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    Clinical Trial Results:
    A prospective, open, randomized, academic phase II, two-arm trial evaluating the effect of fibrin-coated collagen (TachoSil®) on postoperative pancreatic leakage and fistula formation from the pancreato-enteric anastomosis in patients undergoing partial pancreaticoduodenectomy

    Summary
    EudraCT number
    		 2013-000639-29
    Trial protocol
    		 AT  
    Global end of trial date
    20 Feb 2017

    Results information
    Results version number
    		 v1(current)
    This version publication date
    26 Aug 2021
    First version publication date
    26 Aug 2021
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    ABCSG_P00
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 -
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    ABCSG (Austrian Breast & Colorectal Cancer Study Group)
    Sponsor organisation address
    Nußdorfer Platz 8/12, Vienna, Austria, 1190
    Public contact
    Hannes Fohler (Trial Office Director), ABCSG (Austrian Breast & Colorectal Cancer Study Group), +43 14089230, info@abcsg.at
    Scientific contact
    Prof. Martin Schindl, ABCSG (Austrian Breast & Colorectal Cancer Study Group), +43 14089230, info@abcsg.at
    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
    22 Mar 2015
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    22 Mar 2015
    Global end of trial reached?
    Yes
    Global end of trial date
    20 Feb 2017
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To demonstrate that fibrin-coated collagen patch (TachoSil) significantly decreases postoperative pancreatic leakage and prevents pancreatic fistula formation in patients undergoing partial pancreatico-duodenectomy with pancreato-enteric anastomosis.
    Protection of trial subjects
    A Data Monitoring Committee (DMC) was established to obtain patient safety. The responsibility of the DMC was to evaluate deviations of medical relevance and safety issues. The DMC decided whether or not the patient should continue the study treatment due to safety issues. Important protocol deviations (IPDs) include all deviations endangering the basal medical concept of the study jeopardizing the safety of the patient. Other protocol deviations (PDs) include all other protocol deviations.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    05 Sep 2013
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Austria: 142
    Worldwide total number of subjects
    142
    EEA total number of subjects
    142
    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)
    55
    From 65 to 84 years
    86
    85 years and over
    1

    Subject disposition

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    Recruitment
    Recruitment details
    		 The study consisted of a planned recruitment phase of 36 months, the actual recruitment was completed in a shorter time frame (Sep 2013 - Feb 2015).

    Pre-assignment
    Screening details
    		 Eligibility had to be assessed max 14 days prior to surgery.

    Pre-assignment period milestones
    Number of subjects started
    		 142
    Number of subjects completed
    		 142

    Period 1
    Period 1 title
    overall trial (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Tachosil
    Arm description
    		 TachoSil® 9.5 cm x 4.8 cm (Non Investigational Medicinal Product, NIMP); Arm A (treatment arm): pancreato-jejunostomy was sealed with two patches of Tachosil® that were placed onto the anterior and posterior aspect of the anastomosis according to the manufacturer’s user guide thereby wrapping it up entirely with a 2 cm rim on both the jejunal wall and the pancreatic tissue, respectively.
    Arm type
    		 NIMP intra-operative treatment

    Investigational medicinal product name
    TachoSil
    Investigational medicinal product code
    B02BC30
    Other name
    Pharmaceutical forms
    Medicated sponge
    Routes of administration
    Local use
    Dosage and administration details
    2 patches (9,5cm x 4,8cm) during the surgery

    Arm title
    		 No Tachosil
    Arm description
    		 Arm B (control arm): pancreatico-jejunostomy was left without any sealant.
    Arm type
    		 No intervention

    Investigational medicinal product name
    No investigational medicinal product assigned in this arm
    Number of subjects in period 1
    		Tachosil No Tachosil
    Started
    71
    71
    Completed
    64
    58
    Not completed
    7
    13
         Adverse event, serious fatal
    1
    4
         Consent withdrawn by subject
    1
    -
         Lost to follow-up
    5
    9

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Tachosil
    Reporting group description
    		 TachoSil® 9.5 cm x 4.8 cm (Non Investigational Medicinal Product, NIMP); Arm A (treatment arm): pancreato-jejunostomy was sealed with two patches of Tachosil® that were placed onto the anterior and posterior aspect of the anastomosis according to the manufacturer’s user guide thereby wrapping it up entirely with a 2 cm rim on both the jejunal wall and the pancreatic tissue, respectively.

    Reporting group title
    No Tachosil
    Reporting group description
    		 Arm B (control arm): pancreatico-jejunostomy was left without any sealant.

    Reporting group values
    		 Tachosil No Tachosil Total
    Number of subjects
    		 71 71 142
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0
        Newborns (0-27 days)
    		 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0
        Children (2-11 years)
    		 0 0 0
        Adolescents (12-17 years)
    		 0 0 0
        Adults (18-64 years)
    		 29 26 55
        From 65-84 years
    		 42 44 86
        85 years and over
    		 0 1 1
    Age continuous
    Units: years
        median (full range (min-max))
    		 66 (48 to 83) 68 (39 to 86) -
    Gender categorical
    Units: Subjects
        Female
    		 37 38 75
        Male
    		 34 33 67
    Body Mass Index (BMI)
    in kg/m²
    Units: Subjects
        <30
    		 57 60 117
        >=30
    		 14 8 22
        Missing
    		 0 3 3
    Neoadjuvant therapy
    Units: Subjects
        Yes
    		 3 3 6
        No
    		 68 68 136
    Pancreatic duct size
    in mm
    Units: Subjects
        <=4
    		 50 47 97
        >4
    		 21 24 45
    Pancreatic gland texture
    Units: Subjects
        Soft
    		 42 35 77
        Normal-firm
    		 29 34 63
        Missing
    		 0 2 2

    End points

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    End points reporting groups
    Reporting group title
    Tachosil
    Reporting group description
    		 TachoSil® 9.5 cm x 4.8 cm (Non Investigational Medicinal Product, NIMP); Arm A (treatment arm): pancreato-jejunostomy was sealed with two patches of Tachosil® that were placed onto the anterior and posterior aspect of the anastomosis according to the manufacturer’s user guide thereby wrapping it up entirely with a 2 cm rim on both the jejunal wall and the pancreatic tissue, respectively.

    Reporting group title
    No Tachosil
    Reporting group description
    		 Arm B (control arm): pancreatico-jejunostomy was left without any sealant.

    Subject analysis set title
    ITT
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    The primary analysis was based upon the ITT population, which consisted of all randomized patients with signed informed consent. Every patient was analyzed according to the randomized treatment group. Secondary endpoint analyses were based on all randomized patients with one exception: for the analysis of pancreatic fistula formation grading patients who underwent other types of surgery than PDPJ were not considered.

    Primary: Leakage/Fistula

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    End point title
    		 Leakage/Fistula
    End point description
    Primary endpoint of the study was the evidence of pancreatic leakage or fistula according to International Study Group on Pancreatic Fistula Definition (ISGPF) definition. The definition of pancreatic fistula by the International Study Group on Pancreatic Fistula Definition (ISGPF), defining a pancreatic leak / fistula as fluid drainage rich in amylase > 3x serum amylase concentration on or after the 3rd postoperative day by an operative or interventional placed drainage was used to determine pancreatic leakage on a daily basis. Drains were removed, if the concentration of enzymes in the drain fluid was less 3x serum concentration for 2 consecutive days. If the enzyme concentration was above this limit, by definition a pancreatic leak / fistula was present and drains had to stay in place either until enzyme concentration was below this limit or the drain volume was less than 50 ml/day. If this was the case, drains were retracted stepwise until complete removal.
    End point type
    Primary
    End point timeframe
    During post surgery assessment starting from the third postoperative day.
    End point values
    		 Tachosil No Tachosil
    Number of subjects analysed
    71
    71
    Units: Subjects
        fistula
    45
    40
        no fistula
    26
    31
    Statistical analysis title
    		 Primary endpoint analysis
    Statistical analysis description
    The proportions of patients with leakage/fistula between the experimental and the control group were compared using a Chi-squared test or Fisher’s exact test depending on the underlying distribution. The effect of TachoSil® was considered meaningful if the proportion of patients with leakage/fistula was significantly lower in the experimental group compared to the control group.
    Comparison groups
    Tachosil v No Tachosil
    Number of subjects included in analysis
    142
    Analysis specification
    Pre-specified
    Analysis type
    		 other [1]
    P-value
    		 = 0.392
    Method
    		 Chi-squared
    Confidence interval
    Notes
    [1] - The null hypothesis (H0) of this study states that the proportion of patients with pancreatic leakage and fistula rates are the same between treatment group and control group. The alternative hypothesis (H1) states that the proportion of patients with pancreatic leakage and fistula rates are different between treatment group and control group.

    Secondary: Leakage/Fistula - grading

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    End point title
    		 Leakage/Fistula - grading
    End point description
    One secondary endpoint was the evidence of any conditions / complications in association with pancreatic fistula formation measured according to the clinical severity grading classification of pancreatic fistula (Grades A – C). Patients who underwent other types of surgery than pancreato-duodenectomy with pancreato-jejunostomy (PDPJ) were not considered for the pancreatic fistula grading endpoint.
    End point type
    Secondary
    End point timeframe
    During post surgery assessment starting from the third postoperative day.
    End point values
    		 Tachosil No Tachosil
    Number of subjects analysed
    70
    69
    Units: Subjects
        No fistula
    26
    31
        Grade A fistula
    28
    28
        Grade B fistula
    13
    7
        Grade C fistula
    3
    3
    Statistical analysis title
    		 Secondary endpoint analysis - grading
    Statistical analysis description
    For the pancreatic fistula formation grading (worst grading over all visits), absolute and relative numbers of patients per grade or class were summarized descriptively and compared between the two groups using Fisher tests.
    Comparison groups
    Tachosil v No Tachosil
    Number of subjects included in analysis
    139
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.5339
    Method
    		 Fisher exact
    Confidence interval

    Secondary: Clavien-Dindo classification

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    End point title
    		 Clavien-Dindo classification
    End point description
    One secondary endpoint was surgery associated and any other perioperative complications according to the classification described by Clavien and Dindo. Clavien–Dindo grade missing for one patient.
    End point type
    Secondary
    End point timeframe
    During post surgery assessment starting from the third postoperative day.
    End point values
    		 Tachosil No Tachosil
    Number of subjects analysed
    71
    70
    Units: Subjects
        no complications
    17
    20
        Grade I
    13
    12
        Grade II
    21
    19
        Grade III
    18
    14
        Grade IV
    1
    2
        Grade V
    1
    3
    Statistical analysis title
    		 Secondary endpoint analysis - Clavien-Dindo
    Statistical analysis description
    For the classification according to Clavien and Dindo (worst classification over all visits), absolute and relative numbers of patients per grade or class were summarized descriptively and compared between the two groups using Fisher tests.
    Comparison groups
    Tachosil v No Tachosil
    Number of subjects included in analysis
    141
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.8394
    Method
    		 Fisher exact
    Confidence interval

    Secondary: Drainage fluid

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    End point title
    		 Drainage fluid
    End point description
    The daily amount of fluid from the drainage at days 3, 5, 7, 9 and 11 (if applicable) was compared between groups. Daily amount of fluid from the drainage was calculated as the sum of the reported volume of both sides (left and right). These derived volumes per patient were aggregated for the predefined time points using the mean (or median, if applicable). Summary statistics were derived and descriptively compared between groups for the predefined time points.
    End point type
    Secondary
    End point timeframe
    During post surgery assessment starting from the third postoperative day.
    End point values
    		 Tachosil No Tachosil
    Number of subjects analysed
    68
    67
    Units: ml
        median (full range (min-max))
    318.5 (67.5 to 2090)
    424 (86.7 to 4980)
    Attachments
    		 Untitled (Filename: 170222_ABCSG P00_1_drainage volume plot.pdf)
    Statistical analysis title
    		 Secondary endpoint analysis - drainage fluid
    Statistical analysis description
    The median per patient over all predefined time points for daily amount of fluid from the drainage, was also derived and compared between groups by Wilcoxon test.
    Comparison groups
    Tachosil v No Tachosil
    Number of subjects included in analysis
    135
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.156
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval

    Secondary: Ex-drain site fluid

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    End point title
    		 Ex-drain site fluid
    End point description
    The daily amount of fluid from the ex drain site at days 3, 5, 7, 9 and 11 (if applicable) was compared between groups. The daily amount of fluid from the ex drain site was calculated as the sum of the reported volume of both sides (left and right). These derived volumes per patient were aggregated for the predefined time points using the mean (or median, if applicable). Summary statistics were derived and descriptively compared between groups for the predefined time points. Due to a huge amount of missing data (for some time points no data were available at all), only the time point with most available data (Day 9) is shown.
    End point type
    Secondary
    End point timeframe
    During post surgery assessment starting from the third postoperative day.
    End point values
    		 Tachosil No Tachosil
    Number of subjects analysed
    19
    15
    Units: ml
        median (full range (min-max))
    100 (0 to 660)
    100 (1 to 1000)
    Attachments
    		 Untitled (Filename: 170222_ABCSG P00_2_ex drainage volume plot.pdf)
    No statistical analyses for this end point

    Secondary: Total drain amylase

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    End point title
    		 Total drain amylase
    End point description
    Daily content of drain amylase at days 3, 5, 7, 9 and 11 (if applicable) was compared between groups. For the content of amylase the maximum of both drainage sides was used at the patient level. Summary statistics were derived and descriptively compared between groups for the predefined time points.
    End point type
    Secondary
    End point timeframe
    During post surgery assessment starting from the third postoperative day.
    End point values
    		 Tachosil No Tachosil
    Number of subjects analysed
    53
    48
    Units: U/L
        median (full range (min-max))
    110.5 (5.3 to 24207)
    90.5 (4 to 20537)
    Attachments
    		 Untitled (Filename: 170222_ABCSG P00_3_total amylase plot.pdf)
    Statistical analysis title
    		 Secondary endpoint analysis - total drain amylase
    Statistical analysis description
    The median per patient over all predefined time points for content of amylase was also derived and compared between groups with the Wilcoxon test.
    Comparison groups
    Tachosil v No Tachosil
    Number of subjects included in analysis
    101
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.494
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval

    Secondary: Pancreatic specific drain amylase

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    End point title
    		 Pancreatic specific drain amylase
    End point description
    Daily content of drain amylase at days 3, 5, 7, 9 and 11 (if applicable) was compared between groups. For the content of amylase the maximum of both drainage sides was used at the patient level. Summary statistics were derived and descriptively compared between groups for the predefined time points.
    End point type
    Secondary
    End point timeframe
    During post surgery assessment starting from the third postoperative day.
    End point values
    		 Tachosil No Tachosil
    Number of subjects analysed
    35
    37
    Units: U/L
        median (full range (min-max))
    34 (1 to 5422.5)
    38.5 (1 to 49919)
    Attachments
    		 Untitled (Filename: 170222_ABCSG P00_4_pancreatic amylase plot.pdf)
    Statistical analysis title
    		 Secondary endpoint analysis - pancreatic amylase
    Statistical analysis description
    The median per patient over all predefined time points for content of amylase was also derived and compared between groups with the Wilcoxon test.
    Comparison groups
    No Tachosil v Tachosil
    Number of subjects included in analysis
    72
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.632
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval

    Secondary: Drain lipase

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    End point title
    		 Drain lipase
    End point description
    Daily content of drain lipase at days 3, 5, 7, 9 and 11 (if applicable) was compared between groups. For the content of lipase the maximum of both drainage sides was used at the patient level. Summary statistics were derived and descriptively compared between groups for the predefined time points.
    End point type
    Secondary
    End point timeframe
    During post surgery assessment starting from the third postoperative day.
    End point values
    		 Tachosil No Tachosil
    Number of subjects analysed
    67
    65
    Units: U/L
        median (full range (min-max))
    267.3 (3 to 27390)
    213.3 (3.6 to 145310)
    Attachments
    		 Untitled (Filename: 170222_ABCSG P00_5_lipase plot.pdf)
    Statistical analysis title
    		 Secondary endpoint analysis - drain lipase
    Statistical analysis description
    The median per patient over all predefined time points for content of lipase was also derived and compared between groups with the Wilcoxon test.
    Comparison groups
    Tachosil v No Tachosil
    Number of subjects included in analysis
    132
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.613
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval

    Secondary: Time to drain removal

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    End point title
    		 Time to drain removal
    End point description
    The time (days) until drain removal was compared between groups.
    End point type
    Secondary
    End point timeframe
    Time until drain removal.
    End point values
    		 Tachosil No Tachosil
    Number of subjects analysed
    71
    71
    Units: days
        arithmetic mean (standard error)
    11.56 ± 1.0
    13.28 ± 1.29
    Statistical analysis title
    		 Secondary endpoint analysis - drainage removal
    Statistical analysis description
    The time (days) until drain removal was compared between groups by log-rank test.
    Comparison groups
    Tachosil v No Tachosil
    Number of subjects included in analysis
    142
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.6131
    Method
    		 Logrank
    Confidence interval

    Secondary: Time to fistula closure

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    End point title
    		 Time to fistula closure
    End point description
    The time (days) until fistula closure was compared between groups.
    End point type
    Secondary
    End point timeframe
    Time until fistula closure.
    End point values
    		 Tachosil No Tachosil
    Number of subjects analysed
    44
    38
    Units: days
        arithmetic mean (standard error)
    17.62 ± 2.23
    16.47 ± 2.14
    Statistical analysis title
    		 Secondary endpoint analysis - fistula closure
    Statistical analysis description
    The time (days) until fistula closure was compared between groups by log-rank test.
    Comparison groups
    Tachosil v No Tachosil
    Number of subjects included in analysis
    82
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.7397
    Method
    		 Logrank
    Confidence interval

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    from ICF signature until 42 days after surgery
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    16.0
    Reporting groups
    Reporting group title
    No Tachosil
    Reporting group description
    		 -

    Reporting group title
    Tachosil
    Reporting group description
    		 -

    Serious adverse events
    		 No Tachosil Tachosil
    Total subjects affected by serious adverse events
         subjects affected / exposed
    21 / 71 (29.58%)
    27 / 71 (38.03%)
         number of deaths (all causes)
    4
    1
         number of deaths resulting from adverse events
    4
    1
    Injury, poisoning and procedural complications
    Abdominal wound dehiscence
    Additional description: Abdominal wound dehiscence
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 71 (1.41%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anastomotic fistula
    Additional description: Anastomotic fistula
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anastomotic stenosis
    Additional description: Anastomotic stenosis
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Failure to anastomose
    Additional description: Failure to anastomose
         subjects affected / exposed
    1 / 71 (1.41%)
    1 / 71 (1.41%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatic leak
    Additional description: Pancreatic leak
         subjects affected / exposed
    3 / 71 (4.23%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 12
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Post procedural bile leak
    Additional description: Post procedural bile leak
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Post procedural haemorrhage
    Additional description: Post procedural haemorrhage
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Seroma
    Additional description: Seroma
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 71 (1.41%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular disorders
    Haematoma
    Additional description: Haematoma
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 71 (1.41%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 9
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemorrhagic infarction
    Additional description: Haemorrhagic infarction
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Lymphatic fistula
    Additional description: Lymphatic fistula
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 71 (1.41%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Myocardial infarction
    Additional description: Myocardial infarction
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Nervous system disorders
    Parkinson's disease
    Additional description: Parkinson's disease
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 71 (1.41%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Status epilepticus
    Additional description: Status epilepticus
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    General physical health deterioration
    Additional description: General physical health deterioration
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Multi-organ failure
    Additional description: Multi-organ failure
         subjects affected / exposed
    2 / 71 (2.82%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    Pyrexia
    Additional description: Pyrexia
         subjects affected / exposed
    1 / 71 (1.41%)
    1 / 71 (1.41%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal pain
    Additional description: Abdominal pain
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastric ulcer
    Additional description: Gastric ulcer
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 71 (1.41%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Coeliac artery compression syndrome
    Additional description: Coeliac artery compression syndrome
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 71 (1.41%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intestinal obstruction
    Additional description: Intestinal obstruction
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intestinal perforation
    Additional description: Intestinal perforation
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intra-abdominal haemorrhage
    Additional description: Intra-abdominal haemorrhage
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nausea
    Additional description: Nausea
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 71 (1.41%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatic fistula
    Additional description: Pancreatic fistula
         subjects affected / exposed
    2 / 71 (2.82%)
    5 / 71 (7.04%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 16
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Upper gastrointestinal haemorrhage
    Additional description: Upper gastrointestinal haemorrhage
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 71 (1.41%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vomiting
    Additional description: Vomiting
         subjects affected / exposed
    1 / 71 (1.41%)
    1 / 71 (1.41%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Biliary fistula
    Additional description: Biliary fistula
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholangitis
    Additional description: Cholangitis
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatic infarction
    Additional description: Hepatic infarction
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Acute respiratory distress syndrome
    Additional description: Acute respiratory distress syndrome
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary embolism
    Additional description: Pulmonary embolism
         subjects affected / exposed
    2 / 71 (2.82%)
    1 / 71 (1.41%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Respiratory failure
    Additional description: Respiratory failure
         subjects affected / exposed
    1 / 71 (1.41%)
    1 / 71 (1.41%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Infections and infestations
    Abdominal abscess
    Additional description: Abdominal abscess
         subjects affected / exposed
    0 / 71 (0.00%)
    4 / 71 (5.63%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 13
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abscess
    Additional description: Abscess
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 71 (1.41%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fungal sepsis
    Additional description: Fungal sepsis
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 71 (1.41%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infection
    Additional description: Infection
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Liver abscess
    Additional description: Liver abscess
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sepsis
    Additional description: Sepsis
         subjects affected / exposed
    0 / 71 (0.00%)
    2 / 71 (2.82%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Urosepsis
    Additional description: Urosepsis
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 71 (1.41%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Decreased appetite
    Additional description: Decreased appetite
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 71 (1.41%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dehydration
    Additional description: Dehydration
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fluid retention
    Additional description: Fluid retention
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 71 (1.41%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Malnutrition
    Additional description: Malnutrition
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 71 (1.41%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    		 No Tachosil Tachosil
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    51 / 71 (71.83%)
    52 / 71 (73.24%)
    Vascular disorders
    Blood pressure fluctuation
    Additional description: Blood pressure fluctuation
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 71 (1.41%)
         occurrences all number
    0
    1
    Haematoma
    Additional description: Haematoma
         subjects affected / exposed
    2 / 71 (2.82%)
    0 / 71 (0.00%)
         occurrences all number
    3
    0
    Hot flush
    Additional description: Hot flush
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 71 (1.41%)
         occurrences all number
    0
    1
    Hypertension
    Additional description: Hypertension
         subjects affected / exposed
    4 / 71 (5.63%)
    4 / 71 (5.63%)
         occurrences all number
    5
    6
    Hypotension
    Additional description: Hypotension
         subjects affected / exposed
    1 / 71 (1.41%)
    1 / 71 (1.41%)
         occurrences all number
    2
    2
    Lymphatic fistula
    Additional description: Lymphatic fistula
         subjects affected / exposed
    2 / 71 (2.82%)
    1 / 71 (1.41%)
         occurrences all number
    2
    1
    Phlebitis
    Additional description: Phlebitis
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 71 (0.00%)
         occurrences all number
    1
    0
    Shock haemorrhagic
    Additional description: Shock haemorrhagic
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 71 (0.00%)
         occurrences all number
    1
    0
    Pregnancy, puerperium and perinatal conditions
    Perineal haematoma
    Additional description: Perineal haematoma
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 71 (0.00%)
         occurrences all number
    1
    0
    General disorders and administration site conditions
    Catheter site haematoma
    Additional description: Catheter site haematoma
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 71 (0.00%)
         occurrences all number
    1
    0
    Chills
    Additional description: Chills
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 71 (0.00%)
         occurrences all number
    3
    0
    Fatigue
    Additional description: Fatigue
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 71 (1.41%)
         occurrences all number
    0
    1
    General physical health deterioration
    Additional description: General physical health deterioration
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 71 (1.41%)
         occurrences all number
    0
    3
    Generalised oedema
    Additional description: Generalised oedema
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 71 (1.41%)
         occurrences all number
    0
    1
    Multi-organ failure
    Additional description: Multi-organ failure
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 71 (0.00%)
         occurrences all number
    1
    0
    Impaired healing
    Additional description: Impaired healing
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 71 (1.41%)
         occurrences all number
    0
    2
    Oedema peripheral
    Additional description: Oedema peripheral
         subjects affected / exposed
    0 / 71 (0.00%)
    3 / 71 (4.23%)
         occurrences all number
    0
    4
    Oedema
    Additional description: Oedema
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 71 (0.00%)
         occurrences all number
    2
    0
    Pain
    Additional description: Pain
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 71 (0.00%)
         occurrences all number
    1
    0
    Pyrexia
    Additional description: Pyrexia
         subjects affected / exposed
    6 / 71 (8.45%)
    4 / 71 (5.63%)
         occurrences all number
    8
    10
    Systemic inflammatory response syndrome
    Additional description: Systemic inflammatory response syndrome
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 71 (1.41%)
         occurrences all number
    0
    1
    Immune system disorders
    Hypersensitivity
    Additional description: Hypersensitivity
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 71 (1.41%)
         occurrences all number
    0
    1
    Respiratory, thoracic and mediastinal disorders
    Oropharyngeal pain
    Additional description: Oropharyngeal pain
         subjects affected / exposed
    1 / 71 (1.41%)
    2 / 71 (2.82%)
         occurrences all number
    2
    4
    Cough
    Additional description: Cough
         subjects affected / exposed
    1 / 71 (1.41%)
    3 / 71 (4.23%)
         occurrences all number
    2
    4
    Pleural effusion
    Additional description: Pleural effusion
         subjects affected / exposed
    4 / 71 (5.63%)
    1 / 71 (1.41%)
         occurrences all number
    9
    4
    Pulmonary embolism
    Additional description: Pulmonary embolism
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 71 (1.41%)
         occurrences all number
    0
    6
    Psychiatric disorders
    Delirium
    Additional description: Delirium
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 71 (1.41%)
         occurrences all number
    0
    1
    Adjustment disorder with depressed mood
    Additional description: Adjustment disorder with depressed mood
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 71 (0.00%)
         occurrences all number
    2
    0
    Depressed mood
    Additional description: Depressed mood
         subjects affected / exposed
    0 / 71 (0.00%)
    3 / 71 (4.23%)
         occurrences all number
    0
    4
    Insomnia
    Additional description: Insomnia
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 71 (0.00%)
         occurrences all number
    1
    0
    Depression
    Additional description: Depression
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 71 (1.41%)
         occurrences all number
    0
    1
    Korsakoff's syndrome
    Additional description: Korsakoff's syndrome
         subjects affected / exposed
    1 / 71 (1.41%)
    1 / 71 (1.41%)
         occurrences all number
    2
    2
    Panic attack
    Additional description: Panic attack
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 71 (1.41%)
         occurrences all number
    0
    1
    Restlessness
    Additional description: Restlessness
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 71 (1.41%)
         occurrences all number
    0
    2
    Sleep disorder
    Additional description: Sleep disorder
         subjects affected / exposed
    1 / 71 (1.41%)
    1 / 71 (1.41%)
         occurrences all number
    2
    1
    Tobacco withdrawal symptoms
    Additional description: Tobacco withdrawal symptoms
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 71 (0.00%)
         occurrences all number
    1
    0
    Investigations
    Enterococcus test positive
    Additional description: Enterococcus test positive
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 71 (1.41%)
         occurrences all number
    0
    1
    Bile output
    Additional description: Bile output
         subjects affected / exposed
    2 / 71 (2.82%)
    0 / 71 (0.00%)
         occurrences all number
    2
    0
    Haemoglobin decreased
    Additional description: Haemoglobin decreased
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 71 (1.41%)
         occurrences all number
    0
    1
    Inflammatory marker increased
    Additional description: Inflammatory marker increased
         subjects affected / exposed
    5 / 71 (7.04%)
    2 / 71 (2.82%)
         occurrences all number
    7
    2
    Lipase increased
    Additional description: Lipase increased
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 71 (1.41%)
         occurrences all number
    0
    1
    Weight decreased
    Additional description: Weight decreased
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 71 (0.00%)
         occurrences all number
    2
    0
    Injury, poisoning and procedural complications
    Abdominal wound dehiscence
    Additional description: Abdominal wound dehiscence
         subjects affected / exposed
    1 / 71 (1.41%)
    1 / 71 (1.41%)
         occurrences all number
    4
    2
    Anastomotic complication
    Additional description: Anastomotic complication
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 71 (1.41%)
         occurrences all number
    0
    2
    Anastomotic haemorrhage
    Additional description: Anastomotic haemorrhage
         subjects affected / exposed
    2 / 71 (2.82%)
    0 / 71 (0.00%)
         occurrences all number
    5
    0
    Excoriation
    Additional description: Excoriation
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 71 (1.41%)
         occurrences all number
    0
    2
    Hepatic haematoma
    Additional description: Hepatic haematoma
         subjects affected / exposed
    1 / 71 (1.41%)
    1 / 71 (1.41%)
         occurrences all number
    1
    1
    Incisional hernia
    Additional description: Incisional hernia
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 71 (0.00%)
         occurrences all number
    1
    0
    Laceration
    Additional description: Laceration
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 71 (0.00%)
         occurrences all number
    1
    0
    Post procedural haematoma
    Additional description: Post procedural haematoma
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 71 (0.00%)
         occurrences all number
    1
    0
    Postoperative hernia
    Additional description: Postoperative hernia
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 71 (1.41%)
         occurrences all number
    0
    3
    Postoperative fever
    Additional description: Postoperative fever
         subjects affected / exposed
    1 / 71 (1.41%)
    2 / 71 (2.82%)
         occurrences all number
    1
    2
    Seroma
    Additional description: Seroma
         subjects affected / exposed
    1 / 71 (1.41%)
    1 / 71 (1.41%)
         occurrences all number
    2
    1
    Procedural pain
    Additional description: Procedural pain
         subjects affected / exposed
    1 / 71 (1.41%)
    3 / 71 (4.23%)
         occurrences all number
    2
    6
    Subcutaneous haematoma
    Additional description: Subcutaneous haematoma
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 71 (1.41%)
         occurrences all number
    0
    1
    Wound dehiscence
    Additional description: Wound dehiscence
         subjects affected / exposed
    0 / 71 (0.00%)
    3 / 71 (4.23%)
         occurrences all number
    0
    3
    Thermal burn
    Additional description: Thermal burn
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 71 (1.41%)
         occurrences all number
    0
    1
    Wound secretion
    Additional description: Wound secretion
         subjects affected / exposed
    1 / 71 (1.41%)
    2 / 71 (2.82%)
         occurrences all number
    2
    2
    Cardiac disorders
    Angina pectoris
    Additional description: Angina pectoris
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 71 (1.41%)
         occurrences all number
    0
    3
    Atrial fibrillation
    Additional description: Atrial fibrillation
         subjects affected / exposed
    2 / 71 (2.82%)
    2 / 71 (2.82%)
         occurrences all number
    4
    2
    Cyanosis
    Additional description: Cyanosis
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 71 (0.00%)
         occurrences all number
    1
    0
    Long QT syndrome
    Additional description: Long QT syndrome
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 71 (0.00%)
         occurrences all number
    1
    0
    Tachycardia
    Additional description: Tachycardia
         subjects affected / exposed
    3 / 71 (4.23%)
    2 / 71 (2.82%)
         occurrences all number
    6
    4
    Nervous system disorders
    Brain injury
    Additional description: Brain injury
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 71 (0.00%)
         occurrences all number
    1
    0
    Dizziness
    Additional description: Dizziness
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 71 (0.00%)
         occurrences all number
    1
    0
    Cerebral atrophy
    Additional description: Cerebral atrophy
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 71 (0.00%)
         occurrences all number
    2
    0
    Dysaesthesia
    Additional description: Dysaesthesia
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 71 (0.00%)
         occurrences all number
    1
    0
    Headache
    Additional description: Headache
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 71 (0.00%)
         occurrences all number
    1
    0
    Hypoaesthesia
    Additional description: Hypoaesthesia
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 71 (0.00%)
         occurrences all number
    1
    0
    Intercostal neuralgia
    Additional description: Intercostal neuralgia
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 71 (1.41%)
         occurrences all number
    0
    1
    Leukoencephalopathy
    Additional description: Leukoencephalopathy
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 71 (0.00%)
         occurrences all number
    2
    0
    Paraesthesia
    Additional description: Paraesthesia
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 71 (1.41%)
         occurrences all number
    0
    1
    Paralysis
    Additional description: Paralysis
         subjects affected / exposed
    0 / 71 (0.00%)
    3 / 71 (4.23%)
         occurrences all number
    0
    4
    Parkinson's disease
    Additional description: Parkinson's disease
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 71 (0.00%)
         occurrences all number
    2
    0
    Presyncope
    Additional description: Presyncope
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 71 (0.00%)
         occurrences all number
    1
    0
    Syncope
    Additional description: Syncope
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 71 (0.00%)
         occurrences all number
    7
    0
    Blood and lymphatic system disorders
    Anaemia
    Additional description: Anaemia
         subjects affected / exposed
    7 / 71 (9.86%)
    6 / 71 (8.45%)
         occurrences all number
    8
    13
    Anaemia folate deficiency
    Additional description: Anaemia folate deficiency
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 71 (1.41%)
         occurrences all number
    0
    1
    Coagulopathy
    Additional description: Coagulopathy
         subjects affected / exposed
    2 / 71 (2.82%)
    0 / 71 (0.00%)
         occurrences all number
    3
    0
    Leukocytosis
    Additional description: Leukocytosis
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 71 (0.00%)
         occurrences all number
    1
    0
    Leukopenia
    Additional description: Leukopenia
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 71 (0.00%)
         occurrences all number
    1
    0
    Normochromic normocytic anaemia
    Additional description: Normochromic normocytic anaemia
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 71 (0.00%)
         occurrences all number
    1
    0
    Splenic infarction
    Additional description: Splenic infarction
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 71 (1.41%)
         occurrences all number
    0
    3
    Ear and labyrinth disorders
    Vertigo
    Additional description: Vertigo
         subjects affected / exposed
    2 / 71 (2.82%)
    0 / 71 (0.00%)
         occurrences all number
    4
    0
    Gastrointestinal disorders
    Abdominal distension
    Additional description: Abdominal distension
         subjects affected / exposed
    1 / 71 (1.41%)
    2 / 71 (2.82%)
         occurrences all number
    1
    5
    Abdominal pain
    Additional description: Abdominal pain
         subjects affected / exposed
    0 / 71 (0.00%)
    4 / 71 (5.63%)
         occurrences all number
    0
    6
    Abnormal faeces
    Additional description: Abnormal faeces
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 71 (0.00%)
         occurrences all number
    3
    0
    Ascites
    Additional description: Ascites
         subjects affected / exposed
    0 / 71 (0.00%)
    3 / 71 (4.23%)
         occurrences all number
    0
    8
    Colitis
    Additional description: Colitis
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 71 (1.41%)
         occurrences all number
    0
    2
    Diarrhoea
    Additional description: Diarrhoea
         subjects affected / exposed
    10 / 71 (14.08%)
    6 / 71 (8.45%)
         occurrences all number
    16
    9
    Constipation
    Additional description: Constipation
         subjects affected / exposed
    2 / 71 (2.82%)
    3 / 71 (4.23%)
         occurrences all number
    2
    8
    Diverticulum oesophageal
    Additional description: Diverticulum oesophageal
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 71 (1.41%)
         occurrences all number
    0
    3
    Dysphagia
    Additional description: Dysphagia
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 71 (1.41%)
         occurrences all number
    0
    2
    Dyspepsia
    Additional description: Dyspepsia
         subjects affected / exposed
    1 / 71 (1.41%)
    2 / 71 (2.82%)
         occurrences all number
    2
    2
    Faecal incontinence
    Additional description: Faecal incontinence
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 71 (1.41%)
         occurrences all number
    0
    1
    Flatulence
    Additional description: Flatulence
         subjects affected / exposed
    1 / 71 (1.41%)
    1 / 71 (1.41%)
         occurrences all number
    1
    2
    Faecaloma
    Additional description: Faecaloma
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 71 (1.41%)
         occurrences all number
    0
    1
    Gastric haemorrhage
    Additional description: Gastric haemorrhage
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 71 (0.00%)
         occurrences all number
    3
    0
    Gastric ulcer
    Additional description: Gastric ulcer
         subjects affected / exposed
    3 / 71 (4.23%)
    1 / 71 (1.41%)
         occurrences all number
    5
    1
    Gastrooesophageal reflux disease
    Additional description: Gastrooesophageal reflux disease
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 71 (1.41%)
         occurrences all number
    0
    3
    Haemorrhoidal haemorrhage
    Additional description: Haemorrhoidal haemorrhage
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 71 (0.00%)
         occurrences all number
    2
    0
    Ileus
    Additional description: Ileus
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 71 (0.00%)
         occurrences all number
    1
    0
    Impaired gastric emptying
    Additional description: Impaired gastric emptying
         subjects affected / exposed
    1 / 71 (1.41%)
    5 / 71 (7.04%)
         occurrences all number
    2
    7
    Inguinal hernia
    Additional description: Inguinal hernia
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 71 (0.00%)
         occurrences all number
    1
    0
    Nausea
    Additional description: Nausea
         subjects affected / exposed
    5 / 71 (7.04%)
    3 / 71 (4.23%)
         occurrences all number
    8
    4
    Melaena
    Additional description: Melaena
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 71 (0.00%)
         occurrences all number
    4
    0
    Oesophagitis
    Additional description: Oesophagitis
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 71 (1.41%)
         occurrences all number
    0
    4
    Oral discomfort
    Additional description: Oral discomfort
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 71 (1.41%)
         occurrences all number
    0
    1
    Pancreatic necrosis
    Additional description: Pancreatic necrosis
         subjects affected / exposed
    0 / 71 (0.00%)
    2 / 71 (2.82%)
         occurrences all number
    0
    5
    Pancreatitis
    Additional description: Pancreatitis
         subjects affected / exposed
    1 / 71 (1.41%)
    1 / 71 (1.41%)
         occurrences all number
    1
    1
    Subileus
    Additional description: Subileus
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 71 (1.41%)
         occurrences all number
    0
    3
    Vomiting
    Additional description: Vomiting
         subjects affected / exposed
    4 / 71 (5.63%)
    6 / 71 (8.45%)
         occurrences all number
    9
    9
    Hepatobiliary disorders
    Cholestasis
    Additional description: Cholestasis
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 71 (0.00%)
         occurrences all number
    2
    0
    Biliary fistula
    Additional description: Biliary fistula
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 71 (0.00%)
         occurrences all number
    2
    0
    Hepatic fibrosis
    Additional description: Hepatic fibrosis
         subjects affected / exposed
    0 / 71 (0.00%)
    2 / 71 (2.82%)
         occurrences all number
    0
    2
    Hepatic necrosis
    Additional description: Hepatic necrosis
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 71 (0.00%)
         occurrences all number
    1
    0
    Hepatic lesion
    Additional description: Hepatic lesion
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 71 (0.00%)
         occurrences all number
    8
    0
    Hepatic steatosis
    Additional description: Hepatic steatosis
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 71 (1.41%)
         occurrences all number
    0
    1
    Hepatorenal syndrome
    Additional description: Hepatorenal syndrome
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 71 (1.41%)
         occurrences all number
    0
    2
    Skin and subcutaneous tissue disorders
    Alopecia areata
    Additional description: Alopecia areata
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 71 (1.41%)
         occurrences all number
    0
    1
    Blister
    Additional description: Blister
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 71 (1.41%)
         occurrences all number
    0
    2
    Decubitus ulcer
    Additional description: Decubitus ulcer
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 71 (0.00%)
         occurrences all number
    1
    0
    Dermatitis
    Additional description: Dermatitis
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 71 (0.00%)
         occurrences all number
    1
    0
    Dermatitis contact
    Additional description: Dermatitis contact
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 71 (1.41%)
         occurrences all number
    0
    1
    Drug eruption
    Additional description: Drug eruption
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 71 (1.41%)
         occurrences all number
    0
    1
    Eczema
    Additional description: Eczema
         subjects affected / exposed
    1 / 71 (1.41%)
    2 / 71 (2.82%)
         occurrences all number
    1
    3
    Erythema
    Additional description: Erythema
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 71 (1.41%)
         occurrences all number
    0
    1
    Rash
    Additional description: Rash
         subjects affected / exposed
    1 / 71 (1.41%)
    2 / 71 (2.82%)
         occurrences all number
    1
    2
    Intertrigo
    Additional description: Intertrigo
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 71 (1.41%)
         occurrences all number
    0
    2
    Skin erosion
    Additional description: Skin erosion
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 71 (1.41%)
         occurrences all number
    0
    2
    Urticaria
    Additional description: Urticaria
         subjects affected / exposed
    0 / 71 (0.00%)
    2 / 71 (2.82%)
         occurrences all number
    0
    3
    Renal and urinary disorders
    Dysuria
    Additional description: Dysuria
         subjects affected / exposed
    2 / 71 (2.82%)
    0 / 71 (0.00%)
         occurrences all number
    3
    0
    Nephrolithiasis
    Additional description: Nephrolithiasis
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 71 (1.41%)
         occurrences all number
    0
    1
    Leukocyturia
    Additional description: Leukocyturia
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 71 (1.41%)
         occurrences all number
    0
    1
    Pollakiuria
    Additional description: Pollakiuria
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 71 (0.00%)
         occurrences all number
    2
    0
    Endocrine disorders
    Goitre
    Additional description: Goitre
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 71 (0.00%)
         occurrences all number
    1
    0
    Hyperthyroidism
    Additional description: Hyperthyroidism
         subjects affected / exposed
    0 / 71 (0.00%)
    2 / 71 (2.82%)
         occurrences all number
    0
    2
    Musculoskeletal and connective tissue disorders
    Arthralgia
    Additional description: Arthralgia
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 71 (0.00%)
         occurrences all number
    2
    0
    Musculoskeletal pain
    Additional description: Musculoskeletal pain
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 71 (0.00%)
         occurrences all number
    1
    0
    Back pain
    Additional description: Back pain
         subjects affected / exposed
    1 / 71 (1.41%)
    3 / 71 (4.23%)
         occurrences all number
    1
    4
    Pain in extremity
    Additional description: Pain in extremity
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 71 (1.41%)
         occurrences all number
    0
    1
    Infections and infestations
    Abdominal abscess
    Additional description: Abdominal abscess
         subjects affected / exposed
    1 / 71 (1.41%)
    2 / 71 (2.82%)
         occurrences all number
    5
    4
    Candidiasis
    Additional description: Candidiasis
         subjects affected / exposed
    0 / 71 (0.00%)
    2 / 71 (2.82%)
         occurrences all number
    0
    3
    Clostridium difficile colitis
    Additional description: Clostridium difficile colitis
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 71 (0.00%)
         occurrences all number
    2
    0
    Clostridium difficile infection
    Additional description: Clostridium difficile infection
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 71 (0.00%)
         occurrences all number
    1
    0
    Cystitis
    Additional description: Cystitis
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 71 (0.00%)
         occurrences all number
    1
    0
    Device related infection
    Additional description: Device related infection
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 71 (0.00%)
         occurrences all number
    1
    0
    Douglas' abscess
    Additional description: Douglas' abscess
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 71 (1.41%)
         occurrences all number
    0
    1
    Herpes zoster
    Additional description: Herpes zoster
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 71 (1.41%)
         occurrences all number
    0
    2
    Enterococcal sepsis
    Additional description: Enterococcal sepsis
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 71 (1.41%)
         occurrences all number
    0
    2
    Infection
    Additional description: Infection
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 71 (1.41%)
         occurrences all number
    0
    1
    Paronychia
    Additional description: Paronychia
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 71 (0.00%)
         occurrences all number
    1
    0
    Perihepatic abscess
    Additional description: Perihepatic abscess
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 71 (0.00%)
         occurrences all number
    4
    0
    Peritonitis
    Additional description: Peritonitis
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 71 (1.41%)
         occurrences all number
    0
    2
    Pseudomonas infection
    Additional description: Pseudomonas infection
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 71 (0.00%)
         occurrences all number
    1
    0
    Pyelonephritis
    Additional description: Pyelonephritis
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 71 (0.00%)
         occurrences all number
    1
    0
    Rhinitis
    Additional description: Rhinitis
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 71 (0.00%)
         occurrences all number
    1
    0
    Sepsis
    Additional description: Sepsis
         subjects affected / exposed
    2 / 71 (2.82%)
    1 / 71 (1.41%)
         occurrences all number
    3
    1
    Septic shock
    Additional description: Septic shock
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 71 (0.00%)
         occurrences all number
    1
    0
    Staphylococcal infection
    Additional description: Staphylococcal infection
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 71 (0.00%)
         occurrences all number
    1
    0
    Staphylococcal sepsis
    Additional description: Staphylococcal sepsis
         subjects affected / exposed
    0 / 71 (0.00%)
    2 / 71 (2.82%)
         occurrences all number
    0
    2
    Streptococcal bacteraemia
    Additional description: Streptococcal bacteraemia
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 71 (0.00%)
         occurrences all number
    1
    0
    Subcutaneous abscess
    Additional description: Subcutaneous abscess
         subjects affected / exposed
    1 / 71 (1.41%)
    1 / 71 (1.41%)
         occurrences all number
    5
    1
    Upper respiratory tract infection
    Additional description: Upper respiratory tract infection
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 71 (1.41%)
         occurrences all number
    0
    1
    Urinary tract infection
    Additional description: Urinary tract infection
         subjects affected / exposed
    6 / 71 (8.45%)
    3 / 71 (4.23%)
         occurrences all number
    8
    3
    Wound infection
    Additional description: Wound infection
         subjects affected / exposed
    1 / 71 (1.41%)
    2 / 71 (2.82%)
         occurrences all number
    1
    5
    Metabolism and nutrition disorders
    Decreased appetite
    Additional description: Decreased appetite
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 71 (1.41%)
         occurrences all number
    0
    1
    Fluid retention
    Additional description: Fluid retention
         subjects affected / exposed
    0 / 71 (0.00%)
    2 / 71 (2.82%)
         occurrences all number
    0
    3
    Gout
    Additional description: Gout
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 71 (1.41%)
         occurrences all number
    0
    1
    Hypoalbuminaemia
    Additional description: Hypoalbuminaemia
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 71 (1.41%)
         occurrences all number
    0
    2
    Hyperglycaemia
    Additional description: Hyperglycaemia
         subjects affected / exposed
    2 / 71 (2.82%)
    1 / 71 (1.41%)
         occurrences all number
    4
    3
    Hypocalcaemia
    Additional description: Hypocalcaemia
         subjects affected / exposed
    3 / 71 (4.23%)
    0 / 71 (0.00%)
         occurrences all number
    6
    0
    Hypokalaemia
    Additional description: Hypokalaemia
         subjects affected / exposed
    6 / 71 (8.45%)
    6 / 71 (8.45%)
         occurrences all number
    8
    7
    Hypomagnesaemia
    Additional description: Hypomagnesaemia
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 71 (1.41%)
         occurrences all number
    0
    2
    Malnutrition
    Additional description: Malnutrition
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 71 (1.41%)
         occurrences all number
    0
    1
    Type 1 diabetes mellitus
    Additional description: Type 1 diabetes mellitus
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 71 (0.00%)
         occurrences all number
    3
    0

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? No

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

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

    Online references
    http://www.ncbi.nlm.nih.gov/pubmed/29664999
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    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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