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    Clinical Trial Results:
    A Phase 2B, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate The Safety And Efficacy Of Staphylococcus Aureus 4 Antigen Vaccine (SA4Ag) In Adults Undergoing Elective Open Posterior Spinal Fusion Procedures With Multilevel Instrumentation

    Summary
    EudraCT number
    		 2014-002644-40
    Trial protocol
    		 ES   GB   DE   HU   AT   SE   BG  
    Global end of trial date
    27 Jun 2019

    Results information
    Results version number
    		 v2(current)
    This version publication date
    27 Dec 2020
    First version publication date
    21 Jun 2020
    Other versions
    		 v1
    Version creation reason

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    B3451002
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02388165
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Pfizer Inc.
    Sponsor organisation address
    235 E 42nd Street, New York, United States, 10017
    Public contact
    Pfizer ClinicalTrials.gov Call Center, Pfizer Inc., +1 1-800-718-1021, ClinicalTrials.gov_Inquiries@pfizer.com
    Scientific contact
    Pfizer ClinicalTrials.gov Call Center, Pfizer Inc., +1 1-800-718-1021, ClinicalTrials.gov_Inquiries@pfizer.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    12 Sep 2019
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    27 Jun 2019
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    To assess the efficacy of Staphylococcus (S.) aureus 4-antigen (SA4Ag) in the prevention of postoperative S. aureus Bloodstream Infection (BSI) and/or deep incisional or organ/space surgical-site infection (SSI) occurring within 90 days of elective open posterior spinal fusion procedures with multilevel instrumentation, in adults aged 18 to less than (<) 86 years. To describe the safety and tolerability of a single vaccination of SA4Ag in adults aged 18 to <86 years undergoing elective open posterior spinal fusion procedures with multilevel instrumentation, by measuring local reactions, systemic events, and adverse events (AEs).
    Protection of trial subjects
    The study was in compliance with the ethical principles derived from the Declaration of Helsinki and in compliance with all International Conference on Harmonisation (ICH) Good Clinical Practice (GCP) Guidelines. All the local regulatory requirements pertinent to safety of trial subjects were followed.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    02 Jul 2015
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    		 Safety
    Long term follow-up duration
    		 8 Months
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Austria: 13
    Country: Number of subjects enrolled
    Bulgaria: 14
    Country: Number of subjects enrolled
    Canada: 174
    Country: Number of subjects enrolled
    France: 275
    Country: Number of subjects enrolled
    Germany: 101
    Country: Number of subjects enrolled
    Hungary: 87
    Country: Number of subjects enrolled
    Japan: 560
    Country: Number of subjects enrolled
    Spain: 324
    Country: Number of subjects enrolled
    Sweden: 17
    Country: Number of subjects enrolled
    United Kingdom: 16
    Country: Number of subjects enrolled
    United States: 1836
    Worldwide total number of subjects
    3417
    EEA total number of subjects
    847
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    1660
    From 65 to 84 years
    1748
    85 years and over
    9

    Subject disposition

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    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 A total of 3450 subjects were enrolled and randomized in the study. Out of 3450, only 3417 subjects received the investigational product.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Staphylococcus aureus 4-antigen (SA4Ag)
    Arm description
    		 Subjects randomized to SA4Ag received a single dose of 0.5 milliliter (mL) SA4Ag vaccine intramuscularly, 10 to 60 days prior to their scheduled surgery. Subjects were followed from vaccination up to 6 months after their spinal surgical procedure.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Staphylococcus aureus 4-antigen
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Subjects randomized to SA4Ag received a single dose of 0.5 mL SA4Ag vaccine intramuscularly, 10 to 60 days prior to their scheduled surgery. Subjects were followed from vaccination up to 6 months after their spinal surgical procedure.

    Arm title
    		 Placebo
    Arm description
    		 Subjects randomized to this arm received placebo containing the vaccine excipients reconstituted in 0.5mL water for injection. It was administered via intramuscular injection, 10 to 60 days prior to scheduled surgery. Subjects were followed from vaccination up to 6 months after their spinal surgical procedure.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Subjects randomized to this arm received placebo containing the vaccine excipients reconstituted in 0.5mL water for injection. It was administered via intramuscular injection, 10 to 60 days prior to scheduled surgery. Subjects were followed from vaccination up to 6 months after their spinal surgical procedure.

    Number of subjects in period 1
    		Staphylococcus aureus 4-antigen (SA4Ag) Placebo
    Started
    1708
    1709
    Completed
    1599
    1594
    Not completed
    109
    115
         Consent withdrawn by subject
    26
    27
         No longer meet eligibility criteria
    33
    38
         Death
    13
    10
         Study terminated by sponsor
    5
    5
         Adverse event
    3
    5
         Unspecified
    10
    10
         Lost to follow-up
    19
    20

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Staphylococcus aureus 4-antigen (SA4Ag)
    Reporting group description
    		 Subjects randomized to SA4Ag received a single dose of 0.5 milliliter (mL) SA4Ag vaccine intramuscularly, 10 to 60 days prior to their scheduled surgery. Subjects were followed from vaccination up to 6 months after their spinal surgical procedure.

    Reporting group title
    Placebo
    Reporting group description
    		 Subjects randomized to this arm received placebo containing the vaccine excipients reconstituted in 0.5mL water for injection. It was administered via intramuscular injection, 10 to 60 days prior to scheduled surgery. Subjects were followed from vaccination up to 6 months after their spinal surgical procedure.

    Reporting group values
    		 Staphylococcus aureus 4-antigen (SA4Ag) Placebo Total
    Number of subjects
    		 1708 1709 3417
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0
        Newborns (0-27 days)
    		 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0
        Children (2-11 years)
    		 0 0 0
        Adolescents (12-17 years)
    		 0 0 0
        Adults (18-64 years)
    		 824 836 1660
        From 65-84 years
    		 880 868 1748
        85 years and over
    		 4 5 9
    Age Continuous
    Units: Years
        arithmetic mean (standard deviation)
    		 62.7 ± 12.3 62.6 ± 12.6 -
    Sex: Female, Male
    Units: Subjects
        Female
    		 950 940 1890
        Male
    		 758 769 1527
    Race (NIH/OMB)
    Units: Subjects
        American Indian or Alaska Native
    		 0 0 0
        Asian
    		 295 290 585
        Native Hawaiian or Other Pacific Islander
    		 0 0 0
        Black or African American
    		 90 111 201
        White
    		 1295 1283 2578
        More than one race
    		 0 0 0
        Unknown or Not Reported
    		 28 25 53
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    		 69 69 138
        Not Hispanic or Latino
    		 1634 1639 3273
        Unknown or Not Reported
    		 5 1 6

    End points

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    End points reporting groups
    Reporting group title
    Staphylococcus aureus 4-antigen (SA4Ag)
    Reporting group description
    		 Subjects randomized to SA4Ag received a single dose of 0.5 milliliter (mL) SA4Ag vaccine intramuscularly, 10 to 60 days prior to their scheduled surgery. Subjects were followed from vaccination up to 6 months after their spinal surgical procedure.

    Reporting group title
    Placebo
    Reporting group description
    		 Subjects randomized to this arm received placebo containing the vaccine excipients reconstituted in 0.5mL water for injection. It was administered via intramuscular injection, 10 to 60 days prior to scheduled surgery. Subjects were followed from vaccination up to 6 months after their spinal surgical procedure.

    Primary: Number of Subjects With Postoperative Staphylococcus Aureus Bloodstream Infection (BSI) and/or Surgical-site Infection (SSI-including Deep Incisional or Organ/Space) Occurring Within 90 Days After Spinal Surgery

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    End point title
    		 Number of Subjects With Postoperative Staphylococcus Aureus Bloodstream Infection (BSI) and/or Surgical-site Infection (SSI-including Deep Incisional or Organ/Space) Occurring Within 90 Days After Spinal Surgery
    End point description
    BSI: clinical infection involving a recognized pathogen (S. aureus) cultured from >=1 blood cultures or commensal organism cultured from >=2 blood cultures. SSI: surgical site infection. Types of SSI in this measure: Deep incisional SSI=infection in deep soft tissues of incision (fascial, muscle layers), Organ space SSI=infection in any part of body (excluding skin incision, fascia or muscle layers) opened/manipulated during surgery. Overall Number of subjects with postoperative BSI and/or SSI (deep incisional or organ/space) confirmed by event adjudication committee were reported. A subject may have met criteria for both BSI and SSI (deep incisional or organ/space). Per-protocol efficacy population: all eligible subjects, vaccinated as randomized, underwent surgery per study criteria within 9-90 days (inclusive) post vaccination (expanded from 10-60 days in protocol), had no infection/malignancy at surgery and no major protocol violations prior to S. aureus infection.
    End point type
    Primary
    End point timeframe
    Day of surgery (Day 1) up to Day 90
    End point values
    		 Staphylococcus aureus 4-antigen (SA4Ag) Placebo
    Number of subjects analysed
    1544
    1547
    Units: Subjects
    14
    14
    Statistical analysis title
    		 Staphylococcus aureus 4-antigen (SA4Ag) Vs Placebo
    Comparison groups
    Staphylococcus aureus 4-antigen (SA4Ag) v Placebo
    Number of subjects included in analysis
    3091
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [1]
    Method
    Parameter type
    		 VE
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -126.3
         upper limit
    		 55.81
    Notes
    [1] - Vaccine Efficacy (VE): calculated as 1-(P/[1-P]*100), where P is the number of SA4Ag cases divided by the total number of cases. The confidence interval (CI) was calculated using the Clopper-Pearson method.

    Primary: Percentage of Subjects With Local Reactions Within 10 Days After Vaccination

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    End point title
    		 Percentage of Subjects With Local Reactions Within 10 Days After Vaccination
    End point description
    Local reactions were recorded using an electronic diary (e-diary). Local reactions included redness, swelling and pain at the injection site. Redness and swelling were categorized as mild (2.5 to 5.0 centimeters [cm]), moderate (5.5 to 10.0 cm) and, severe (greater than or equal to [>=] 10.5 cm). Pain at the injection site was defined as mild (did not interfere with activity), moderate (interfered with activity), and severe (prevented daily activity). Subjects may be represented in more than 1 row. Here, “Any” for redness, swelling, pain at the injection site represents any grade of these local reactions among mild, moderate or severe. Safety population: all subjects who received investigational product in this study. Here, "Overall Number of Subjects Analysed, N" signifies number of subjects analysed for this endpoint.
    End point type
    Primary
    End point timeframe
    Within 10 days after Vaccination
    End point values
    		 Staphylococcus aureus 4-antigen (SA4Ag) Placebo
    Number of subjects analysed
    1692
    1685
    Units: Percentage of subjects
    number (confidence interval 95%)
        Redness: Any
    9.2 (7.9 to 10.7)
    0.9 (0.5 to 1.5)
        Redness: Mild
    5.3 (4.2 to 6.4)
    0.9 (0.5 to 1.5)
        Redness: Moderate
    3.1 (2.4 to 4.1)
    0.1 (0.0 to 0.3)
        Redness: Severe
    0.8 (0.5 to 1.4)
    0.0 (0.0 to 0.2)
        Swelling: Any
    8.0 (6.7 to 9.4)
    1.0 (0.6 to 1.6)
        Swelling: Mild
    4.6 (3.6 to 5.7)
    0.7 (0.4 to 1.2)
        Swelling: Moderate
    2.7 (2.0 to 3.6)
    0.3 (0.1 to 0.7)
        Swelling: Severe
    0.7 (0.4 to 1.2)
    0.0 (0.0 to 0.2)
        Pain at the injection site: Any
    24.1 (22.1 to 26.2)
    8.4 (7.1 to 9.9)
        Pain at the injection site: Mild
    19.2 (17.4 to 21.2)
    7.0 (5.8 to 8.3)
        Pain at the injection site: Moderate
    4.3 (3.4 to 5.4)
    1.3 (0.8 to 2.0)
        Pain at the injection site: Severe
    0.6 (0.3 to 1.1)
    0.1 (0.0 to 0.4)
    Statistical analysis title
    		 Staphylococcus aureus 4-antigen (SA4Ag) Vs Placebo
    Statistical analysis description
    Redness: Any
    Comparison groups
    Staphylococcus aureus 4-antigen (SA4Ag) v Placebo
    Number of subjects included in analysis
    3377
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Miettinen and Nurminen
    Parameter type
    		 Difference in percentage of subjects
    Point estimate
    8.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 6.9
         upper limit
    		 9.8
    Statistical analysis title
    		 Staphylococcus aureus 4-antigen (SA4Ag) Vs Placebo
    Statistical analysis description
    Redness: Mild
    Comparison groups
    Staphylococcus aureus 4-antigen (SA4Ag) v Placebo
    Number of subjects included in analysis
    3377
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Difference in percentage of subjects
    Point estimate
    4.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 3.3
         upper limit
    		 5.6
    Statistical analysis title
    		 Staphylococcus aureus 4-antigen (SA4Ag) Vs Placebo
    Statistical analysis description
    Redness: Moderate
    Comparison groups
    Staphylococcus aureus 4-antigen (SA4Ag) v Placebo
    Number of subjects included in analysis
    3377
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Difference in percentage of subjects
    Point estimate
    3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 2.3
         upper limit
    		 4
    Statistical analysis title
    		 Staphylococcus aureus 4-antigen (SA4Ag) Vs Placebo
    Statistical analysis description
    Redness: Severe
    Comparison groups
    Staphylococcus aureus 4-antigen (SA4Ag) v Placebo
    Number of subjects included in analysis
    3377
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Difference in percentage of subjects
    Point estimate
    0.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.5
         upper limit
    		 1.4
    Statistical analysis title
    		 Staphylococcus aureus 4-antigen (SA4Ag) Vs Placebo
    Statistical analysis description
    Swelling: Any
    Comparison groups
    Staphylococcus aureus 4-antigen (SA4Ag) v Placebo
    Number of subjects included in analysis
    3377
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Miettinen and Nurminen
    Parameter type
    		 Difference in percentage of subjects
    Point estimate
    7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 5.7
         upper limit
    		 8.4
    Statistical analysis title
    		 Staphylococcus aureus 4-antigen (SA4Ag) Vs Placebo
    Statistical analysis description
    Swelling: Mild
    Comparison groups
    Staphylococcus aureus 4-antigen (SA4Ag) v Placebo
    Number of subjects included in analysis
    3377
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Difference in percentage of subjects
    Point estimate
    3.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 2.8
         upper limit
    		 5
    Statistical analysis title
    		 Staphylococcus aureus 4-antigen (SA4Ag) Vs Placebo
    Statistical analysis description
    Swelling: Moderate
    Comparison groups
    Staphylococcus aureus 4-antigen (SA4Ag) v Placebo
    Number of subjects included in analysis
    3377
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Difference in percentage of subjects
    Point estimate
    2.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.7
         upper limit
    		 3.3
    Statistical analysis title
    		 Staphylococcus aureus 4-antigen (SA4Ag) Vs Placebo
    Statistical analysis description
    Swelling: Severe
    Comparison groups
    Staphylococcus aureus 4-antigen (SA4Ag) v Placebo
    Number of subjects included in analysis
    3377
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Difference in percentage of subjects
    Point estimate
    0.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.4
         upper limit
    		 1.2
    Statistical analysis title
    		 Staphylococcus aureus 4-antigen (SA4Ag) Vs Placebo
    Statistical analysis description
    Pain at the injection site: Any
    Comparison groups
    Staphylococcus aureus 4-antigen (SA4Ag) v Placebo
    Number of subjects included in analysis
    3377
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Miettinen and Nurminen
    Parameter type
    		 Difference in percentage of subjects
    Point estimate
    15.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 13.3
         upper limit
    		 18.1
    Statistical analysis title
    		 Staphylococcus aureus 4-antigen (SA4Ag) Vs Placebo
    Statistical analysis description
    Pain at the injection site: Mild
    Comparison groups
    Staphylococcus aureus 4-antigen (SA4Ag) v Placebo
    Number of subjects included in analysis
    3377
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Difference in percentage of subjects
    Point estimate
    12.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 10
         upper limit
    		 14.5
    Statistical analysis title
    		 Staphylococcus aureus 4-antigen (SA4Ag) Vs Placebo
    Statistical analysis description
    Pain at the injection site: Moderate
    Comparison groups
    Staphylococcus aureus 4-antigen (SA4Ag) v Placebo
    Number of subjects included in analysis
    3377
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Difference in percentage of subjects
    Point estimate
    3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.9
         upper limit
    		 4.2
    Statistical analysis title
    		 Staphylococcus aureus 4-antigen (SA4Ag) Vs Placebo
    Statistical analysis description
    Pain at the injection site: Severe
    Comparison groups
    Staphylococcus aureus 4-antigen (SA4Ag) v Placebo
    Number of subjects included in analysis
    3377
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Difference in percentage of subjects
    Point estimate
    0.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.1
         upper limit
    		 1

    Primary: Percentage of Subjects With Systemic Events Within 10 Days After Vaccination

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    End point title
    		 Percentage of Subjects With Systemic Events Within 10 Days After Vaccination
    End point description
    Systemic reactions:fever, fatigue, headache, diarrhea, vomiting, muscle pain and joint pain, recorded using an e-diary. Fever graded:38.0-38.4 degree Celsius(C), 38.5-38.9 degree C, 39.0-40.0 degree C and greater than(>)40.0 degree C. Vomiting graded: mild(1-2 times in 24 hours), moderate(>2 times in 24 hours), severe(required intravenous hydration). Diarrhea: graded as mild(2-3 loose stools in 24 hours), moderate(4-5 loose stools in 24 hours), severe(>=6 loose stools in 24 hours). Headache, fatigue, muscle pain and joint pain graded: mild(no interference with activity), moderate(some interference with activity) and severe(prevented daily routine activity). Subjects may be represented in >1 row. Here“any” for fever, fatigue, headache, vomiting, diarrhea, muscle pain, joint pain represents any grade of these systemic reactions among mild, moderate or severe. Safety population:all subjects who received investigational product in study. "N":number of subjects analysed for this endpoint.
    End point type
    Primary
    End point timeframe
    Within 10 days after Vaccination
    End point values
    		 Staphylococcus aureus 4-antigen (SA4Ag) Placebo
    Number of subjects analysed
    1692
    1685
    Units: Percentage of subjects
    number (confidence interval 95%)
        Fever: Any
    2.0 (1.4 to 2.8)
    1.4 (0.9 to 2.0)
        Fever: 38.0 degree C to 38.4 degree C
    1.3 (0.8 to 2.0)
    0.9 (0.5 to 1.5)
        Fever: 38.5 degree C to 38.9 degree C
    0.5 (0.2 to 0.9)
    0.4 (0.2 to 0.9)
        Fever: 39.0 degree C to 40.0 degree C
    0.2 (0.0 to 0.5)
    0.1 (0.0 to 0.3)
        Fever: >40.0 degree C
    0.1 (0.0 to 0.3)
    0.0 (0.0 to 0.2)
        Fatigue: Any
    43.3 (40.9 to 45.7)
    40.4 (38.1 to 42.8)
        Fatigue: Mild
    14.0 (12.4 to 15.8)
    12.6 (11.1 to 14.3)
        Fatigue: Moderate
    24.9 (22.8 to 27.0)
    23.6 (21.6 to 25.7)
        Fatigue: Severe
    4.4 (3.4 to 5.5)
    4.2 (3.3 to 5.2)
        Headache: Any
    32.4 (30.2 to 34.7)
    31.2 (29.0 to 33.5)
        Headache: Mild
    17.7 (15.9 to 19.6)
    18.0 (16.2 to 19.9)
        Headache: Moderate
    13.5 (11.9 to 15.3)
    12.0 (10.5 to 13.6)
        Headache: Severe
    1.2 (0.8 to 1.9)
    1.2 (0.8 to 1.9)
        Diarrhea: Any
    17.0 (15.2 to 18.8)
    16.0 (14.3 to 17.9)
        Diarrhea: Mild
    13.0 (11.4 to 14.7)
    12.2 (10.7 to 13.9)
        Diarrhea: Moderate
    3.4 (2.6 to 4.4)
    2.9 (2.2 to 3.8)
        Diarrhea: Severe
    0.5 (0.2 to 1.0)
    0.9 (0.5 to 1.5)
        Vomiting: Any
    2.7 (1.9 to 3.5)
    3.3 (2.5 to 4.2)
        Vomiting: Mild
    2.4 (1.7 to 3.2)
    2.6 (1.9 to 3.5)
        Vomiting: Moderate
    0.3 (0.1 to 0.7)
    0.7 (0.3 to 1.2)
        Vomiting: Severe
    0.0 (0.0 to 0.2)
    0.0 (0.0 to 0.2)
        Muscle pain: Any
    27.9 (25.8 to 30.1)
    26.2 (24.1 to 28.4)
        Muscle pain: Mild
    10.1 (8.7 to 11.6)
    9.3 (8.0 to 10.8)
        Muscle pain: Moderate
    15.7 (14.0 to 17.5)
    14.6 (12.9 to 16.4)
        Muscle pain: Severe
    2.1 (1.5 to 2.9)
    2.3 (1.7 to 3.2)
        Joint pain: Any
    27.5 (25.4 to 29.7)
    25.8 (23.7 to 28.0)
        Joint pain: Mild
    9.6 (8.3 to 11.1)
    8.0 (6.7 to 9.3)
        Joint pain: Moderate
    16.1 (14.4 to 17.9)
    16.1 (14.4 to 18.0)
        Joint pain: Severe
    1.8 (1.2 to 2.5)
    1.7 (1.2 to 2.5)
    Statistical analysis title
    		 Staphylococcus aureus 4-antigen (SA4Ag) Vs Placebo
    Statistical analysis description
    Fever: Any
    Comparison groups
    Staphylococcus aureus 4-antigen (SA4Ag) v Placebo
    Number of subjects included in analysis
    3377
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.146
    Method
    		 Miettinen and Nurminen
    Parameter type
    		 Difference in percentage of subjects
    Point estimate
    0.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.2
         upper limit
    		 1.6
    Statistical analysis title
    		 Staphylococcus aureus 4-antigen (SA4Ag) Vs Placebo
    Statistical analysis description
    Fever: 38.0 degree C to 38.4 degree C
    Comparison groups
    Staphylococcus aureus 4-antigen (SA4Ag) v Placebo
    Number of subjects included in analysis
    3377
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Difference in percentage of subjects
    Point estimate
    0.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.3
         upper limit
    		 1.2
    Statistical analysis title
    		 Staphylococcus aureus 4-antigen (SA4Ag) Vs Placebo
    Statistical analysis description
    Fever: 38.5 degree C to 38.9 degree C
    Comparison groups
    Staphylococcus aureus 4-antigen (SA4Ag) v Placebo
    Number of subjects included in analysis
    3377
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Difference in percentage of subjects
    Point estimate
    0.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.4
         upper limit
    		 0.6
    Statistical analysis title
    		 Staphylococcus aureus 4-antigen (SA4Ag) Vs Placebo
    Statistical analysis description
    Fever: 39.0 degree C to 40.0 degree C
    Comparison groups
    Staphylococcus aureus 4-antigen (SA4Ag) v Placebo
    Number of subjects included in analysis
    3377
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Difference in percentage of subjects
    Point estimate
    0.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.2
         upper limit
    		 0.5
    Statistical analysis title
    		 Staphylococcus aureus 4-antigen (SA4Ag) Vs Placebo
    Statistical analysis description
    Fever: >40.0 degree C
    Comparison groups
    Staphylococcus aureus 4-antigen (SA4Ag) v Placebo
    Number of subjects included in analysis
    3377
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Difference in percentage of subjects
    Point estimate
    0.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.2
         upper limit
    		 0.3
    Statistical analysis title
    		 Staphylococcus aureus 4-antigen (SA4Ag) Vs Placebo
    Statistical analysis description
    Fatigue: Any
    Comparison groups
    Staphylococcus aureus 4-antigen (SA4Ag) v Placebo
    Number of subjects included in analysis
    3377
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.093
    Method
    		 Miettinen and Nurminen
    Parameter type
    		 Difference in percentage of subjects
    Point estimate
    2.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.5
         upper limit
    		 6.2
    Statistical analysis title
    		 Staphylococcus aureus 4-antigen (SA4Ag) Vs Placebo
    Statistical analysis description
    Fatigue: Mild
    Comparison groups
    Staphylococcus aureus 4-antigen (SA4Ag) v Placebo
    Number of subjects included in analysis
    3377
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Difference in percentage of subjects
    Point estimate
    1.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.9
         upper limit
    		 3.7
    Statistical analysis title
    		 Staphylococcus aureus 4-antigen (SA4Ag) Vs Placebo
    Statistical analysis description
    Fatigue: Moderate
    Comparison groups
    Staphylococcus aureus 4-antigen (SA4Ag) v Placebo
    Number of subjects included in analysis
    3377
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Difference in percentage of subjects
    Point estimate
    1.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.6
         upper limit
    		 4.2
    Statistical analysis title
    		 Staphylococcus aureus 4-antigen (SA4Ag) Vs Placebo
    Statistical analysis description
    Fatigue: Severe
    Comparison groups
    Staphylococcus aureus 4-antigen (SA4Ag) v Placebo
    Number of subjects included in analysis
    3377
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Difference in percentage of subjects
    Point estimate
    0.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.2
         upper limit
    		 1.6
    Statistical analysis title
    		 Staphylococcus aureus 4-antigen (SA4Ag) Vs Placebo
    Statistical analysis description
    Headache: Any
    Comparison groups
    Staphylococcus aureus 4-antigen (SA4Ag) v Placebo
    Number of subjects included in analysis
    3377
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.443
    Method
    		 Miettinen and Nurminen
    Parameter type
    		 Difference in percentage of subjects
    Point estimate
    1.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.9
         upper limit
    		 4.4
    Statistical analysis title
    		 Staphylococcus aureus 4-antigen (SA4Ag) Vs Placebo
    Statistical analysis description
    Headache: Mild
    Comparison groups
    Staphylococcus aureus 4-antigen (SA4Ag) v Placebo
    Number of subjects included in analysis
    3377
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Difference in percentage of subjects
    Point estimate
    -0.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.9
         upper limit
    		 2.3
    Statistical analysis title
    		 Staphylococcus aureus 4-antigen (SA4Ag) Vs Placebo
    Statistical analysis description
    Headache: Moderate
    Comparison groups
    Staphylococcus aureus 4-antigen (SA4Ag) v Placebo
    Number of subjects included in analysis
    3377
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Difference in percentage of subjects
    Point estimate
    1.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.7
         upper limit
    		 3.8
    Statistical analysis title
    		 Staphylococcus aureus 4-antigen (SA4Ag) Vs Placebo
    Statistical analysis description
    Headache: Severe
    Comparison groups
    Staphylococcus aureus 4-antigen (SA4Ag) v Placebo
    Number of subjects included in analysis
    3377
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Difference in percentage of subjects
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.8
         upper limit
    		 0.8
    Statistical analysis title
    		 Staphylococcus aureus 4-antigen (SA4Ag) Vs Placebo
    Statistical analysis description
    Diarrhea: Any
    Comparison groups
    Staphylococcus aureus 4-antigen (SA4Ag) v Placebo
    Number of subjects included in analysis
    3377
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.462
    Method
    		 Miettinen and Nurminen
    Parameter type
    		 Difference in percentage of subjects
    Point estimate
    1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.6
         upper limit
    		 3.4
    Statistical analysis title
    		 Staphylococcus aureus 4-antigen (SA4Ag) Vs Placebo
    Statistical analysis description
    Diarrhea: Mild
    Comparison groups
    Staphylococcus aureus 4-antigen (SA4Ag) v Placebo
    Number of subjects included in analysis
    3377
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Difference in percentage of subjects
    Point estimate
    0.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.5
         upper limit
    		 3
    Statistical analysis title
    		 Staphylococcus aureus 4-antigen (SA4Ag) Vs Placebo
    Statistical analysis description
    Diarrhea: Moderate
    Comparison groups
    Staphylococcus aureus 4-antigen (SA4Ag) v Placebo
    Number of subjects included in analysis
    3377
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Difference in percentage of subjects
    Point estimate
    0.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.7
         upper limit
    		 1.7
    Statistical analysis title
    		 Staphylococcus aureus 4-antigen (SA4Ag) Vs Placebo
    Statistical analysis description
    Diarrhea: Severe
    Comparison groups
    Staphylococcus aureus 4-antigen (SA4Ag) v Placebo
    Number of subjects included in analysis
    3377
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Difference in percentage of subjects
    Point estimate
    -0.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1
         upper limit
    		 0.2
    Statistical analysis title
    		 Staphylococcus aureus 4-antigen (SA4Ag) Vs Placebo
    Statistical analysis description
    Vomiting: Any
    Comparison groups
    Staphylococcus aureus 4-antigen (SA4Ag) v Placebo
    Number of subjects included in analysis
    3377
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.3
    Method
    		 Miettinen and Nurminen
    Parameter type
    		 Difference in percentage of subjects
    Point estimate
    -0.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.8
         upper limit
    		 0.5
    Statistical analysis title
    		 Staphylococcus aureus 4-antigen (SA4Ag) Vs Placebo
    Statistical analysis description
    Vomiting: Mild
    Comparison groups
    Staphylococcus aureus 4-antigen (SA4Ag) v Placebo
    Number of subjects included in analysis
    3377
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Difference in percentage of subjects
    Point estimate
    -0.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.3
         upper limit
    		 0.8
    Statistical analysis title
    		 Staphylococcus aureus 4-antigen (SA4Ag) Vs Placebo
    Statistical analysis description
    Vomiting: Moderate
    Comparison groups
    Staphylococcus aureus 4-antigen (SA4Ag) v Placebo
    Number of subjects included in analysis
    3377
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Difference in percentage of subjects
    Point estimate
    -0.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.9
         upper limit
    		 0.1
    Statistical analysis title
    		 Staphylococcus aureus 4-antigen (SA4Ag) Vs Placebo
    Statistical analysis description
    Muscle pain: Any
    Comparison groups
    Staphylococcus aureus 4-antigen (SA4Ag) v Placebo
    Number of subjects included in analysis
    3377
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.276
    Method
    		 Miettinen and Nurminen
    Parameter type
    		 Difference in percentage of subjects
    Point estimate
    1.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.3
         upper limit
    		 4.7
    Statistical analysis title
    		 Staphylococcus aureus 4-antigen (SA4Ag) Vs Placebo
    Statistical analysis description
    Muscle pain: Mild
    Comparison groups
    Staphylococcus aureus 4-antigen (SA4Ag) v Placebo
    Number of subjects included in analysis
    3377
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Difference in percentage of subjects
    Point estimate
    0.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.2
         upper limit
    		 2.8
    Statistical analysis title
    		 Staphylococcus aureus 4-antigen (SA4Ag) Vs Placebo
    Statistical analysis description
    Muscle pain: Moderate
    Comparison groups
    Staphylococcus aureus 4-antigen (SA4Ag) v Placebo
    Number of subjects included in analysis
    3377
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Difference in percentage of subjects
    Point estimate
    1.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.4
         upper limit
    		 3.5
    Statistical analysis title
    		 Staphylococcus aureus 4-antigen (SA4Ag) Vs Placebo
    Statistical analysis description
    Muscle pain: Severe
    Comparison groups
    Staphylococcus aureus 4-antigen (SA4Ag) v Placebo
    Number of subjects included in analysis
    3377
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Difference in percentage of subjects
    Point estimate
    -0.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.2
         upper limit
    		 0.8
    Statistical analysis title
    		 Staphylococcus aureus 4-antigen (SA4Ag) Vs Placebo
    Statistical analysis description
    Joint pain: Any
    Comparison groups
    Staphylococcus aureus 4-antigen (SA4Ag) v Placebo
    Number of subjects included in analysis
    3377
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.273
    Method
    		 Miettinen and Nurminen
    Parameter type
    		 Difference in percentage of subjects
    Point estimate
    1.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.3
         upper limit
    		 4.6
    Statistical analysis title
    		 Staphylococcus aureus 4-antigen (SA4Ag) Vs Placebo
    Statistical analysis description
    Joint pain: Mild
    Comparison groups
    Staphylococcus aureus 4-antigen (SA4Ag) v Placebo
    Number of subjects included in analysis
    3377
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Difference in percentage of subjects
    Point estimate
    1.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.2
         upper limit
    		 3.6
    Statistical analysis title
    		 Staphylococcus aureus 4-antigen (SA4Ag) Vs Placebo
    Statistical analysis description
    Joint pain: Moderate
    Comparison groups
    Staphylococcus aureus 4-antigen (SA4Ag) v Placebo
    Number of subjects included in analysis
    3377
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Difference in percentage of subjects
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.6
         upper limit
    		 2.4
    Statistical analysis title
    		 Staphylococcus aureus 4-antigen (SA4Ag)
    Statistical analysis description
    Joint pain: Severe
    Comparison groups
    Staphylococcus aureus 4-antigen (SA4Ag) v Placebo
    Number of subjects included in analysis
    3377
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Difference in percentage of subjects
    Point estimate
    0.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.9
         upper limit
    		 1

    Primary: Number of Subjects With Adverse Events (AEs) From Vaccination Until The Day of Surgery (Day 1)

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    End point title
    		 Number of Subjects With Adverse Events (AEs) From Vaccination Until The Day of Surgery (Day 1) [2]
    End point description
    An adverse event (AE) was any untoward medical occurrence in a subject who received study vaccine without regard to possibility of causal relationship. AEs including serious as well non-serious AEs. Safety population: all subjects who received investigational product in this study.
    End point type
    Primary
    End point timeframe
    From vaccination up to Day of surgery (Day 1) (10-60 days after vaccination)
    Notes
    [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No statistical analysis has been performed for this endpoint
    End point values
    		 Staphylococcus aureus 4-antigen (SA4Ag) Placebo
    Number of subjects analysed
    1708
    1709
    Units: Subjects
    213
    178
    No statistical analyses for this end point

    Primary: Number of Subjects With Adverse Events (AEs) From Vaccination Until First Postoperative Evaluation on Day 42

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    End point title
    		 Number of Subjects With Adverse Events (AEs) From Vaccination Until First Postoperative Evaluation on Day 42 [3]
    End point description
    An AE was any untoward medical occurrence in a subject who received study vaccine without regard to possibility of causal relationship. AEs including serious as well non-serious AEs. Safety population: all subjects who received investigational product in this study.
    End point type
    Primary
    End point timeframe
    From vaccination until Day 42 after surgery (52-102 days after vaccination)
    Notes
    [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No statistical analysis has been performed for this endpoint
    End point values
    		 Staphylococcus aureus 4-antigen (SA4Ag) Placebo
    Number of subjects analysed
    1708
    1709
    Units: Subjects
    1198
    1213
    No statistical analyses for this end point

    Primary: Number of Subjects With Adverse Events (AEs) From The Day of Surgery (Day 1) Until First Postoperative Evaluation on Day 42

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    End point title
    		 Number of Subjects With Adverse Events (AEs) From The Day of Surgery (Day 1) Until First Postoperative Evaluation on Day 42 [4]
    End point description
    An AE was any untoward medical occurrence in a subject who received study vaccine without regard to possibility of causal relationship. AEs including serious as well non-serious AEs. Safety population: all subjects who received investigational product in this study.
    End point type
    Primary
    End point timeframe
    Day of surgery (Day 1) up to Day 42 after surgery
    Notes
    [4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No statistical analysis has been performed for this endpoint
    End point values
    		 Staphylococcus aureus 4-antigen (SA4Ag) Placebo
    Number of subjects analysed
    1708
    1709
    Units: Subjects
    1136
    1167
    No statistical analyses for this end point

    Primary: Number of Subjects With Newly Diagnosed Chronic Medical Disorders From First Postoperative Evaluation on Day 42 Until Last Postoperative Evaluation on Day 180

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    End point title
    		 Number of Subjects With Newly Diagnosed Chronic Medical Disorders From First Postoperative Evaluation on Day 42 Until Last Postoperative Evaluation on Day 180 [5]
    End point description
    A newly diagnosed chronic medical disorder was defined as a disease or medical condition, not previously identified, that was expected to be persistent or otherwise long-lasting in its effects. Safety population: all subjects who received investigational product in this study.
    End point type
    Primary
    End point timeframe
    Day 42 up to Day 180 (up to 138 days)
    Notes
    [5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No statistical analysis has been performed for this endpoint
    End point values
    		 Staphylococcus aureus 4-antigen (SA4Ag) Placebo
    Number of subjects analysed
    1708
    1709
    Units: Subjects
    29
    41
    No statistical analyses for this end point

    Primary: Number of Subjects With Serious Adverse Events (SAEs) From Vaccination Until Last Postoperative Evaluation on Day 180

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    End point title
    		 Number of Subjects With Serious Adverse Events (SAEs) From Vaccination Until Last Postoperative Evaluation on Day 180 [6]
    End point description
    An AE was any untoward medical occurrence in a subject who received study vaccine without regard to possibility of causal relationship. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death, initial or prolonged inpatient hospitalization, life-threatening experience (immediate risk of dying), persistent or significant disability/incapacity, congenital anomaly. Safety population: all subjects who received investigational product in this study.
    End point type
    Primary
    End point timeframe
    From vaccination up to Day 180 after surgery (190-240 days after vaccination)
    Notes
    [6] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No statistical analysis has been performed for this endpoint
    End point values
    		 Staphylococcus aureus 4-antigen (SA4Ag) Placebo
    Number of subjects analysed
    1708
    1709
    Units: Subjects
    403
    424
    No statistical analyses for this end point

    Primary: Number of Subjects With Serious Adverse Events (SAEs) From Vaccination Until Day of Surgery (Day 1)

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    End point title
    		 Number of Subjects With Serious Adverse Events (SAEs) From Vaccination Until Day of Surgery (Day 1) [7]
    End point description
    An AE was any untoward medical occurrence in a subject who received study vaccine without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death, initial or prolonged inpatient hospitalization, life-threatening experience (immediate risk of dying), persistent or significant disability/incapacity, congenital anomaly. Safety population: all subjects who received investigational product in this study.
    End point type
    Primary
    End point timeframe
    From vaccination up to Day of surgery (Day 1) (10-60 days after vaccination)
    Notes
    [7] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No statistical analysis has been performed for this endpoint
    End point values
    		 Staphylococcus aureus 4-antigen (SA4Ag) Placebo
    Number of subjects analysed
    1708
    1709
    Units: Subjects
    27
    26
    No statistical analyses for this end point

    Primary: Number of Subjects With Serious Adverse Events (SAEs) From The Day of Surgery (Day 1) Until Last Postoperative Evaluation on Day 180

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    End point title
    		 Number of Subjects With Serious Adverse Events (SAEs) From The Day of Surgery (Day 1) Until Last Postoperative Evaluation on Day 180 [8]
    End point description
    An AE was any untoward medical occurrence in a subject who received study vaccine without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death, initial or prolonged inpatient hospitalization, life-threatening experience (immediate risk of dying), persistent or significant disability/incapacity, congenital anomaly. Safety population: all subjects who received investigational product in this study.
    End point type
    Primary
    End point timeframe
    Day of surgery (Day 1) up to Day 180 after surgery
    Notes
    [8] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No statistical analysis has been performed for this endpoint
    End point values
    		 Staphylococcus aureus 4-antigen (SA4Ag) Placebo
    Number of subjects analysed
    1708
    1709
    Units: Subjects
    384
    401
    No statistical analyses for this end point

    Secondary: Number of Subjects With Postoperative S. Aureus Blood Stream Infection (BSI) and/or Surgical-site Infection (SSI-including Deep Incisional or Organ/Space) Occurring Within 180 Days After Surgery

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    End point title
    		 Number of Subjects With Postoperative S. Aureus Blood Stream Infection (BSI) and/or Surgical-site Infection (SSI-including Deep Incisional or Organ/Space) Occurring Within 180 Days After Surgery
    End point description
    BSI: clinical infection involving a recognized pathogen (S. aureus) cultured from >=1 blood cultures or commensal organism cultured from >=2 blood cultures. SSI: surgical site infection. Types of SSI in this measure: Deep incisional SSI=infection in deep soft tissues of incision (fascial, muscle layers); Organ space SSI=infection in any part of body (excluding skin incision, fascia or muscle layers) opened or manipulated during surgery. Overall number of subjects with postoperative BSI and/or SSI (deep incisional or organ/space), confirmed by event adjudication committee were reported. A subject may have met criteria for both BSI and SSI (deep incisional or organ/space). Per-protocol efficacy population: all eligible subjects, vaccinated as randomized, underwent surgery per study criteria within 9-90 days (inclusive) post vaccination (expanded from 10-60 days in protocol), had no infection/malignancy at surgery and no major protocol violations prior to S. aureus infection.
    End point type
    Secondary
    End point timeframe
    Day of surgery (Day 1) up to Day 180 after surgery
    End point values
    		 Staphylococcus aureus 4-antigen (SA4Ag) Placebo
    Number of subjects analysed
    1544
    1547
    Units: Subjects
    14
    14
    Statistical analysis title
    		 Staphylococcus aureus 4-antigen (SA4Ag) Vs Placebo
    Comparison groups
    Staphylococcus aureus 4-antigen (SA4Ag) v Placebo
    Number of subjects included in analysis
    3091
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [9]
    Method
    Parameter type
    		 VE
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -126.3
         upper limit
    		 55.81
    Notes
    [9] - VE: calculated as 1-(P/[1-P]*100), where P is the number of SA4Ag cases divided by the total number of cases. The CI was calculated using the Clopper-Pearson method.

    Secondary: Number of Subjects With any Postoperative S. Aureus Surgical-site Infection (SSI-Superficial, Deep Incisional or Organ/Space) Occurring Within 90 Days After Surgery

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    End point title
    		 Number of Subjects With any Postoperative S. Aureus Surgical-site Infection (SSI-Superficial, Deep Incisional or Organ/Space) Occurring Within 90 Days After Surgery
    End point description
    SSI: surgical site infection. Types of SSI in this measure: Superficial SSI: infection involving skin and subcutaneous tissue of incision, Deep incisional SSI: infection involving deep soft tissues of incision (fascial and muscle layers), Organ/space SSI: infection involving any part of body, (excluding skin incision, fascia, or muscle layers) opened/manipulated during surgery. Overall number of subjects with postoperative SSI (including superficial, deep incisional and/or organ/space SSI) confirmed by event adjudication committee were reported. Per-protocol efficacy population: all eligible subjects, vaccinated as randomized, underwent surgery per study-defined criteria within 9-90 days post vaccination (expanded from 10-60 days in protocol), had no infection/malignancy at surgery and no major protocol violations prior to S. aureus infection.
    End point type
    Secondary
    End point timeframe
    Day of surgery (Day 1) up to Day 90 after surgery
    End point values
    		 Staphylococcus aureus 4-antigen (SA4Ag) Placebo
    Number of subjects analysed
    1544
    1547
    Units: Subjects
    24
    22
    Statistical analysis title
    		 Staphylococcus aureus 4-antigen (SA4Ag) Vs Placebo
    Comparison groups
    Staphylococcus aureus 4-antigen (SA4Ag) v Placebo
    Number of subjects included in analysis
    3091
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [10]
    Method
    Parameter type
    		 VE
    Point estimate
    -9.09
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -104.06
         upper limit
    		 41.41
    Notes
    [10] - VE: calculated as 1-(P/[1-P]*100), where P is the number of SA4Ag cases divided by the total number of cases. The CI was calculated using the Clopper-Pearson method.

    Secondary: Number of Subjects With Any Postoperative S. Aureus Surgical-site Infection (SSI-Superficial, Deep Incisional or Organ/Space) Occurring Within 180 Days After Surgery

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    End point title
    		 Number of Subjects With Any Postoperative S. Aureus Surgical-site Infection (SSI-Superficial, Deep Incisional or Organ/Space) Occurring Within 180 Days After Surgery
    End point description
    SSI: surgical site infection. Types of SSI in this measure: Superficial SSI: infection involving skin and subcutaneous tissue of incision, Deep incisional SSI: infection involving deep soft tissues of incision (fascial and muscle layers), Organ/space SSI: infection involving any part of body, (excluding skin incision, fascia, or muscle layers) opened/manipulated during surgery. Overall number of subjects with postoperative SSI (including superficial, deep incisional and/or organ/space SSI) confirmed by event adjudication committee were reported. Per-protocol efficacy population: all eligible subjects, vaccinated as randomized, underwent surgery per study-defined criteria within 9-90 days post vaccination (expanded from 10-60 days in protocol), had no infection/malignancy at surgery and no major protocol violations prior to S. aureus infection.
    End point type
    Secondary
    End point timeframe
    Day of surgery (Day 1) up to Day 180 after surgery
    End point values
    		 Staphylococcus aureus 4-antigen (SA4Ag) Placebo
    Number of subjects analysed
    1544
    1547
    Units: Subjects
    25
    23
    Statistical analysis title
    		 Staphylococcus aureus 4-antigen (SA4Ag) Vs Placebo
    Comparison groups
    Staphylococcus aureus 4-antigen (SA4Ag) v Placebo
    Number of subjects included in analysis
    3091
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [11]
    Method
    Parameter type
    		 VE
    Point estimate
    -8.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -100.42
         upper limit
    		 40.8
    Notes
    [11] - VE: calculated as 1-(P/[1-P]*100), where P is the number of SA4Ag cases divided by the total number of cases. The CI was calculated using the Clopper-Pearson method.

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    SAE and non-SAE: From vaccination up to Day 180 (190-240 days after vaccination). Local and systemic reactions: within 10 days after vaccination (systematic assessment).
    Adverse event reporting additional description
    Safety population. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as non-serious in another subject or one subject may have experienced both a serious and non-serious event during the analysis population.
    Assessment type
    		 Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    22.0
    Reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Subjects randomized to this arm received placebo containing the vaccine excipients reconstituted in 0.5mL water for injection. It was administered via intramuscular injection, 10 to 60 days prior to scheduled surgery. Subjects were followed from vaccination up to 6 months after their spinal surgical procedure.

    Reporting group title
    Staphylococcus aureus 4-antigen (SA4Ag)
    Reporting group description
    		 Subjects randomized to SA4Ag received a single dose of 0.5 mL SA4Ag vaccine intramuscularly, 10 to 60 days prior to their scheduled surgery. Subjects were followed from vaccination up to 6 months after their spinal surgical procedure.

    Serious adverse events
    		 Placebo Staphylococcus aureus 4-antigen (SA4Ag)
    Total subjects affected by serious adverse events
         subjects affected / exposed
    424 / 1709 (24.81%)
    403 / 1708 (23.59%)
         number of deaths (all causes)
    10
    13
         number of deaths resulting from adverse events
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Adenocarcinoma of colon
         subjects affected / exposed
    1 / 1709 (0.06%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Basal cell carcinoma
         subjects affected / exposed
    0 / 1709 (0.00%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bone neoplasm
         subjects affected / exposed
    0 / 1709 (0.00%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Breast cancer
         subjects affected / exposed
    1 / 1709 (0.06%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Clear cell renal cell carcinoma
         subjects affected / exposed
    1 / 1709 (0.06%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastric neoplasm
         subjects affected / exposed
    1 / 1709 (0.06%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Glioblastoma
         subjects affected / exposed
    0 / 1709 (0.00%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Invasive breast carcinoma
         subjects affected / exposed
    1 / 1709 (0.06%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lung neoplasm malignant
         subjects affected / exposed
    1 / 1709 (0.06%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Malignant neoplasm of ampulla of vater
         subjects affected / exposed
    0 / 1709 (0.00%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mediastinum neoplasm
         subjects affected / exposed
    0 / 1709 (0.00%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metastases to liver
         subjects affected / exposed
    0 / 1709 (0.00%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myeloid leukaemia
         subjects affected / exposed
    1 / 1709 (0.06%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Non-Hodgkin's lymphoma
         subjects affected / exposed
    0 / 1709 (0.00%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ovarian cancer
         subjects affected / exposed
    0 / 1709 (0.00%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Pancreatic carcinoma metastatic
         subjects affected / exposed
    0 / 1709 (0.00%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Prostate cancer
         subjects affected / exposed
    1 / 1709 (0.06%)
    2 / 1708 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal cancer
         subjects affected / exposed
    0 / 1709 (0.00%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal meningioma benign
         subjects affected / exposed
    1 / 1709 (0.06%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Squamous cell carcinoma
         subjects affected / exposed
    1 / 1709 (0.06%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular disorders
    Deep vein thrombosis
         subjects affected / exposed
    19 / 1709 (1.11%)
    21 / 1708 (1.23%)
         occurrences causally related to treatment / all
    0 / 19
    0 / 21
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haematoma
         subjects affected / exposed
    3 / 1709 (0.18%)
    2 / 1708 (0.12%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemodynamic instability
         subjects affected / exposed
    0 / 1709 (0.00%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemorrhage
         subjects affected / exposed
    1 / 1709 (0.06%)
    2 / 1708 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypertension
         subjects affected / exposed
    1 / 1709 (0.06%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypotension
         subjects affected / exposed
    10 / 1709 (0.59%)
    13 / 1708 (0.76%)
         occurrences causally related to treatment / all
    0 / 10
    0 / 14
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypovolaemic shock
         subjects affected / exposed
    3 / 1709 (0.18%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Iliac artery occlusion
         subjects affected / exposed
    1 / 1709 (0.06%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intermittent claudication
         subjects affected / exposed
    1 / 1709 (0.06%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ischaemia
         subjects affected / exposed
    1 / 1709 (0.06%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Labile blood pressure
         subjects affected / exposed
    0 / 1709 (0.00%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Orthostatic hypotension
         subjects affected / exposed
    1 / 1709 (0.06%)
    2 / 1708 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pelvic venous thrombosis
         subjects affected / exposed
    0 / 1709 (0.00%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral artery thrombosis
         subjects affected / exposed
    1 / 1709 (0.06%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral ischaemia
         subjects affected / exposed
    0 / 1709 (0.00%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Shock
         subjects affected / exposed
    0 / 1709 (0.00%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Shock haemorrhagic
         subjects affected / exposed
    0 / 1709 (0.00%)
    3 / 1708 (0.18%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Subclavian vein thrombosis
         subjects affected / exposed
    1 / 1709 (0.06%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thrombophlebitis superficial
         subjects affected / exposed
    0 / 1709 (0.00%)
    2 / 1708 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Venous thrombosis limb
         subjects affected / exposed
    1 / 1709 (0.06%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Surgical and medical procedures
    Arthrodesis
         subjects affected / exposed
    0 / 1709 (0.00%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Muscle flap operation
         subjects affected / exposed
    0 / 1709 (0.00%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal fusion surgery
         subjects affected / exposed
    0 / 1709 (0.00%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    1 / 1709 (0.06%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Calcinosis
         subjects affected / exposed
    0 / 1709 (0.00%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chest pain
         subjects affected / exposed
    5 / 1709 (0.29%)
    3 / 1708 (0.18%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Complication associated with device
         subjects affected / exposed
    2 / 1709 (0.12%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Complication of device insertion
         subjects affected / exposed
    1 / 1709 (0.06%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dysplasia
         subjects affected / exposed
    2 / 1709 (0.12%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fatigue
         subjects affected / exposed
    1 / 1709 (0.06%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fibrosis
         subjects affected / exposed
    0 / 1709 (0.00%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gait disturbance
         subjects affected / exposed
    0 / 1709 (0.00%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hernia
         subjects affected / exposed
    1 / 1709 (0.06%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Impaired healing
         subjects affected / exposed
    1 / 1709 (0.06%)
    2 / 1708 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Medical device site reaction
         subjects affected / exposed
    0 / 1709 (0.00%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Multiple organ dysfunction syndrome
         subjects affected / exposed
    3 / 1709 (0.18%)
    4 / 1708 (0.23%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 4
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Pain
         subjects affected / exposed
    3 / 1709 (0.18%)
    3 / 1708 (0.18%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral swelling
         subjects affected / exposed
    1 / 1709 (0.06%)
    2 / 1708 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    7 / 1709 (0.41%)
    6 / 1708 (0.35%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Surgical failure
         subjects affected / exposed
    1 / 1709 (0.06%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Immune system disorders
    Anaphylactic reaction
         subjects affected / exposed
    1 / 1709 (0.06%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anaphylactic shock
         subjects affected / exposed
    1 / 1709 (0.06%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Drug hypersensitivity
         subjects affected / exposed
    2 / 1709 (0.12%)
    2 / 1708 (0.12%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Benign prostatic hyperplasia
         subjects affected / exposed
    1 / 1709 (0.06%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Erectile dysfunction
         subjects affected / exposed
    1 / 1709 (0.06%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Prostatic haemorrhage
         subjects affected / exposed
    1 / 1709 (0.06%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Acute respiratory distress syndrome
         subjects affected / exposed
    0 / 1709 (0.00%)
    2 / 1708 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Acute respiratory failure
         subjects affected / exposed
    4 / 1709 (0.23%)
    7 / 1708 (0.41%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 8
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Aspiration
         subjects affected / exposed
    0 / 1709 (0.00%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Asthma
         subjects affected / exposed
    1 / 1709 (0.06%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atelectasis
         subjects affected / exposed
    1 / 1709 (0.06%)
    2 / 1708 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    0 / 1709 (0.00%)
    2 / 1708 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dyspnoea
         subjects affected / exposed
    2 / 1709 (0.12%)
    2 / 1708 (0.12%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Eosinophilic pneumonia
         subjects affected / exposed
    0 / 1709 (0.00%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemothorax
         subjects affected / exposed
    1 / 1709 (0.06%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypoxia
         subjects affected / exposed
    4 / 1709 (0.23%)
    3 / 1708 (0.18%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Interstitial lung disease
         subjects affected / exposed
    1 / 1709 (0.06%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pharyngeal oedema
         subjects affected / exposed
    1 / 1709 (0.06%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pharyngeal ulceration
         subjects affected / exposed
    0 / 1709 (0.00%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pleural effusion
         subjects affected / exposed
    1 / 1709 (0.06%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia aspiration
         subjects affected / exposed
    2 / 1709 (0.12%)
    2 / 1708 (0.12%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumothorax
         subjects affected / exposed
    0 / 1709 (0.00%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    17 / 1709 (0.99%)
    22 / 1708 (1.29%)
         occurrences causally related to treatment / all
    0 / 17
    0 / 22
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Pulmonary hypertension
         subjects affected / exposed
    1 / 1709 (0.06%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary infarction
         subjects affected / exposed
    1 / 1709 (0.06%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary oedema
         subjects affected / exposed
    2 / 1709 (0.12%)
    3 / 1708 (0.18%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary thrombosis
         subjects affected / exposed
    1 / 1709 (0.06%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory arrest
         subjects affected / exposed
    0 / 1709 (0.00%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory depression
         subjects affected / exposed
    0 / 1709 (0.00%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory distress
         subjects affected / exposed
    1 / 1709 (0.06%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory failure
         subjects affected / exposed
    7 / 1709 (0.41%)
    3 / 1708 (0.18%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory tract oedema
         subjects affected / exposed
    1 / 1709 (0.06%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sleep apnoea syndrome
         subjects affected / exposed
    0 / 1709 (0.00%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psychiatric disorders
    Alcohol withdrawal syndrome
         subjects affected / exposed
    0 / 1709 (0.00%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anxiety
         subjects affected / exposed
    1 / 1709 (0.06%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Confusional state
         subjects affected / exposed
    2 / 1709 (0.12%)
    2 / 1708 (0.12%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Delirium
         subjects affected / exposed
    4 / 1709 (0.23%)
    3 / 1708 (0.18%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Delirium tremens
         subjects affected / exposed
    0 / 1709 (0.00%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mental disorder
         subjects affected / exposed
    1 / 1709 (0.06%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mental status changes
         subjects affected / exposed
    7 / 1709 (0.41%)
    4 / 1708 (0.23%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Suicidal ideation
         subjects affected / exposed
    1 / 1709 (0.06%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Product issues
    Device breakage
         subjects affected / exposed
    2 / 1709 (0.12%)
    2 / 1708 (0.12%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Device dislocation
         subjects affected / exposed
    6 / 1709 (0.35%)
    11 / 1708 (0.64%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 11
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Device failure
         subjects affected / exposed
    6 / 1709 (0.35%)
    3 / 1708 (0.18%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Device fastener issue
         subjects affected / exposed
    1 / 1709 (0.06%)
    3 / 1708 (0.18%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Device loosening
         subjects affected / exposed
    2 / 1709 (0.12%)
    3 / 1708 (0.18%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Implant subsidence
         subjects affected / exposed
    1 / 1709 (0.06%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Bile duct stone
         subjects affected / exposed
    0 / 1709 (0.00%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholecystitis
         subjects affected / exposed
    1 / 1709 (0.06%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholecystitis acute
         subjects affected / exposed
    4 / 1709 (0.23%)
    4 / 1708 (0.23%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholelithiasis
         subjects affected / exposed
    0 / 1709 (0.00%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Investigations
    Blood glucose increased
         subjects affected / exposed
    0 / 1709 (0.00%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Electrocardiogram abnormal
         subjects affected / exposed
    0 / 1709 (0.00%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemoglobin decreased
         subjects affected / exposed
    1 / 1709 (0.06%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatic enzyme increased
         subjects affected / exposed
    2 / 1709 (0.12%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oxygen saturation decreased
         subjects affected / exposed
    0 / 1709 (0.00%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Troponin increased
         subjects affected / exposed
    0 / 1709 (0.00%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Adjacent segment degeneration
         subjects affected / exposed
    1 / 1709 (0.06%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anaemia postoperative
         subjects affected / exposed
    3 / 1709 (0.18%)
    8 / 1708 (0.47%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ankle fracture
         subjects affected / exposed
    2 / 1709 (0.12%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Aortic injury
         subjects affected / exposed
    0 / 1709 (0.00%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Cardiac function disturbance postoperative
         subjects affected / exposed
    0 / 1709 (0.00%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cervical vertebral fracture
         subjects affected / exposed
    1 / 1709 (0.06%)
    2 / 1708 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Concussion
         subjects affected / exposed
    0 / 1709 (0.00%)
    2 / 1708 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Contusion
         subjects affected / exposed
    0 / 1709 (0.00%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cystitis radiation
         subjects affected / exposed
    0 / 1709 (0.00%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Device deployment issue
         subjects affected / exposed
    1 / 1709 (0.06%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Device dispensing error
         subjects affected / exposed
    1 / 1709 (0.06%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dural tear
         subjects affected / exposed
    9 / 1709 (0.53%)
    9 / 1708 (0.53%)
         occurrences causally related to treatment / all
    0 / 10
    0 / 9
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Endotracheal intubation complication
         subjects affected / exposed
    1 / 1709 (0.06%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Exposure to communicable disease
         subjects affected / exposed
    1 / 1709 (0.06%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Extradural haematoma
         subjects affected / exposed
    1 / 1709 (0.06%)
    4 / 1708 (0.23%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Facial bones fracture
         subjects affected / exposed
    1 / 1709 (0.06%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fall
         subjects affected / exposed
    3 / 1709 (0.18%)
    9 / 1708 (0.53%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 9
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Femoral neck fracture
         subjects affected / exposed
    2 / 1709 (0.12%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Femur fracture
         subjects affected / exposed
    2 / 1709 (0.12%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Flatback syndrome
         subjects affected / exposed
    1 / 1709 (0.06%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Foreign body
         subjects affected / exposed
    1 / 1709 (0.06%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fracture
         subjects affected / exposed
    0 / 1709 (0.00%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fractured sacrum
         subjects affected / exposed
    3 / 1709 (0.18%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Graft complication
         subjects affected / exposed
    1 / 1709 (0.06%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Heart injury
         subjects affected / exposed
    0 / 1709 (0.00%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hip fracture
         subjects affected / exposed
    2 / 1709 (0.12%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Humerus fracture
         subjects affected / exposed
    1 / 1709 (0.06%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Incision site haematoma
         subjects affected / exposed
    1 / 1709 (0.06%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Incomplete spinal fusion
         subjects affected / exposed
    0 / 1709 (0.00%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Joint dislocation
         subjects affected / exposed
    1 / 1709 (0.06%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lumbar vertebral fracture
         subjects affected / exposed
    5 / 1709 (0.29%)
    6 / 1708 (0.35%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Multiple fractures
         subjects affected / exposed
    0 / 1709 (0.00%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Multiple injuries
         subjects affected / exposed
    0 / 1709 (0.00%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Muscle strain
         subjects affected / exposed
    0 / 1709 (0.00%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Overdose
         subjects affected / exposed
    3 / 1709 (0.18%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Periprosthetic fracture
         subjects affected / exposed
    1 / 1709 (0.06%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Post laminectomy syndrome
         subjects affected / exposed
    0 / 1709 (0.00%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Post procedural complication
         subjects affected / exposed
    1 / 1709 (0.06%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Post procedural constipation
         subjects affected / exposed
    0 / 1709 (0.00%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Post procedural discharge
         subjects affected / exposed
    2 / 1709 (0.12%)
    3 / 1708 (0.18%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Post procedural fever
         subjects affected / exposed
    0 / 1709 (0.00%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Post procedural haematoma
         subjects affected / exposed
    7 / 1709 (0.41%)
    3 / 1708 (0.18%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Post procedural haemorrhage
         subjects affected / exposed
    0 / 1709 (0.00%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Postoperative delirium
         subjects affected / exposed
    3 / 1709 (0.18%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Postoperative ileus
         subjects affected / exposed
    7 / 1709 (0.41%)
    3 / 1708 (0.18%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Procedural complication
         subjects affected / exposed
    0 / 1709 (0.00%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Procedural haemorrhage
         subjects affected / exposed
    3 / 1709 (0.18%)
    4 / 1708 (0.23%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Procedural hypotension
         subjects affected / exposed
    0 / 1709 (0.00%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Procedural pain
         subjects affected / exposed
    9 / 1709 (0.53%)
    7 / 1708 (0.41%)
         occurrences causally related to treatment / all
    0 / 9
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pseudomeningocele
         subjects affected / exposed
    1 / 1709 (0.06%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Road traffic accident
         subjects affected / exposed
    2 / 1709 (0.12%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Seroma
         subjects affected / exposed
    4 / 1709 (0.23%)
    6 / 1708 (0.35%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal column injury
         subjects affected / exposed
    0 / 1709 (0.00%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal compression fracture
         subjects affected / exposed
    2 / 1709 (0.12%)
    6 / 1708 (0.35%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal cord injury cauda equina
         subjects affected / exposed
    1 / 1709 (0.06%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal fracture
         subjects affected / exposed
    2 / 1709 (0.12%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Subdural haematoma
         subjects affected / exposed
    2 / 1709 (0.12%)
    2 / 1708 (0.12%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Subdural haemorrhage
         subjects affected / exposed
    0 / 1709 (0.00%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Suture rupture
         subjects affected / exposed
    0 / 1709 (0.00%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thoracic vertebral fracture
         subjects affected / exposed
    4 / 1709 (0.23%)
    4 / 1708 (0.23%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tibia fracture
         subjects affected / exposed
    1 / 1709 (0.06%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Toxicity to various agents
         subjects affected / exposed
    1 / 1709 (0.06%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    Urethral injury
         subjects affected / exposed
    0 / 1709 (0.00%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary retention postoperative
         subjects affected / exposed
    1 / 1709 (0.06%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular injury
         subjects affected / exposed
    0 / 1709 (0.00%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Venous injury
         subjects affected / exposed
    1 / 1709 (0.06%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Wound dehiscence
         subjects affected / exposed
    4 / 1709 (0.23%)
    5 / 1708 (0.29%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Wound secretion
         subjects affected / exposed
    2 / 1709 (0.12%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lower limb fracture
         subjects affected / exposed
    0 / 1709 (0.00%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Congenital, familial and genetic disorders
    Spinal muscular atrophy
         subjects affected / exposed
    1 / 1709 (0.06%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Acute coronary syndrome
         subjects affected / exposed
    1 / 1709 (0.06%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acute myocardial infarction
         subjects affected / exposed
    4 / 1709 (0.23%)
    3 / 1708 (0.18%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acute right ventricular failure
         subjects affected / exposed
    0 / 1709 (0.00%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Angina pectoris
         subjects affected / exposed
    2 / 1709 (0.12%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Angina unstable
         subjects affected / exposed
    0 / 1709 (0.00%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arteriospasm coronary
         subjects affected / exposed
    0 / 1709 (0.00%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrial fibrillation
         subjects affected / exposed
    10 / 1709 (0.59%)
    12 / 1708 (0.70%)
         occurrences causally related to treatment / all
    0 / 10
    0 / 14
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrial flutter
         subjects affected / exposed
    1 / 1709 (0.06%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bradycardia
         subjects affected / exposed
    2 / 1709 (0.12%)
    2 / 1708 (0.12%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac arrest
         subjects affected / exposed
    2 / 1709 (0.12%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Cardiac failure
         subjects affected / exposed
    0 / 1709 (0.00%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Cardiac failure acute
         subjects affected / exposed
    1 / 1709 (0.06%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac failure chronic
         subjects affected / exposed
    1 / 1709 (0.06%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac failure congestive
         subjects affected / exposed
    4 / 1709 (0.23%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Cardiac ventricular thrombosis
         subjects affected / exposed
    1 / 1709 (0.06%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardio-respiratory arrest
         subjects affected / exposed
    1 / 1709 (0.06%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Cardiogenic shock
         subjects affected / exposed
    0 / 1709 (0.00%)
    2 / 1708 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 2
    Coronary artery disease
         subjects affected / exposed
    4 / 1709 (0.23%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Coronary artery occlusion
         subjects affected / exposed
    1 / 1709 (0.06%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Coronary artery stenosis
         subjects affected / exposed
    2 / 1709 (0.12%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Left ventricular dysfunction
         subjects affected / exposed
    1 / 1709 (0.06%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    2 / 1709 (0.12%)
    4 / 1708 (0.23%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 2
    Sinus node dysfunction
         subjects affected / exposed
    0 / 1709 (0.00%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sinus tachycardia
         subjects affected / exposed
    0 / 1709 (0.00%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Supraventricular tachycardia
         subjects affected / exposed
    1 / 1709 (0.06%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tachycardia
         subjects affected / exposed
    3 / 1709 (0.18%)
    2 / 1708 (0.12%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ventricular tachycardia
         subjects affected / exposed
    2 / 1709 (0.12%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Carpal tunnel syndrome
         subjects affected / exposed
    1 / 1709 (0.06%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cauda equina syndrome
         subjects affected / exposed
    0 / 1709 (0.00%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebral haemorrhage
         subjects affected / exposed
    1 / 1709 (0.06%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebral infarction
         subjects affected / exposed
    1 / 1709 (0.06%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebrospinal fistula
         subjects affected / exposed
    2 / 1709 (0.12%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebrospinal fluid leakage
         subjects affected / exposed
    5 / 1709 (0.29%)
    5 / 1708 (0.29%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebrovascular accident
         subjects affected / exposed
    2 / 1709 (0.12%)
    2 / 1708 (0.12%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cervical radiculopathy
         subjects affected / exposed
    0 / 1709 (0.00%)
    2 / 1708 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cervical spinal cord paralysis
         subjects affected / exposed
    2 / 1709 (0.12%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Decreased vibratory sense
         subjects affected / exposed
    1 / 1709 (0.06%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dizziness
         subjects affected / exposed
    1 / 1709 (0.06%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dysarthria
         subjects affected / exposed
    0 / 1709 (0.00%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Encephalopathy
         subjects affected / exposed
    5 / 1709 (0.29%)
    4 / 1708 (0.23%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Facial paralysis
         subjects affected / exposed
    0 / 1709 (0.00%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Generalised tonic-clonic seizure
         subjects affected / exposed
    0 / 1709 (0.00%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Headache
         subjects affected / exposed
    2 / 1709 (0.12%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hemiparesis
         subjects affected / exposed
    0 / 1709 (0.00%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatic encephalopathy
         subjects affected / exposed
    0 / 1709 (0.00%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    IIIrd nerve paresis
         subjects affected / exposed
    0 / 1709 (0.00%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ischaemic stroke
         subjects affected / exposed
    1 / 1709 (0.06%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Loss of consciousness
         subjects affected / exposed
    1 / 1709 (0.06%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lumbar radiculopathy
         subjects affected / exposed
    2 / 1709 (0.12%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolic encephalopathy
         subjects affected / exposed
    2 / 1709 (0.12%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Miller Fisher syndrome
         subjects affected / exposed
    0 / 1709 (0.00%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Monoparesis
         subjects affected / exposed
    1 / 1709 (0.06%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Monoplegia
         subjects affected / exposed
    1 / 1709 (0.06%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myelopathy
         subjects affected / exposed
    1 / 1709 (0.06%)
    2 / 1708 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neuropathy peripheral
         subjects affected / exposed
    1 / 1709 (0.06%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Normal pressure hydrocephalus
         subjects affected / exposed
    0 / 1709 (0.00%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Paralysis
         subjects affected / exposed
    0 / 1709 (0.00%)
    3 / 1708 (0.18%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Paraesthesia
         subjects affected / exposed
    2 / 1709 (0.12%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Paraparesis
         subjects affected / exposed
    0 / 1709 (0.00%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Parkinson's disease
         subjects affected / exposed
    1 / 1709 (0.06%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Paraplegia
         subjects affected / exposed
    1 / 1709 (0.06%)
    2 / 1708 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Polyneuropathy
         subjects affected / exposed
    0 / 1709 (0.00%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Presyncope
         subjects affected / exposed
    1 / 1709 (0.06%)
    2 / 1708 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Radiculopathy
         subjects affected / exposed
    2 / 1709 (0.12%)
    2 / 1708 (0.12%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sciatica
         subjects affected / exposed
    4 / 1709 (0.23%)
    2 / 1708 (0.12%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Seizure
         subjects affected / exposed
    1 / 1709 (0.06%)
    3 / 1708 (0.18%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sedation
         subjects affected / exposed
    0 / 1709 (0.00%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal cord compression
         subjects affected / exposed
    0 / 1709 (0.00%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal cord disorder
         subjects affected / exposed
    1 / 1709 (0.06%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal epidural haematoma
         subjects affected / exposed
    1 / 1709 (0.06%)
    2 / 1708 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Syncope
         subjects affected / exposed
    5 / 1709 (0.29%)
    2 / 1708 (0.12%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thalamus haemorrhage
         subjects affected / exposed
    0 / 1709 (0.00%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thrombotic cerebral infarction
         subjects affected / exposed
    1 / 1709 (0.06%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Transient ischaemic attack
         subjects affected / exposed
    4 / 1709 (0.23%)
    4 / 1708 (0.23%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Trigeminal neuralgia
         subjects affected / exposed
    1 / 1709 (0.06%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Visual field defect
         subjects affected / exposed
    0 / 1709 (0.00%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vocal cord paralysis
         subjects affected / exposed
    0 / 1709 (0.00%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    4 / 1709 (0.23%)
    4 / 1708 (0.23%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood loss anaemia
         subjects affected / exposed
    1 / 1709 (0.06%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Coagulopathy
         subjects affected / exposed
    1 / 1709 (0.06%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Disseminated intravascular coagulation
         subjects affected / exposed
    0 / 1709 (0.00%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Heparin-induced thrombocytopenia
         subjects affected / exposed
    1 / 1709 (0.06%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Iron deficiency anaemia
         subjects affected / exposed
    1 / 1709 (0.06%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Leukocytosis
         subjects affected / exposed
    1 / 1709 (0.06%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Normocytic anaemia
         subjects affected / exposed
    0 / 1709 (0.00%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancytopenia
         subjects affected / exposed
    1 / 1709 (0.06%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Platelet disorder
         subjects affected / exposed
    1 / 1709 (0.06%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thrombocytopenia
         subjects affected / exposed
    0 / 1709 (0.00%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    Vertigo positional
         subjects affected / exposed
    1 / 1709 (0.06%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Eye disorders
    Blindness unilateral
         subjects affected / exposed
    0 / 1709 (0.00%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cataract
         subjects affected / exposed
    2 / 1709 (0.12%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Retinal detachment
         subjects affected / exposed
    0 / 1709 (0.00%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    1 / 1709 (0.06%)
    2 / 1708 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal pain upper
         subjects affected / exposed
    1 / 1709 (0.06%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anal incontinence
         subjects affected / exposed
    1 / 1709 (0.06%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anorectal disorder
         subjects affected / exposed
    0 / 1709 (0.00%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colitis
         subjects affected / exposed
    2 / 1709 (0.12%)
    2 / 1708 (0.12%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colitis ischaemic
         subjects affected / exposed
    1 / 1709 (0.06%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Constipation
         subjects affected / exposed
    4 / 1709 (0.23%)
    3 / 1708 (0.18%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    1 / 1709 (0.06%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diverticulum
         subjects affected / exposed
    1 / 1709 (0.06%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Duodenal ulcer
         subjects affected / exposed
    0 / 1709 (0.00%)
    2 / 1708 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Duodenal ulcer haemorrhage
         subjects affected / exposed
    1 / 1709 (0.06%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dysphagia
         subjects affected / exposed
    1 / 1709 (0.06%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastric haemorrhage
         subjects affected / exposed
    1 / 1709 (0.06%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastritis
         subjects affected / exposed
    1 / 1709 (0.06%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal haemorrhage
         subjects affected / exposed
    1 / 1709 (0.06%)
    3 / 1708 (0.18%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal ulcer
         subjects affected / exposed
    0 / 1709 (0.00%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrooesophageal reflux disease
         subjects affected / exposed
    1 / 1709 (0.06%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ileus
         subjects affected / exposed
    5 / 1709 (0.29%)
    2 / 1708 (0.12%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Impaired gastric emptying
         subjects affected / exposed
    1 / 1709 (0.06%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Inguinal hernia
         subjects affected / exposed
    1 / 1709 (0.06%)
    3 / 1708 (0.18%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intestinal obstruction
         subjects affected / exposed
    0 / 1709 (0.00%)
    2 / 1708 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Large intestine perforation
         subjects affected / exposed
    0 / 1709 (0.00%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Large intestine polyp
         subjects affected / exposed
    2 / 1709 (0.12%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lower gastrointestinal haemorrhage
         subjects affected / exposed
    0 / 1709 (0.00%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Melaena
         subjects affected / exposed
    0 / 1709 (0.00%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nausea
         subjects affected / exposed
    1 / 1709 (0.06%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Obstruction gastric
         subjects affected / exposed
    1 / 1709 (0.06%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatitis
         subjects affected / exposed
    0 / 1709 (0.00%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatitis acute
         subjects affected / exposed
    3 / 1709 (0.18%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumoperitoneum
         subjects affected / exposed
    0 / 1709 (0.00%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Proctitis
         subjects affected / exposed
    1 / 1709 (0.06%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rectal haemorrhage
         subjects affected / exposed
    2 / 1709 (0.12%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rectal prolapse
         subjects affected / exposed
    1 / 1709 (0.06%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Retroperitoneal haematoma
         subjects affected / exposed
    0 / 1709 (0.00%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Small intestinal obstruction
         subjects affected / exposed
    1 / 1709 (0.06%)
    4 / 1708 (0.23%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Subileus
         subjects affected / exposed
    1 / 1709 (0.06%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    0 / 1709 (0.00%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal distension
         subjects affected / exposed
    1 / 1709 (0.06%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Decubitus ulcer
         subjects affected / exposed
    0 / 1709 (0.00%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin ulcer
         subjects affected / exposed
    0 / 1709 (0.00%)
    2 / 1708 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Swelling face
         subjects affected / exposed
    2 / 1709 (0.12%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    8 / 1709 (0.47%)
    6 / 1708 (0.35%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bladder disorder
         subjects affected / exposed
    0 / 1709 (0.00%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bladder neck obstruction
         subjects affected / exposed
    1 / 1709 (0.06%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chronic kidney disease
         subjects affected / exposed
    1 / 1709 (0.06%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dysuria
         subjects affected / exposed
    0 / 1709 (0.00%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haematuria
         subjects affected / exposed
    1 / 1709 (0.06%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nephrolithiasis
         subjects affected / exposed
    1 / 1709 (0.06%)
    2 / 1708 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nephropathy
         subjects affected / exposed
    1 / 1709 (0.06%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neurogenic bladder
         subjects affected / exposed
    0 / 1709 (0.00%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal failure
         subjects affected / exposed
    2 / 1709 (0.12%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal injury
         subjects affected / exposed
    1 / 1709 (0.06%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ureterolithiasis
         subjects affected / exposed
    0 / 1709 (0.00%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urethral stenosis
         subjects affected / exposed
    2 / 1709 (0.12%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary incontinence
         subjects affected / exposed
    1 / 1709 (0.06%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary retention
         subjects affected / exposed
    3 / 1709 (0.18%)
    4 / 1708 (0.23%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Endocrine disorders
    Inappropriate antidiuretic hormone secretion
         subjects affected / exposed
    0 / 1709 (0.00%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    2 / 1709 (0.12%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arthritis
         subjects affected / exposed
    2 / 1709 (0.12%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arthropathy
         subjects affected / exposed
    1 / 1709 (0.06%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Back pain
         subjects affected / exposed
    7 / 1709 (0.41%)
    8 / 1708 (0.47%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bone disorder
         subjects affected / exposed
    1 / 1709 (0.06%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bursitis
         subjects affected / exposed
    1 / 1709 (0.06%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Compartment syndrome
         subjects affected / exposed
    0 / 1709 (0.00%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Foot deformity
         subjects affected / exposed
    1 / 1709 (0.06%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fracture nonunion
         subjects affected / exposed
    1 / 1709 (0.06%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intervertebral disc degeneration
         subjects affected / exposed
    2 / 1709 (0.12%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intervertebral disc disorder
         subjects affected / exposed
    1 / 1709 (0.06%)
    2 / 1708 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intervertebral disc protrusion
         subjects affected / exposed
    3 / 1709 (0.18%)
    2 / 1708 (0.12%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Joint instability
         subjects affected / exposed
    1 / 1709 (0.06%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Kyphosis
         subjects affected / exposed
    0 / 1709 (0.00%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mobility decreased
         subjects affected / exposed
    0 / 1709 (0.00%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Muscle spasms
         subjects affected / exposed
    2 / 1709 (0.12%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Muscular weakness
         subjects affected / exposed
    3 / 1709 (0.18%)
    4 / 1708 (0.23%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal chest pain
         subjects affected / exposed
    1 / 1709 (0.06%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal disorder
         subjects affected / exposed
    1 / 1709 (0.06%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myalgia
         subjects affected / exposed
    1 / 1709 (0.06%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myopathy
         subjects affected / exposed
    0 / 1709 (0.00%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neck pain
         subjects affected / exposed
    1 / 1709 (0.06%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Osteoarthritis
         subjects affected / exposed
    12 / 1709 (0.70%)
    3 / 1708 (0.18%)
         occurrences causally related to treatment / all
    0 / 13
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pain in extremity
         subjects affected / exposed
    1 / 1709 (0.06%)
    7 / 1708 (0.41%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Polymyalgia rheumatica
         subjects affected / exposed
    1 / 1709 (0.06%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Polymyositis
         subjects affected / exposed
    1 / 1709 (0.06%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rhabdomyolysis
         subjects affected / exposed
    1 / 1709 (0.06%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rheumatoid arthritis
         subjects affected / exposed
    0 / 1709 (0.00%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rotator cuff syndrome
         subjects affected / exposed
    3 / 1709 (0.18%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Scoliosis
         subjects affected / exposed
    0 / 1709 (0.00%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal deformity
         subjects affected / exposed
    1 / 1709 (0.06%)
    2 / 1708 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal disorder
         subjects affected / exposed
    1 / 1709 (0.06%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal instability
         subjects affected / exposed
    3 / 1709 (0.18%)
    5 / 1708 (0.29%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal ligament ossification
         subjects affected / exposed
    0 / 1709 (0.00%)
    2 / 1708 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal osteoarthritis
         subjects affected / exposed
    0 / 1709 (0.00%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal segmental dysfunction
         subjects affected / exposed
    1 / 1709 (0.06%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal stenosis
         subjects affected / exposed
    1 / 1709 (0.06%)
    4 / 1708 (0.23%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spondylolisthesis
         subjects affected / exposed
    2 / 1709 (0.12%)
    3 / 1708 (0.18%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vertebral foraminal stenosis
         subjects affected / exposed
    1 / 1709 (0.06%)
    2 / 1708 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Abscess jaw
         subjects affected / exposed
    0 / 1709 (0.00%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abscess limb
         subjects affected / exposed
    0 / 1709 (0.00%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atypical pneumonia
         subjects affected / exposed
    1 / 1709 (0.06%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bacteraemia
         subjects affected / exposed
    3 / 1709 (0.18%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bacterial disease carrier
         subjects affected / exposed
    0 / 1709 (0.00%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchitis
         subjects affected / exposed
    2 / 1709 (0.12%)
    3 / 1708 (0.18%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    4 / 1709 (0.23%)
    5 / 1708 (0.29%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Clostridium colitis
         subjects affected / exposed
    0 / 1709 (0.00%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Clostridium difficile colitis
         subjects affected / exposed
    1 / 1709 (0.06%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Clostridium difficile infection
         subjects affected / exposed
    1 / 1709 (0.06%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cystitis
         subjects affected / exposed
    1 / 1709 (0.06%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Device related infection
         subjects affected / exposed
    2 / 1709 (0.12%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diverticulitis
         subjects affected / exposed
    1 / 1709 (0.06%)
    2 / 1708 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Encephalitis
         subjects affected / exposed
    0 / 1709 (0.00%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Enterobacter bacteraemia
         subjects affected / exposed
    0 / 1709 (0.00%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Escherichia bacteraemia
         subjects affected / exposed
    1 / 1709 (0.06%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Escherichia urinary tract infection
         subjects affected / exposed
    1 / 1709 (0.06%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Extradural abscess
         subjects affected / exposed
    1 / 1709 (0.06%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fournier's gangrene
         subjects affected / exposed
    1 / 1709 (0.06%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    1 / 1709 (0.06%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Herpes zoster
         subjects affected / exposed
    1 / 1709 (0.06%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Incision site abscess
         subjects affected / exposed
    1 / 1709 (0.06%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infected skin ulcer
         subjects affected / exposed
    1 / 1709 (0.06%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Influenza
         subjects affected / exposed
    1 / 1709 (0.06%)
    2 / 1708 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intervertebral discitis
         subjects affected / exposed
    2 / 1709 (0.12%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lice infestation
         subjects affected / exposed
    0 / 1709 (0.00%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lymphangitis
         subjects affected / exposed
    0 / 1709 (0.00%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Medical device site joint infection
         subjects affected / exposed
    1 / 1709 (0.06%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Meningitis
         subjects affected / exposed
    1 / 1709 (0.06%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Osteomyelitis
         subjects affected / exposed
    2 / 1709 (0.12%)
    2 / 1708 (0.12%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Osteomyelitis chronic
         subjects affected / exposed
    0 / 1709 (0.00%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Perirectal abscess
         subjects affected / exposed
    1 / 1709 (0.06%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    12 / 1709 (0.70%)
    19 / 1708 (1.11%)
         occurrences causally related to treatment / all
    0 / 12
    0 / 19
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia bacterial
         subjects affected / exposed
    0 / 1709 (0.00%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Post procedural infection
         subjects affected / exposed
    1 / 1709 (0.06%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Postoperative wound infection
         subjects affected / exposed
    32 / 1709 (1.87%)
    27 / 1708 (1.58%)
         occurrences causally related to treatment / all
    0 / 33
    0 / 28
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyelonephritis
         subjects affected / exposed
    2 / 1709 (0.12%)
    2 / 1708 (0.12%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyelonephritis acute
         subjects affected / exposed
    0 / 1709 (0.00%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    10 / 1709 (0.59%)
    11 / 1708 (0.64%)
         occurrences causally related to treatment / all
    0 / 10
    0 / 12
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Septic shock
         subjects affected / exposed
    1 / 1709 (0.06%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Skin infection
         subjects affected / exposed
    3 / 1709 (0.18%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Staphylococcal infection
         subjects affected / exposed
    1 / 1709 (0.06%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Upper respiratory tract infection
         subjects affected / exposed
    0 / 1709 (0.00%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    7 / 1709 (0.41%)
    6 / 1708 (0.35%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urosepsis
         subjects affected / exposed
    1 / 1709 (0.06%)
    2 / 1708 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Viral infection
         subjects affected / exposed
    0 / 1709 (0.00%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Wound infection
         subjects affected / exposed
    5 / 1709 (0.29%)
    5 / 1708 (0.29%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Wound infection bacterial
         subjects affected / exposed
    3 / 1709 (0.18%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Wound infection fungal
         subjects affected / exposed
    1 / 1709 (0.06%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Wound infection staphylococcal
         subjects affected / exposed
    3 / 1709 (0.18%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Uncoded System Organ Class
         subjects affected / exposed
    1 / 1709 (0.06%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Meningoencephalitis septic shock
         subjects affected / exposed
    1 / 1709 (0.06%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    3 / 1709 (0.18%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diabetic ketoacidosis
         subjects affected / exposed
    1 / 1709 (0.06%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Failure to thrive
         subjects affected / exposed
    2 / 1709 (0.12%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Fluid overload
         subjects affected / exposed
    0 / 1709 (0.00%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gout
         subjects affected / exposed
    1 / 1709 (0.06%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyperkalaemia
         subjects affected / exposed
    0 / 1709 (0.00%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypoglycaemia
         subjects affected / exposed
    0 / 1709 (0.00%)
    1 / 1708 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyponatraemia
         subjects affected / exposed
    1 / 1709 (0.06%)
    3 / 1708 (0.18%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypovolaemia
         subjects affected / exposed
    3 / 1709 (0.18%)
    3 / 1708 (0.18%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolic acidosis
         subjects affected / exposed
    1 / 1709 (0.06%)
    0 / 1708 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 1%
    Non-serious adverse events
    		 Placebo Staphylococcus aureus 4-antigen (SA4Ag)
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    1489 / 1709 (87.13%)
    1530 / 1708 (89.58%)
    Vascular disorders
    Hypertension
         subjects affected / exposed
    20 / 1709 (1.17%)
    15 / 1708 (0.88%)
         occurrences all number
    20
    15
    Hypotension
         subjects affected / exposed
    84 / 1709 (4.92%)
    79 / 1708 (4.63%)
         occurrences all number
    89
    81
    General disorders and administration site conditions
    Chest pain
         subjects affected / exposed
    13 / 1709 (0.76%)
    18 / 1708 (1.05%)
         occurrences all number
    13
    18
    Pyrexia 1
         subjects affected / exposed
    114 / 1709 (6.67%)
    121 / 1708 (7.08%)
         occurrences all number
    118
    130
    Oedema peripheral
         subjects affected / exposed
    29 / 1709 (1.70%)
    22 / 1708 (1.29%)
         occurrences all number
    30
    23
    Injection site erythema
    alternative assessment type: Systematic
         subjects affected / exposed
    16 / 1709 (0.94%)
    156 / 1708 (9.13%)
         occurrences all number
    16
    156
    Fatigue
    alternative assessment type: Systematic
         subjects affected / exposed
    681 / 1709 (39.85%)
    732 / 1708 (42.86%)
         occurrences all number
    681
    732
    Injection site pain
    alternative assessment type: Systematic
         subjects affected / exposed
    142 / 1709 (8.31%)
    408 / 1708 (23.89%)
         occurrences all number
    142
    408
    Pyrexia 2
    alternative assessment type: Systematic
         subjects affected / exposed
    23 / 1709 (1.35%)
    34 / 1708 (1.99%)
         occurrences all number
    23
    34
    Injection site swelling
    alternative assessment type: Systematic
         subjects affected / exposed
    17 / 1709 (0.99%)
    135 / 1708 (7.90%)
         occurrences all number
    17
    135
    Respiratory, thoracic and mediastinal disorders
    Atelectasis
         subjects affected / exposed
    21 / 1709 (1.23%)
    10 / 1708 (0.59%)
         occurrences all number
    21
    10
    Cough
         subjects affected / exposed
    19 / 1709 (1.11%)
    8 / 1708 (0.47%)
         occurrences all number
    19
    8
    Hypoxia
         subjects affected / exposed
    35 / 1709 (2.05%)
    24 / 1708 (1.41%)
         occurrences all number
    35
    27
    Psychiatric disorders
    Insomnia
         subjects affected / exposed
    63 / 1709 (3.69%)
    68 / 1708 (3.98%)
         occurrences all number
    65
    68
    Injury, poisoning and procedural complications
    Anaemia postoperative
         subjects affected / exposed
    108 / 1709 (6.32%)
    109 / 1708 (6.38%)
         occurrences all number
    108
    111
    Dural tear
         subjects affected / exposed
    73 / 1709 (4.27%)
    60 / 1708 (3.51%)
         occurrences all number
    75
    61
    Fall
         subjects affected / exposed
    44 / 1709 (2.57%)
    60 / 1708 (3.51%)
         occurrences all number
    48
    61
    Incision site pain
         subjects affected / exposed
    63 / 1709 (3.69%)
    67 / 1708 (3.92%)
         occurrences all number
    64
    69
    Procedural pain
         subjects affected / exposed
    84 / 1709 (4.92%)
    92 / 1708 (5.39%)
         occurrences all number
    85
    92
    Wound complication
         subjects affected / exposed
    21 / 1709 (1.23%)
    19 / 1708 (1.11%)
         occurrences all number
    21
    19
    Cardiac disorders
    Tachycardia
         subjects affected / exposed
    30 / 1709 (1.76%)
    32 / 1708 (1.87%)
         occurrences all number
    31
    33
    Nervous system disorders
    Headache 1
         subjects affected / exposed
    26 / 1709 (1.52%)
    33 / 1708 (1.93%)
         occurrences all number
    27
    33
    Dizziness
         subjects affected / exposed
    35 / 1709 (2.05%)
    30 / 1708 (1.76%)
         occurrences all number
    36
    33
    Hypoaesthesia
         subjects affected / exposed
    38 / 1709 (2.22%)
    50 / 1708 (2.93%)
         occurrences all number
    40
    55
    Paraesthesia
         subjects affected / exposed
    12 / 1709 (0.70%)
    24 / 1708 (1.41%)
         occurrences all number
    12
    26
    Headache 2
    alternative assessment type: Systematic
         subjects affected / exposed
    526 / 1709 (30.78%)
    549 / 1708 (32.14%)
         occurrences all number
    526
    549
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    122 / 1709 (7.14%)
    97 / 1708 (5.68%)
         occurrences all number
    128
    98
    Blood loss anaemia
         subjects affected / exposed
    42 / 1709 (2.46%)
    58 / 1708 (3.40%)
         occurrences all number
    43
    60
    Leukocytosis
         subjects affected / exposed
    20 / 1709 (1.17%)
    18 / 1708 (1.05%)
         occurrences all number
    20
    18
    Thrombocytopenia
         subjects affected / exposed
    23 / 1709 (1.35%)
    26 / 1708 (1.52%)
         occurrences all number
    23
    26
    Gastrointestinal disorders
    Constipation
         subjects affected / exposed
    192 / 1709 (11.23%)
    201 / 1708 (11.77%)
         occurrences all number
    194
    202
    Diarrhoea 1
         subjects affected / exposed
    30 / 1709 (1.76%)
    31 / 1708 (1.81%)
         occurrences all number
    30
    32
    Vomiting 1
         subjects affected / exposed
    67 / 1709 (3.92%)
    80 / 1708 (4.68%)
         occurrences all number
    71
    84
    Nausea
         subjects affected / exposed
    140 / 1709 (8.19%)
    162 / 1708 (9.48%)
         occurrences all number
    140
    174
    Diarrhoea 2
    alternative assessment type: Systematic
         subjects affected / exposed
    270 / 1709 (15.80%)
    287 / 1708 (16.80%)
         occurrences all number
    270
    287
    Vomiting 2
    alternative assessment type: Systematic
         subjects affected / exposed
    55 / 1709 (3.22%)
    45 / 1708 (2.63%)
         occurrences all number
    55
    45
    Skin and subcutaneous tissue disorders
    Pruritus
         subjects affected / exposed
    33 / 1709 (1.93%)
    27 / 1708 (1.58%)
         occurrences all number
    33
    27
    Erythema
         subjects affected / exposed
    61 / 1709 (3.57%)
    57 / 1708 (3.34%)
         occurrences all number
    83
    79
    Rash
         subjects affected / exposed
    15 / 1709 (0.88%)
    21 / 1708 (1.23%)
         occurrences all number
    15
    21
    Renal and urinary disorders
    Urinary retention
         subjects affected / exposed
    59 / 1709 (3.45%)
    58 / 1708 (3.40%)
         occurrences all number
    62
    59
    Acute kidney injury
         subjects affected / exposed
    13 / 1709 (0.76%)
    24 / 1708 (1.41%)
         occurrences all number
    15
    24
    Musculoskeletal and connective tissue disorders
    Arthralgia 1
         subjects affected / exposed
    29 / 1709 (1.70%)
    27 / 1708 (1.58%)
         occurrences all number
    32
    30
    Back pain
         subjects affected / exposed
    36 / 1709 (2.11%)
    39 / 1708 (2.28%)
         occurrences all number
    40
    40
    Muscular weakness
         subjects affected / exposed
    24 / 1709 (1.40%)
    25 / 1708 (1.46%)
         occurrences all number
    25
    28
    Muscle spasms
         subjects affected / exposed
    30 / 1709 (1.76%)
    21 / 1708 (1.23%)
         occurrences all number
    31
    22
    Musculoskeletal pain
         subjects affected / exposed
    20 / 1709 (1.17%)
    24 / 1708 (1.41%)
         occurrences all number
    21
    25
    Pain in extremity
         subjects affected / exposed
    59 / 1709 (3.45%)
    55 / 1708 (3.22%)
         occurrences all number
    64
    60
    Myalgia (muscle pain)
    alternative assessment type: Systematic
         subjects affected / exposed
    442 / 1709 (25.86%)
    472 / 1708 (27.63%)
         occurrences all number
    442
    472
    Arthralgia 2
    alternative assessment type: Systematic
         subjects affected / exposed
    435 / 1709 (25.45%)
    465 / 1708 (27.22%)
         occurrences all number
    435
    465
    Infections and infestations
    Nasopharyngitis
         subjects affected / exposed
    23 / 1709 (1.35%)
    28 / 1708 (1.64%)
         occurrences all number
    24
    29
    Urinary tract infection
         subjects affected / exposed
    103 / 1709 (6.03%)
    96 / 1708 (5.62%)
         occurrences all number
    113
    102
    Metabolism and nutrition disorders
    Hypokalaemia
         subjects affected / exposed
    18 / 1709 (1.05%)
    24 / 1708 (1.41%)
         occurrences all number
    18
    24
    Hyperglycaemia
         subjects affected / exposed
    25 / 1709 (1.46%)
    28 / 1708 (1.64%)
         occurrences all number
    25
    29
    Hyponatraemia
         subjects affected / exposed
    20 / 1709 (1.17%)
    22 / 1708 (1.29%)
         occurrences all number
    20
    23

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    15 Sep 2015
    Protocol Amendment 2: 1. All invasive infections were adjudicated by the event adjudication committee (EAC); previously only those associated with S. aureus were to be adjudicated (change requested by the EAC). 2. Any preexisting spinal instrumentation or tissue removed during a revisional surgical procedure, must be cultured (to detect preexisting pathogens) 3. Spinal steroids added to concomitant medications (may have an effect on the immune response). 4. Added missing text to criteria for vertebral disc space infection and superficial SSI (previous omissions). Appendix 3: Added collection of data regarding composition of implanted devices (request by investigators).
    01 Jun 2016
    Protocol Amendment 3: 1. Clarified the remit of the endpoint adjudication committee (EAC); ie, the remit of the EAC is not restricted to S. aureus infections. 2. Refined evaluation periods for protocol-defined infections and organ failure events. 2. Amended an exclusion criterion (No. 19) to exclude subjects with indwelling central nervous system shunts and implanted devices. 3. Added details of periodic checks for study futility that will be performed prior to the interim analysis. This includes the data monitoring committee’s role in these assessments.
    05 Feb 2018
    Protocol amendment 4: 1. Changed the expected number of enrolled subjects from 2600 to 6000 and target number of endpoint cases changed from 42 to 48. 2. Amended an exclusion criterion to clarify that subjects with rheumatologic disorders that are not being treated with immunosuppressant medications can enter the study. 3. Modified interim analysis case count from 21 to 24; removed all REFs to hierarchical testing of proof of principle/high-level efficacy. 4. Modified sample size and power calculations based on increased sample size, primary endpoint case count, VE and incidence rates.

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
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    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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