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    Clinical Trial Results:
    Prospective, randomised, controlled, double-blind, multi-centre, multinational study on the safety and efficacy of 6% Hydroxyethyl starch (HES) solution versus an electrolyte solution in patients undergoing elective abdominal surgery (PHOENICS)

    Summary
    EudraCT number
    2016-002162-30
    Trial protocol
    BE   CZ   NL   ES   FR   AT   HR   RO  
    Global end of trial date
    06 Jul 2022

    Results information
    Results version number
    v1(current)
    This version publication date
    04 Aug 2023
    First version publication date
    04 Aug 2023
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    HC-G-H-1504
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT03278548
    WHO universal trial number (UTN)
    -
    Other trial identifiers
    Fresenius Kabi ID: VOLU-024-CP4
    Sponsors
    Sponsor organisation name
    Fresenius Kabi Deutschland GmbH
    Sponsor organisation address
    Else-Kröner-Str. 1, Bad Homburg, Germany, 61352
    Public contact
    Medical Scientific Affairs Pharma and Nutrition, Fresenius Kabi Deutschland GmbH, Trial-Disclosure@Fresenius-Kabi.com
    Scientific contact
    Medical Scientific Affairs Pharma and Nutrition, Fresenius Kabi Deutschland GmbH, Trial-Disclosure@Fresenius-Kabi.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
    16 Feb 2023
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    06 Jul 2022
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    Primary objective was to investigate non-inferiority regarding the safety of a 6% HES solution for infusion (Volulyte 6%) compared to an electrolyte solution for infusion (Ionolyte) in patients with acute blood loss undergoing elective abdominal surgery
    Protection of trial subjects
    Subject protection was ensured by medical and ethical standards in accordance with Declaration of Helsinki, Good Clinical Practice and applicable national and local laws and regulation. The signed informed consent was obtained prior to inclusion in the study. The patients were informed in writing about their right to withdraw from the study at any time. Furthermore, a data safety monitoring board was established to protect the patients participating in the study
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    25 Sep 2017
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    Safety
    Long term follow-up duration
    1 Years
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Netherlands: 133
    Country: Number of subjects enrolled
    Poland: 83
    Country: Number of subjects enrolled
    Romania: 24
    Country: Number of subjects enrolled
    Spain: 896
    Country: Number of subjects enrolled
    Croatia: 17
    Country: Number of subjects enrolled
    Austria: 4
    Country: Number of subjects enrolled
    Belgium: 144
    Country: Number of subjects enrolled
    Czechia: 235
    Country: Number of subjects enrolled
    France: 320
    Country: Number of subjects enrolled
    Germany: 490
    Worldwide total number of subjects
    2346
    EEA total number of subjects
    2346
    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)
    1056
    From 65 to 84 years
    1279
    85 years and over
    11

    Subject disposition

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    Recruitment
    Recruitment details
    -

    Pre-assignment
    Screening details
    Potential candidates for study participation were considered for the screening period. Before enrolling into screening informed consent had to be provided in writing. A patient was randomized only after eligibility was proven by checking the inclusion and exclusion criteria

    Period 1
    Period 1 title
    Overall trial without 1 year follow-up (overall period)
    Is this the baseline period?
    Yes
    Allocation method
    Randomised - controlled
    Blinding used
    Double blind
    Roles blinded
    Subject, Investigator, Monitor, Data analyst

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Volulyte
    Arm description
    Started = Number of patients randomised for this arm
    Arm type
    Experimental

    Investigational medicinal product name
    Volulyte 6% solution for infusion
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Dosing was individualised to the patient’s volume needs and guided by a volume algorithm based on either mean arterial pressure or other haemodynamic parameters. The daily dose of 30 ml/kg should not have been exceeded. If patients were still hypotensive during administration of the investigational test product, they could also receive vasoactive/inotropic drugs, if regarded necessary due to the patient’s clinical condition. Since HES preparations may rarely cause allergic reactions, the first 10-20 ml of the solution should have been infused slowly. In case of an allergic reaction, the infusion had to be stopped immediately, and appropriate treatment given.

    Arm title
    Ionolyte
    Arm description
    Started = Number of patients randomised for this arm
    Arm type
    Active comparator

    Investigational medicinal product name
    Ionolyte solution for infusion
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Dosing was individualised to the patient’s volume needs and guided by a volume algorithm based on either mean arterial pressure or other haemodynamic parameters. The daily dose of 30 ml/kg should not have been exceeded. If patients were still hypotensive during administration of the investigational reference product, they could also receive vasoactive/inotropic drugs, if regarded necessary due to the patient’s clinical condition.

    Number of subjects in period 1 [1]
    Volulyte Ionolyte
    Started
    1147
    1142
    Completed
    852
    861
    Not completed
    295
    281
         Adverse event, serious fatal
    32
    31
         Consent withdrawn by subject
    57
    42
         Adverse event, non-fatal
    2
    -
         Other
    187
    189
         Lost to follow-up
    15
    18
         Protocol deviation
    2
    1
    Notes
    [1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
    Justification: In ‘period 1’ only the eligible and randomized subjects are mentioned whereas under ‘population of trial subjects’ and ‘subjects enrolled per age group’ all patients enrolled (including screen failures) are mentioned.

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Volulyte
    Reporting group description
    Started = Number of patients randomised for this arm

    Reporting group title
    Ionolyte
    Reporting group description
    Started = Number of patients randomised for this arm

    Reporting group values
    Volulyte Ionolyte Total
    Number of subjects
    1147 1142 2289
    Age categorical
    Units: Subjects
        In utero
    0
        Preterm newborn infants (gestational age < 37 wks)
    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)
    0
        From 65-84 years
    0
        85 years and over
    0
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    64.9 ± 9.51 64.9 ± 9.92 -
    Gender categorical
    Units: Subjects
        Female
    414 446 860
        Male
    733 696 1429
    Subject analysis sets

    Subject analysis set title
    Safety analysis set (SAF)
    Subject analysis set type
    Safety analysis
    Subject analysis set description
    All patients with at least one administration of study medication were included in the SAF.

    Subject analysis set title
    Full analysis set for the primary endpoint (FAS‑pEP)
    Subject analysis set type
    Full analysis
    Subject analysis set description
    The FAS‑pEP comprised all patients from the SAF reaching the post-operative period and being monitored at least once with respect to the changes in cystatin C-based eGFR at POD1, POD2 or POD3.

    Subject analysis set title
    Full analysis set for efficacy analyses (FAS‑Eff)
    Subject analysis set type
    Full analysis
    Subject analysis set description
    The FAS‑Eff comprised all patients from the SAF providing any efficacy data after IP start.

    Subject analysis set title
    Per-protocol set for the primary endpoint (PPS‑pEP)
    Subject analysis set type
    Per protocol
    Subject analysis set description
    The PPS‑pEP comprised all subjects from the FAS‑pEP who did not have any major protocol deviations with regard to the primary endpoint.

    Subject analysis set title
    Per-protocol set for the key secondary endpoint (PPS‑KScEP)
    Subject analysis set type
    Per protocol
    Subject analysis set description
    The PPS‑KScEP comprised all subjects from the SAF who did not have any major protocol deviations with regard to the key secondary endpoint.

    Subject analysis sets values
    Safety analysis set (SAF) Full analysis set for the primary endpoint (FAS‑pEP) Full analysis set for efficacy analyses (FAS‑Eff) Per-protocol set for the primary endpoint (PPS‑pEP) Per-protocol set for the key secondary endpoint (PPS‑KScEP)
    Number of subjects
    1958
    1946
    1958
    1857
    1868
    Age categorical
    Units: Subjects
        In utero
        Preterm newborn infants (gestational age < 37 wks)
        Newborns (0-27 days)
        Infants and toddlers (28 days-23 months)
        Children (2-11 years)
        Adolescents (12-17 years)
        Adults (18-64 years)
        From 65-84 years
        85 years and over
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    64.9 ± 9.68
    64.9 ± 9.67
    64.9 ± 9.68
    64.9 ± 9.59
    64.9 ± 9.60
    Gender categorical
    Units: Subjects
        Female
    724
    721
    724
    682
    685
        Male
    1234
    1225
    1234
    1175
    1183

    End points

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    End points reporting groups
    Reporting group title
    Volulyte
    Reporting group description
    Started = Number of patients randomised for this arm

    Reporting group title
    Ionolyte
    Reporting group description
    Started = Number of patients randomised for this arm

    Subject analysis set title
    Safety analysis set (SAF)
    Subject analysis set type
    Safety analysis
    Subject analysis set description
    All patients with at least one administration of study medication were included in the SAF.

    Subject analysis set title
    Full analysis set for the primary endpoint (FAS‑pEP)
    Subject analysis set type
    Full analysis
    Subject analysis set description
    The FAS‑pEP comprised all patients from the SAF reaching the post-operative period and being monitored at least once with respect to the changes in cystatin C-based eGFR at POD1, POD2 or POD3.

    Subject analysis set title
    Full analysis set for efficacy analyses (FAS‑Eff)
    Subject analysis set type
    Full analysis
    Subject analysis set description
    The FAS‑Eff comprised all patients from the SAF providing any efficacy data after IP start.

    Subject analysis set title
    Per-protocol set for the primary endpoint (PPS‑pEP)
    Subject analysis set type
    Per protocol
    Subject analysis set description
    The PPS‑pEP comprised all subjects from the FAS‑pEP who did not have any major protocol deviations with regard to the primary endpoint.

    Subject analysis set title
    Per-protocol set for the key secondary endpoint (PPS‑KScEP)
    Subject analysis set type
    Per protocol
    Subject analysis set description
    The PPS‑KScEP comprised all subjects from the SAF who did not have any major protocol deviations with regard to the key secondary endpoint.

    Primary: Change in cystatin C-based estimated glomerular filtration rate (eGFR) from pre-operative baseline to eGFR value calculated from the highest cystatin C level measured during post-operative days 1–3 (POD1–3) (i.e., minimal eGFR during POD1–3)

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    End point title
    Change in cystatin C-based estimated glomerular filtration rate (eGFR) from pre-operative baseline to eGFR value calculated from the highest cystatin C level measured during post-operative days 1–3 (POD1–3) (i.e., minimal eGFR during POD1–3)
    End point description
    The primary endpoint of this study was the change in cystatin C-based eGFR from pre-operative baseline to eGFR value calculated from the highest cystatin C level measured during post-operative days 1–3 (i.e., minimal eGFR during post-operative days 1–3). To calculate cystatin C-based eGFR the Chronic Kidney Disease Epidemiology Collaboration equation developed by Inker et al., 2012 was used.
    End point type
    Primary
    End point timeframe
    From pre-operative baseline to post-operative days 1-3
    End point values
    Volulyte Ionolyte Per-protocol set for the primary endpoint (PPS‑pEP)
    Number of subjects analysed
    922 [1]
    935 [2]
    1857 [3]
    Units: ml/min/1.73m²
        least squares mean (confidence interval 95%)
    -1.713 (-3.274 to -0.153)
    0.667 (-0.906 to 2.241)
    -2.381 (-3.899 to -0.862)
    Notes
    [1] - PPS-pEP
    [2] - PPS-pEP
    [3] - 922 (Volulyte) + 935 (Ionolyte) LS mean value below is the difference in LS means between groups
    Statistical analysis title
    Analysis of Primary Endpoint
    Statistical analysis description
    This study was intended to test confirmatively the primary hypothesis that treatment with Volulyte is non-inferior to treatment with Ionolyte regarding the primary endpoint change in cystatin C-based eGFR from pre-operative baseline to eGFR value calculated from the highest cystatin C level measured during POD 1–3 (i.e., minimal eGFR during POD1–3) considering a non-inferiority margin of Δ = 8.1 ml/min/1.73 m² and a type I error rate of α = 2.5% one-sided
    Comparison groups
    Volulyte v Ionolyte
    Number of subjects included in analysis
    1857
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority
    P-value
    < 0.0001 [4]
    Method
    ANCOVA
    Confidence interval
    Notes
    [4] - The treatment group difference was -2.381 ml/min/1.73m² (95% CI: -3.899 to -0.862 ml/min/1.73 m²). Since the lower limit of the 95% CI was greater than -Δ (i.e.,-8.1ml/min/1.73m²), non-inferiority to Ionolyte was demonstrated (p<0.0001)

    Secondary: Key secondary endpoint: Mortality and major post-operative complications (including renal) until day 90

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    End point title
    Key secondary endpoint: Mortality and major post-operative complications (including renal) until day 90
    End point description
    This composite endpoint summarises the occurrence of death and major post-operative complications according to predefined criteria for the assessment of complications during the first 90 post-operative days.
    End point type
    Secondary
    End point timeframe
    End of surgery - 90 post-operative days
    End point values
    Volulyte Ionolyte
    Number of subjects analysed
    887 [5]
    907 [6]
    Units: cases
    324
    322
    Notes
    [5] - SAF, N missing = 90
    [6] - SAF, N missing = 74
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    The reporting period for adverse events (AEs) started at T0 i.e. baseline (after randomization and prior induction of anaesthesia) and ended after T8 (90 days after surgery)
    Adverse event reporting additional description
    Only treatment-emergent adverse events included
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    25.0
    Reporting groups
    Reporting group title
    Volulyte
    Reporting group description
    -

    Reporting group title
    Ionolyte
    Reporting group description
    -

    Serious adverse events
    Volulyte Ionolyte
    Total subjects affected by serious adverse events
         subjects affected / exposed
    296 / 977 (30.30%)
    291 / 981 (29.66%)
         number of deaths (all causes)
    32
    31
         number of deaths resulting from adverse events
    0
    1
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Colon neoplasm
    Additional description: Treatment-emergent
         subjects affected / exposed
    1 / 977 (0.10%)
    0 / 981 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metastases to peritoneum
    Additional description: Treatment-emergent
         subjects affected / exposed
    2 / 977 (0.20%)
    0 / 981 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Neoplasm progression
    Additional description: Treatment-emergent
         subjects affected / exposed
    1 / 977 (0.10%)
    0 / 981 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Ovarian neoplasm
         subjects affected / exposed
    1 / 977 (0.10%)
    1 / 981 (0.10%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bladder cancer
    Additional description: Treatment-emergent
         subjects affected / exposed
    0 / 977 (0.00%)
    1 / 981 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholangiocarcinoma
    Additional description: Cholangiocarcinoma
         subjects affected / exposed
    0 / 977 (0.00%)
    1 / 981 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Malignant neoplasm progression
    Additional description: Treatment-emergent
         subjects affected / exposed
    0 / 977 (0.00%)
    3 / 981 (0.31%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 2
    Oesophageal carcinoma
    Additional description: Treatment-emergent
         subjects affected / exposed
    0 / 977 (0.00%)
    1 / 981 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Ureteral neoplasm
    Additional description: Treatment-emergent
         subjects affected / exposed
    0 / 977 (0.00%)
    1 / 981 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular disorders
    Arterial haemorrhage
    Additional description: Treatment-emergent
         subjects affected / exposed
    1 / 977 (0.10%)
    0 / 981 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Deep vein thrombosis
    Additional description: Treatment-emergent
         subjects affected / exposed
    1 / 977 (0.10%)
    2 / 981 (0.20%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haematoma
    Additional description: Treatment-emergent
         subjects affected / exposed
    1 / 977 (0.10%)
    1 / 981 (0.10%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemodynamic instability
    Additional description: Treatment-emergent
         subjects affected / exposed
    1 / 977 (0.10%)
    2 / 981 (0.20%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemorrhage
    Additional description: Treatment-emergent
         subjects affected / exposed
    4 / 977 (0.41%)
    2 / 981 (0.20%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Hypotension
    Additional description: Treatment-emergent
         subjects affected / exposed
    1 / 977 (0.10%)
    0 / 981 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypovolaemic shock
    Additional description: Treatment-emergent
         subjects affected / exposed
    2 / 977 (0.20%)
    1 / 981 (0.10%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Lymphocele
    Additional description: Treatment-emergent
         subjects affected / exposed
    7 / 977 (0.72%)
    9 / 981 (0.92%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 9
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lymphorrhoea
    Additional description: Treatment-emergent
         subjects affected / exposed
    1 / 977 (0.10%)
    0 / 981 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral ischaemia
    Additional description: Treatment-emergent
         subjects affected / exposed
    2 / 977 (0.20%)
    2 / 981 (0.20%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Shock haemorrhagic
    Additional description: Treatment-emergent
         subjects affected / exposed
    9 / 977 (0.92%)
    5 / 981 (0.51%)
         occurrences causally related to treatment / all
    0 / 9
    0 / 5
         deaths causally related to treatment / all
    0 / 1
    0 / 2
    Peripheral arterial occlusive disease
    Additional description: Treatment-emergent
         subjects affected / exposed
    0 / 977 (0.00%)
    1 / 981 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral artery occlusion
    Additional description: Treatment-emergent
         subjects affected / exposed
    0 / 977 (0.00%)
    1 / 981 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Venous thrombosis limb
    Additional description: Treatment-emergent
         subjects affected / exposed
    0 / 977 (0.00%)
    1 / 981 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Surgical and medical procedures
    Therapy cessation
    Additional description: Treatment-emergent
         subjects affected / exposed
    1 / 977 (0.10%)
    0 / 981 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Thyroid operation
    Additional description: Treatment-emergent
         subjects affected / exposed
    0 / 977 (0.00%)
    1 / 981 (0.10%)
         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
    Chest pain
    Additional description: Treatment-emergent
         subjects affected / exposed
    1 / 977 (0.10%)
    0 / 981 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Death
    Additional description: Treatment-emergent
         subjects affected / exposed
    1 / 977 (0.10%)
    0 / 981 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    General physical health deterioration
    Additional description: Treatment-emergent
         subjects affected / exposed
    1 / 977 (0.10%)
    2 / 981 (0.20%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Multiple organ dysfunction syndrome
    Additional description: Treatment-emergent
         subjects affected / exposed
    2 / 977 (0.20%)
    5 / 981 (0.51%)
         occurrences causally related to treatment / all
    0 / 2
    1 / 5
         deaths causally related to treatment / all
    0 / 2
    1 / 5
    Pyrexia
    Additional description: Treatment-emergent
         subjects affected / exposed
    4 / 977 (0.41%)
    0 / 981 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Systemic inflammatory response syndrome
    Additional description: Treatment-emergent
         subjects affected / exposed
    1 / 977 (0.10%)
    1 / 981 (0.10%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Impaired healing
    Additional description: Treatment-emergent
         subjects affected / exposed
    0 / 977 (0.00%)
    3 / 981 (0.31%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Inflammation
    Additional description: Treatment-emergent
         subjects affected / exposed
    0 / 977 (0.00%)
    1 / 981 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Localised oedema
    Additional description: Treatment-emergent
         subjects affected / exposed
    0 / 977 (0.00%)
    1 / 981 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pain
    Additional description: Treatment-emergent
         subjects affected / exposed
    0 / 977 (0.00%)
    2 / 981 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sudden death
    Additional description: Treatment-emergent
         subjects affected / exposed
    0 / 977 (0.00%)
    1 / 981 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Immune system disorders
    Contrast media allergy
    Additional description: Treatment-emergent
         subjects affected / exposed
    0 / 977 (0.00%)
    1 / 981 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Vaginal fistula
    Additional description: Treatment-emergent
         subjects affected / exposed
    1 / 977 (0.10%)
    0 / 981 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pelvic haematoma
    Additional description: Treatment-emergent
         subjects affected / exposed
    0 / 977 (0.00%)
    1 / 981 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Respiratory, thoracic and mediastinal disorders
    Acute pulmonary oedema
    Additional description: Treatment-emergent
         subjects affected / exposed
    1 / 977 (0.10%)
    0 / 981 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acute respiratory distress syndrome
    Additional description: Treatment-emergent
         subjects affected / exposed
    6 / 977 (0.61%)
    3 / 981 (0.31%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 3
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Acute respiratory failure
    Additional description: Treatment-emergent
         subjects affected / exposed
    2 / 977 (0.20%)
    2 / 981 (0.20%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 2
    Chronic obstructive pulmonary disease
    Additional description: Treatment-emergent
         subjects affected / exposed
    2 / 977 (0.20%)
    1 / 981 (0.10%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chylothorax
    Additional description: Treatment-emergent
         subjects affected / exposed
    1 / 977 (0.10%)
    0 / 981 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemothorax
    Additional description: Treatment-emergent
         subjects affected / exposed
    1 / 977 (0.10%)
    0 / 981 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypoxia
    Additional description: Treatment-emergent
         subjects affected / exposed
    1 / 977 (0.10%)
    0 / 981 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lung disorder
    Additional description: Treatment-emergent
         subjects affected / exposed
    1 / 977 (0.10%)
    0 / 981 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pleural effusion
    Additional description: Treatment-emergent
         subjects affected / exposed
    8 / 977 (0.82%)
    9 / 981 (0.92%)
         occurrences causally related to treatment / all
    1 / 9
    0 / 10
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumothorax
    Additional description: Treatment-emergent
         subjects affected / exposed
    2 / 977 (0.20%)
    1 / 981 (0.10%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary embolism
    Additional description: Treatment-emergent
         subjects affected / exposed
    9 / 977 (0.92%)
    7 / 981 (0.71%)
         occurrences causally related to treatment / all
    0 / 9
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 2
    Pulmonary oedema
    Additional description: Treatment-emergent
         subjects affected / exposed
    1 / 977 (0.10%)
    1 / 981 (0.10%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory failure
    Additional description: Treatment-emergent
         subjects affected / exposed
    7 / 977 (0.72%)
    1 / 981 (0.10%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atelectasis
    Additional description: Treatment-emergent
         subjects affected / exposed
    0 / 977 (0.00%)
    1 / 981 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pleurisy
    Additional description: Treatment-emergent
         subjects affected / exposed
    0 / 977 (0.00%)
    2 / 981 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psychiatric disorders
    Delirium
    Additional description: Treatment-emergent
         subjects affected / exposed
    0 / 977 (0.00%)
    1 / 981 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Product issues
    Device dislocation
    Additional description: Treatment-emergent
         subjects affected / exposed
    1 / 977 (0.10%)
    0 / 981 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Device occlusion
    Additional description: Treatment-emergent
         subjects affected / exposed
    1 / 977 (0.10%)
    0 / 981 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Investigations
    Blood creatine increased
    Additional description: Treatment-emergent
         subjects affected / exposed
    1 / 977 (0.10%)
    0 / 981 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    International normalised ratio increased
    Additional description: Treatment-emergent
         subjects affected / exposed
    1 / 977 (0.10%)
    0 / 981 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oxygen saturation decreased
    Additional description: Treatment-emergent
         subjects affected / exposed
    1 / 977 (0.10%)
    0 / 981 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    SARS-CoV-2 test positive
    Additional description: Treatment-emergent
         subjects affected / exposed
    3 / 977 (0.31%)
    0 / 981 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 3
    0 / 0
    Transaminases increased
    Additional description: Treatment-emergent
         subjects affected / exposed
    0 / 977 (0.00%)
    1 / 981 (0.10%)
         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
    Anastomotic fistula
    Additional description: Treatment-emergent
         subjects affected / exposed
    2 / 977 (0.20%)
    2 / 981 (0.20%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anastomotic haemorrhage
    Additional description: Treatment-emergent
         subjects affected / exposed
    1 / 977 (0.10%)
    1 / 981 (0.10%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anastomotic leak
    Additional description: Treatment-emergent
         subjects affected / exposed
    26 / 977 (2.66%)
    15 / 981 (1.53%)
         occurrences causally related to treatment / all
    1 / 26
    0 / 15
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Femoral nerve injury
    Additional description: Treatment-emergent
         subjects affected / exposed
    1 / 977 (0.10%)
    0 / 981 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Flap necrosis
    Additional description: Treatment-emergent
         subjects affected / exposed
    2 / 977 (0.20%)
    3 / 981 (0.31%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal anastomotic complication
    Additional description: Treatment-emergent
         subjects affected / exposed
    1 / 977 (0.10%)
    0 / 981 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal anastomotic leak
    Additional description: Treatment-emergent
         subjects affected / exposed
    7 / 977 (0.72%)
    1 / 981 (0.10%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal stoma complication
    Additional description: Treatment-emergent
         subjects affected / exposed
    2 / 977 (0.20%)
    0 / 981 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Incisional hernia
    Additional description: Treatment-emergent
         subjects affected / exposed
    1 / 977 (0.10%)
    0 / 981 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intestinal anastomosis complication
    Additional description: Treatment-emergent
         subjects affected / exposed
    1 / 977 (0.10%)
    0 / 981 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatic leak
    Additional description: Treatment-emergent
         subjects affected / exposed
    4 / 977 (0.41%)
    0 / 981 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripancreatic fluid collection
    Additional description: Treatment-emergent
         subjects affected / exposed
    1 / 977 (0.10%)
    1 / 981 (0.10%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Post procedural bile leak
    Additional description: Treatment-emergent
         subjects affected / exposed
    1 / 977 (0.10%)
    4 / 981 (0.41%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Post procedural complication
    Additional description: Treatment-emergent
         subjects affected / exposed
    1 / 977 (0.10%)
    1 / 981 (0.10%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Post procedural fever
    Additional description: Treatment-emergent
         subjects affected / exposed
    2 / 977 (0.20%)
    3 / 981 (0.31%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Post procedural haemorrhage
    Additional description: Treatment-emergent
         subjects affected / exposed
    9 / 977 (0.92%)
    8 / 981 (0.82%)
         occurrences causally related to treatment / all
    0 / 9
    0 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Post procedural pulmonary embolism
    Additional description: Treatment-emergent
         subjects affected / exposed
    1 / 977 (0.10%)
    0 / 981 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Post procedural urine leak
    Additional description: Treatment-emergent
         subjects affected / exposed
    2 / 977 (0.20%)
    2 / 981 (0.20%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Procedural haemorrhage
    Additional description: Treatment-emergent
         subjects affected / exposed
    4 / 977 (0.41%)
    3 / 981 (0.31%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Procedural intestinal perforation
    Additional description: Treatment-emergent
         subjects affected / exposed
    1 / 977 (0.10%)
    0 / 981 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Procedural pain
    Additional description: Treatment-emergent
         subjects affected / exposed
    1 / 977 (0.10%)
    0 / 981 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Procedural shock
    Additional description: Treatment-emergent
         subjects affected / exposed
    1 / 977 (0.10%)
    0 / 981 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Stoma complication
    Additional description: Treatment-emergent
         subjects affected / exposed
    1 / 977 (0.10%)
    0 / 981 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Suture related complication
    Additional description: Treatment-emergent
         subjects affected / exposed
    1 / 977 (0.10%)
    1 / 981 (0.10%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ureteric injury
    Additional description: Treatment-emergent
         subjects affected / exposed
    1 / 977 (0.10%)
    0 / 981 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vaginal cuff dehiscence
    Additional description: Treatment-emergent
         subjects affected / exposed
    1 / 977 (0.10%)
    0 / 981 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Wound dehiscence
    Additional description: Treatment-emergent
         subjects affected / exposed
    1 / 977 (0.10%)
    1 / 981 (0.10%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Wound evisceration
    Additional description: Treatment-emergent
         subjects affected / exposed
    2 / 977 (0.20%)
    3 / 981 (0.31%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Wound haematoma
    Additional description: Treatment-emergent
         subjects affected / exposed
    1 / 977 (0.10%)
    0 / 981 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal wound dehiscence
    Additional description: Treatment-emergent
         subjects affected / exposed
    0 / 977 (0.00%)
    2 / 981 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Craniocerebral injury
    Additional description: Treatment-emergent
         subjects affected / exposed
    0 / 977 (0.00%)
    1 / 981 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Drain site complication
    Additional description: Treatment-emergent
         subjects affected / exposed
    0 / 977 (0.00%)
    1 / 981 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Post procedural fistula
    Additional description: Treatment-emergent
         subjects affected / exposed
    0 / 977 (0.00%)
    1 / 981 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Post procedural stroke
    Additional description: Treatment-emergent
         subjects affected / exposed
    0 / 977 (0.00%)
    1 / 981 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Postoperative ileus
    Additional description: Treatment-emergent
         subjects affected / exposed
    0 / 977 (0.00%)
    1 / 981 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Postoperative renal failure
    Additional description: Treatment-emergent
         subjects affected / exposed
    0 / 977 (0.00%)
    2 / 981 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Postoperative respiratory failure
    Additional description: Treatment-emergent
         subjects affected / exposed
    0 / 977 (0.00%)
    1 / 981 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Procedural pneumothorax
    Additional description: Treatment-emergent
         subjects affected / exposed
    0 / 977 (0.00%)
    1 / 981 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Seroma
    Additional description: Treatment-emergent
         subjects affected / exposed
    0 / 977 (0.00%)
    2 / 981 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Suture rupture
    Additional description: Treatment-emergent
         subjects affected / exposed
    0 / 977 (0.00%)
    2 / 981 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Toxicity to various agents
    Additional description: Treatment-emergent
         subjects affected / exposed
    0 / 977 (0.00%)
    1 / 981 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vena cava injury
    Additional description: Treatment-emergent
         subjects affected / exposed
    0 / 977 (0.00%)
    1 / 981 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Wound necrosis
    Additional description: Treatment-emergent
         subjects affected / exposed
    0 / 977 (0.00%)
    1 / 981 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Acute myocardial infarction
    Additional description: Treatment-emergent
         subjects affected / exposed
    1 / 977 (0.10%)
    2 / 981 (0.20%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Arrhythmia
    Additional description: Treatment-emergent
         subjects affected / exposed
    1 / 977 (0.10%)
    1 / 981 (0.10%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrial fibrillation
    Additional description: Treatment-emergent
         subjects affected / exposed
    7 / 977 (0.72%)
    3 / 981 (0.31%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrial flutter
    Additional description: Treatment-emergent
         subjects affected / exposed
    3 / 977 (0.31%)
    0 / 981 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Bradyarrhythmia
    Additional description: Treatment-emergent
         subjects affected / exposed
    1 / 977 (0.10%)
    0 / 981 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Cardiac arrest
    Additional description: Treatment-emergent
         subjects affected / exposed
    2 / 977 (0.20%)
    0 / 981 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Cardio-respiratory arrest
    Additional description: Treatment-emergent
         subjects affected / exposed
    4 / 977 (0.41%)
    0 / 981 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 4
    0 / 0
    Cardiovascular disorder
    Additional description: Treatment-emergent
         subjects affected / exposed
    1 / 977 (0.10%)
    0 / 981 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Pericardial effusion
    Additional description: Treatment-emergent
         subjects affected / exposed
    1 / 977 (0.10%)
    0 / 981 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Supraventricular tachycardia
    Additional description: Treatment-emergent
         subjects affected / exposed
    1 / 977 (0.10%)
    0 / 981 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Torsade de pointes
    Additional description: Treatment-emergent
         subjects affected / exposed
    1 / 977 (0.10%)
    0 / 981 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    Cardiac failure
    Additional description: Treatment-emergent
         subjects affected / exposed
    0 / 977 (0.00%)
    1 / 981 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Cardiac failure congestive
    Additional description: Treatment-emergent
         subjects affected / exposed
    0 / 977 (0.00%)
    2 / 981 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myocardial infarction
    Additional description: Treatment-emergent
         subjects affected / exposed
    0 / 977 (0.00%)
    1 / 981 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myocardial ischaemia
    Additional description: Treatment-emergent
         subjects affected / exposed
    0 / 977 (0.00%)
    2 / 981 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulseless electrical activity
    Additional description: Treatment-emergent
         subjects affected / exposed
    0 / 977 (0.00%)
    1 / 981 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Cerebral infarction
    Additional description: Treatment-emergent
         subjects affected / exposed
    1 / 977 (0.10%)
    0 / 981 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Embolic stroke
    Additional description: Treatment-emergent
         subjects affected / exposed
    1 / 977 (0.10%)
    0 / 981 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Hemiparesis
    Additional description: Treatment-emergent
         subjects affected / exposed
    1 / 977 (0.10%)
    0 / 981 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hemiplegia
    Additional description: Treatment-emergent
         subjects affected / exposed
    1 / 977 (0.10%)
    0 / 981 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatic encephalopathy
    Additional description: Treatment-emergent
         subjects affected / exposed
    1 / 977 (0.10%)
    0 / 981 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Syncope
    Additional description: Treatment-emergent
         subjects affected / exposed
    1 / 977 (0.10%)
    2 / 981 (0.20%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Brain stem syndrome
    Additional description: Treatment-emergent
         subjects affected / exposed
    0 / 977 (0.00%)
    1 / 981 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Epilepsy
    Additional description: Treatment-emergent
         subjects affected / exposed
    0 / 977 (0.00%)
    2 / 981 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
    Additional description: Treatment-emergent
         subjects affected / exposed
    2 / 977 (0.20%)
    1 / 981 (0.10%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neutropenia
    Additional description: Treatment-emergent
         subjects affected / exposed
    1 / 977 (0.10%)
    0 / 981 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Splenic haemorrhage
    Additional description: Treatment-emergent
         subjects affected / exposed
    0 / 977 (0.00%)
    1 / 981 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal hernia
    Additional description: Treatment-emergent
         subjects affected / exposed
    1 / 977 (0.10%)
    1 / 981 (0.10%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal pain
    Additional description: Treatment-emergent
         subjects affected / exposed
    1 / 977 (0.10%)
    2 / 981 (0.20%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal pain upper
    Additional description: Treatment-emergent
         subjects affected / exposed
    1 / 977 (0.10%)
    0 / 981 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anal haemorrhage
    Additional description: Treatment-emergent
         subjects affected / exposed
    1 / 977 (0.10%)
    0 / 981 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ascites
    Additional description: Treatment-emergent
         subjects affected / exposed
    2 / 977 (0.20%)
    1 / 981 (0.10%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colitis
    Additional description: Treatment-emergent
         subjects affected / exposed
    1 / 977 (0.10%)
    0 / 981 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diarrhoea
    Additional description: Treatment-emergent
         subjects affected / exposed
    2 / 977 (0.20%)
    0 / 981 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Enterocutaneous fistula
    Additional description: Treatment-emergent
         subjects affected / exposed
    1 / 977 (0.10%)
    0 / 981 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Enterovesical fistula
    Additional description: Treatment-emergent
         subjects affected / exposed
    1 / 977 (0.10%)
    0 / 981 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Functional gastrointestinal disorder
    Additional description: Treatment-emergent
         subjects affected / exposed
    1 / 977 (0.10%)
    0 / 981 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastric perforation
    Additional description: Treatment-emergent
         subjects affected / exposed
    2 / 977 (0.20%)
    0 / 981 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Gastric ulcer
    Additional description: Treatment-emergent
         subjects affected / exposed
    1 / 977 (0.10%)
    0 / 981 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal haemorrhage
    Additional description: Treatment-emergent
         subjects affected / exposed
    6 / 977 (0.61%)
    2 / 981 (0.20%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Haemoperitoneum
    Additional description: Treatment-emergent
         subjects affected / exposed
    1 / 977 (0.10%)
    2 / 981 (0.20%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ileus
    Additional description: Treatment-emergent
         subjects affected / exposed
    1 / 977 (0.10%)
    1 / 981 (0.10%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ileus paralytic
    Additional description: Treatment-emergent
         subjects affected / exposed
    20 / 977 (2.05%)
    21 / 981 (2.14%)
         occurrences causally related to treatment / all
    0 / 21
    0 / 21
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Impaired gastric emptying
    Additional description: Treatment-emergent
         subjects affected / exposed
    6 / 977 (0.61%)
    5 / 981 (0.51%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intestinal haemorrhage
    Additional description: Treatment-emergent
         subjects affected / exposed
    1 / 977 (0.10%)
    0 / 981 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intestinal ischaemia
    Additional description: Treatment-emergent
         subjects affected / exposed
    2 / 977 (0.20%)
    5 / 981 (0.51%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 5
         deaths causally related to treatment / all
    0 / 1
    0 / 2
    Intestinal obstruction
    Additional description: Treatment-emergent
         subjects affected / exposed
    9 / 977 (0.92%)
    3 / 981 (0.31%)
         occurrences causally related to treatment / all
    0 / 9
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intestinal perforation
    Additional description: Treatment-emergent
         subjects affected / exposed
    1 / 977 (0.10%)
    1 / 981 (0.10%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intra-abdominal fluid collection
    Additional description: Treatment-emergent
         subjects affected / exposed
    14 / 977 (1.43%)
    15 / 981 (1.53%)
         occurrences causally related to treatment / all
    0 / 14
    0 / 15
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intra-abdominal haemorrhage
    Additional description: Treatment-emergent
         subjects affected / exposed
    3 / 977 (0.31%)
    1 / 981 (0.10%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Jejunal perforation
    Additional description: Treatment-emergent
         subjects affected / exposed
    1 / 977 (0.10%)
    0 / 981 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Large intestine perforation
    Additional description: Treatment-emergent
         subjects affected / exposed
    3 / 977 (0.31%)
    0 / 981 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mechanical ileus
    Additional description: Treatment-emergent
         subjects affected / exposed
    3 / 977 (0.31%)
    1 / 981 (0.10%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Melaena
    Additional description: Treatment-emergent
         subjects affected / exposed
    3 / 977 (0.31%)
    1 / 981 (0.10%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mesenteric haemorrhage
    Additional description: Treatment-emergent
         subjects affected / exposed
    1 / 977 (0.10%)
    1 / 981 (0.10%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oesophagopleural fistula
    Additional description: Treatment-emergent
         subjects affected / exposed
    1 / 977 (0.10%)
    0 / 981 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatic fistula
    Additional description: Treatment-emergent
         subjects affected / exposed
    4 / 977 (0.41%)
    5 / 981 (0.51%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatic pseudocyst
    Additional description: Treatment-emergent
         subjects affected / exposed
    1 / 977 (0.10%)
    0 / 981 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatitis acute
    Additional description: Treatment-emergent
         subjects affected / exposed
    1 / 977 (0.10%)
    1 / 981 (0.10%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peptic ulcer haemorrhage
    Additional description: Treatment-emergent
         subjects affected / exposed
    1 / 977 (0.10%)
    0 / 981 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal wall haematoma
    Additional description: Treatment-emergent
         subjects affected / exposed
    0 / 977 (0.00%)
    1 / 981 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diaphragmatic hernia
    Additional description: Treatment-emergent
         subjects affected / exposed
    0 / 977 (0.00%)
    1 / 981 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Duodenal obstruction
    Additional description: Treatment-emergent
         subjects affected / exposed
    0 / 977 (0.00%)
    1 / 981 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Duodenal perforation
    Additional description: Treatment-emergent
         subjects affected / exposed
    0 / 977 (0.00%)
    1 / 981 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dysphagia
    Additional description: Treatment-emergent
         subjects affected / exposed
    0 / 977 (0.00%)
    1 / 981 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastritis
    Additional description: Treatment-emergent
         subjects affected / exposed
    0 / 977 (0.00%)
    1 / 981 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroduodenal haemorrhage
    Additional description: Treatment-emergent
         subjects affected / exposed
    0 / 977 (0.00%)
    1 / 981 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal necrosis
    Additional description: Treatment-emergent
         subjects affected / exposed
    0 / 977 (0.00%)
    2 / 981 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrooesophageal reflux disease
    Additional description: Treatment-emergent
         subjects affected / exposed
    0 / 977 (0.00%)
    1 / 981 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haematemesis
    Additional description: Treatment-emergent
         subjects affected / exposed
    0 / 977 (0.00%)
    1 / 981 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Inguinal hernia
    Additional description: Treatment-emergent
         subjects affected / exposed
    0 / 977 (0.00%)
    1 / 981 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intestinal fistula
    Additional description: Treatment-emergent
         subjects affected / exposed
    0 / 977 (0.00%)
    2 / 981 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intra-abdominal haematoma
    Additional description: Treatment-emergent
         subjects affected / exposed
    0 / 977 (0.00%)
    1 / 981 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatic failure
    Additional description: Treatment-emergent
         subjects affected / exposed
    0 / 977 (0.00%)
    1 / 981 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatitis
    Additional description: Treatment-emergent
         subjects affected / exposed
    0 / 977 (0.00%)
    2 / 981 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatitis necrotising
    Additional description: Treatment-emergent
         subjects affected / exposed
    0 / 977 (0.00%)
    1 / 981 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumatosis intestinalis
    Additional description: Treatment-emergent
         subjects affected / exposed
    0 / 977 (0.00%)
    1 / 981 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tooth disorder
    Additional description: Treatment-emergent
         subjects affected / exposed
    0 / 977 (0.00%)
    1 / 981 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vomiting
    Additional description: Treatment-emergent
         subjects affected / exposed
    0 / 977 (0.00%)
    1 / 981 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Retroperitoneal haematoma
    Additional description: Treatment-emergent
         subjects affected / exposed
    1 / 977 (0.10%)
    1 / 981 (0.10%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Acute hepatic failure
    Additional description: Treatment-emergent
         subjects affected / exposed
    1 / 977 (0.10%)
    2 / 981 (0.20%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 2
    Cholangitis
    Additional description: Treatment-emergent
         subjects affected / exposed
    2 / 977 (0.20%)
    0 / 981 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholestasis
    Additional description: Treatment-emergent
         subjects affected / exposed
    1 / 977 (0.10%)
    0 / 981 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatic artery aneurysm
    Additional description: Treatment-emergent
         subjects affected / exposed
    1 / 977 (0.10%)
    0 / 981 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatic function abnormal
    Additional description: Treatment-emergent
         subjects affected / exposed
    1 / 977 (0.10%)
    0 / 981 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatic vascular thrombosis
    Additional description: Treatment-emergent
         subjects affected / exposed
    1 / 977 (0.10%)
    0 / 981 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Hepatorenal failure
    Additional description: Treatment-emergent
         subjects affected / exposed
    1 / 977 (0.10%)
    0 / 981 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Ischaemic hepatitis
    Additional description: Treatment-emergent
         subjects affected / exposed
    1 / 977 (0.10%)
    0 / 981 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Portal vein thrombosis
    Additional description: Treatment-emergent
         subjects affected / exposed
    2 / 977 (0.20%)
    0 / 981 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholecystitis
    Additional description: Treatment-emergent
         subjects affected / exposed
    0 / 977 (0.00%)
    1 / 981 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholelithiasis
    Additional description: Treatment-emergent
         subjects affected / exposed
    0 / 977 (0.00%)
    1 / 981 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemobilia
    Additional description: Treatment-emergent
         subjects affected / exposed
    0 / 977 (0.00%)
    1 / 981 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Hepatic artery occlusion
    Additional description: Treatment-emergent
         subjects affected / exposed
    0 / 977 (0.00%)
    1 / 981 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatic haemorrhage
    Additional description: Treatment-emergent
         subjects affected / exposed
    0 / 977 (0.00%)
    1 / 981 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Renal and urinary disorders
    Acute kidney injury
    Additional description: Treatment-emergent
         subjects affected / exposed
    21 / 977 (2.15%)
    38 / 981 (3.87%)
         occurrences causally related to treatment / all
    1 / 21
    1 / 42
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bladder tamponade
    Additional description: Treatment-emergent
         subjects affected / exposed
    1 / 977 (0.10%)
    2 / 981 (0.20%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chronic kidney disease
    Additional description: Treatment-emergent
         subjects affected / exposed
    1 / 977 (0.10%)
    0 / 981 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haematuria
    Additional description: Treatment-emergent
         subjects affected / exposed
    3 / 977 (0.31%)
    1 / 981 (0.10%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nephrolithiasis
    Additional description: Treatment-emergent
         subjects affected / exposed
    1 / 977 (0.10%)
    1 / 981 (0.10%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nephropathy toxic
    Additional description: Treatment-emergent
         subjects affected / exposed
    1 / 977 (0.10%)
    0 / 981 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Postrenal failure
    Additional description: Treatment-emergent
         subjects affected / exposed
    1 / 977 (0.10%)
    0 / 981 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Prerenal failure
    Additional description: Treatment-emergent
         subjects affected / exposed
    1 / 977 (0.10%)
    1 / 981 (0.10%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal impairment
    Additional description: Treatment-emergent
         subjects affected / exposed
    1 / 977 (0.10%)
    0 / 981 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ureteric perforation
    Additional description: Treatment-emergent
         subjects affected / exposed
    1 / 977 (0.10%)
    0 / 981 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary retention
    Additional description: Treatment-emergent
         subjects affected / exposed
    1 / 977 (0.10%)
    3 / 981 (0.31%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary tract obstruction
    Additional description: Treatment-emergent
         subjects affected / exposed
    2 / 977 (0.20%)
    0 / 981 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinoma
    Additional description: Treatment-emergent
         subjects affected / exposed
    1 / 977 (0.10%)
    0 / 981 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bladder perforation
    Additional description: Treatment-emergent
         subjects affected / exposed
    0 / 977 (0.00%)
    1 / 981 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hydronephrosis
    Additional description: Treatment-emergent
         subjects affected / exposed
    0 / 977 (0.00%)
    2 / 981 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal failure
    Additional description: Treatment-emergent
         subjects affected / exposed
    0 / 977 (0.00%)
    1 / 981 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urogenital fistula
    Additional description: Treatment-emergent
         subjects affected / exposed
    0 / 977 (0.00%)
    1 / 981 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Endocrine disorders
    Hyperthyroidism
    Additional description: Treatment-emergent
         subjects affected / exposed
    1 / 977 (0.10%)
    0 / 981 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Compartment syndrome
    Additional description: Treatment-emergent
         subjects affected / exposed
    1 / 977 (0.10%)
    0 / 981 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Back pain
    Additional description: Treatment-emergent
         subjects affected / exposed
    0 / 977 (0.00%)
    1 / 981 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Abdominal abscess
    Additional description: Treatment-emergent
         subjects affected / exposed
    5 / 977 (0.51%)
    6 / 981 (0.61%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal infection
    Additional description: Treatment-emergent
         subjects affected / exposed
    4 / 977 (0.41%)
    2 / 981 (0.20%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Abdominal sepsis
    Additional description: Treatment-emergent
         subjects affected / exposed
    3 / 977 (0.31%)
    1 / 981 (0.10%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal wall abscess
    Additional description: Treatment-emergent
         subjects affected / exposed
    1 / 977 (0.10%)
    0 / 981 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bacteraemia
    Additional description: Treatment-emergent
         subjects affected / exposed
    1 / 977 (0.10%)
    0 / 981 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bacterial sepsis
    Additional description: Treatment-emergent
         subjects affected / exposed
    1 / 977 (0.10%)
    0 / 981 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Biliary sepsis
    Additional description: Treatment-emergent
         subjects affected / exposed
    1 / 977 (0.10%)
    1 / 981 (0.10%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    COVID-19
    Additional description: Treatment-emergent
         subjects affected / exposed
    2 / 977 (0.20%)
    0 / 981 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Catheter site infection
    Additional description: Treatment-emergent
         subjects affected / exposed
    1 / 977 (0.10%)
    0 / 981 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholangitis infective
    Additional description: Treatment-emergent
         subjects affected / exposed
    1 / 977 (0.10%)
    0 / 981 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Clostridium difficile colitis
    Additional description: Treatment-emergent
         subjects affected / exposed
    1 / 977 (0.10%)
    0 / 981 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cystitis
    Additional description: Treatment-emergent
         subjects affected / exposed
    1 / 977 (0.10%)
    0 / 981 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Device related infection
    Additional description: Treatment-emergent
         subjects affected / exposed
    3 / 977 (0.31%)
    2 / 981 (0.20%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Device related sepsis
    Additional description: Treatment-emergent
         subjects affected / exposed
    2 / 977 (0.20%)
    1 / 981 (0.10%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Incision site abscess
    Additional description: Treatment-emergent
         subjects affected / exposed
    1 / 977 (0.10%)
    0 / 981 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infection
    Additional description: Treatment-emergent
         subjects affected / exposed
    6 / 977 (0.61%)
    4 / 981 (0.41%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intervertebral discitis
    Additional description: Treatment-emergent
         subjects affected / exposed
    1 / 977 (0.10%)
    0 / 981 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Liver abscess
    Additional description: Treatment-emergent
         subjects affected / exposed
    2 / 977 (0.20%)
    2 / 981 (0.20%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lower respiratory tract infection
    Additional description: Treatment-emergent
         subjects affected / exposed
    1 / 977 (0.10%)
    0 / 981 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nosocomial infection
    Additional description: Treatment-emergent
         subjects affected / exposed
    2 / 977 (0.20%)
    2 / 981 (0.20%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Osteomyelitis
    Additional description: Treatment-emergent
         subjects affected / exposed
    1 / 977 (0.10%)
    0 / 981 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Paraspinal abscess
    Additional description: Treatment-emergent
         subjects affected / exposed
    1 / 977 (0.10%)
    0 / 981 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pelvic abscess
    Additional description: Treatment-emergent
         subjects affected / exposed
    4 / 977 (0.41%)
    4 / 981 (0.41%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pelvic infection
    Additional description: Treatment-emergent
         subjects affected / exposed
    1 / 977 (0.10%)
    0 / 981 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Perihepatic abscess
    Additional description: Treatment-emergent
         subjects affected / exposed
    1 / 977 (0.10%)
    1 / 981 (0.10%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Perineal abscess
    Additional description: Treatment-emergent
         subjects affected / exposed
    1 / 977 (0.10%)
    0 / 981 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Perinephric abscess
    Additional description: Treatment-emergent
         subjects affected / exposed
    1 / 977 (0.10%)
    0 / 981 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peritonitis
    Additional description: Treatment-emergent
         subjects affected / exposed
    7 / 977 (0.72%)
    1 / 981 (0.10%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia
    Additional description: Treatment-emergent
         subjects affected / exposed
    8 / 977 (0.82%)
    9 / 981 (0.92%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 9
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Pneumonia aspiration
    Additional description: Treatment-emergent
         subjects affected / exposed
    1 / 977 (0.10%)
    2 / 981 (0.20%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Post procedural infection
    Additional description: Treatment-emergent
         subjects affected / exposed
    1 / 977 (0.10%)
    0 / 981 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Postoperative abscess
    Additional description: Treatment-emergent
         subjects affected / exposed
    1 / 977 (0.10%)
    0 / 981 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Postoperativ wound infection
    Additional description: Treatment-emergent
         subjects affected / exposed
    17 / 977 (1.74%)
    19 / 981 (1.94%)
         occurrences causally related to treatment / all
    0 / 17
    0 / 19
         deaths causally related to treatment / all
    0 / 1
    0 / 2
    Pyelonephritis
    Additional description: Treatment-emergent
         subjects affected / exposed
    4 / 977 (0.41%)
    1 / 981 (0.10%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyelonephritis acute
    Additional description: Treatment-emergent
         subjects affected / exposed
    2 / 977 (0.20%)
    2 / 981 (0.20%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sepsis
    Additional description: Treatment-emergent
         subjects affected / exposed
    8 / 977 (0.82%)
    6 / 981 (0.61%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 6
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    Septic shock
    Additional description: Treatment-emergent
         subjects affected / exposed
    2 / 977 (0.20%)
    7 / 981 (0.71%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Skin infection
    Additional description: Treatment-emergent
         subjects affected / exposed
    1 / 977 (0.10%)
    0 / 981 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Subdiaphragmatic abscess
    Additional description: Treatment-emergent
         subjects affected / exposed
    1 / 977 (0.10%)
    1 / 981 (0.10%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Systemic candida
    Additional description: Treatment-emergent
         subjects affected / exposed
    1 / 977 (0.10%)
    0 / 981 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary tract infection
    Additional description: Treatment-emergent
         subjects affected / exposed
    14 / 977 (1.43%)
    11 / 981 (1.12%)
         occurrences causally related to treatment / all
    0 / 14
    0 / 11
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urosepsis
    Additional description: Treatment-emergent
         subjects affected / exposed
    2 / 977 (0.20%)
    3 / 981 (0.31%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anal abscess
    Additional description: Treatment-emergent
         subjects affected / exposed
    0 / 977 (0.00%)
    1 / 981 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    COVID-19 pneumonia
    Additional description: Treatment-emergent
         subjects affected / exposed
    0 / 977 (0.00%)
    1 / 981 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Empyema
    Additional description: Treatment-emergent
         subjects affected / exposed
    0 / 977 (0.00%)
    1 / 981 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Epididymitis
    Additional description: Treatment-emergent
         subjects affected / exposed
    0 / 977 (0.00%)
    1 / 981 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gallbladder abscess
    Additional description: Treatment-emergent
         subjects affected / exposed
    0 / 977 (0.00%)
    1 / 981 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis
    Additional description: Treatment-emergent
         subjects affected / exposed
    0 / 977 (0.00%)
    1 / 981 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Large intestine infection
    Additional description: Treatment-emergent
         subjects affected / exposed
    0 / 977 (0.00%)
    1 / 981 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatic abscess
    Additional description: Treatment-emergent
         subjects affected / exposed
    0 / 977 (0.00%)
    2 / 981 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Perirectal abscess
    Additional description: Treatment-emergent
         subjects affected / exposed
    0 / 977 (0.00%)
    1 / 981 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia pseudomonal
    Additional description: Treatment-emergent
         subjects affected / exposed
    0 / 977 (0.00%)
    1 / 981 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Post procedural sepsis
    Additional description: Treatment-emergent
         subjects affected / exposed
    0 / 977 (0.00%)
    1 / 981 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Staphylococcal bacteraemia
    Additional description: Treatment-emergent
         subjects affected / exposed
    0 / 977 (0.00%)
    1 / 981 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Wound infection
    Additional description: Treatment-emergent
         subjects affected / exposed
    0 / 977 (0.00%)
    1 / 981 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Hypokalaemia
    Additional description: Treatment-emergent
         subjects affected / exposed
    2 / 977 (0.20%)
    1 / 981 (0.10%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypovolaemia
    Additional description: Treatment-emergent
         subjects affected / exposed
    1 / 977 (0.10%)
    0 / 981 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lactic acidosis
    Additional description: Treatment-emergent
         subjects affected / exposed
    2 / 977 (0.20%)
    0 / 981 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Dehydration
    Additional description: Treatment-emergent
         subjects affected / exposed
    0 / 977 (0.00%)
    1 / 981 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fluid retention
    Additional description: Treatment-emergent
         subjects affected / exposed
    0 / 977 (0.00%)
    1 / 981 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyponatraemia
    Additional description: Treatment-emergent
         subjects affected / exposed
    0 / 977 (0.00%)
    1 / 981 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Malnutrition
    Additional description: Treatment-emergent
         subjects affected / exposed
    0 / 977 (0.00%)
    1 / 981 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    Volulyte Ionolyte
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    617 / 977 (63.15%)
    630 / 981 (64.22%)
    Injury, poisoning and procedural complications
    Procedural pain
    Additional description: Treatment-emergent
         subjects affected / exposed
    76 / 977 (7.78%)
    79 / 981 (8.05%)
         occurrences all number
    78
    83
    Vascular disorders
    Hypotension
    Additional description: Treatment-emergent
         subjects affected / exposed
    46 / 977 (4.71%)
    55 / 981 (5.61%)
         occurrences all number
    46
    56
    Blood and lymphatic system disorders
    Anaemia
    Additional description: Treatment-emergent
         subjects affected / exposed
    138 / 977 (14.12%)
    136 / 981 (13.86%)
         occurrences all number
    178
    168
    General disorders and administration site conditions
    Pain
    Additional description: Treatment-emergent
         subjects affected / exposed
    77 / 977 (7.88%)
    73 / 981 (7.44%)
         occurrences all number
    79
    81
    Gastrointestinal disorders
    Constipation
    Additional description: Treatment-emergent
         subjects affected / exposed
    53 / 977 (5.42%)
    50 / 981 (5.10%)
         occurrences all number
    55
    53
    Diarrhoea
    Additional description: Treatment-emergent
         subjects affected / exposed
    51 / 977 (5.22%)
    53 / 981 (5.40%)
         occurrences all number
    53
    57
    Nausea
    Additional description: Treatment-emergent
         subjects affected / exposed
    95 / 977 (9.72%)
    95 / 981 (9.68%)
         occurrences all number
    102
    101
    Vomiting
    Additional description: Treatment-emergent
         subjects affected / exposed
    58 / 977 (5.94%)
    75 / 981 (7.65%)
         occurrences all number
    62
    75
    Renal and urinary disorders
    Acute kidney injury
    Additional description: Treatment-emergent
         subjects affected / exposed
    91 / 977 (9.31%)
    82 / 981 (8.36%)
         occurrences all number
    101
    91
    Metabolism and nutrition disorders
    Hypocalcaemia
    Additional description: Treatment-emergent
         subjects affected / exposed
    91 / 977 (9.31%)
    80 / 981 (8.15%)
         occurrences all number
    97
    91
    Hypokalaemia
    Additional description: Treatment-emergent
         subjects affected / exposed
    91 / 977 (9.31%)
    79 / 981 (8.05%)
         occurrences all number
    101
    85

    More information

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    14 Dec 2016
    The main reasons for this amendment* were the following: - Adjustment of “concomitant medication”, “duration per patient” and “duration of whole study” - Clarification that (serious) adverse events/ reactions are recorded and processed on timepoints T6-T8 - Addition of discontinuation criteria related to the study site and to the patient - Explanation of actions in case of a breach against the data protection. T6: post-operative day 8 until post-operative day 10 or hospital discharge, whatever occurs first T8: 90 days after surgery * Depending on the ethics committees' and national authorities’ feedback and on timepoint of initial submission the number of amendments, the amendment dates, as well as the changes to the protocol may differ between the participating countries. As representative information, the overview of amendments in Germany is given here.
    20 Apr 2017
    The main reason for this amendment* was the addition of subgroup analysis for gender. * Depending on the ethics committees' and national authorities’ feedback and on timepoint of initial submission the number of amendments, the amendment dates, as well as the changes to the protocol may differ between the participating countries. As representative information, the overview of amendments in Germany is given here.
    27 Feb 2018
    The main reason for this amendment* was to reflect the referral procedure in relation to risk-benefit-assessment. * Depending on the ethics committees' and national authorities’ feedback and on timepoint of initial submission the number of amendments, the amendment dates, as well as the changes to the protocol may differ between the participating countries. As representative information, the overview of amendments in Germany is given here.
    01 Aug 2019
    The main reason for this amendment* was to reflect sponsor transfer from B. Braun to Fresenius Kabi. * Depending on the ethics committees' and national authorities’ feedback and on timepoint of initial submission the number of amendments, the amendment dates, as well as the changes to the protocol may differ between the participating countries. As representative information, the overview of amendments in Germany is given here.
    05 Nov 2019
    The main reason for this amendment* was to adapt MAP-guided volume algorithm to increase patient recruitment. MAP=Mean arterial (blood) pressure. * Depending on the ethics committees' and national authorities’ feedback and on timepoint of initial submission the number of amendments, the amendment dates, as well as the changes to the protocol may differ between the participating countries. As representative information, the overview of amendments in Germany is given here.
    30 Jul 2021
    The main reason for this amendment* was to clarify some statistical aspects. * Depending on the ethics committees' and national authorities’ feedback and on timepoint of initial submission the number of amendments, the amendment dates, as well as the changes to the protocol may differ between the participating countries. As representative information, the overview of amendments in Germany is given here.

    Interruptions (globally)

    Were there any global interruptions to the trial? Yes
    Date
    Interruption
    Restart date
    12 Jan 2018
    The study was set on temporary recruitment hold on 12.01.2018. The decision was taken after a meeting with the Pharmacovigilance Risk Assessment Committee (PRAC) and their recommendation to suspend the market authorisation of HES based on the off-label use in certain patient populations (e.g., critically ill or severe sepsis/septic shock patients). Although this did not directly affect the use of HES in the present study in abdominal surgery patients, where patient selection was controlled and in line with the SmPCs, the risk/benefit assessment of the study protocol and the ICF had to be adapted. Recruitment re-started in the respective countries after the approval of the updated protocol and ICF.
    -

    Limitations and caveats

    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported

    Online references

    http://www.ncbi.nlm.nih.gov/pubmed/35193648
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