7254 (0%) 0/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Renal surgery 0/7254 (0%) 0/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Surgery 0/7254 (0%) 0/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Vascular disorders
    Accelerated hypertension 0/7254 (0%) 1/7243 (0%) 0/8738 (0%) 2/8748 (0%)
    Aneurysm ruptured 0/7254 (0%) 1/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Aortic aneurysm 5/7254 (0.1%) 3/7243 (0%) 5/8738 (0.1%) 6/8748 (0.1%)
    Aortic aneurysm rupture 0/7254 (0%) 0/7243 (0%) 2/8738 (0%) 0/8748 (0%)
    Aortic dissection 0/7254 (0%) 0/7243 (0%) 2/8738 (0%) 0/8748 (0%)
    Aortic rupture 1/7254 (0%) 0/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Aortic stenosis 2/7254 (0%) 2/7243 (0%) 2/8738 (0%) 2/8748 (0%)
    Arterial occlusive disease 1/7254 (0%) 0/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Arterial stenosis limb 1/7254 (0%) 0/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Arterial thrombosis limb 0/7254 (0%) 0/7243 (0%) 1/8738 (0%) 0/8748 (0%)
    Arteriosclerosis 1/7254 (0%) 1/7243 (0%) 0/8738 (0%) 3/8748 (0%)
    Arteriovenous fistula 0/7254 (0%) 1/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Deep vein thrombosis 5/7254 (0.1%) 5/7243 (0.1%) 1/8738 (0%) 6/8748 (0.1%)
    Embolism venous 0/7254 (0%) 0/7243 (0%) 1/8738 (0%) 0/8748 (0%)
    Femoral artery occlusion 1/7254 (0%) 0/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Haematoma 4/7254 (0.1%) 2/7243 (0%) 1/8738 (0%) 0/8748 (0%)
    Hypertension 8/7254 (0.1%) 4/7243 (0.1%) 4/8738 (0%) 3/8748 (0%)
    Hypertensive crisis 0/7254 (0%) 0/7243 (0%) 1/8738 (0%) 0/8748 (0%)
    Hypertensive emergency 1/7254 (0%) 0/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Hypotension 8/7254 (0.1%) 4/7243 (0.1%) 2/8738 (0%) 2/8748 (0%)
    Hypovolaemic shock 0/7254 (0%) 0/7243 (0%) 1/8738 (0%) 0/8748 (0%)
    Infarction 0/7254 (0%) 1/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Intermittent claudication 1/7254 (0%) 1/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Intra-abdominal haematoma 0/7254 (0%) 1/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Ischaemia 0/7254 (0%) 1/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Malignant hypertension 1/7254 (0%) 0/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Orthostatic hypertension 0/7254 (0%) 0/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Orthostatic hypotension 1/7254 (0%) 5/7243 (0.1%) 0/8738 (0%) 1/8748 (0%)
    Peripheral arterial occlusive disease 1/7254 (0%) 0/7243 (0%) 2/8738 (0%) 1/8748 (0%)
    Peripheral artery aneurysm 0/7254 (0%) 0/7243 (0%) 1/8738 (0%) 0/8748 (0%)
    Peripheral ischaemia 0/7254 (0%) 0/7243 (0%) 3/8738 (0%) 0/8748 (0%)
    Peripheral vascular disorder 1/7254 (0%) 1/7243 (0%) 1/8738 (0%) 2/8748 (0%)
    Shock 0/7254 (0%) 0/7243 (0%) 1/8738 (0%) 0/8748 (0%)
    Steal syndrome 0/7254 (0%) 0/7243 (0%) 0/8738 (0%) 1/8748 (0%)
    Thrombosis 1/7254 (0%) 1/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Venous insufficiency 0/7254 (0%) 1/7243 (0%) 0/8738 (0%) 0/8748 (0%)
    Other (Not Including 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 (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/7254 (0%) 0/7243 (0%) 0/8738 (0%) 0/8748 (0%)

    Limitations/Caveats

    [Not Specified]

    More Information

    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

    Name/Title Medical Director
    Organization Sanofi Pasteur Inc.
    Phone
    Email RegistryContactUs@sanofipasteur.com
    Responsible Party:
    Sanofi Pasteur, a Sanofi Company
    ClinicalTrials.gov Identifier:
    NCT01427309
    Other Study ID Numbers:
    • FIM12
    • U1111-1120-1300
    First Posted:
    Sep 1, 2011
    Last Update Posted:
    Apr 20, 2015
    Last Verified:
    Mar 1, 2015