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    Clinical Trial Results:
    EARLY ORAL SWITCH THERAPY IN LOW-RISK STAPHYLOCOCCUS AUREUS BLOODSTREAM INFECTION ACRONYM: SABATO (Staphylococcus Aureus Bacteremia Antibiotic Treatment Options)

    Summary
    EudraCT number
    		 2013-000577-77
    Trial protocol
    		 DE   ES   NL  
    Global end of trial date
    26 Apr 2020

    Results information
    Results version number
    		 v1(current)
    This version publication date
    04 Oct 2022
    First version publication date
    04 Oct 2022
    Other versions
    Summary report(s)
    		 Result Report

    Trial information

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    Trial identification
    Sponsor protocol code
    Uni-Koeln-1400
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT01792804
    WHO universal trial number (UTN)
    		 -
    Other trial identifiers
    		 German Clinical Trials Register identifier: DRKS00004741
    Sponsors
    Sponsor organisation name
    Heinrich-Heine University Düsseldorf
    Sponsor organisation address
    Universitätsstr. 1, Düsseldorf, Germany, 40225
    Public contact
    Institute of Medical Microbiology and Hospital Hygiene, Otto-von-Guericke University Magdeburg, 49 3916713392, kerstin.brennecke@med.ovgu.de
    Scientific contact
    Institute of Medical Microbiology and Hospital Hygiene, Otto-von-Guericke University Magdeburg, 49 3916713392, kerstin.brennecke@med.ovgu.de
    Sponsor organisation name
    University of Cologne
    Sponsor organisation address
    Gleueler Str. 269, Cologne, Germany, 50935
    Public contact
    Institute of Medical Microbiology and Hospital Hygiene, Otto-von-Guericke-University Magdeburg, 49 3916713392, kerstin.brennecke@med.ovgu.de
    Scientific contact
    Institute of Medical Microbiology and Hospital Hygiene, Otto-von-Guericke-University Magdeburg, 49 3916713392, kerstin.brennecke@med.ovgu.de
    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
    07 Jul 2021
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    26 Apr 2020
    Global end of trial reached?
    Yes
    Global end of trial date
    26 Apr 2020
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To demonstrate that in patients with low-risk S. aureus bloodstream infection (SAB) a switch from intravenous to oral antimicrobial therapy (oral switch therapy, OST) is non-inferior to a conventional course of intravenous therapy (intravenous standard therapy, IST).
    Protection of trial subjects
    To protect trial subjects a Data Monitoring Committee (DMC) was implemented that regularly discussed trial safety. Furthermore, stopping rules for the trial were defined.
    Background therapy
    		 Before start of the intervention all participants received 5-7 days of adequate intravenous antibiotic therapy.
    Evidence for comparator
    		 Comparator drugs are the current standard of care for Staphylococcus aureus bacteremia. To reduce variability the following licensed drugs were allowed as intravenous treatment: flucloxacillin (cloxacillin in Spain and France), cefazolin, vancomycin, daptomycin.
    Actual start date of recruitment
    20 Dec 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
    Netherlands: 7
    Country: Number of subjects enrolled
    Spain: 64
    Country: Number of subjects enrolled
    France: 69
    Country: Number of subjects enrolled
    Germany: 73
    Worldwide total number of subjects
    213
    EEA total number of subjects
    213
    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)
    100
    From 65 to 84 years
    97
    85 years and over
    16

    Subject disposition

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    Recruitment
    Recruitment details
    		 Recruitment periods: Germany: 20 Dec 2013 to 26 Apr 2021 The Netherlands: 17 Jun 2015 to 26 Apr 2021 Spain: 10 Oct 2014 to 26 Apr 2021 France: 12 Jun 2017 to 26 Apr 2021

    Pre-assignment
    Screening details
    		 5,330 patients with Staphylococcus aureus bacteremia were screened (5,063 patients with complete basic information). The main inclusion criterion was 5-7 days of adequate intravenous therapy. Main exclusion criteria were polymicrobial bloodstream infection, signs and symptoms of complicated bacteremia, foreign bodies, and severe comorbidity

    Period 1
    Period 1 title
    Overall Trial (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded
    Blinding implementation details
    The assessors of the endpoint, the adjudication committee (clinical review committee), were masked regarding treatment arm.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 OST (oral switch therapy)
    Arm description
    		 Oral Switch Therapy
    Arm type
    		 Experimental

    Investigational medicinal product name
    Trimethoprim-Sulfamethoxazol
    Investigational medicinal product code
    J01EE51
    Other name
    Cotrimoxazol; 723-46-6; SUB10711MIG; SUB11310MIG
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    160/800 mg twice daily per os

    Investigational medicinal product name
    Clindamycin
    Investigational medicinal product code
    D10AF01
    Other name
    SUB06665MIG
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Daily dose: 1800 mg in three doses per os

    Investigational medicinal product name
    Linezolid
    Investigational medicinal product code
    J01XX08
    Other name
    SUB08520MIG
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Daily dose: 1200 mg in two doses per os

    Arm title
    		 IST (intravenous standard therapy)
    Arm description
    		 Intravenous Standard Therapy
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Flucloxacillin
    Investigational medicinal product code
    J01CF05
    Other name
    CAS-Nr 5250-39-5; EV code SUB07673MIG
    Pharmaceutical forms
    Powder for solution for injection/infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    recommended daily dose: 8.000 mg i.v. in 4 doses

    Investigational medicinal product name
    Cloxacillin
    Investigational medicinal product code
    J01CF02
    Other name
    CAS 61-72-3; EV SUB06780MIG
    Pharmaceutical forms
    Powder for solution for injection/infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Recommended daily dose: 8.000 mg in 4 doses

    Investigational medicinal product name
    Cefazolin
    Investigational medicinal product code
    J01DB04
    Other name
    CAS 25953-19-9; EV SUB07379MIG
    Pharmaceutical forms
    Powder for solution for injection/infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Recommended daily dose: 6.000 mg in 3 doses

    Investigational medicinal product name
    Vancomycin
    Investigational medicinal product code
    A07AA09
    Other name
    CAS 1404-90-6; EV SUB05076MIG
    Pharmaceutical forms
    Powder for solution for injection/infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Recommended daily dosing: 2.000 mg in 2 doses

    Investigational medicinal product name
    Daptomycin
    Investigational medicinal product code
    J01XX09
    Other name
    CAS 103060-53-3; EV SUB06910MIG
    Pharmaceutical forms
    Powder for solution for injection/infusion
    Routes of administration
    Solution for infusion
    Dosage and administration details
    Daily dose: 10 mg/kilogram once per day

    Number of subjects in period 1
    		OST (oral switch therapy) IST (intravenous standard therapy)
    Started
    108
    105
    Completed
    86
    79
    Not completed
    22
    26
         non-evaluable in per protocol population
    22
    26

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    OST (oral switch therapy)
    Reporting group description
    		 Oral Switch Therapy

    Reporting group title
    IST (intravenous standard therapy)
    Reporting group description
    		 Intravenous Standard Therapy

    Reporting group values
    		 OST (oral switch therapy) IST (intravenous standard therapy) Total
    Number of subjects
    		 108 105 213
    Age categorical
    Units: Subjects
        Adults (18-64 years)
    		 48 52 100
        From 65-84 years
    		 50 47 97
        85 years and over
    		 10 6 16
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 64.35 ( 16.78 ) 62.56 ( 17.56 ) -
    Gender categorical
    Units: Subjects
        Female
    		 37 28 65
        Male
    		 71 77 148
    Charlson Comorbidity Index
    Measure for the presence of comorbidities (values = 0 to 21)
    Units: arbitrary
        median (inter-quartile range (Q1-Q3))
    		 3.00 (1.00 to 5.00) 3.00 (1.00 to 4.00) -
    Subject analysis sets

    Subject analysis set title
    Per Protocol Analysis
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    The per protocol set includes all study subjects who were essentially treated according to protocol and reached a defined endpoint in the trial (SAB-unrelated deaths will be excluded).

    Subject analysis set title
    Intention-to-treat 1
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    The intention-to-treat dataset includes all randomized study subjects, analyzed as assigned, with indeterminate and missing outcomes counted as failures. For time-to-event outcomes these cases are censored. The ITT population will be analysed as (ITT-1) any patient randomized, (ITT-2) only patients that were randomized AND received study drug without patients in whom a major inclusion criterion was violated.

    Subject analysis set title
    Intention-to-treat 2
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    The intention-to-treat dataset includes all randomized study subjects, analyzed as assigned, with indeterminate and missing outcomes counted as failures. For time-to-event outcomes these cases are censored. The ITT population will be analysed as (ITT-1) any patient randomized, (ITT-2) only patients that were randomized AND received study drug without patients in whom a major inclusion criterion was violated.

    Subject analysis set title
    Safety Set
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    The safety set includes all study subjects who received any study drug as treated. Specifically, patients who ever received an oral antibiotic are compared to patients who never received an oral antibiotic.

    Subject analysis sets values
    		 Per Protocol Analysis Intention-to-treat 1 Intention-to-treat 2 Safety Set
    Number of subjects
    165
    213
    206
    210
    Age categorical
    Units: Subjects
        Adults (18-64 years)
    81
    100
    96
    99
        From 65-84 years
    75
    97
    95
    95
        85 years and over
    9
    16
    15
    16
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    62.22 ( 17.41 )
    63.47 ( 17.15 )
    63.50 ( 17.16 )
    63.42 ( 17.20 )
    Gender categorical
    Units: Subjects
        Female
    48
    65
    62
    65
        Male
    117
    148
    144
    145
    Charlson Comorbidity Index
    Measure for the presence of comorbidities (values = 0 to 21)
    Units: arbitrary
        median (inter-quartile range (Q1-Q3))
    2.00 (1.0 to 4.0)
    3.00 (1.0 to 5.0)
    3.00 (1.0 to 5.0)
    3.00 (1.00 to 5.00)

    End points

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    End points reporting groups
    Reporting group title
    OST (oral switch therapy)
    Reporting group description
    		 Oral Switch Therapy

    Reporting group title
    IST (intravenous standard therapy)
    Reporting group description
    		 Intravenous Standard Therapy

    Subject analysis set title
    Per Protocol Analysis
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    The per protocol set includes all study subjects who were essentially treated according to protocol and reached a defined endpoint in the trial (SAB-unrelated deaths will be excluded).

    Subject analysis set title
    Intention-to-treat 1
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    The intention-to-treat dataset includes all randomized study subjects, analyzed as assigned, with indeterminate and missing outcomes counted as failures. For time-to-event outcomes these cases are censored. The ITT population will be analysed as (ITT-1) any patient randomized, (ITT-2) only patients that were randomized AND received study drug without patients in whom a major inclusion criterion was violated.

    Subject analysis set title
    Intention-to-treat 2
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    The intention-to-treat dataset includes all randomized study subjects, analyzed as assigned, with indeterminate and missing outcomes counted as failures. For time-to-event outcomes these cases are censored. The ITT population will be analysed as (ITT-1) any patient randomized, (ITT-2) only patients that were randomized AND received study drug without patients in whom a major inclusion criterion was violated.

    Subject analysis set title
    Safety Set
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    The safety set includes all study subjects who received any study drug as treated. Specifically, patients who ever received an oral antibiotic are compared to patients who never received an oral antibiotic.

    Primary: SAB-related complications

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    End point title
    		 SAB-related complications
    End point description
    Staphylococcus aureus bloodstream infection-related complications is a composite endpoint consisting of relapsing SAB, deep-seated infection with S. aureus, or attributable mortality all within 90 days.
    End point type
    Primary
    End point timeframe
    Follow-up period of 90 days
    End point values
    		 OST (oral switch therapy) IST (intravenous standard therapy) Per Protocol Analysis Intention-to-treat 1 Intention-to-treat 2
    Number of subjects analysed
    108
    105
    165
    213
    206
    Units: patients
    14
    13
    7
    27
    22
    Statistical analysis title
    		 Zhao's test
    Statistical analysis description
    The primary endpoint SAB-related complications (relapsing SAB, deep-seated infection with S. aureus, or mortality attributable to SAB) within 90 days will be evaluated regarding non-inferiority of oral vs. intravenous antimicrobial therapy by Zhao’s test (test 1) of non-null hypothesis on proportions stratified by study center at one-sided level 5% and with a non-inferiority margin of 10%.
    Comparison groups
    OST (oral switch therapy) v IST (intravenous standard therapy)
    Number of subjects included in analysis
    213
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [1]
    P-value
    		 = 0.013 [2]
    Method
    		 Zhao's test 1
    Parameter type
    		 Risk difference (RD)
    Point estimate
    0.0065
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.0666
         upper limit
    		 0.0797
    Notes
    [1] - (A) (null hypothesis) H0: pOST > pIST + 0.10 vs (alternative hypothesis) Ha: pOST ≤ pIST + 0.10 If this null hypothesis can be rejected (alpha=5%, one-sided), the above hypothesis (A) will be tested again at one-sided alpha=2.5%. (B) If the above second null hypothesis can also be rejected, the non-inferiority margin of 5% will be applied. If the null hypothesis can be rejected (alpha=5%, one-sided), the hypothesis will be tested again at one-sided alpha=2.5%.
    [2] - (A) ITT-1; (B) p=0.2075, ITT-1 (PP: (A) p<0.0001, (B) p=0.0095; ITT-2: (A) p=0.0024, (B) p=0.0882)

    Secondary: Length of hospital stay

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    End point title
    		 Length of hospital stay
    End point description
    Length of hospital stay
    End point type
    Secondary
    End point timeframe
    90 days
    End point values
    		 OST (oral switch therapy) IST (intravenous standard therapy) Per Protocol Analysis Intention-to-treat 1 Intention-to-treat 2
    Number of subjects analysed
    108
    105
    165
    213
    206
    Units: days
        arithmetic mean (standard deviation)
    17.38 ( 15.80 )
    18.76 ( 14.58 )
    16.49 ( 14.11 )
    18.06 ( 15.19 )
    18.04 ( 15.37 )
    Statistical analysis title
    		 Time-to-event analysis
    Statistical analysis description
    Kaplan-Meier curves and log-rank test. Patients who died in hospital or were discharged counted as event.
    Comparison groups
    OST (oral switch therapy) v IST (intravenous standard therapy)
    Number of subjects included in analysis
    213
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0551 [3]
    Method
    		 Wilcoxon test
    Confidence interval
    Notes
    [3] - ITT-1, two-sided (PP: p=0.0199; ITT-2: p=0.0295)

    Secondary: 14-day survival

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    End point title
    		 14-day survival
    End point description
    Survival at 14 days
    End point type
    Secondary
    End point timeframe
    14 days
    End point values
    		 OST (oral switch therapy) IST (intravenous standard therapy) Per Protocol Analysis Intention-to-treat 1 Intention-to-treat 2
    Number of subjects analysed
    108
    105
    165
    213
    206
    Units: patients
    2
    0
    1
    2
    1
    Statistical analysis title
    		 Time-to-event analysis
    Statistical analysis description
    Kaplan-Meier curves and log-rank test
    Comparison groups
    OST (oral switch therapy) v IST (intravenous standard therapy)
    Number of subjects included in analysis
    213
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.1633 [4]
    Method
    		 Logrank
    Confidence interval
    Notes
    [4] - ITT-1, two-sided (PP: p=0.3378; ITT-2: p=0.3268)

    Secondary: Complications of intravenous therapy

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    End point title
    		 Complications of intravenous therapy
    End point description
    Complications of intravenous therapy, such as thrombophlebitis
    End point type
    Secondary
    End point timeframe
    90 days
    End point values
    		 OST (oral switch therapy) IST (intravenous standard therapy) Per Protocol Analysis Intention-to-treat 1 Intention-to-treat 2
    Number of subjects analysed
    108
    105
    165
    213
    206
    Units: persons
    20
    22
    19
    42
    38
    Statistical analysis title
    		 Fisher's exact test
    Comparison groups
    IST (intravenous standard therapy) v OST (oral switch therapy)
    Number of subjects included in analysis
    213
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.7314 [5]
    Method
    		 Fisher exact
    Confidence interval
    Notes
    [5] - ITT-1, two-sided (PP: p=0.0856; ITT-2: p=0.7200)

    Secondary: 30-day survival

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    End point title
    		 30-day survival
    End point description
    Survival at 14, 30, and 90 days
    End point type
    Secondary
    End point timeframe
    30 days
    End point values
    		 OST (oral switch therapy) IST (intravenous standard therapy) Per Protocol Analysis Intention-to-treat 1 Intention-to-treat 2
    Number of subjects analysed
    108
    105
    165
    213
    206
    Units: patients
    6
    4
    2
    10
    9
    Statistical analysis title
    		 Time-to-event analysis
    Statistical analysis description
    Kaplan-Meier curves and log-rank test
    Comparison groups
    OST (oral switch therapy) v IST (intravenous standard therapy)
    Number of subjects included in analysis
    213
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.5362 [6]
    Method
    		 Logrank
    Confidence interval
    Notes
    [6] - ITT-1, two-sided (PP: p=0.9552; ITT-2: p=0.7579)

    Secondary: 90-day survival

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    End point title
    		 90-day survival
    End point description
    End point type
    Secondary
    End point timeframe
    90 days
    End point values
    		 OST (oral switch therapy) IST (intravenous standard therapy) Per Protocol Analysis Intention-to-treat 1 Intention-to-treat 2
    Number of subjects analysed
    108
    105
    165
    213
    206
    Units: patients
    17
    11
    10
    28
    27
    Statistical analysis title
    		 Time-to-event analysis
    Statistical analysis description
    Kaplan-Meier curves and log-rank test
    Comparison groups
    IST (intravenous standard therapy) v OST (oral switch therapy)
    Number of subjects included in analysis
    213
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.2614 [7]
    Method
    		 Logrank
    Confidence interval
    Notes
    [7] - ITT-1, two-sided (PP: p=0.6155; ITT-2: p=0.3546)

    Other pre-specified: Clostridium difficile associated diarrhea

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    End point title
    		 Clostridium difficile associated diarrhea
    End point description
    Clostridium difficile associated diarrhea
    End point type
    Other pre-specified
    End point timeframe
    90 days
    End point values
    		 OST (oral switch therapy) IST (intravenous standard therapy) Per Protocol Analysis Intention-to-treat 1 Intention-to-treat 2
    Number of subjects analysed
    108
    105
    165
    213
    206
    Units: patients
    14
    12
    3
    26
    22
    Statistical analysis title
    		 Fisher's exact test
    Comparison groups
    IST (intravenous standard therapy) v OST (oral switch therapy)
    Number of subjects included in analysis
    213
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.8351 [8]
    Method
    		 Fisher exact
    Confidence interval
    Notes
    [8] - ITT-1, two-sided (PP: p=1.0000; ITT-2: p=0.8229)

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    AE were systematically assessed at 30 days and 90 days. Additionally, adverse events were reported to the study sites by the patients when the AE occured.
    Adverse event reporting additional description
    Adverse events were recorded from CTCAE grade 3 or higher. Relatedness was classified as "related" (classification terms used in the study: certain, probably/likely, possible, conditional/unclassified, unassessable/unclassifiable) and "unrelated" (study term: unlikely). Analysis of adverse was events based on the safety set.
    Assessment type
    		 Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    19.0
    Reporting groups
    Reporting group title
    OST (oral switch therapy)
    Reporting group description
    		 -

    Reporting group title
    IST (intravenous standard therapy)
    Reporting group description
    		 -

    Serious adverse events
    		 OST (oral switch therapy) IST (intravenous standard therapy)
    Total subjects affected by serious adverse events
         subjects affected / exposed
    41 / 107 (38.32%)
    32 / 103 (31.07%)
         number of deaths (all causes)
    18
    12
         number of deaths resulting from adverse events
    18
    12
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    B-cell lymphoma
    Additional description: B-cell lymphoma
         subjects affected / exposed
    0 / 107 (0.00%)
    1 / 103 (0.97%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchial carcinoma
    Additional description: Bronchial carcinoma
         subjects affected / exposed
    1 / 107 (0.93%)
    0 / 103 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Malignant melanoma stage IV
    Additional description: Malignant melanoma stage IV
         subjects affected / exposed
    1 / 107 (0.93%)
    0 / 103 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Hepatocellular carcinoma
    Additional description: Hepatocellular carcinoma
         subjects affected / exposed
    1 / 107 (0.93%)
    0 / 103 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Ovarian cancer metastatic
    Additional description: Ovarian cancer metastatic
         subjects affected / exposed
    1 / 107 (0.93%)
    0 / 103 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Prostate cancer
    Additional description: Prostate cancer
         subjects affected / exposed
    0 / 107 (0.00%)
    1 / 103 (0.97%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatic neoplasm
    Additional description: Pancreatic neoplasm
         subjects affected / exposed
    1 / 107 (0.93%)
    0 / 103 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Vascular disorders
    Aortic dissection
    Additional description: Aortic dissection
         subjects affected / exposed
    1 / 107 (0.93%)
    0 / 103 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    Peripheral arterial occlusive disease
    Additional description: Peripheral arterial occlusive disease
         subjects affected / exposed
    0 / 107 (0.00%)
    1 / 103 (0.97%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Shock haemorrhagic
    Additional description: Shock haemorrhagic
         subjects affected / exposed
    1 / 107 (0.93%)
    0 / 103 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Asthenia
    Additional description: Asthenia
         subjects affected / exposed
    1 / 107 (0.93%)
    0 / 103 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Disease progression
    Additional description: Disease progression
         subjects affected / exposed
    1 / 107 (0.93%)
    0 / 103 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Malaise
    Additional description: Malaise
         subjects affected / exposed
    0 / 107 (0.00%)
    1 / 103 (0.97%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Impaired healing
    Additional description: Impaired healing
         subjects affected / exposed
    0 / 107 (0.00%)
    1 / 103 (0.97%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Generalised oedema
    Additional description: Generalised oedema
         subjects affected / exposed
    2 / 107 (1.87%)
    0 / 103 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General physical health deterioration
    Additional description: General physical health deterioration
         subjects affected / exposed
    0 / 107 (0.00%)
    1 / 103 (0.97%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Pyrexia
    Additional description: Pyrexia
         subjects affected / exposed
    1 / 107 (0.93%)
    0 / 103 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pain
    Additional description: Pain
         subjects affected / exposed
    1 / 107 (0.93%)
    0 / 103 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Bronchospasm
    Additional description: Bronchospasm
         subjects affected / exposed
    0 / 107 (0.00%)
    1 / 103 (0.97%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dyspnoea
    Additional description: Dyspnoea
         subjects affected / exposed
    1 / 107 (0.93%)
    0 / 103 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chronic obstructive pulmonary disease
    Additional description: Chronic obstructive pulmonary disease
         subjects affected / exposed
    0 / 107 (0.00%)
    1 / 103 (0.97%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pharyngeal fistula
    Additional description: Pharyngeal fistula
         subjects affected / exposed
    0 / 107 (0.00%)
    1 / 103 (0.97%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary embolism
    Additional description: Pulmonary embolism
         subjects affected / exposed
    1 / 107 (0.93%)
    1 / 103 (0.97%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Pneumonia aspiration
    Additional description: Pneumonia aspiration
         subjects affected / exposed
    1 / 107 (0.93%)
    0 / 103 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Respiratory failure
    Additional description: Respiratory failure
         subjects affected / exposed
    0 / 107 (0.00%)
    1 / 103 (0.97%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Injury, poisoning and procedural complications
    Fall
    Additional description: Fall
         subjects affected / exposed
    1 / 107 (0.93%)
    0 / 103 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Facial bones fracture
    Additional description: Facial bones fracture
         subjects affected / exposed
    1 / 107 (0.93%)
    0 / 103 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Toxicity to various agents
    Additional description: Toxicity to various agents
         subjects affected / exposed
    0 / 107 (0.00%)
    1 / 103 (0.97%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Acute myocardial infarction
    Additional description: Acute myocardial infarction
         subjects affected / exposed
    1 / 107 (0.93%)
    0 / 103 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Atrial flutter
    Additional description: Atrial flutter
         subjects affected / exposed
    0 / 107 (0.00%)
    1 / 103 (0.97%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac arrest
    Additional description: Cardiac arrest
         subjects affected / exposed
    1 / 107 (0.93%)
    1 / 103 (0.97%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    Cardiac failure
    Additional description: Cardiac failure
         subjects affected / exposed
    1 / 107 (0.93%)
    3 / 103 (2.91%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 3
         deaths causally related to treatment / all
    1 / 1
    0 / 3
    Cardio-respiratory arrest
    Additional description: Cardio-respiratory arrest
         subjects affected / exposed
    3 / 107 (2.80%)
    0 / 103 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 3
    0 / 0
    Myocardial ischaemia
    Additional description: Myocardial ischaemia
         subjects affected / exposed
    1 / 107 (0.93%)
    0 / 103 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Left ventricular failure
    Additional description: Left ventricular failure
         subjects affected / exposed
    1 / 107 (0.93%)
    0 / 103 (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
    Syncope
    Additional description: Syncope
         subjects affected / exposed
    1 / 107 (0.93%)
    1 / 103 (0.97%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatic encephalopathy
    Additional description: Hepatic encephalopathy
         subjects affected / exposed
    1 / 107 (0.93%)
    1 / 103 (0.97%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Blood and lymphatic system disorders
    Anaemia
    Additional description: Anaemia
         subjects affected / exposed
    2 / 107 (1.87%)
    0 / 103 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Retroperitoneal lymphadenopathy
    Additional description: Retroperitoneal lymphadenopathy
         subjects affected / exposed
    1 / 107 (0.93%)
    0 / 103 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sickle cell anaemia with crisis
    Additional description: Sickle cell anaemia with crisis
         subjects affected / exposed
    1 / 107 (0.93%)
    1 / 103 (0.97%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thrombocytopenic purpura
    Additional description: Thrombocytopenic purpura
         subjects affected / exposed
    0 / 107 (0.00%)
    1 / 103 (0.97%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Gastritis
    Additional description: Gastritis
         subjects affected / exposed
    1 / 107 (0.93%)
    0 / 103 (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: Intestinal ischaemia
         subjects affected / exposed
    0 / 107 (0.00%)
    1 / 103 (0.97%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Vomiting
    Additional description: Vomiting
         subjects affected / exposed
    1 / 107 (0.93%)
    0 / 103 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Upper gastrointestinal haemorrhage
    Additional description: Upper gastrointestinal haemorrhage
         subjects affected / exposed
    1 / 107 (0.93%)
    0 / 103 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rectal haemorrhage
    Additional description: Rectal haemorrhage
         subjects affected / exposed
    0 / 107 (0.00%)
    1 / 103 (0.97%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Hepatitis acute
    Additional description: Hepatitis acute
         subjects affected / exposed
    0 / 107 (0.00%)
    1 / 103 (0.97%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ischaemic hepatitis
    Additional description: Ischaemic hepatitis
         subjects affected / exposed
    0 / 107 (0.00%)
    1 / 103 (0.97%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Skin and subcutaneous tissue disorders
    Petechiae
    Additional description: Petechiae
         subjects affected / exposed
    1 / 107 (0.93%)
    0 / 103 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
    Additional description: Acute kidney injury
         subjects affected / exposed
    1 / 107 (0.93%)
    0 / 103 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal failure
    Additional description: Renal failure
         subjects affected / exposed
    1 / 107 (0.93%)
    0 / 103 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Anal abscess
    Additional description: Anal abscess
         subjects affected / exposed
    0 / 107 (0.00%)
    1 / 103 (0.97%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abscess
    Additional description: Abscess
         subjects affected / exposed
    1 / 107 (0.93%)
    0 / 103 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arthritis bacterial
    Additional description: Arthritis bacterial
         subjects affected / exposed
    1 / 107 (0.93%)
    0 / 103 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Clostridium difficile colitis
    Additional description: Clostridium difficile colitis
         subjects affected / exposed
    1 / 107 (0.93%)
    0 / 103 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Endocarditis
    Additional description: Endocarditis
         subjects affected / exposed
    0 / 107 (0.00%)
    2 / 103 (1.94%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Osteomyelitis
    Additional description: Osteomyelitis
         subjects affected / exposed
    1 / 107 (0.93%)
    2 / 103 (1.94%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Klebsiella infection
    Additional description: Klebsiella infection
         subjects affected / exposed
    1 / 107 (0.93%)
    0 / 103 (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: Infection
         subjects affected / exposed
    1 / 107 (0.93%)
    0 / 103 (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: Peritonitis
         subjects affected / exposed
    0 / 107 (0.00%)
    1 / 103 (0.97%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Pneumonia
    Additional description: Pneumonia
         subjects affected / exposed
    1 / 107 (0.93%)
    1 / 103 (0.97%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Postoperative wound infection
    Additional description: Postoperative wound infection
         subjects affected / exposed
    1 / 107 (0.93%)
    0 / 103 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory tract infection
    Additional description: Respiratory tract infection
         subjects affected / exposed
    1 / 107 (0.93%)
    0 / 103 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Pseudomembranous colitis
    Additional description: Pseudomembranous colitis
         subjects affected / exposed
    0 / 107 (0.00%)
    1 / 103 (0.97%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sepsis
    Additional description: Sepsis
         subjects affected / exposed
    4 / 107 (3.74%)
    1 / 103 (0.97%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    Septic shock
    Additional description: Septic shock
         subjects affected / exposed
    2 / 107 (1.87%)
    1 / 103 (0.97%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Skin bacterial infection
    Additional description: Skin bacterial infection
         subjects affected / exposed
    1 / 107 (0.93%)
    0 / 103 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Staphylococcal bacteraemia
    Additional description: Staphylococcal bacteraemia
         subjects affected / exposed
    1 / 107 (0.93%)
    1 / 103 (0.97%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary tract infection
    Additional description: Urinary tract infection
         subjects affected / exposed
    0 / 107 (0.00%)
    1 / 103 (0.97%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary tract infection staphylococcal
    Additional description: Urinary tract infection staphylococcal
         subjects affected / exposed
    0 / 107 (0.00%)
    1 / 103 (0.97%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Wound infection
    Additional description: Wound infection
         subjects affected / exposed
    0 / 107 (0.00%)
    1 / 103 (0.97%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Diabetes mellitus
    Additional description: Diabetes mellitus
         subjects affected / exposed
    0 / 107 (0.00%)
    1 / 103 (0.97%)
         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: 0%
    Non-serious adverse events
    		 OST (oral switch therapy) IST (intravenous standard therapy)
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    20 / 107 (18.69%)
    17 / 103 (16.50%)
    Vascular disorders
    Hypertension
    Additional description: Hypertension
         subjects affected / exposed
    1 / 107 (0.93%)
    0 / 103 (0.00%)
         occurrences all number
    1
    0
    Phlebitis
    Additional description: Phlebitis
         subjects affected / exposed
    1 / 107 (0.93%)
    0 / 103 (0.00%)
         occurrences all number
    1
    0
    Poor venous access
    Additional description: Poor venous access
         subjects affected / exposed
    0 / 107 (0.00%)
    1 / 103 (0.97%)
         occurrences all number
    0
    1
    General disorders and administration site conditions
    Asthenia
    Additional description: Asthenia
         subjects affected / exposed
    1 / 107 (0.93%)
    0 / 103 (0.00%)
         occurrences all number
    1
    0
    Oedema
    Additional description: Oedema
         subjects affected / exposed
    1 / 107 (0.93%)
    0 / 103 (0.00%)
         occurrences all number
    1
    0
    Pyrexia
    Additional description: Pyrexia
         subjects affected / exposed
    3 / 107 (2.80%)
    1 / 103 (0.97%)
         occurrences all number
    3
    1
    Pain
    Additional description: Pain
         subjects affected / exposed
    1 / 107 (0.93%)
    0 / 103 (0.00%)
         occurrences all number
    1
    0
    Immune system disorders
    Transplant rejection
    Additional description: Transplant rejection
         subjects affected / exposed
    0 / 107 (0.00%)
    1 / 103 (0.97%)
         occurrences all number
    0
    1
    Respiratory, thoracic and mediastinal disorders
    Chronic obstructive pulmonary disease
    Additional description: Chronic obstructive pulmonary disease
         subjects affected / exposed
    1 / 107 (0.93%)
    0 / 103 (0.00%)
         occurrences all number
    1
    0
    Dyspnoea
    Additional description: Dyspnoea
         subjects affected / exposed
    0 / 107 (0.00%)
    1 / 103 (0.97%)
         occurrences all number
    0
    1
    Pulmonary oedema
    Additional description: Pulmonary oedema
         subjects affected / exposed
    0 / 107 (0.00%)
    1 / 103 (0.97%)
         occurrences all number
    0
    1
    Pulmonary embolism
    Additional description: Pulmonary embolism
         subjects affected / exposed
    0 / 107 (0.00%)
    1 / 103 (0.97%)
         occurrences all number
    0
    1
    Pleurisy
    Additional description: Pleurisy
         subjects affected / exposed
    0 / 107 (0.00%)
    1 / 103 (0.97%)
         occurrences all number
    0
    1
    Hypoxia
    Additional description: Hypoxia
         subjects affected / exposed
    0 / 107 (0.00%)
    1 / 103 (0.97%)
         occurrences all number
    0
    1
    Investigations
    Blood creatinine increased
    Additional description: Blood creatinine increased
         subjects affected / exposed
    1 / 107 (0.93%)
    0 / 103 (0.00%)
         occurrences all number
    1
    0
    Hepatic enzyme increased
    Additional description: Hepatic enzyme increased
         subjects affected / exposed
    0 / 107 (0.00%)
    1 / 103 (0.97%)
         occurrences all number
    0
    1
    Cardiac disorders
    Coronary artery disease
    Additional description: Coronary artery disease
         subjects affected / exposed
    1 / 107 (0.93%)
    0 / 103 (0.00%)
         occurrences all number
    1
    0
    Nervous system disorders
    Depressed level of consciousness
    Additional description: Depressed level of consciousness
         subjects affected / exposed
    0 / 107 (0.00%)
    1 / 103 (0.97%)
         occurrences all number
    0
    1
    Ischaemic stroke
    Additional description: Ischaemic stroke
         subjects affected / exposed
    1 / 107 (0.93%)
    0 / 103 (0.00%)
         occurrences all number
    1
    0
    Blood and lymphatic system disorders
    Anaemia
    Additional description: Anaemia
         subjects affected / exposed
    1 / 107 (0.93%)
    2 / 103 (1.94%)
         occurrences all number
    1
    2
    Eye disorders
    Cataract
    Additional description: Cataract
         subjects affected / exposed
    1 / 107 (0.93%)
    0 / 103 (0.00%)
         occurrences all number
    1
    0
    Gastrointestinal disorders
    Colitis ulcerative
    Additional description: Colitis ulcerative
         subjects affected / exposed
    0 / 107 (0.00%)
    1 / 103 (0.97%)
         occurrences all number
    0
    1
    Constipation
    Additional description: Constipation
         subjects affected / exposed
    1 / 107 (0.93%)
    0 / 103 (0.00%)
         occurrences all number
    1
    0
    Diverticulum intestinal
    Additional description: Diverticulum intestinal
         subjects affected / exposed
    1 / 107 (0.93%)
    0 / 103 (0.00%)
         occurrences all number
    1
    0
    Skin and subcutaneous tissue disorders
    Dermatitis atopic
    Additional description: Dermatitis atopic
         subjects affected / exposed
    0 / 107 (0.00%)
    1 / 103 (0.97%)
         occurrences all number
    0
    1
    Renal and urinary disorders
    Urinary retention
    Additional description: Urinary retention
         subjects affected / exposed
    0 / 107 (0.00%)
    1 / 103 (0.97%)
         occurrences all number
    0
    1
    Musculoskeletal and connective tissue disorders
    Back pain
    Additional description: Back pain
         subjects affected / exposed
    0 / 107 (0.00%)
    1 / 103 (0.97%)
         occurrences all number
    0
    1
    Gouty arthritis
    Additional description: Gouty arthritis
         subjects affected / exposed
    1 / 107 (0.93%)
    0 / 103 (0.00%)
         occurrences all number
    1
    0
    Muscle spasms
    Additional description: Muscle spasms
         subjects affected / exposed
    1 / 107 (0.93%)
    0 / 103 (0.00%)
         occurrences all number
    1
    0
    Infections and infestations
    Bronchitis
    Additional description: Bronchitis
         subjects affected / exposed
    1 / 107 (0.93%)
    0 / 103 (0.00%)
         occurrences all number
    1
    0
    Erysipelas
    Additional description: Erysipelas
         subjects affected / exposed
    1 / 107 (0.93%)
    0 / 103 (0.00%)
         occurrences all number
    1
    0
    Cystitis
    Additional description: Cystitis
         subjects affected / exposed
    1 / 107 (0.93%)
    0 / 103 (0.00%)
         occurrences all number
    1
    0
    Influenza
    Additional description: Influenza
         subjects affected / exposed
    0 / 107 (0.00%)
    1 / 103 (0.97%)
         occurrences all number
    0
    1
    Pneumonia
    Additional description: Pneumonia
         subjects affected / exposed
    1 / 107 (0.93%)
    1 / 103 (0.97%)
         occurrences all number
    1
    1
    Wound infection
    Additional description: Wound infection
         subjects affected / exposed
    1 / 107 (0.93%)
    1 / 103 (0.97%)
         occurrences all number
    1
    1
    Urinary tract infection
    Additional description: Urinary tract infection
         subjects affected / exposed
    4 / 107 (3.74%)
    1 / 103 (0.97%)
         occurrences all number
    4
    1
    Pseudomonas infection
    Additional description: Pseudomonas infection
         subjects affected / exposed
    1 / 107 (0.93%)
    0 / 103 (0.00%)
         occurrences all number
    1
    0
    Metabolism and nutrition disorders
    Malnutrition
    Additional description: Malnutrition
         subjects affected / exposed
    0 / 107 (0.00%)
    1 / 103 (0.97%)
         occurrences all number
    0
    1
    Electrolyte imbalance
    Additional description: Electrolyte imbalance
         subjects affected / exposed
    1 / 107 (0.93%)
    0 / 103 (0.00%)
         occurrences all number
    1
    0

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    03 Dec 2014
    In amendment I, in- and exclusion criteria were relaxed to facilitate enrolment.
    20 Jul 2016
    Amendment II, change of sponsor
    20 Mar 2018
    Amendment III, adjustment of sample size, conversion of interim analysis to final analysis
    18 Jul 2019
    Amendment IV, extension of the recruitment period

    Interruptions (globally)
    Were there any global interruptions to the trial? Yes
    Date
    Interruption
    Restart date
    25 Jun 2018
    The trial was suspended on advice from the Data Monitoring Committee (DMC). After a more detailed data analysis, the DMC recommended to proceed with enrolment.
    18 Jul 2018

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    Sample size was adjusted during the trial and the initially planned interim analysis was converted into the final analysis.

    Online references
    http://www.ncbi.nlm.nih.gov/pubmed/26452342
    http://www.ncbi.nlm.nih.gov/pubmed/32051007
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    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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