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    Clinical Trial Results:
    A RANDOMIZED, OPEN-LABEL, MULTICENTER, CONTROLLED STUDY TO ASSESS SAFETY AND EFFICACY OF ELAD IN SUBJECTS WITH SEVERE ACUTE ALCOHOLIC HEPATITIS (SAAH) AND LILLE SCORE FAILURE

    Summary
    EudraCT number
    		 2013-001884-21
    Trial protocol
    		 GB   DE   ES   AT  
    Global end of trial date
    16 Sep 2015

    Results information
    Results version number
    		 v1(current)
    This version publication date
    09 Apr 2017
    First version publication date
    09 Apr 2017
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    VTI-210
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT01829347
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Vital Therapies, Inc.
    Sponsor organisation address
    15010 Avenue of Science, Suite 200, San Diego, United States, 92128
    Public contact
    Duane Nash, Vital Therapies, Inc., 001 858-673-6840, dnash@vitaltherapies.com
    Scientific contact
    Robert Ashley, Chief Technical Officer, Vital Therapies, Inc., 001 858-673-6840, rashley@vitaltherapies.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
    11 Jul 2016
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    16 Sep 2015
    Global end of trial reached?
    Yes
    Global end of trial date
    16 Sep 2015
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    The primary objective of the study is to evaluate safety and efficacy of ELAD with respect to overall survival (OS) in subjects with a clinical diagnosis of severe acute alcoholic hepatitis (sAAH) who are Lille score failures (Lille score >0.45). Follow-up Protocol VTI 210E will provide additional survival data up to a maximum of 5 years that will be included, as available, through VTI-210 study termination (after all enrolled subjects complete Study Day 91, are lost to follow up or withdraw consent, or die before that Study Day). This will be assessed using a Kaplan-Meier survival analysis of the intent-to-treat (ITT) population utilizing a log-rank test to evaluate the null hypothesis of equality of survival curves. The randomization and the analysis model will be stratified by whether or not the clinical diagnosis of sAAH was confirmed with a liver biopsy.
    Protection of trial subjects
    Continuous monitoring of the ELAD System by trained ELAD Specialists during ELAD treatment. Administration of diphenhydramine or equivalent immediately prior to initiation of ELAD treatment to prevent hypersensitivity reactions.
    Background therapy
    		 The standard of care (background therapy) for the secondary medical problems associated with alcoholic hepatitis (AH) was derived from the practice guidelines issued by the American Association for the Study of Liver Disease (AASLD) and the European Association for the Study of Liver (EASL). These guidelines were applied to both the ELAD-treated and Control subjects during this study.
    Evidence for comparator
    		 VTI-210 was a randomized, open-label, multicenter, controlled study of subjects with severe acute alcoholic hepatitis (sAAH). Subjects meeting eligibility requirements of the study received either standard of care treatment for sAAH (as defined in the protocol) plus treatment with the ELAD System (ELAD group) or standard of care treatment for sAAH alone (Control group). Treatment options for patients with sAAH are limited. Patients with severe AH (defined as a Maddrey Discriminant Function of ≥32) have a poor prognosis, with 90-day survival of around 50%. Regimens that have been used for the past 40 years, including corticosteroids, theophylline with corticosteroids, pentoxifylline, and infliximab, have had no significant effect on the long-term survival of patients with sAAH. Of particular importance are the results of the UK NIHR-supported STOPAH study, a study in alcoholic hepatitis reporting out in 2015. Results from this study, which randomized 1103 subjects in 40 clinical sites in the UK, showed that the administration of steroids and pentoxifylline had no effect on survival at 90 days either alone or in combination. While a sham control is a potential comparator, regulatory and ethical bodies have determined that the administration of a sham extracorporeal therapy without the possibility of benefit is unethical, and therefore could not be considered for study VTI-210. Consequently, the best available standard of care in accord with AASLD and EASL guidelines was recommended in the VTI-210 study protocol for all participants irrespective of treatment arm.
    Actual start date of recruitment
    30 Sep 2014
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    		 Safety, Efficacy, Ethical reason, Regulatory reason, Scientific research
    Long term follow-up duration
    		 5 Years
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Spain: 9
    Country: Number of subjects enrolled
    United Kingdom: 4
    Country: Number of subjects enrolled
    United States: 5
    Worldwide total number of subjects
    18
    EEA total number of subjects
    13
    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)
    18
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 Participants with clinical (protocol-guided) or biopsy-proven evidence of sAAH who met study inclusion/exclusion criteria, including Lille score >0.45, were eligible for participation in the study. Subjects were recruited from September 2014 through August 2015 in the United States, United Kingdom and Spain.

    Pre-assignment
    Screening details
    		 A total of 31 participants diagnosed with alcoholic hepatitis were screened, out of which 13 were screen failures, and 18 were randomized, of which 9 received ELAD treatment. Participants who successfully completed the initial 91-day treatment period were entered into a 5-year extension phase (VTI-210) of the study.

    Period 1
    Period 1 title
    VTI-210
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded
    Blinding implementation details
    Investigative staff who carried out follow-up treatment visits were blinded to participant treatment assignment. Home visit staff who carried out weekly home visits for participants discharged from the hospital were also blinded to participant treatment assignment. Sponsor staff, with the exception of those involved in the monitoring of the study safety, were blinded to treatment outcomes. The Data and Safety Monitoring Board was blinded to study outcomes.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 ELAD Treatment
    Arm description
    		 Participants randomized to the ELAD group received ELAD treatment plus protocol-directed standard of care treatment for a period of up to 10 days followed by standard of care treatment through Study Day 91.
    Arm type
    		 Experimental

    Investigational medicinal product name
    ELAD
    Investigational medicinal product code
    ELAD System
    Other name
    VTL C3A cells
    Pharmaceutical forms
    Living tissue equivalent
    Routes of administration
    Haemodialysis
    Dosage and administration details
    Four cartridges, each containing approximately 110 grams of VTL C3A cells (approximately 440 grams total or approximately 20% to 30% of the native liver, a residual mass necessary for survival). ELAD treatment duration spans for up to 10 days. Continuous extracorporeal circulation by central venous catheter allowing plasma fraction interaction with VTL C3A cells incorporated in ELAD C3A cell cartridges.

    Arm title
    		 Control
    Arm description
    		 Participants randomized to the Control group received protocol-directed standard of care treatment in accord with AASLD and EASL guidelines for up to 91 days.
    Arm type
    		 No intervention

    Investigational medicinal product name
    No investigational medicinal product assigned in this arm
    Number of subjects in period 1
    		ELAD Treatment Control
    Started
    9
    9
    Completed
    4
    6
    Not completed
    5
    3
         Adverse event, serious fatal
    4
    3
         Consent withdrawn by subject
    1
    -
    Period 2
    Period 2 title
    VTI-210E
    Is this the baseline period?
    		 No
    Allocation method
    Not applicable
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 ELAD Treatment
    Arm description
    		 Participants randomized to the ELAD group and who received ELAD treatment plus protocol-directed standard of care treatment for a period of up to 10 days during study VTI-210 were followed up for up to 5 years in VTI-210E.
    Arm type
    		 Experimental

    Investigational medicinal product name
    ELAD
    Investigational medicinal product code
    ELAD System
    Other name
    VTL C3A cells
    Pharmaceutical forms
    Living tissue equivalent
    Routes of administration
    Haemodialysis
    Dosage and administration details
    Four cartridges, each containing approximately 110 grams of VTL C3A cells (approximately 440 grams total or approximately 20% to 30% of the native liver, a residual mass necessary for survival). ELAD treatment duration spans for up to 10 days. Continuous extracorporeal circulation by central venous catheter allowing plasma fraction interaction with VTL C3A cells incorporated in ELAD C3A cell cartridges.

    Arm title
    		 Control
    Arm description
    		 Participants randomized to the Control group and who received protocol-directed standard of care during the VTI-210 study in accord with AASLD and EASL guidelines were followed up for up to 5 years.
    Arm type
    		 No intervention

    Investigational medicinal product name
    No investigational medicinal product assigned in this arm
    Number of subjects in period 2
    		ELAD Treatment Control
    Started
    4
    6
    Completed
    0
    0
    Not completed
    4
    6
         Death
    3
    2
         VTI-210E ongoing
    1
    4

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    ELAD Treatment
    Reporting group description
    		 Participants randomized to the ELAD group received ELAD treatment plus protocol-directed standard of care treatment for a period of up to 10 days followed by standard of care treatment through Study Day 91.

    Reporting group title
    Control
    Reporting group description
    		 Participants randomized to the Control group received protocol-directed standard of care treatment in accord with AASLD and EASL guidelines for up to 91 days.

    Reporting group values
    		 ELAD Treatment Control Total
    Number of subjects
    		 9 9 18
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0
        Newborns (0-27 days)
    		 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0
        Children (2-11 years)
    		 0 0 0
        Adolescents (12-17 years)
    		 0 0 0
        Adults (18-64 years)
    		 9 9 18
        From 65-84 years
    		 0 0 0
        85 years and over
    		 0 0 0
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 46.1 ± 7.29 50 ± 9.79 -
    Gender categorical
    Units: Subjects
        Female
    		 6 3 9
        Male
    		 3 6 9
    Race
    Units: Subjects
        White
    		 9 9 18
    Baseline MELD
    Baseline value of the Model for End-stage Liver Disease score.
    Units: MELD score
        arithmetic mean (standard deviation)
    		 27.531 ± 2.887 26.323 ± 2.8524 -

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    ELAD Treatment
    Reporting group description
    		 Participants randomized to the ELAD group received ELAD treatment plus protocol-directed standard of care treatment for a period of up to 10 days followed by standard of care treatment through Study Day 91.

    Reporting group title
    Control
    Reporting group description
    		 Participants randomized to the Control group received protocol-directed standard of care treatment in accord with AASLD and EASL guidelines for up to 91 days.
    Reporting group title
    ELAD Treatment
    Reporting group description
    		 Participants randomized to the ELAD group and who received ELAD treatment plus protocol-directed standard of care treatment for a period of up to 10 days during study VTI-210 were followed up for up to 5 years in VTI-210E.

    Reporting group title
    Control
    Reporting group description
    		 Participants randomized to the Control group and who received protocol-directed standard of care during the VTI-210 study in accord with AASLD and EASL guidelines were followed up for up to 5 years.

    Primary: Overall Survival

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    End point title
    		 Overall Survival
    End point description
    The primary endpoint of the study was a comparison of overall survival between ELAD-treated and Control groups defined by a Kaplan-Meier analysis of survival up to at least Study Day 91, wtih protocol VTI-210E providing additional survival data up to a maximum of 5 years, that was included as available at the time of database lock (11 July 2016).
    End point type
    Primary
    End point timeframe
    Up to at least Study Day 91, with protocol VTI-210E providing additional survival data up to 5 years from randomization.
    End point values
    		 ELAD Treatment Control
    Number of subjects analysed
    9
    9
    Units: Subjects
        Alive
    1
    4
        Dead
    7
    5
        Withdrew Consent
    1
    0
    Statistical analysis title
    		 Kaplan-Meier Analysis of Overall Survival
    Statistical analysis description
    The primary endpoint was assessed using a Kaplan-Meier survival analysis of the Intent-to-treat (ITT) population utilizing a log-rank test.
    Comparison groups
    ELAD Treatment v Control
    Number of subjects included in analysis
    18
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 > 0.05 [1]
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.305
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.083
         upper limit
    		 1.127
    Notes
    [1] - VTI-210E remains ongoing. Subjects were censored at last known time point alive. Data reflects information through 31 December 2016.

    Secondary: Proportion of Survivors at Study Day 91

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    End point title
    		 Proportion of Survivors at Study Day 91
    End point description
    Proportion of survivors at Study Day 91.
    End point type
    Secondary
    End point timeframe
    Up to Study Day 91.
    End point values
    		 ELAD Treatment Control
    Number of subjects analysed
    8
    9
    Units: Subjects
        Alive
    4
    6
        Dead
    4
    3
    Statistical analysis title
    		 Proportion of Survivors at Study Day 91
    Statistical analysis description
    Proportion of Survivors at Study Day 91
    Comparison groups
    ELAD Treatment v Control
    Number of subjects included in analysis
    17
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 > 0.05
    Method
    		 Fisher exact
    Confidence interval

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Randomization through Study Day 91.
    Adverse event reporting additional description
    It should be noted that the outcome of the serious adverse event is recorded as the subject status at Study Day 91. Note, one serious adverse event (melaena) was ongoing at Study Day 91, and ultimately resulted in death of the subject at Study Day 94 at which time the subject had entered VTI-210E.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    14.1
    Reporting groups
    Reporting group title
    ELAD Treatment
    Reporting group description
    		 Participants received ELAD treatment plus protocol-guided standard of care for a period of up to 10 days followed by standard of care through Study Day 91.

    Reporting group title
    Control
    Reporting group description
    		 Subjects randomized to the Control group received protocol-guided standard of care in accord with AASLD and EASL guidelines for up to 91 days.

    Serious adverse events
    		 ELAD Treatment Control
    Total subjects affected by serious adverse events
         subjects affected / exposed
    6 / 9 (66.67%)
    5 / 9 (55.56%)
         number of deaths (all causes)
    4
    3
         number of deaths resulting from adverse events
    0
    0
    Vascular disorders
    Haematoma
         subjects affected / exposed
    1 / 9 (11.11%)
    0 / 9 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Cardiac disorders
    Cardiac arrest
         subjects affected / exposed
    0 / 9 (0.00%)
    1 / 9 (11.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Nervous system disorders
    Hepatic encephalopathy
         subjects affected / exposed
    1 / 9 (11.11%)
    0 / 9 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Ascites
         subjects affected / exposed
    0 / 9 (0.00%)
    1 / 9 (11.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal haemorrhage
         subjects affected / exposed
    1 / 9 (11.11%)
    0 / 9 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Melaena
         subjects affected / exposed
    1 / 9 (11.11%)
    0 / 9 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Alcoholic liver disease
         subjects affected / exposed
    0 / 9 (0.00%)
    1 / 9 (11.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatitis alcoholic
         subjects affected / exposed
    1 / 9 (11.11%)
    1 / 9 (11.11%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    Respiratory, thoracic and mediastinal disorders
    Respiratory failure
         subjects affected / exposed
    1 / 9 (11.11%)
    1 / 9 (11.11%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    1 / 9 (11.11%)
    0 / 9 (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
    Peritonitis bacterial
         subjects affected / exposed
    0 / 9 (0.00%)
    1 / 9 (11.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    1 / 9 (11.11%)
    0 / 9 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Septic shock
         subjects affected / exposed
    1 / 9 (11.11%)
    0 / 9 (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
    Fluid retention
         subjects affected / exposed
    1 / 9 (11.11%)
    0 / 9 (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 / 9 (11.11%)
    0 / 9 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 1%
    Non-serious adverse events
    		 ELAD Treatment Control
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    9 / 9 (100.00%)
    9 / 9 (100.00%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Skin papilloma
         subjects affected / exposed
    0 / 9 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    1
    Vascular disorders
    Hypotension
         subjects affected / exposed
    6 / 9 (66.67%)
    1 / 9 (11.11%)
         occurrences all number
    7
    1
    Peripheral venous disease
         subjects affected / exposed
    0 / 9 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    1
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    1 / 9 (11.11%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    Catheter site haemorrhage
         subjects affected / exposed
    1 / 9 (11.11%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    Device malfunction
         subjects affected / exposed
    2 / 9 (22.22%)
    0 / 9 (0.00%)
         occurrences all number
    2
    0
    Generalised oedema
         subjects affected / exposed
    3 / 9 (33.33%)
    0 / 9 (0.00%)
         occurrences all number
    3
    0
    Medical device complication
         subjects affected / exposed
    2 / 9 (22.22%)
    0 / 9 (0.00%)
         occurrences all number
    2
    0
    Non-cardiac chest pain
         subjects affected / exposed
    1 / 9 (11.11%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    Oedema
         subjects affected / exposed
    1 / 9 (11.11%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    Oedema peripheral
         subjects affected / exposed
    3 / 9 (33.33%)
    3 / 9 (33.33%)
         occurrences all number
    4
    3
    Pain
         subjects affected / exposed
    1 / 9 (11.11%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    Pyrexia
         subjects affected / exposed
    2 / 9 (22.22%)
    2 / 9 (22.22%)
         occurrences all number
    6
    3
    Xerosis
         subjects affected / exposed
    0 / 9 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    1
    Reproductive system and breast disorders
    Hydrocele
         subjects affected / exposed
    0 / 9 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    1
    Scrotal oedema
         subjects affected / exposed
    1 / 9 (11.11%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    Respiratory, thoracic and mediastinal disorders
    Acute respiratory failure
         subjects affected / exposed
    1 / 9 (11.11%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    Atelectasis
         subjects affected / exposed
    2 / 9 (22.22%)
    1 / 9 (11.11%)
         occurrences all number
    3
    1
    Bronchospasm
         subjects affected / exposed
    1 / 9 (11.11%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    Cough
         subjects affected / exposed
    1 / 9 (11.11%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    Dyspnoea
         subjects affected / exposed
    3 / 9 (33.33%)
    0 / 9 (0.00%)
         occurrences all number
    4
    0
    Epistaxis
         subjects affected / exposed
    2 / 9 (22.22%)
    1 / 9 (11.11%)
         occurrences all number
    3
    1
    Haemoptysis
         subjects affected / exposed
    1 / 9 (11.11%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    Hiccups
         subjects affected / exposed
    1 / 9 (11.11%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    Pneumonia aspiration
         subjects affected / exposed
    0 / 9 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    1
    Pulmonary oedema
         subjects affected / exposed
    1 / 9 (11.11%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    Respiratory failure
         subjects affected / exposed
    1 / 9 (11.11%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    Tachypnoea
         subjects affected / exposed
    2 / 9 (22.22%)
    0 / 9 (0.00%)
         occurrences all number
    2
    0
    Wheezing
         subjects affected / exposed
    1 / 9 (11.11%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    Psychiatric disorders
    Depression
         subjects affected / exposed
    0 / 9 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    1
    Flat affect
         subjects affected / exposed
    1 / 9 (11.11%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    Insomnia
         subjects affected / exposed
    2 / 9 (22.22%)
    0 / 9 (0.00%)
         occurrences all number
    2
    0
    Injury, poisoning and procedural complications
    Perineal injury
         subjects affected / exposed
    0 / 9 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    1
    Periorbital haematoma
         subjects affected / exposed
    1 / 9 (11.11%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    Cardiac disorders
    Cardiomegaly
         subjects affected / exposed
    0 / 9 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    1
    Nervous system disorders
    Asterixis
         subjects affected / exposed
    1 / 9 (11.11%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    Headache
         subjects affected / exposed
    1 / 9 (11.11%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    Hepatic encephalopathy
         subjects affected / exposed
    3 / 9 (33.33%)
    1 / 9 (11.11%)
         occurrences all number
    4
    1
    Irregular sleep phase
         subjects affected / exposed
    0 / 9 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    1
    Stupor
         subjects affected / exposed
    0 / 9 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    1
    Tremor
         subjects affected / exposed
    1 / 9 (11.11%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    7 / 9 (77.78%)
    2 / 9 (22.22%)
         occurrences all number
    7
    2
    Coagulopathy
         subjects affected / exposed
    2 / 9 (22.22%)
    1 / 9 (11.11%)
         occurrences all number
    2
    1
    Haemolysis
         subjects affected / exposed
    1 / 9 (11.11%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    Leukocytosis
         subjects affected / exposed
    0 / 9 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    1
    Splenomegaly
         subjects affected / exposed
    1 / 9 (11.11%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    Thrombocytopenia
         subjects affected / exposed
    1 / 9 (11.11%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    Ear and labyrinth disorders
    Middle ear effusion
         subjects affected / exposed
    0 / 9 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    1
    Gastrointestinal disorders
    Abdominal distension
         subjects affected / exposed
    2 / 9 (22.22%)
    0 / 9 (0.00%)
         occurrences all number
    2
    0
    Abdominal pain
         subjects affected / exposed
    3 / 9 (33.33%)
    1 / 9 (11.11%)
         occurrences all number
    3
    1
    Abdominal tenderness
         subjects affected / exposed
    1 / 9 (11.11%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    Ascites
         subjects affected / exposed
    3 / 9 (33.33%)
    4 / 9 (44.44%)
         occurrences all number
    4
    4
    Colonic pseudo-obstruction
         subjects affected / exposed
    0 / 9 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    1
    Constipation
         subjects affected / exposed
    2 / 9 (22.22%)
    1 / 9 (11.11%)
         occurrences all number
    2
    1
    Diarrhoea
         subjects affected / exposed
    2 / 9 (22.22%)
    2 / 9 (22.22%)
         occurrences all number
    3
    2
    Duodenal ulcer
         subjects affected / exposed
    1 / 9 (11.11%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    Gastrointestinal angiodysplasia
         subjects affected / exposed
    1 / 9 (11.11%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    Gastrooesophageal reflux disease
         subjects affected / exposed
    1 / 9 (11.11%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    Haemorrhoidal haemorrhage
         subjects affected / exposed
    1 / 9 (11.11%)
    1 / 9 (11.11%)
         occurrences all number
    1
    1
    Nausea
         subjects affected / exposed
    2 / 9 (22.22%)
    0 / 9 (0.00%)
         occurrences all number
    3
    0
    Rectal haemorrhage
         subjects affected / exposed
    1 / 9 (11.11%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    Stomatitis
         subjects affected / exposed
    1 / 9 (11.11%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    Varices oesophageal
         subjects affected / exposed
    1 / 9 (11.11%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    Vomiting
         subjects affected / exposed
    0 / 9 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    1
    Skin and subcutaneous tissue disorders
    Blister
         subjects affected / exposed
    0 / 9 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    1
    Contusion
         subjects affected / exposed
    0 / 9 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    1
    Decubitus ulcer
         subjects affected / exposed
    1 / 9 (11.11%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    Dermatitis
         subjects affected / exposed
    0 / 9 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    1
    Ecchymosis
         subjects affected / exposed
    2 / 9 (22.22%)
    0 / 9 (0.00%)
         occurrences all number
    2
    0
    Excoriation
         subjects affected / exposed
    0 / 9 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    1
    Hyperhidrosis
         subjects affected / exposed
    1 / 9 (11.11%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    Pruritus
         subjects affected / exposed
    1 / 9 (11.11%)
    0 / 9 (0.00%)
         occurrences all number
    2
    0
    Pruritus generalised
         subjects affected / exposed
    1 / 9 (11.11%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    Rash
         subjects affected / exposed
    1 / 9 (11.11%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    Skin plaque
         subjects affected / exposed
    0 / 9 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    1
    Skin ulcer
         subjects affected / exposed
    0 / 9 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    1
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    2 / 9 (22.22%)
    2 / 9 (22.22%)
         occurrences all number
    2
    2
    Renal failure
         subjects affected / exposed
    1 / 9 (11.11%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    Renal impairment
         subjects affected / exposed
    0 / 9 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    1
    Endocrine disorders
    Hypothyroidism
         subjects affected / exposed
    0 / 9 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    1
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    1 / 9 (11.11%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    Critical illness myopathy
         subjects affected / exposed
    0 / 9 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    1
    Pain in extremity
         subjects affected / exposed
    1 / 9 (11.11%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    Infections and infestations
    Bacteraemia
         subjects affected / exposed
    3 / 9 (33.33%)
    2 / 9 (22.22%)
         occurrences all number
    7
    4
    Cellulitis
         subjects affected / exposed
    1 / 9 (11.11%)
    2 / 9 (22.22%)
         occurrences all number
    1
    2
    Gingival abscess
         subjects affected / exposed
    0 / 9 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    1
    Oesophageal candidiasis
         subjects affected / exposed
    0 / 9 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    1
    Pneumonia
         subjects affected / exposed
    1 / 9 (11.11%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    Sepsis
         subjects affected / exposed
    0 / 9 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    1
    Septic shock
         subjects affected / exposed
    1 / 9 (11.11%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    Urinary tract infection
         subjects affected / exposed
    2 / 9 (22.22%)
    1 / 9 (11.11%)
         occurrences all number
    2
    1
    Urinary tract infection fungal
         subjects affected / exposed
    1 / 9 (11.11%)
    0 / 9 (0.00%)
         occurrences all number
    2
    0
    Vulval cellulitis
         subjects affected / exposed
    0 / 9 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    1
    Metabolism and nutrition disorders
    Fluid overload
         subjects affected / exposed
    1 / 9 (11.11%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    Hyperammonaemia
         subjects affected / exposed
    0 / 9 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    1
    Hyperglycaemia
         subjects affected / exposed
    2 / 9 (22.22%)
    2 / 9 (22.22%)
         occurrences all number
    2
    2
    Hypernatraemia
         subjects affected / exposed
    0 / 9 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    1
    Hypocalcaemia
         subjects affected / exposed
    1 / 9 (11.11%)
    1 / 9 (11.11%)
         occurrences all number
    1
    1
    Hypokalaemia
         subjects affected / exposed
    1 / 9 (11.11%)
    1 / 9 (11.11%)
         occurrences all number
    1
    1
    Hypomagnesaemia
         subjects affected / exposed
    2 / 9 (22.22%)
    0 / 9 (0.00%)
         occurrences all number
    2
    0
    Hyponatraemia
         subjects affected / exposed
    0 / 9 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    1
    Hypophosphataemia
         subjects affected / exposed
    1 / 9 (11.11%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    Lactic acidosis
         subjects affected / exposed
    1 / 9 (11.11%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    Metabolic acidosis
         subjects affected / exposed
    1 / 9 (11.11%)
    0 / 9 (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
    18 Sep 2013
    Amendment 1, Version 2 - The number of planned subjects was increased from 100 to 120 in order to increase the power to achieve the planned significance level of 0.05 while maintaining the same assumptions for the treatment effect. Removed the maximum treatment age of 65. Modified the inclusion/exclusion criteria. Added a quality of life questionnaire (EQ-5D-5L). Made clarifications of the Screening Phase of the study.
    17 Oct 2013
    Amendment 2, Version 3 - Changes were made to correct the schedule of evaluations tables.
    06 Aug 2014
    Amendment 3 - Global harmonization of the protocol to better assist investigators and clinical sites in the conduct of the trial. Significant changes were made to the inclusion/exclusion criteria, the statistical sections, and the overall conduct of the study. However, no subjects were enrolled under any previous versions of the VTI-210 study protocol.
    03 Dec 2014
    Amendment 4 - Changes were made as a consequence of the STOPAH study results (Thursz et al., 2014). A change to the study title, inclusion/exclusion criteria, and general conduct of the study. This amendment no longer mandates steroid use during the period of Lille score assessment as an entry criterion, but rather continues to assess subject's mortality risk by Lille score, independent of steroid use.

    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.
    This study was terminated early after enrollment of only 18/150 planned subjects due to findings from previous VTI-208 study. Thus, sample size of VTI-210 was very small leading to statistical analyses that cannot be meaningfully interpreted.
    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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