Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   43865   clinical trials with a EudraCT protocol, of which   7286   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Download PDF

    Clinical Trial Results:
    A Phase 3, Double-Blind, Multicenter, Randomized, Placebo-Controlled Study to Assess the Efficacy, Safety and Tolerability of Prophylactic Liposomal Amphotericin B (AmBisome®) for the Prevention of Invasive Fungal Infections (IFIs) in Subjects Receiving Remission-Induction Chemotherapy for Acute Lymphoblastic Leukemia (ALL)

    Summary
    EudraCT number
    		 2010-019562-91
    Trial protocol
    		 AT   PT   ES   DE   GR   BE   IT  
    Global end of trial date
    29 Jan 2014

    Results information
    Results version number
    		 v1(current)
    This version publication date
    22 Mar 2016
    First version publication date
    05 Aug 2015
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    GS-EU-131-0247
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT01259713
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Gilead Sciences
    Sponsor organisation address
    Flowers Building, Granta Park, Abington, Cambridge, United Kingdom, CB21 6GT
    Public contact
    Clinical Trial Mailbox, Gilead Sciences International Ltd, ClinicalTrialDisclosures@gilead.com
    Scientific contact
    Clinical Trial Mailbox, Gilead Sciences International Ltd, ClinicalTrialDisclosures@gilead.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    29 Jan 2014
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    29 Jan 2014
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The study investigated whether prophylaxis with liposomal amphotericin B (AmBisome®) can reduce the incidence of invasive fungal infections (IFIs) in patients with Acute Lymphoblastic Leukemia (ALL) who are undergoing their first remission induction.
    Protection of trial subjects
    The protocol and consent/assent forms were submitted by each investigator to a duly constituted Independent Ethics Committee (IEC) or Institutional Review Board (IRB) for review and approval before study initiation. All revisions to the consent/assent forms (if applicable) after initial IEC/IRB approval were submitted by the investigator to the IEC/IRB for review and approval before implementation in accordance with regulatory requirements. This study was conducted in accordance with recognized international scientific and ethical standards, including but not limited to the International Conference on Harmonization guideline for Good Clinical Practice (ICH GCP) and the original principles embodied in the Declaration of Helsinki.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    13 Apr 2011
    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
    Greece: 27
    Country: Number of subjects enrolled
    Italy: 66
    Country: Number of subjects enrolled
    Turkey: 11
    Country: Number of subjects enrolled
    Israel: 9
    Country: Number of subjects enrolled
    Switzerland: 7
    Country: Number of subjects enrolled
    Brazil: 15
    Country: Number of subjects enrolled
    Argentina: 8
    Country: Number of subjects enrolled
    Portugal: 17
    Country: Number of subjects enrolled
    Spain: 28
    Country: Number of subjects enrolled
    Austria: 9
    Country: Number of subjects enrolled
    Belgium: 31
    Country: Number of subjects enrolled
    France: 52
    Country: Number of subjects enrolled
    Germany: 75
    Worldwide total number of subjects
    355
    EEA total number of subjects
    305
    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)
    313
    From 65 to 84 years
    42
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 Participants were enrolled at a total of 86 study sites. The first participant was screened on 13 April 2011. The last study visit occurred on 29 January 2014.

    Pre-assignment
    Screening details
    		 391 participants were screened.

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Liposomal amphotericin B
    Arm description
    		 Liposomal amphotericin B twice weekly during induction chemotherapy
    Arm type
    		 Experimental

    Investigational medicinal product name
    Liposomal amphotericin B
    Investigational medicinal product code
    Other name
    AmBisome®
    Pharmaceutical forms
    Powder for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Liposomal amphotericin B 5 mg/kg administered by IV route over 2 hours twice weekly (each dose separated alternately by 2 and 3 days each week)

    Arm title
    		 Placebo
    Arm description
    		 Placebo to match liposomal amphotericin B twice weekly during induction chemotherapy
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo to match liposomal amphotericin B
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Placebo to match liposomal amphotericin B administered by IV route over 2 hours twice weekly (each dose separated alternately by 2 and 3 days each week)

    Number of subjects in period 1
    		Liposomal amphotericin B Placebo
    Started
    237
    118
    Completed
    142
    77
    Not completed
    95
    41
         Subject Withdrew Consent
    12
    7
         Adverse event, non-fatal
    54
    23
         Protocol violation
    5
    4
         Investigators Discretion
    14
    6
         Death Not Related to IFI
    8
    1
         Lack of efficacy
    2
    -

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Liposomal amphotericin B
    Reporting group description
    		 Liposomal amphotericin B twice weekly during induction chemotherapy

    Reporting group title
    Placebo
    Reporting group description
    		 Placebo to match liposomal amphotericin B twice weekly during induction chemotherapy

    Reporting group values
    		 Liposomal amphotericin B Placebo Total
    Number of subjects
    		 237 118 355
    Age categorical
    Units: Subjects
        ≤ 25 years
    		 37 25 62
        > 25 to ≤ 60 years
    		 160 64 224
        > 60 years
    		 40 29 69
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    		 44.5 ± 15.16 44.8 ± 17.52 -
    Gender, Male/Female
    Units: participants
        Female
    		 98 58 156
        Male
    		 139 60 199
    Race/Ethnicity, Customized
    Units: Subjects
        Asian
    		 1 0 1
        Black
    		 4 3 7
        White
    		 211 100 311
        Not Permitted
    		 17 15 32
        Other
    		 4 0 4
    Region of Enrollment
    Units: Subjects
        Germany
    		 52 23 75
        Italy
    		 41 25 66
        France
    		 33 19 52
        Belgium
    		 20 11 31
        Spain
    		 21 7 28
        Greece
    		 14 13 27
        Portugal
    		 13 4 17
        Turkey
    		 7 4 11
        Austria
    		 6 3 9
        Israel
    		 9 0 9
        Switzerland
    		 6 1 7
        Brazil
    		 8 7 15
        Argentina
    		 7 1 8

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Liposomal amphotericin B
    Reporting group description
    		 Liposomal amphotericin B twice weekly during induction chemotherapy

    Reporting group title
    Placebo
    Reporting group description
    		 Placebo to match liposomal amphotericin B twice weekly during induction chemotherapy

    Primary: Percentage of participants with proven or probable IFIs during remission-induction chemotherapy for acute lymphoblastic leukemia (ALL)

    		 Close Top of page
    End point title
    		 Percentage of participants with proven or probable IFIs during remission-induction chemotherapy for acute lymphoblastic leukemia (ALL)
    End point description
    Diagnoses of proven or probable invasive fungal infections (IFI) were assessed according to European Organization for Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) criteria by the independent data review board (IDRB) who were blinded to treatment assignment. The duration of remission-induction chemotherapy was defined as the period from the initiation of remission-induction chemotherapy administration to the start of consolidation or salvage therapy.
    End point type
    Primary
    End point timeframe
    During remission-induction chemotherapy (average 7 weeks)
    End point values
    		 Liposomal amphotericin B Placebo
    Number of subjects analysed
    228
    111
    Units: percentage of participants
        number (not applicable)
    7.9
    11.7
    Statistical analysis title
    		 Difference in relative risk reduction
    Statistical analysis description
    A two-group Cochran-Mantel-Haenszel (CMH) test with a 0.05 two-sided significance level and 2:1 allocation of 354 randomized subjects (236 AmBisome, 118 placebo) would have 81% power to detect a relative reduction of 75% if the rate of IFI is 10% in the placebo group (based on unpublished data from the German Multicenter Acute Lymphoblastic Leukemia Working Group (GMALL) and consistent with the published rate of 16.4% in patients with hematological malignancies undergoing remission induction).
    Comparison groups
    Placebo v Liposomal amphotericin B
    Number of subjects included in analysis
    339
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [1]
    P-value
    		 = 0.24 [2]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Relative risk reduction
    Point estimate
    0.33
    Confidence interval
         level
    		 95.03%
         sides
    2-sided
         lower limit
    		 -0.32
         upper limit
    		 0.66
    Notes
    [1] - For the interim analysis performed when 50% of the subjects had completed the study, an alpha of 0.0003 was spent. Therefore, the significance level for the 2-sided test in the primary analysis at the end of the study was 0.0497 (corresponding to 95.03% confidence interval (CI)). Relative risk reduction = 1- risk ratio.
    [2] - P-value was from a stratum-adjusted (stratified by region) CMH test.

    Secondary: Percentage of participants with pulmonary infiltrates according to the Central Image Reader

    		 Close Top of page
    End point title
    		 Percentage of participants with pulmonary infiltrates according to the Central Image Reader
    End point description
    End point type
    Secondary
    End point timeframe
    During remission-induction chemotherapy (average 7 weeks)
    End point values
    		 Liposomal amphotericin B Placebo
    Number of subjects analysed
    228
    111
    Units: percentage of participants
        number (not applicable)
    20.2
    27
    Statistical analysis title
    		 Difference in relative risk reduction
    Comparison groups
    Liposomal amphotericin B v Placebo
    Number of subjects included in analysis
    339
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.15 [3]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Relative risk reduction
    Point estimate
    0.25
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.11
         upper limit
    		 0.5
    Notes
    [3] - P-value was from a stratum-adjusted (stratified by region) CMH test. Relative risk reduction = 1- risk ratio.

    Secondary: Percentage of participants diagnosed with proven or probable IFIs according to the EORTC/MSG criteria, as assessed by the investigator

    		 Close Top of page
    End point title
    		 Percentage of participants diagnosed with proven or probable IFIs according to the EORTC/MSG criteria, as assessed by the investigator
    End point description
    End point type
    Secondary
    End point timeframe
    During remission-induction chemotherapy (average 7 weeks)
    End point values
    		 Liposomal amphotericin B Placebo
    Number of subjects analysed
    228
    111
    Units: percentage of participants
        number (not applicable)
    11
    10.8
    Statistical analysis title
    		 Difference in risk reduction
    Comparison groups
    Placebo v Liposomal amphotericin B
    Number of subjects included in analysis
    339
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.97 [4]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Relative risk reduction
    Point estimate
    -0.01
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.94
         upper limit
    		 0.47
    Notes
    [4] - P-value was from a stratum-adjusted (stratified by region) CMH test. Relative risk reduction = 1- risk ratio.

    Secondary: Percentage of Participants Requiring Antifungal Treatment During Remission-Induction Chemotherapy

    		 Close Top of page
    End point title
    		 Percentage of Participants Requiring Antifungal Treatment During Remission-Induction Chemotherapy
    End point description
    End point type
    Secondary
    End point timeframe
    During remission-induction chemotherapy (average 7 weeks)
    End point values
    		 Liposomal amphotericin B Placebo
    Number of subjects analysed
    228
    111
    Units: percentage of participants
        number (not applicable)
    16.2
    21.6
    Statistical analysis title
    		 Difference in rates of antifungal treatment
    Comparison groups
    Placebo v Liposomal amphotericin B
    Number of subjects included in analysis
    339
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.22 [5]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Relative risk reduction
    Point estimate
    0.25
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.19
         upper limit
    		 0.53
    Notes
    [5] - P-value was from a stratum-adjusted (stratified by region) CMH test. Relative risk reduction = 1- risk ratio.

    Secondary: Percentage of participants who died due to fungal infection; causality as assessed by the IDRB.

    		 Close Top of page
    End point title
    		 Percentage of participants who died due to fungal infection; causality as assessed by the IDRB.
    End point description
    End point type
    Secondary
    End point timeframe
    During remission-induction chemotherapy (average 7 weeks)
    End point values
    		 Liposomal amphotericin B Placebo
    Number of subjects analysed
    228
    111
    Units: percentage of participants
        number (not applicable)
    0.9
    0
    Statistical analysis title
    		 Difference in rates of death due to IFI
    Comparison groups
    Placebo v Liposomal amphotericin B
    Number of subjects included in analysis
    339
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.32 [6]
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
         sides
    2-sided
         lower limit
    		 -
         upper limit
    		 -
    Notes
    [6] - P-value was from a stratum-adjusted (stratified by region) CMH test.

    Secondary: Percentage of participants who died due to fungal infection; causality as assessed by the investigator.

    		 Close Top of page
    End point title
    		 Percentage of participants who died due to fungal infection; causality as assessed by the investigator.
    End point description
    End point type
    Secondary
    End point timeframe
    During remission-induction chemotherapy (average 7 weeks)
    End point values
    		 Liposomal amphotericin B Placebo
    Number of subjects analysed
    228
    111
    Units: percentage of participants
        number (not applicable)
    0.9
    0
    Statistical analysis title
    		 Difference in rates of death due to IFI
    Comparison groups
    Placebo v Liposomal amphotericin B
    Number of subjects included in analysis
    339
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.32 [7]
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Notes
    [7] - P-value was from a stratum-adjusted (stratified by region) CMH test.

    Secondary: Time from beginning of remission-induction chemotherapy until the beginning of consolidation therapy

    		 Close Top of page
    End point title
    		 Time from beginning of remission-induction chemotherapy until the beginning of consolidation therapy
    End point description
    This endpoint was to evaluate the potential impact of IFI prevention on the efficacy of remission-induction chemotherapy for ALL.
    End point type
    Secondary
    End point timeframe
    During remission-induction chemotherapy (average 7 weeks)
    End point values
    		 Liposomal amphotericin B Placebo
    Number of subjects analysed
    228
    111
    Units: days
        median (inter-quartile range (Q1-Q3))
    50 (38 to 75)
    55 (36 to 75)
    Statistical analysis title
    		 Difference in days
    Comparison groups
    Placebo v Liposomal amphotericin B
    Number of subjects included in analysis
    339
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.69 [8]
    Method
    		 Logrank
    Confidence interval
    Notes
    [8] - The p-value was from the log-rank test stratified by region.

    Secondary: Percentage of participants with complete remission at the end of remission induction

    		 Close Top of page
    End point title
    		 Percentage of participants with complete remission at the end of remission induction
    End point description
    This endpoint was to evaluate the potential impact of IFI prevention on the efficacy of remission-induction chemotherapy for ALL.
    End point type
    Secondary
    End point timeframe
    During remission-induction chemotherapy (average 7 weeks)
    End point values
    		 Liposomal amphotericin B Placebo
    Number of subjects analysed
    228
    111
    Units: percentage of participants
        number (not applicable)
    72.8
    79.3
    Statistical analysis title
    		 Difference in rate of remission-induction response
    Statistical analysis description
    Participants were not stratified for leukemia risk.
    Comparison groups
    Placebo v Liposomal amphotericin B
    Number of subjects included in analysis
    339
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.2 [9]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Relative risk reduction
    Point estimate
    0.08
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.04
         upper limit
    		 0.19
    Notes
    [9] - P-value was from a stratum-adjusted (stratified by region) CMH test. Relative risk reduction = 1- risk ratio.

    Secondary: Time to Diagnosis of Proven or Probable IFIs According to the EORTC/MSG Criteria, as Assessed by the IDRB.

    		 Close Top of page
    End point title
    		 Time to Diagnosis of Proven or Probable IFIs According to the EORTC/MSG Criteria, as Assessed by the IDRB.
    End point description
    Time to diagnosis of proven or probable IFIs is presented as the median (Q1,Q3) days to diagnosis of those participants who experienced a proven or probable IFI. Median was not reached if < 50% of participants had an event; Q1 was not reached if < 25% of participants had an event; Q3 was not reached if < 75% of participants had an event. 999 / 9999 / 99999 = not reached due to insufficient number of events
    End point type
    Secondary
    End point timeframe
    During remission-induction chemotherapy (average 7 weeks)
    End point values
    		 Liposomal amphotericin B Placebo
    Number of subjects analysed
    228
    111
    Units: days
        median (inter-quartile range (Q1-Q3))
    9999 (999 to 99999)
    9999 (999 to 99999)
    Statistical analysis title
    		 Difference in time to IFI
    Comparison groups
    Placebo v Liposomal amphotericin B
    Number of subjects included in analysis
    339
    Analysis specification
    Pre-specified
    Analysis type
    		 other [10]
    P-value
    		 = 0.33 [11]
    Method
    		 Logrank
    Confidence interval
    Notes
    [10] - Comparative analysis.
    [11] - The p-value is from the log-rank test stratified by region.

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    From first dose to last dose of study drug plus 30 days.
    Adverse event reporting additional description
    Safety Analysis Set; participants were randomized and received at least 1 dose of study drug. MedDRA version 11.1 was used for the Tenofovir and Placebo columns; MedDRA version 16.1 was used for the All TDF column. All AEs are reported by system order class and preferred term as determined by the investigator.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    16.1
    Reporting groups
    Reporting group title
    Liposomal amphotericin B
    Reporting group description
    		 Liposomal amphotericin B 5 mg/kg twice weekly administered by IV route over 2 hours twice weekly (each dose separated alternately by 2 and 3 days each week) during induction chemotherapy

    Reporting group title
    Placebo
    Reporting group description
    		 Placebo to match liposomal amphotericin B twice weekly administered by IV route over 2 hours twice weekly (each dose separated alternately by 2 and 3 days each week) during induction chemotherapy

    Serious adverse events
    		 Liposomal amphotericin B Placebo
    Total subjects affected by serious adverse events
         subjects affected / exposed
    79 / 237 (33.33%)
    38 / 118 (32.20%)
         number of deaths (all causes)
    17
    8
         number of deaths resulting from adverse events
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Metastases to bone marrow
         subjects affected / exposed
    1 / 237 (0.42%)
    0 / 118 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metastases to central nervous system
         subjects affected / exposed
    1 / 237 (0.42%)
    0 / 118 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular disorders
    Deep vein thrombosis
         subjects affected / exposed
    0 / 237 (0.00%)
    1 / 118 (0.85%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypotension
         subjects affected / exposed
    1 / 237 (0.42%)
    0 / 118 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thrombosis
         subjects affected / exposed
    0 / 237 (0.00%)
    1 / 118 (0.85%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Pyrexia
         subjects affected / exposed
    2 / 237 (0.84%)
    3 / 118 (2.54%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Systemic inflammatory response syndrome
         subjects affected / exposed
    0 / 237 (0.00%)
    2 / 118 (1.69%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chills
         subjects affected / exposed
    1 / 237 (0.42%)
    0 / 118 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chest pain
         subjects affected / exposed
    1 / 237 (0.42%)
    0 / 118 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Inflammation
         subjects affected / exposed
    0 / 237 (0.00%)
    1 / 118 (0.85%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Multi-organ failure
         subjects affected / exposed
    1 / 237 (0.42%)
    0 / 118 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mucosal inflammation
         subjects affected / exposed
    1 / 237 (0.42%)
    0 / 118 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Immune system disorders
    Allergic oedema
         subjects affected / exposed
    1 / 237 (0.42%)
    0 / 118 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Drug hypersensitivity
         subjects affected / exposed
    1 / 237 (0.42%)
    0 / 118 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypersensitivity
         subjects affected / exposed
    1 / 237 (0.42%)
    0 / 118 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Acute respiratory distress syndrome
         subjects affected / exposed
    2 / 237 (0.84%)
    0 / 118 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    Pulmonary haemorrhage
         subjects affected / exposed
    2 / 237 (0.84%)
    0 / 118 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Respiratory failure
         subjects affected / exposed
    1 / 237 (0.42%)
    1 / 118 (0.85%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchial obstruction
         subjects affected / exposed
    1 / 237 (0.42%)
    0 / 118 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchospasm
         subjects affected / exposed
    1 / 237 (0.42%)
    0 / 118 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dyspnoea
         subjects affected / exposed
    1 / 237 (0.42%)
    0 / 118 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Interstitial lung disease
         subjects affected / exposed
    0 / 237 (0.00%)
    1 / 118 (0.85%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonitis
         subjects affected / exposed
    0 / 237 (0.00%)
    1 / 118 (0.85%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumothorax
         subjects affected / exposed
    1 / 237 (0.42%)
    0 / 118 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory distress
         subjects affected / exposed
    1 / 237 (0.42%)
    0 / 118 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Investigations
    Blood creatinine increased
         subjects affected / exposed
    3 / 237 (1.27%)
    0 / 118 (0.00%)
         occurrences causally related to treatment / all
    3 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Creatinine renal clearance decreased
         subjects affected / exposed
    2 / 237 (0.84%)
    0 / 118 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Alanine aminotransferase increased
         subjects affected / exposed
    0 / 237 (0.00%)
    1 / 118 (0.85%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Aspartate aminotransferase increased
         subjects affected / exposed
    0 / 237 (0.00%)
    1 / 118 (0.85%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    White blood cell count decreased
         subjects affected / exposed
    1 / 237 (0.42%)
    0 / 118 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lymphocyte count decreased
         subjects affected / exposed
    1 / 237 (0.42%)
    0 / 118 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Post lumbar puncture syndrome
         subjects affected / exposed
    2 / 237 (0.84%)
    1 / 118 (0.85%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Subdural haematoma
         subjects affected / exposed
    2 / 237 (0.84%)
    1 / 118 (0.85%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Cardiac arrest
         subjects affected / exposed
    4 / 237 (1.69%)
    0 / 118 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    Arrhythmia
         subjects affected / exposed
    0 / 237 (0.00%)
    1 / 118 (0.85%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrial fibrillation
         subjects affected / exposed
    0 / 237 (0.00%)
    1 / 118 (0.85%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardio-respiratory arrest
         subjects affected / exposed
    1 / 237 (0.42%)
    0 / 118 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Encephalopathy
         subjects affected / exposed
    2 / 237 (0.84%)
    2 / 118 (1.69%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Cerebral ischaemia
         subjects affected / exposed
    1 / 237 (0.42%)
    0 / 118 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebrovascular accident
         subjects affected / exposed
    1 / 237 (0.42%)
    0 / 118 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Encephalitis
         subjects affected / exposed
    1 / 237 (0.42%)
    0 / 118 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Hepatic encephalopathy
         subjects affected / exposed
    1 / 237 (0.42%)
    0 / 118 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intracranial venous sinus thrombosis
         subjects affected / exposed
    1 / 237 (0.42%)
    0 / 118 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Meningism
         subjects affected / exposed
    1 / 237 (0.42%)
    0 / 118 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Somnolence
         subjects affected / exposed
    0 / 237 (0.00%)
    1 / 118 (0.85%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Febrile neutropenia
         subjects affected / exposed
    10 / 237 (4.22%)
    6 / 118 (5.08%)
         occurrences causally related to treatment / all
    0 / 10
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thrombocytopenia
         subjects affected / exposed
    2 / 237 (0.84%)
    0 / 118 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anaemia
         subjects affected / exposed
    1 / 237 (0.42%)
    0 / 118 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neutropenia
         subjects affected / exposed
    1 / 237 (0.42%)
    0 / 118 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancytopenia
         subjects affected / exposed
    1 / 237 (0.42%)
    0 / 118 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Eye disorders
    Visual acuity reduced
         subjects affected / exposed
    0 / 237 (0.00%)
    1 / 118 (0.85%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Colitis
         subjects affected / exposed
    1 / 237 (0.42%)
    1 / 118 (0.85%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatitis
         subjects affected / exposed
    2 / 237 (0.84%)
    0 / 118 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Caecitis
         subjects affected / exposed
    1 / 237 (0.42%)
    0 / 118 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ileitis
         subjects affected / exposed
    0 / 237 (0.00%)
    1 / 118 (0.85%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ileus
         subjects affected / exposed
    1 / 237 (0.42%)
    0 / 118 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intestinal obstruction
         subjects affected / exposed
    1 / 237 (0.42%)
    0 / 118 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intra-abdominal haemorrhage
         subjects affected / exposed
    0 / 237 (0.00%)
    1 / 118 (0.85%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Upper gastrointestinal haemorrhage
         subjects affected / exposed
    1 / 237 (0.42%)
    0 / 118 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Vomiting
         subjects affected / exposed
    1 / 237 (0.42%)
    0 / 118 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Bile duct stone
         subjects affected / exposed
    1 / 237 (0.42%)
    0 / 118 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatic failure
         subjects affected / exposed
    2 / 237 (0.84%)
    0 / 118 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholecystitis
         subjects affected / exposed
    1 / 237 (0.42%)
    0 / 118 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholecystitis acute
         subjects affected / exposed
    1 / 237 (0.42%)
    0 / 118 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatic steatosis
         subjects affected / exposed
    1 / 237 (0.42%)
    0 / 118 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatocellular injury
         subjects affected / exposed
    1 / 237 (0.42%)
    0 / 118 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyperbilirubinaemia
         subjects affected / exposed
    1 / 237 (0.42%)
    0 / 118 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Liver disorder
         subjects affected / exposed
    1 / 237 (0.42%)
    0 / 118 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Rash papular
         subjects affected / exposed
    1 / 237 (0.42%)
    0 / 118 (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
    Renal failure
         subjects affected / exposed
    4 / 237 (1.69%)
    2 / 118 (1.69%)
         occurrences causally related to treatment / all
    4 / 4
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal failure acute
         subjects affected / exposed
    3 / 237 (1.27%)
    2 / 118 (1.69%)
         occurrences causally related to treatment / all
    1 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nephropathy toxic
         subjects affected / exposed
    1 / 237 (0.42%)
    0 / 118 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal tubular necrosis
         subjects affected / exposed
    1 / 237 (0.42%)
    0 / 118 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    1 / 237 (0.42%)
    0 / 118 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Joint swelling
         subjects affected / exposed
    1 / 237 (0.42%)
    0 / 118 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Septic shock
         subjects affected / exposed
    13 / 237 (5.49%)
    2 / 118 (1.69%)
         occurrences causally related to treatment / all
    0 / 13
    0 / 2
         deaths causally related to treatment / all
    0 / 7
    0 / 2
    Pneumonia
         subjects affected / exposed
    7 / 237 (2.95%)
    3 / 118 (2.54%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 3
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    Sepsis
         subjects affected / exposed
    4 / 237 (1.69%)
    6 / 118 (5.08%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 7
         deaths causally related to treatment / all
    0 / 2
    0 / 3
    Device related infection
         subjects affected / exposed
    3 / 237 (1.27%)
    0 / 118 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bacterial sepsis
         subjects affected / exposed
    2 / 237 (0.84%)
    0 / 118 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Pneumonia bacterial
         subjects affected / exposed
    2 / 237 (0.84%)
    0 / 118 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Escherichia sepsis
         subjects affected / exposed
    0 / 237 (0.00%)
    2 / 118 (1.69%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pseudomonal sepsis
         subjects affected / exposed
    2 / 237 (0.84%)
    0 / 118 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Aspergillus infection
         subjects affected / exposed
    0 / 237 (0.00%)
    1 / 118 (0.85%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Clostridium difficile colitis
         subjects affected / exposed
    1 / 237 (0.42%)
    0 / 118 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Enterococcal bacteraemia
         subjects affected / exposed
    1 / 237 (0.42%)
    0 / 118 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    1 / 237 (0.42%)
    0 / 118 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Klebsiella infection
         subjects affected / exposed
    0 / 237 (0.00%)
    1 / 118 (0.85%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Lower respiratory tract infection
         subjects affected / exposed
    0 / 237 (0.00%)
    1 / 118 (0.85%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumocystis jirovecii infection
         subjects affected / exposed
    0 / 237 (0.00%)
    1 / 118 (0.85%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Pneumonia klebsiella
         subjects affected / exposed
    1 / 237 (0.42%)
    0 / 118 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia necrotising
         subjects affected / exposed
    0 / 237 (0.00%)
    1 / 118 (0.85%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory moniliasis
         subjects affected / exposed
    0 / 237 (0.00%)
    1 / 118 (0.85%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Staphylococcal infection
         subjects affected / exposed
    1 / 237 (0.42%)
    0 / 118 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Streptococcal sepsis
         subjects affected / exposed
    1 / 237 (0.42%)
    0 / 118 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Hyperammonaemia
         subjects affected / exposed
    1 / 237 (0.42%)
    0 / 118 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypokalaemia
         subjects affected / exposed
    2 / 237 (0.84%)
    0 / 118 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyperglycaemia
         subjects affected / exposed
    1 / 237 (0.42%)
    0 / 118 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyponatraemia
         subjects affected / exposed
    1 / 237 (0.42%)
    0 / 118 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Liposomal amphotericin B Placebo
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    233 / 237 (98.31%)
    114 / 118 (96.61%)
    Vascular disorders
    Hypotension
         subjects affected / exposed
    17 / 237 (7.17%)
    15 / 118 (12.71%)
         occurrences all number
    21
    18
    Hypertension
         subjects affected / exposed
    12 / 237 (5.06%)
    7 / 118 (5.93%)
         occurrences all number
    14
    7
    Haematoma
         subjects affected / exposed
    15 / 237 (6.33%)
    3 / 118 (2.54%)
         occurrences all number
    18
    3
    General disorders and administration site conditions
    Pyrexia
         subjects affected / exposed
    65 / 237 (27.43%)
    37 / 118 (31.36%)
         occurrences all number
    98
    50
    Mucosal inflammation
         subjects affected / exposed
    61 / 237 (25.74%)
    32 / 118 (27.12%)
         occurrences all number
    69
    39
    Oedema peripheral
         subjects affected / exposed
    56 / 237 (23.63%)
    18 / 118 (15.25%)
         occurrences all number
    69
    21
    Asthenia
         subjects affected / exposed
    32 / 237 (13.50%)
    19 / 118 (16.10%)
         occurrences all number
    36
    22
    Fatigue
         subjects affected / exposed
    17 / 237 (7.17%)
    10 / 118 (8.47%)
         occurrences all number
    20
    13
    Chest pain
         subjects affected / exposed
    18 / 237 (7.59%)
    8 / 118 (6.78%)
         occurrences all number
    21
    10
    Chills
         subjects affected / exposed
    17 / 237 (7.17%)
    9 / 118 (7.63%)
         occurrences all number
    19
    11
    Oedema
         subjects affected / exposed
    15 / 237 (6.33%)
    6 / 118 (5.08%)
         occurrences all number
    18
    9
    Pain
         subjects affected / exposed
    10 / 237 (4.22%)
    11 / 118 (9.32%)
         occurrences all number
    11
    14
    Reproductive system and breast disorders
    Vaginal haemorrhage
         subjects affected / exposed
    2 / 237 (0.84%)
    6 / 118 (5.08%)
         occurrences all number
    2
    7
    Respiratory, thoracic and mediastinal disorders
    Epistaxis
         subjects affected / exposed
    20 / 237 (8.44%)
    16 / 118 (13.56%)
         occurrences all number
    28
    21
    Cough
         subjects affected / exposed
    29 / 237 (12.24%)
    17 / 118 (14.41%)
         occurrences all number
    32
    19
    Dyspnoea
         subjects affected / exposed
    19 / 237 (8.02%)
    10 / 118 (8.47%)
         occurrences all number
    21
    14
    Oropharyngeal pain
         subjects affected / exposed
    15 / 237 (6.33%)
    13 / 118 (11.02%)
         occurrences all number
    16
    14
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    19 / 237 (8.02%)
    15 / 118 (12.71%)
         occurrences all number
    22
    17
    Insomnia
         subjects affected / exposed
    32 / 237 (13.50%)
    17 / 118 (14.41%)
         occurrences all number
    35
    17
    Depression
         subjects affected / exposed
    12 / 237 (5.06%)
    5 / 118 (4.24%)
         occurrences all number
    12
    5
    Agitation
         subjects affected / exposed
    5 / 237 (2.11%)
    7 / 118 (5.93%)
         occurrences all number
    7
    8
    Investigations
    Antithrombin III decreased
         subjects affected / exposed
    33 / 237 (13.92%)
    14 / 118 (11.86%)
         occurrences all number
    34
    15
    Blood fibrinogen decreased
         subjects affected / exposed
    19 / 237 (8.02%)
    8 / 118 (6.78%)
         occurrences all number
    21
    8
    Alanine aminotransferase increased
         subjects affected / exposed
    17 / 237 (7.17%)
    9 / 118 (7.63%)
         occurrences all number
    21
    9
    Aspartate aminotransferase increased
         subjects affected / exposed
    19 / 237 (8.02%)
    4 / 118 (3.39%)
         occurrences all number
    21
    4
    Blood bilirubin increased
         subjects affected / exposed
    16 / 237 (6.75%)
    4 / 118 (3.39%)
         occurrences all number
    24
    4
    Blood creatinine increased
         subjects affected / exposed
    20 / 237 (8.44%)
    0 / 118 (0.00%)
         occurrences all number
    26
    0
    Weight decreased
         subjects affected / exposed
    13 / 237 (5.49%)
    4 / 118 (3.39%)
         occurrences all number
    13
    5
    Cardiac disorders
    Tachycardia
         subjects affected / exposed
    13 / 237 (5.49%)
    8 / 118 (6.78%)
         occurrences all number
    15
    11
    Nervous system disorders
    Headache
         subjects affected / exposed
    84 / 237 (35.44%)
    45 / 118 (38.14%)
         occurrences all number
    126
    60
    Dizziness
         subjects affected / exposed
    11 / 237 (4.64%)
    12 / 118 (10.17%)
         occurrences all number
    12
    14
    Paraesthesia
         subjects affected / exposed
    14 / 237 (5.91%)
    9 / 118 (7.63%)
         occurrences all number
    14
    9
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    49 / 237 (20.68%)
    27 / 118 (22.88%)
         occurrences all number
    97
    44
    Febrile neutropenia
         subjects affected / exposed
    50 / 237 (21.10%)
    26 / 118 (22.03%)
         occurrences all number
    63
    34
    Neutropenia
         subjects affected / exposed
    40 / 237 (16.88%)
    26 / 118 (22.03%)
         occurrences all number
    58
    33
    Thrombocytopenia
         subjects affected / exposed
    42 / 237 (17.72%)
    14 / 118 (11.86%)
         occurrences all number
    72
    21
    Coagulopathy
         subjects affected / exposed
    13 / 237 (5.49%)
    9 / 118 (7.63%)
         occurrences all number
    14
    10
    Ear and labyrinth disorders
    Vertigo
         subjects affected / exposed
    14 / 237 (5.91%)
    8 / 118 (6.78%)
         occurrences all number
    16
    12
    Gastrointestinal disorders
    Nausea
         subjects affected / exposed
    118 / 237 (49.79%)
    50 / 118 (42.37%)
         occurrences all number
    157
    80
    Vomiting
         subjects affected / exposed
    75 / 237 (31.65%)
    43 / 118 (36.44%)
         occurrences all number
    101
    60
    Constipation
         subjects affected / exposed
    74 / 237 (31.22%)
    40 / 118 (33.90%)
         occurrences all number
    91
    41
    Diarrhoea
         subjects affected / exposed
    66 / 237 (27.85%)
    36 / 118 (30.51%)
         occurrences all number
    83
    49
    Abdominal pain
         subjects affected / exposed
    55 / 237 (23.21%)
    35 / 118 (29.66%)
         occurrences all number
    78
    44
    Abdominal pain upper
         subjects affected / exposed
    39 / 237 (16.46%)
    14 / 118 (11.86%)
         occurrences all number
    44
    19
    Haemorrhoids
         subjects affected / exposed
    18 / 237 (7.59%)
    12 / 118 (10.17%)
         occurrences all number
    19
    12
    Stomatitis
         subjects affected / exposed
    14 / 237 (5.91%)
    11 / 118 (9.32%)
         occurrences all number
    14
    11
    Dyspepsia
         subjects affected / exposed
    14 / 237 (5.91%)
    4 / 118 (3.39%)
         occurrences all number
    16
    4
    Hepatobiliary disorders
    Hyperbilirubinaemia
         subjects affected / exposed
    6 / 237 (2.53%)
    7 / 118 (5.93%)
         occurrences all number
    7
    7
    Skin and subcutaneous tissue disorders
    Rash
         subjects affected / exposed
    39 / 237 (16.46%)
    11 / 118 (9.32%)
         occurrences all number
    46
    11
    Erythema
         subjects affected / exposed
    19 / 237 (8.02%)
    5 / 118 (4.24%)
         occurrences all number
    21
    6
    Alopecia
         subjects affected / exposed
    17 / 237 (7.17%)
    6 / 118 (5.08%)
         occurrences all number
    17
    6
    Pruritus
         subjects affected / exposed
    13 / 237 (5.49%)
    4 / 118 (3.39%)
         occurrences all number
    18
    4
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    34 / 237 (14.35%)
    16 / 118 (13.56%)
         occurrences all number
    37
    20
    Neck pain
         subjects affected / exposed
    14 / 237 (5.91%)
    9 / 118 (7.63%)
         occurrences all number
    15
    10
    Pain in extremity
         subjects affected / exposed
    8 / 237 (3.38%)
    10 / 118 (8.47%)
         occurrences all number
    9
    11
    Bone pain
         subjects affected / exposed
    11 / 237 (4.64%)
    6 / 118 (5.08%)
         occurrences all number
    13
    7
    Infections and infestations
    Oral herpes
         subjects affected / exposed
    22 / 237 (9.28%)
    7 / 118 (5.93%)
         occurrences all number
    24
    7
    Oral candidiasis
         subjects affected / exposed
    8 / 237 (3.38%)
    11 / 118 (9.32%)
         occurrences all number
    8
    11
    Bacterial infection
         subjects affected / exposed
    12 / 237 (5.06%)
    6 / 118 (5.08%)
         occurrences all number
    17
    6
    Pneumonia
         subjects affected / exposed
    15 / 237 (6.33%)
    3 / 118 (2.54%)
         occurrences all number
    15
    3
    Folliculitis
         subjects affected / exposed
    10 / 237 (4.22%)
    6 / 118 (5.08%)
         occurrences all number
    10
    6
    Metabolism and nutrition disorders
    Hypokalaemia
         subjects affected / exposed
    83 / 237 (35.02%)
    21 / 118 (17.80%)
         occurrences all number
    115
    32
    Hyperglycaemia
         subjects affected / exposed
    22 / 237 (9.28%)
    11 / 118 (9.32%)
         occurrences all number
    22
    12
    Hypoalbuminaemia
         subjects affected / exposed
    24 / 237 (10.13%)
    9 / 118 (7.63%)
         occurrences all number
    30
    9
    Decreased appetite
         subjects affected / exposed
    18 / 237 (7.59%)
    9 / 118 (7.63%)
         occurrences all number
    19
    9
    Hypocalcaemia
         subjects affected / exposed
    18 / 237 (7.59%)
    7 / 118 (5.93%)
         occurrences all number
    18
    7
    Fluid retention
         subjects affected / exposed
    15 / 237 (6.33%)
    6 / 118 (5.08%)
         occurrences all number
    27
    7
    Hyperuricaemia
         subjects affected / exposed
    13 / 237 (5.49%)
    4 / 118 (3.39%)
         occurrences all number
    14
    4
    Hypomagnesaemia
         subjects affected / exposed
    12 / 237 (5.06%)
    5 / 118 (4.24%)
         occurrences all number
    20
    7

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    13 Oct 2010
    Removed the restriction that the duration of study treatment be a maximum of 12 weeks; updated the duration of clinical monitoring for IFIs such that it continued until a subject had started consolidation therapy, and was not restricted to 12 weeks; added an interim analysis to the study which allowed for stopping due to futility.
    10 May 2011
    Clarified the end of study-drug administration and the use of salvage therapy for subjects not recovering from neutropenia; adjusted the stratification factors of the study to use region only.
    10 May 2012
    Clarified the end of monitoring for fungal infection; updated directions for emergency unblinding.

    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.
    57 patients received protocol-prohibited antifungal treatment and 30 received a non-myelosuppresive chemotherapy regimen that may have impacted the primary endpoint analysis.
    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.

    European Medicines Agency © 1995-Fri Apr 26 22:21:33 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA