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    Clinical Trial Results:
    A randomised controlled trial of Losartan as an anti-fibrotic agent in non-alcoholic steatohepatitis (FELINE).

    Summary
    EudraCT number
    		 2009-015166-62
    Trial protocol
    		 GB  
    Global end of trial date
    31 Dec 2014

    Results information
    Results version number
    		 v1(current)
    This version publication date
    04 Aug 2016
    First version publication date
    04 Aug 2016
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    EME-08/43/15
    Additional study identifiers
    ISRCTN number
    		 ISRCTN57849521
    US NCT number
    		 NCT01051219
    WHO universal trial number (UTN)
    		 -
    Other trial identifiers
    		 REC Ref: 10/H0904/8, NIHR CSP: 37194
    Sponsors
    Sponsor organisation name
    The Newcastle upon Tyne Hospitals NHS Foundation Trust
    Sponsor organisation address
    Joint Research Office, Level 1, Regent Point, Regent Farm Road, Gosforth, Newcastle upon Tyne , United Kingdom, NE3 3HD
    Public contact
    Professor Christopher Paul Day , Newcastle University, 0191 2227043, c.p.day@ncl.ac.uk
    Scientific contact
    Professor Christopher Paul Day , Newcastle University, 0191 2227043, c.p.day@ncl.ac.uk
    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
    06 Oct 2015
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    24 Nov 2014
    Global end of trial reached?
    Yes
    Global end of trial date
    31 Dec 2014
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The principal research question/objective is to determine whether Losartan, taken as a tablet (50mg once a day) versus a dummy pill (which will look exactly the same as the real medication) is effective at slowing down, halting or reversing liver fibrosis (scar tissue) in patients with non-alcoholic steatohepatitis.
    Protection of trial subjects
    Losartan is already a licensed medication used to treat patients with raised blood pressure, renal disease, diabetes and chronic heart failure. The medication is not currently licensed as an antifibrotic agent, but it is known to be safe. Based on previous studies and patients already taking Losartan, we know that the most common adverse reactions are dizziness, vertigo, hypotension, fatigue, low blood sugar and raised blood potassium levels. Patients will be assessed at regular intervals throughout the study and as patients with NASH are likely to have raised blood pressure, it is not expected that low blood pressure will be a major concern. Any expected drug reactions will be included in the patient information leaflet and, everything will be explained to the patient verbally. Patients will be advised by their doctor to report any unusual symptoms or reactions. Patients will be provided with a contact number on which they may contact a member of the study team to obtain advice and express any concerns, throughout the duration of the study. This information will be included in the patient information leaflet.
    Background therapy
    		 Participants were not prevented from interventions or procedures considered as part of routine care while participating in FELINE
    Evidence for comparator
    		 N/A
    Actual start date of recruitment
    01 May 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
    United Kingdom: 45
    Worldwide total number of subjects
    45
    EEA total number of subjects
    45
    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)
    39
    From 65 to 84 years
    6
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 Participants were identified by research staff, considered by the PI or Co-Investigator for inclusion and then if eligible approached to see whether they were interested. Interested patients were provided with the PIS to take away and read. Those then wishing to participate were made an appointment to return to the clinic to sign the ICF.

    Pre-assignment
    Screening details
    		 Visit 1 was the screening visit and took place directly after the participant had consented – a full screening assessment was then undertaken to ensure participants were definitely eligible to take part and met the eligibility criteria.

    Pre-assignment period milestones
    Number of subjects started
    		 49 [1]
    Number of subjects completed
    		 45

    Pre-assignment subject non-completion reasons
    Reason: Number of subjects
    		 Screen fail (after consented): 4
    Notes
    [1] - The number of subjects reported to have started the pre-assignment period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
    Justification: Potentially eligible patients were consented prior to a full screening assessment being undertaken. 49 patients were consented and screened, of these 45 were eligible to take part in the study. The other 4 patients failed screening and did not meet the eligibility criteria for the study - they did not therefore participate in the study.
    Period 1
    Period 1 title
    Visit 2 - Baseline
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor
    Blinding implementation details
    Randomisation was administered centrally via Newcastle Clinical Trials Unit, using a system to ensure concealment of allocation. A blocked allocation system was used to allocate patients to the 2 groups, with centre as a stratifying factor. Randomisation generated a treatment number for each participant that linked to the corresponding allocated study drug (blinded), in accordance with block size and strata. A code-break list was provided to each site pharmacy at participating hospitals.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Losartan
    Arm description
    		 Active Drug
    Arm type
    		 Experimental

    Investigational medicinal product name
    Losartan
    Investigational medicinal product code
    Other name
    Cozaar
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    one 50mg capsule taken daily

    Arm title
    		 Placebo
    Arm description
    		 Placebo
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    one capsule taken daily

    Number of subjects in period 1
    		Losartan Placebo
    Started
    24
    21
    Completed
    24
    21
    Period 2
    Period 2 title
    Visit 3 - 1 week
    Is this the baseline period?
    		 No
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor
    Blinding implementation details
    Randomisation was administered centrally via Newcastle Clinical Trials Unit, using a system to ensure concealment of allocation. A blocked allocation system was used to allocate patients to the 2 groups, with centre as a stratifying factor. Randomisation generated a treatment number for each participant that linked to the corresponding allocated study drug (blinded), in accordance with block size and strata. A code-break list was provided to each site pharmacy at participating hospitals.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Losartan
    Arm description
    		 Active drug
    Arm type
    		 Experimental

    Investigational medicinal product name
    Losartan
    Investigational medicinal product code
    Other name
    Cozaar
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    one 50mg capsule taken daily

    Arm title
    		 Placebo
    Arm description
    		 Placebo
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    one capsule taken daily

    Number of subjects in period 2
    		Losartan Placebo
    Started
    24
    21
    Completed
    24
    21
    Period 3
    Period 3 title
    Visit 4 - 4 weeks
    Is this the baseline period?
    		 No
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor
    Blinding implementation details
    Randomisation was administered centrally via Newcastle Clinical Trials Unit, using a system to ensure concealment of allocation. A blocked allocation system was used to allocate patients to the 2 groups, with centre as a stratifying factor. Randomisation generated a treatment number for each participant that linked to the corresponding allocated study drug (blinded), in accordance with block size and strata. A code-break list was provided to each site pharmacy at participating hospitals.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Losartan
    Arm description
    		 active drug
    Arm type
    		 Experimental

    Investigational medicinal product name
    Losartan
    Investigational medicinal product code
    Other name
    Cozaar
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    one 50mg capsule taken daily

    Arm title
    		 Placebo
    Arm description
    		 Placebo
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    one capsule taken daily

    Number of subjects in period 3
    		Losartan Placebo
    Started
    24
    21
    Completed
    23
    21
    Not completed
    1
    0
         lost to follow-up
    1
    -
    Period 4
    Period 4 title
    Visit 5 - 24 weeks
    Is this the baseline period?
    		 No
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor
    Blinding implementation details
    Randomisation was administered centrally via Newcastle Clinical Trials Unit, using a system to ensure concealment of allocation. A blocked allocation system was used to allocate patients to the 2 groups, with centre as a stratifying factor. Randomisation generated a treatment number for each participant that linked to the corresponding allocated study drug (blinded), in accordance with block size and strata. A code-break list was provided to each site pharmacy at participating hospitals.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Losartan
    Arm description
    		 active drug
    Arm type
    		 Experimental

    Investigational medicinal product name
    Losartan
    Investigational medicinal product code
    Other name
    Cozaar
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    one 50mg capsule taken daily

    Arm title
    		 Placebo
    Arm description
    		 placebo
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    one capsule taken daily

    Number of subjects in period 4
    		Losartan Placebo
    Started
    23
    21
    Completed
    23
    21
    Period 5
    Period 5 title
    Visit 6 - 48 weeks
    Is this the baseline period?
    		 No
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor
    Blinding implementation details
    Randomisation was administered centrally via Newcastle Clinical Trials Unit, using a system to ensure concealment of allocation. A blocked allocation system was used to allocate patients to the 2 groups, with centre as a stratifying factor. Randomisation generated a treatment number for each participant that linked to the corresponding allocated study drug (blinded), in accordance with block size and strata. A code-break list was provided to each site pharmacy at participating hospitals.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Losartan
    Arm description
    		 active drug
    Arm type
    		 Experimental

    Investigational medicinal product name
    Losartan
    Investigational medicinal product code
    Other name
    Cozaar
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    one 50mg capsule taken daily

    Arm title
    		 Placebo
    Arm description
    		 placebo
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    one capsule taken daily

    Number of subjects in period 5
    		Losartan Placebo
    Started
    23
    21
    Completed
    20
    19
    Not completed
    3
    2
         Consent withdrawn by subject
    1
    2
         lost to follow-up
    2
    -
    Period 6
    Period 6 title
    Visit 7 - 72 weeks
    Is this the baseline period?
    		 No
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor
    Blinding implementation details
    Randomisation was administered centrally via Newcastle Clinical Trials Unit, using a system to ensure concealment of allocation. A blocked allocation system was used to allocate patients to the 2 groups, with centre as a stratifying factor. Randomisation generated a treatment number for each participant that linked to the corresponding allocated study drug (blinded), in accordance with block size and strata. A code-break list was provided to each site pharmacy at participating hospitals.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Losartan
    Arm description
    		 active drug
    Arm type
    		 Experimental

    Investigational medicinal product name
    Losartan
    Investigational medicinal product code
    Other name
    Cozaar
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    one 50mg capsule taken daily

    Arm title
    		 Placebo
    Arm description
    		 placebo
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    one capsule taken daily

    Number of subjects in period 6
    		Losartan Placebo
    Started
    20
    19
    Completed
    19
    19
    Not completed
    1
    0
         lost to follow-up
    1
    -
    Period 7
    Period 7 title
    Visit 8 - 96 weeks
    Is this the baseline period?
    		 No
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor
    Blinding implementation details
    Randomisation was administered centrally via Newcastle Clinical Trials Unit, using a system to ensure concealment of allocation. A blocked allocation system was used to allocate patients to the 2 groups, with centre as a stratifying factor. Randomisation generated a treatment number for each participant that linked to the corresponding allocated study drug (blinded), in accordance with block size and strata. A code-break list was provided to each site pharmacy at participating hospitals.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Losartan
    Arm description
    		 active drug
    Arm type
    		 Experimental

    Investigational medicinal product name
    Losartan
    Investigational medicinal product code
    Other name
    Cozaar
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    one 50mg capsule taken daily

    Arm title
    		 Placebo
    Arm description
    		 placebo
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    one capsule taken daily

    Number of subjects in period 7
    		Losartan Placebo
    Started
    19
    19
    Completed
    20
    21
    Joined
    1
    2
         withdrawals who still completed end of study visit
    1
    2
    Period 8
    Period 8 title
    Visit 9 - 108 weeks
    Is this the baseline period?
    		 No
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor
    Blinding implementation details
    Randomisation was administered centrally via Newcastle Clinical Trials Unit, using a system to ensure concealment of allocation. A blocked allocation system was used to allocate patients to the 2 groups, with centre as a stratifying factor. Randomisation generated a treatment number for each participant that linked to the corresponding allocated study drug (blinded), in accordance with block size and strata. A code-break list was provided to each site pharmacy at participating hospitals.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Losartan
    Arm description
    		 active drug
    Arm type
    		 Experimental

    Investigational medicinal product name
    Losartan
    Investigational medicinal product code
    Other name
    Cozaar
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    one 50mg capsule taken daily

    Arm title
    		 Placebo
    Arm description
    		 placebo
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    one capsule taken daily

    Number of subjects in period 8 [2]
    		Losartan Placebo
    Started
    19
    19
    Completed
    16
    18
    Not completed
    3
    1
         lost to follow-up
    3
    1
    Notes
    [2] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
    Justification: Three participants wished to withdraw from the study after completing visit 5 – they did however still complete an end of study visit and this is why the figures show a slight increase in numbers at visit 8

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Losartan
    Reporting group description
    		 Active Drug

    Reporting group title
    Placebo
    Reporting group description
    		 Placebo

    Reporting group values
    		 Losartan Placebo Total
    Number of subjects
    		 24 21 45
    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)
    		 19 20 39
        From 65-84 years
    		 5 1 6
        85 years and over
    		 0 0 0
    Age continuous
    Units: years
        median (full range (min-max))
    		 58 (25 to 75) 45 (21 to 76) -
    Gender categorical
    Units: Subjects
        Female
    		 11 9 20
        Male
    		 13 12 25
    ethnic group
    Units: Subjects
        White
    		 21 19 40
        other mixed background
    		 1 0 1
        Asian - Indian
    		 1 0 1
        Asian - Pakistani
    		 1 1 2
        Chinese
    		 0 1 1
    units of alcohol consumed
    Units: Subjects
        none
    		 13 9 22
        1-5 units
    		 7 7 14
        6-9 units
    		 0 1 1
        10-15 units
    		 3 2 5
        16-19 units
    		 1 0 1
        20-27 units
    		 0 1 1
        ≥ 28 units
    		 0 1 1
    ECG abnormal
    ECG abnormal from screening
    Units: Subjects
        Yes
    		 5 4 9
        No
    		 19 17 36
    ultrasound abnormal
    number of patients with an abnormal ultrasound
    Units: Subjects
        Yes
    		 13 6 19
        No
    		 5 4 9
        missing
    		 4 7 11
        did not have ultrasound
    		 2 4 6
    stratum
    diabetes
    Units: Subjects
        yes
    		 15 12 27
        no
    		 9 9 18
    CNS
    physical examination of CNS
    Units: Subjects
        Normal
    		 22 19 41
        Abnormal
    		 1 0 1
        Not examined
    		 0 1 1
        Missing
    		 1 1 2
    Neck
    physical examination of neck
    Units: Subjects
        Normal
    		 22 20 42
        Abnormal
    		 0 0 0
        Not examined
    		 1 0 1
        Missing
    		 1 1 2
    HEENT
    Physical Examination of HEENT
    Units: Subjects
        Normal
    		 19 19 38
        Abnormal
    		 0 0 0
        Not examined
    		 4 1 5
        Missing
    		 1 1 2
    Respiratory
    Physical examination of respiratory
    Units: Subjects
        Normal
    		 23 20 43
        Abnormal
    		 0 0 0
        Not examined
    		 0 0 0
        Missing
    		 1 1 2
    Cardiovascular
    physical examination of cardiovascular
    Units: Subjects
        Normal
    		 23 20 43
        Abnormal
    		 0 0 0
        Not examined
    		 0 0 0
        Missing
    		 1 1 2
    Gastrointestinal
    physical examination of gastrointestinal
    Units: Subjects
        Normal
    		 23 18 41
        Abnormal
    		 0 2 2
        Not examined
    		 0 0 0
        Missing
    		 1 1 2
    Abdomen
    physical examination of Abdomen
    Units: Subjects
        Normal
    		 21 18 39
        Abnormal
    		 2 2 4
        Not examined
    		 0 0 0
        Missing
    		 1 1 2
    Musculoskeletal
    physical examination of Musculoskeletal
    Units: Subjects
        Normal
    		 21 19 40
        Abnormal
    		 0 0 0
        Not examined
    		 2 1 3
        Missing
    		 1 1 2
    endocrine and metabolic
    physical examination of endocrine and metabolic
    Units: Subjects
        Normal
    		 22 19 41
        Abnormal
    		 0 0 0
        Not examined
    		 1 1 2
        Missing
    		 1 1 2
    Hematopoietic/Lymphatic
    physical examination of Hematopoietic/Lymphatic
    Units: Subjects
        Normal
    		 20 19 39
        Abnormal
    		 0 0 0
        Not examined
    		 3 1 4
        Missing
    		 1 1 2
    Neurological
    physical examination of neurological
    Units: Subjects
        Normal
    		 21 20 41
        Abnormal
    		 1 0 1
        Not examined
    		 1 0 1
        missing
    		 1 1 2
    dermatological
    physical examination of dermatological
    Units: Subjects
        Normal
    		 19 19 38
        Abnormal
    		 2 1 3
        Not examined
    		 2 0 2
        Missing
    		 1 1 2
    psychiatric/psychological
    physical examination of psychiatric/psychological
    Units: Subjects
        Normal
    		 19 18 37
        Abnormal
    		 0 0 0
        Not examined
    		 4 2 6
        Missing
    		 1 1 2
    Weight
    Weight in KG
    Units: kg
        median (full range (min-max))
    		 85.1 (74.2 to 121) 96.7 (61.6 to 132.5) -
    Height
    Height (taken at screening) in cm
    Units: cm
        median (full range (min-max))
    		 167 (152 to 183) 171.3 (152 to 194) -
    BMI
    Body mass index
    Units: kg/m2
        median (full range (min-max))
    		 32.8 (26.11 to 43.39) 34.11 (26.46 to 45.18) -
    Waist
    waist measurement in cm
    Units: cm
        median (full range (min-max))
    		 105.85 (96 to 126) 111.4 (88 to 136) -
    systolic blood pressure
    Units: mm Hg
        median (full range (min-max))
    		 133.5 (109 to 165) 127 (115 to 180) -
    diastolic blood pressure
    Units: mm Hg
        median (full range (min-max))
    		 78.5 (67 to 95) 81 (70 to 100) -
    sitting heart rate
    Units: bpm
        median (full range (min-max))
    		 75 (59 to 100) 77 (59 to 88) -
    fibroscan liver stiffness
    Units: kpa
        median (full range (min-max))
    		 8.15 (5.2 to 17.3) 6.05 (3 to 11.9) -
    fibroscan stiffness (E) median
    Units: kpa
        median (full range (min-max))
    		 8.9 (1.6 to 26.6) 7.95 (7.1 to 8.8) -
    ELF test result
    ELF test result from screening
    Units: score
        median (full range (min-max))
    		 8.84 (6.54 to 11.83) 7.96 (6.43 to 10.28) -
    sodium
    Units: mmol/L
        median (full range (min-max))
    		 139.5 (135 to 143) 141 (136 to 145) -
    potassium
    Units: mmol/L
        median (full range (min-max))
    		 4.35 (3.8 to 4.8) 4.3 (3.7 to 4.8) -
    Urea
    Units: mmol/L
        median (full range (min-max))
    		 4.9 (3.2 to 7.9) 5 (3.3 to 6.9) -
    Glucose
    Units: mmol/L
        median (full range (min-max))
    		 5.95 (4.44 to 17.1) 6.2 (3.6 to 15.9) -
    AST
    Units: U/L
        median (full range (min-max))
    		 35 (14 to 102) 46 (30 to 70) -
    ALT
    Units: U/L
        median (full range (min-max))
    		 52.5 (21 to 136) 65 (33 to 135) -
    ALP
    Alkaline Phosphatase
    Units: U/L
        median (full range (min-max))
    		 89.5 (44 to 173) 72 (49 to 116) -
    Creatinine
    Units: umol/L
        median (full range (min-max))
    		 75.5 (48 to 105) 72 (5 to 97) -
    Total bilirubin
    Units: umol/L
        median (full range (min-max))
    		 10 (5 to 25) 10 (4 to 45) -
    Albumin
    Units: g/L
        median (full range (min-max))
    		 44.5 (34 to 50) 46 (35 to 75) -
    Triglyceride
    Units: mmol/L
        median (full range (min-max))
    		 1.7 (0.9 to 7.9) 2 (0.4 to 4.4) -
    HDL cholesterol
    Units: mmol/L
        median (full range (min-max))
    		 1.1 (0.7 to 2.8) 1.1 (0.8 to 3.5) -
    total cholesterol
    Units: mmol/L
        median (full range (min-max))
    		 4.3 (2.1 to 7.5) 4.6 (1 to 6.5) -
    LDL cholesterol
    Units: mmol/L
        median (full range (min-max))
    		 2.5 (0.8 to 3.8) 3.2 (1.2 to 4.4) -
    Gamma GT
    Units: U/L
        median (full range (min-max))
    		 70 (18 to 355) 62 (23 to 256) -
    haemaglobin
    Units: g/dL
        median (full range (min-max))
    		 14.6 (12.3 to 142) 14.9 (13.2 to 18) -
    Leukocytes (WBC)
    Units: x10(9)/L
        median (full range (min-max))
    		 7.2 (4.3 to 13.1) 7.3 (4.4 to 12.3) -
    Platelets
    Units: x10(9)/L
        median (full range (min-max))
    		 224 (137 to 360) 224 (158 to 404) -
    MCV
    Units: fL
        median (full range (min-max))
    		 89.55 (76.9 to 99) 87.3 (80.2 to 94.3) -
    HBA1C
    Units: mmol/mol
        median (full range (min-max))
    		 53.5 (34 to 81) 42 (31 to 81) -
    Prothrombus time
    Units: seconds
        median (full range (min-max))
    		 11 (1 to 15) 11 (10 to 22) -
    Apolopoproteins
    Units: µg/L
        median (full range (min-max))
    		 1.35 (1 to 2) 1.35 (1 to 1.7) -
    Alpha-2-macroglobulin
    Units: mg/100ml
        median (full range (min-max))
    		 1.4 (0 to 2.5) 1.9 (1.2 to 4.2) -
    haptoglobins
    Units: n/a
        median (full range (min-max))
    		 1.9 (0.6 to 797) 2 (0.7 to 1651) -
    IgG
    Units: g/L
        median (full range (min-max))
    		 10.4 (6.7 to 15.1) 10.8 (6.6 to 15) -
    IgA
    Units: g/L
        median (full range (min-max))
    		 2.9 (0.87 to 5.08) 2.64 (1 to 6.3) -
    IgM
    Units: g/L
        median (full range (min-max))
    		 1.09 (0.26 to 2.75) 1.02 (0.25 to 7) -
    insulin
    Units: U/g
        median (full range (min-max))
    		 22.2 (9.7 to 81.4) 23.8 (4.4 to 57.6) -
    C-peptide
    Units: n/a
        median (full range (min-max))
    		 2.31 (0.68 to 4138) 2.22 (0.16 to 3054) -

    End points

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    End points reporting groups
    Reporting group title
    Losartan
    Reporting group description
    		 Active Drug

    Reporting group title
    Placebo
    Reporting group description
    		 Placebo
    Reporting group title
    Losartan
    Reporting group description
    		 Active drug

    Reporting group title
    Placebo
    Reporting group description
    		 Placebo
    Reporting group title
    Losartan
    Reporting group description
    		 active drug

    Reporting group title
    Placebo
    Reporting group description
    		 Placebo
    Reporting group title
    Losartan
    Reporting group description
    		 active drug

    Reporting group title
    Placebo
    Reporting group description
    		 placebo
    Reporting group title
    Losartan
    Reporting group description
    		 active drug

    Reporting group title
    Placebo
    Reporting group description
    		 placebo
    Reporting group title
    Losartan
    Reporting group description
    		 active drug

    Reporting group title
    Placebo
    Reporting group description
    		 placebo
    Reporting group title
    Losartan
    Reporting group description
    		 active drug

    Reporting group title
    Placebo
    Reporting group description
    		 placebo
    Reporting group title
    Losartan
    Reporting group description
    		 active drug

    Reporting group title
    Placebo
    Reporting group description
    		 placebo

    Primary: Kleiner fibrosis score

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    End point title
    		 Kleiner fibrosis score [1]
    End point description
    Change in Kleiner fibrosis stage from baseline to 96 weeks (Visit 8). The primary outcome will be change in Kleiner fibrosis score based on histological fibrosis stage (as judged by two independent blinded histopathologists, from liver biopsies), from pre-treatment to end-of-study defined as 24 month score minus baseline score
    End point type
    Primary
    End point timeframe
    24 months
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No inferential statistical testing carried out as study closed to recruitment early
    End point values
    		 Losartan Placebo
    Number of subjects analysed
    15
    17
    Units: score
        median (full range (min-max))
    0 (-1 to 1)
    0 (-1 to 1)
    No statistical analyses for this end point

    Secondary: Length

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    End point title
    		 Length
    End point description
    Change in biopsy length from BL to 24 months defined as 24 months length minus BL length Length is defined as total length of liver tissue core(s)
    End point type
    Secondary
    End point timeframe
    Baseline and 24 months
    End point values
    		 Losartan Placebo
    Number of subjects analysed
    15
    17
    Units: mm
        median (full range (min-max))
    -1.91 (-31.2 to 12.4)
    -3.36 (-28.2 to 20.37)
    No statistical analyses for this end point

    Secondary: Diagnostic Category

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    End point title
    		 Diagnostic Category
    End point description
    Change in diagnostic category from BL to 24 months defined as 24 months diagnostic category minus BL diagnostic category
    End point type
    Secondary
    End point timeframe
    Baseline and 24 months
    End point values
    		 Losartan Placebo
    Number of subjects analysed
    15
    17
    Units: category
        median (full range (min-max))
    0 (-1 to 1)
    0 (-1 to 0)
    No statistical analyses for this end point

    Secondary: Grade of Steatosis

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    End point title
    		 Grade of Steatosis
    End point description
    Change in grade of steatosis from BL to 24 months defined as 24 months value minus BL value
    End point type
    Secondary
    End point timeframe
    Baseline and 24 months
    End point values
    		 Losartan Placebo
    Number of subjects analysed
    15
    17
    Units: percentage
        median (full range (min-max))
    0 (-2 to 1)
    0 (-2 to 0)
    No statistical analyses for this end point

    Secondary: % Steatotic Hepatocytes

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    End point title
    		 % Steatotic Hepatocytes
    End point description
    Change in % steatotic hepatocytes from BL to 24 months defined as 24 months value minus BL value
    End point type
    Secondary
    End point timeframe
    Baseline and 24 months
    End point values
    		 Losartan Placebo
    Number of subjects analysed
    15
    17
    Units: percentage
        median (full range (min-max))
    -10 (-60 to 50)
    -20 (-70 to 20)
    No statistical analyses for this end point

    Secondary: Hepatocyte ballooning

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    End point title
    		 Hepatocyte ballooning
    End point description
    Change in Hepatocyte ballooning from BL to 24 months defined as 24 months value minus BL value
    End point type
    Secondary
    End point timeframe
    baseline and 24 months
    End point values
    		 Losartan Placebo
    Number of subjects analysed
    15
    17
    Units: score
        median (full range (min-max))
    0 (-1 to 1)
    0 (-1 to 1)
    No statistical analyses for this end point

    Secondary: Lobular Inflammation

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    End point title
    		 Lobular Inflammation
    End point description
    Change in lobular inflammation from BL to 24 months defined as 24 months value minus BL value
    End point type
    Secondary
    End point timeframe
    baseline and 24 months
    End point values
    		 Losartan Placebo
    Number of subjects analysed
    15
    17
    Units: score
        median (full range (min-max))
    0 (-1 to 1)
    0 (-2 to 1)
    No statistical analyses for this end point

    Secondary: SAF lobular inflammation

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    End point title
    		 SAF lobular inflammation
    End point description
    Change in SAF lobular inflammation from BL to 24 months defined as 24 months value minus BL value
    End point type
    Secondary
    End point timeframe
    baseline and 24 months
    End point values
    		 Losartan Placebo
    Number of subjects analysed
    15
    17
    Units: score
        median (full range (min-max))
    0 (-1 to 1)
    0 (-1 to 1)
    No statistical analyses for this end point

    Secondary: NAFLD score (NAS)

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    End point title
    		 NAFLD score (NAS)
    End point description
    Change in NAS from BL to 24 months defined as 24 months value minus BL value
    End point type
    Secondary
    End point timeframe
    baseline and 24 months
    End point values
    		 Losartan Placebo
    Number of subjects analysed
    15
    17
    Units: score
        median (full range (min-max))
    0 (-3 to 3)
    -1 (-4 to 1)
    No statistical analyses for this end point

    Secondary: FLIP Activity Score

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    End point title
    		 FLIP Activity Score
    End point description
    Change in FLIP activity score from BL to 24 months defined as 24 months value minus BL value
    End point type
    Secondary
    End point timeframe
    baseline and 24 months
    End point values
    		 Losartan Placebo
    Number of subjects analysed
    15
    17
    Units: score
        median (full range (min-max))
    0 (-2 to 1)
    -1 (-2 to 2)
    No statistical analyses for this end point

    Secondary: Global grade - Brunt 1999

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    End point title
    		 Global grade - Brunt 1999
    End point description
    Change in Global Grade from BL to 24 months defined as 24 months value minus BL value
    End point type
    Secondary
    End point timeframe
    baseline and 24 months
    End point values
    		 Losartan Placebo
    Number of subjects analysed
    15
    17
    Units: grade
        median (full range (min-max))
    -1 (-1 to 1)
    -1 (-2 to 0)
    No statistical analyses for this end point

    Secondary: Sinusoidal/pericellular fibrosis

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    End point title
    		 Sinusoidal/pericellular fibrosis
    End point description
    Change in Sinusoidal/pericellular fibrosis from BL to 24 months defined as 24 months value minus BL value
    End point type
    Secondary
    End point timeframe
    baseline and 24 months
    End point values
    		 Losartan Placebo
    Number of subjects analysed
    15
    17
    Units: score
        median (full range (min-max))
    0 (-1 to 2)
    0 (-2 to 1)
    No statistical analyses for this end point

    Secondary: 7 tier staging system

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    End point title
    		 7 tier staging system
    End point description
    Change in 7 tier staging system fibrosis from BL to 24 months defined as 24 months value minus BL value
    End point type
    Secondary
    End point timeframe
    baseline and 24 months
    End point values
    		 Losartan Placebo
    Number of subjects analysed
    15
    17
    Units: staging system
        median (full range (min-max))
    0 (-2 to 2)
    0 (-2 to 1)
    No statistical analyses for this end point

    Secondary: Portal inflammation

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    End point title
    		 Portal inflammation
    End point description
    Change in portal inflammation from BL to 24 months defined as 24 months value minus BL value
    End point type
    Secondary
    End point timeframe
    baseline and 24 months
    End point values
    		 Losartan Placebo
    Number of subjects analysed
    15
    17
    Units: score
        median (full range (min-max))
    0 (-1 to 2)
    0 (-1 to 1)
    No statistical analyses for this end point

    Secondary: Apopotic bodies

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    End point title
    		 Apopotic bodies
    End point description
    Change in apoptotic bodies from BL to 24 months defined as 24 months value minus BL value
    End point type
    Secondary
    End point timeframe
    Baseline and 24 months
    End point values
    		 Losartan Placebo
    Number of subjects analysed
    15
    17
    Units: score
        median (full range (min-max))
    0 (-1 to 1)
    0 (-1 to 1)
    No statistical analyses for this end point

    Secondary: Mallory-Denk bodies

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    End point title
    		 Mallory-Denk bodies
    End point description
    Change in Mallory-Denk bodies from BL to 24 months defined as 24 months value minus BL value
    End point type
    Secondary
    End point timeframe
    baseline and 24 months
    End point values
    		 Losartan Placebo
    Number of subjects analysed
    14 [2]
    17
    Units: score
        median (full range (min-max))
    0 (-1 to 0)
    0 (-2 to 1)
    Notes
    [2] - one biopsy has a missing score
    No statistical analyses for this end point

    Secondary: SF36 PCS

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    End point title
    		 SF36 PCS
    End point description
    Change in SF36 physical component summary (PCS) from BL to 24 months defined as 24 months value minus BL value
    End point type
    Secondary
    End point timeframe
    baseline and 24 months
    End point values
    		 Losartan Placebo
    Number of subjects analysed
    18
    19
    Units: score
        median (full range (min-max))
    -1.47 (-14.19 to 4.28)
    -2.9 (-15.36 to 28.61)
    No statistical analyses for this end point

    Secondary: SF36 MCS

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    End point title
    		 SF36 MCS
    End point description
    Change in SF36 (mental component summary) MCS from BL to 24 months defined as 24 months value minus BL value
    End point type
    Secondary
    End point timeframe
    baseline and 24 months
    End point values
    		 Losartan Placebo
    Number of subjects analysed
    18
    19
    Units: score
        median (full range (min-max))
    1.1 (-30.05 to 16.38)
    -0.12 (-20.95 to 21.56)
    No statistical analyses for this end point

    Secondary: SF36 - PCS oblique

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    End point title
    		 SF36 - PCS oblique
    End point description
    Change in SF36 (physical component summary) PCS calculated using the oblique method from BL to 24 months defined as 24 months value minus BL value
    End point type
    Secondary
    End point timeframe
    baseline and 24 months
    End point values
    		 Losartan Placebo
    Number of subjects analysed
    18
    19
    Units: score
        median (full range (min-max))
    -1.75 (-20.6 to 5.83)
    -2.83 (-11.87 to 21.75)
    No statistical analyses for this end point

    Secondary: SF36-MCS oblique

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    End point title
    		 SF36-MCS oblique
    End point description
    Change in SF36 (mental component summary) MCS calculated using the oblique method from BL to 24 months defined as 24 months value minus BL value
    End point type
    Secondary
    End point timeframe
    baseline and 24 months
    End point values
    		 Losartan Placebo
    Number of subjects analysed
    18
    19
    Units: score
        median (full range (min-max))
    -0.22 (-32.4 to 14.7)
    -0.55 (-12.61 to 17.78)
    No statistical analyses for this end point

    Secondary: CLDQ AS

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    End point title
    		 CLDQ AS
    End point description
    Change in CLDQ abdominal symptoms (AS) from BL to 24 months defined as 24 months value minus BL value If one element in domain missing then domain set to missing
    End point type
    Secondary
    End point timeframe
    baseline and 24 months
    End point values
    		 Losartan Placebo
    Number of subjects analysed
    17
    19
    Units: score
        median (full range (min-max))
    0 (-3.67 to 2)
    0 (-2.33 to 3.67)
    No statistical analyses for this end point

    Secondary: CLDQ SS

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    End point title
    		 CLDQ SS
    End point description
    Change in CLDQ systemic symptoms (SS) from BL to 24 months defined as 24 months value minus BL value If one element in domain missing then domain set to missing
    End point type
    Secondary
    End point timeframe
    baseline and 24 months
    End point values
    		 Losartan Placebo
    Number of subjects analysed
    16
    20
    Units: score
        median (full range (min-max))
    -0.5 (-1.6 to 0.4)
    -0.3 (-1.4 to 1.4)
    No statistical analyses for this end point

    Secondary: CLDQ FA

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    End point title
    		 CLDQ FA
    End point description
    Change in CLDQ fatigue (FA) from BL to 24 months defined as 24 months value minus BL value If one element in domain missing then domain set to missing
    End point type
    Secondary
    End point timeframe
    baseline and 24 months
    End point values
    		 Losartan Placebo
    Number of subjects analysed
    16
    20
    Units: score
        median (full range (min-max))
    -0.6 (-1.8 to 0.4)
    -0.2 (-1.6 to 0.8)
    No statistical analyses for this end point

    Secondary: CLDQ AC

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    End point title
    		 CLDQ AC
    End point description
    Change in CLDQ activity (AC) from BL to 24 months defined as 24 months value minus BL value If one element in domain missing then domain set to missing
    End point type
    Secondary
    End point timeframe
    baseline and 24 months
    End point values
    		 Losartan Placebo
    Number of subjects analysed
    17
    20
    Units: score
        median (full range (min-max))
    -0.33 (-3.33 to 2.33)
    -0.33 (-3 to 2)
    No statistical analyses for this end point

    Secondary: CLDQ EF

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    End point title
    		 CLDQ EF
    End point description
    Change in CLDQ emotional function (EF) from BL to 24 months defined as 24 months value minus BL value If one element in domain missing then domain set to missing
    End point type
    Secondary
    End point timeframe
    baseline and 24 months
    End point values
    		 Losartan Placebo
    Number of subjects analysed
    17
    18
    Units: score
        median (full range (min-max))
    0 (-3.63 to 1.13)
    -0.13 (-1.75 to 1)
    No statistical analyses for this end point

    Secondary: CLDQ WO

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    End point title
    		 CLDQ WO
    End point description
    Change in CLDQ worry (WO) from BL to 24 months defined as 24 months value minus BL value If one element in domain missing then domain set to missing
    End point type
    Secondary
    End point timeframe
    baseline and 24 months
    End point values
    		 Losartan Placebo
    Number of subjects analysed
    17
    20
    Units: score
        median (full range (min-max))
    0 (-3.6 to 1.2)
    0.1 (-2.2 to 1.2)
    No statistical analyses for this end point

    Secondary: CLDQ overall

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    End point title
    		 CLDQ overall
    End point description
    Change in CLDQ Overall from BL to 24 months defined as 24 months value minus BL value If one element in domain missing then domain set to missing
    End point type
    Secondary
    End point timeframe
    baseline and 24 months
    End point values
    		 Losartan Placebo
    Number of subjects analysed
    15
    17
    Units: score
        median (full range (min-max))
    -0.17 (-2.28 to 0.38)
    -0.1 (-1.07 to 0.79)
    No statistical analyses for this end point

    Secondary: Fibroscan

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    End point title
    		 Fibroscan
    End point description
    liver stiffness
    End point type
    Secondary
    End point timeframe
    Visit 8
    End point values
    		 Losartan Placebo
    Number of subjects analysed
    8
    4
    Units: kpa
        median (full range (min-max))
    5.05 (3.4 to 15.4)
    5.95 (3.6 to 20.6)
    No statistical analyses for this end point

    Secondary: Fibroscan

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    End point title
    		 Fibroscan
    End point description
    Liver stiffness (E) median only received results for those in the losartan reporting arm - none received for the placebo arm and therefore no analysis conducted within this arm.
    End point type
    Secondary
    End point timeframe
    Visit 8
    End point values
    		 Losartan
    Number of subjects analysed
    4
    Units: kpa
        median (full range (min-max))
    9.5 (0 to 14)
    No statistical analyses for this end point

    Secondary: ELF

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    End point title
    		 ELF
    End point description
    ELF score
    End point type
    Secondary
    End point timeframe
    Visit 8
    End point values
    		 Losartan Placebo
    Number of subjects analysed
    18
    16
    Units: score
        median (full range (min-max))
    9.45 (7.91 to 11.03)
    8.97 (7.31 to 10.8)
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Adverse events were collected from Visit 2 (Baseline) through to Visit 9 (108 weeks)
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 as reported
    Dictionary version
    1.0
    Reporting groups
    Reporting group title
    Losartan
    Reporting group description
    		 active drug

    Reporting group title
    Placebo
    Reporting group description
    		 placebo

    Serious adverse events
    		 Losartan Placebo
    Total subjects affected by serious adverse events
         subjects affected / exposed
    2 / 24 (8.33%)
    1 / 21 (4.76%)
         number of deaths (all causes)
    0
    0
         number of deaths resulting from adverse events
    0
    0
    General disorders and administration site conditions
    Epistaxis
    Additional description: nose bleeds
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    2nd right rib fracture
    Additional description: fell over whilst walking dogs
         subjects affected / exposed
    0 / 24 (0.00%)
    1 / 21 (4.76%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    dislocation of left 1st metacarpal
    Additional description: knocked down by bike
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    fracture of left 1st metacarpal
    Additional description: knocked down by bike
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 21 (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: 0%
    Non-serious adverse events
    		 Losartan Placebo
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    21 / 24 (87.50%)
    16 / 21 (76.19%)
    General disorders and administration site conditions
    ankle swelling
         subjects affected / exposed
    0 / 24 (0.00%)
    1 / 21 (4.76%)
         occurrences all number
    0
    2
    anxiety
         subjects affected / exposed
    0 / 24 (0.00%)
    1 / 21 (4.76%)
         occurrences all number
    0
    1
    axilla abscess
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 21 (0.00%)
         occurrences all number
    1
    0
    back pain
         subjects affected / exposed
    0 / 24 (0.00%)
    1 / 21 (4.76%)
         occurrences all number
    0
    1
    Cellulitis
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 21 (0.00%)
         occurrences all number
    1
    0
    cervical spondylosis
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 21 (0.00%)
         occurrences all number
    1
    0
    Chest pain
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 21 (0.00%)
         occurrences all number
    1
    0
    colonoscopy
         subjects affected / exposed
    0 / 24 (0.00%)
    1 / 21 (4.76%)
         occurrences all number
    0
    1
    constipation
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 21 (0.00%)
         occurrences all number
    1
    0
    cough
         subjects affected / exposed
    3 / 24 (12.50%)
    1 / 21 (4.76%)
         occurrences all number
    4
    1
    Diarrhoea
         subjects affected / exposed
    2 / 24 (8.33%)
    2 / 21 (9.52%)
         occurrences all number
    2
    2
    diarrhoea and vomiting
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 21 (0.00%)
         occurrences all number
    1
    0
    dislocated left knee cap
         subjects affected / exposed
    0 / 24 (0.00%)
    1 / 21 (4.76%)
         occurrences all number
    0
    1
    dizzyness
         subjects affected / exposed
    4 / 24 (16.67%)
    6 / 21 (28.57%)
         occurrences all number
    5
    6
    dorsal capsulotomy of mcp (metacapophalangeal) joints in right hand
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 21 (0.00%)
         occurrences all number
    1
    0
    dry mouth
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 21 (0.00%)
         occurrences all number
    2
    0
    dyslipidaemia
         subjects affected / exposed
    2 / 24 (8.33%)
    0 / 21 (0.00%)
         occurrences all number
    2
    0
    dysmenorrhoea
         subjects affected / exposed
    0 / 24 (0.00%)
    1 / 21 (4.76%)
         occurrences all number
    0
    1
    dyspepsia
         subjects affected / exposed
    2 / 24 (8.33%)
    2 / 21 (9.52%)
         occurrences all number
    2
    2
    Dysphagia
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 21 (0.00%)
         occurrences all number
    1
    0
    dysuria
         subjects affected / exposed
    0 / 24 (0.00%)
    1 / 21 (4.76%)
         occurrences all number
    0
    1
    elective removal of screw from left ankle
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 21 (0.00%)
         occurrences all number
    1
    0
    elective surgery for cystoscopy and bladder biopsy
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 21 (0.00%)
         occurrences all number
    1
    0
    Epistaxis
         subjects affected / exposed
    1 / 24 (4.17%)
    1 / 21 (4.76%)
         occurrences all number
    1
    1
    eructation
         subjects affected / exposed
    0 / 24 (0.00%)
    1 / 21 (4.76%)
         occurrences all number
    0
    1
    excision scalp lipoma
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 21 (0.00%)
         occurrences all number
    1
    0
    extreme coldness in extremities-especially hand and feet.
         subjects affected / exposed
    0 / 24 (0.00%)
    1 / 21 (4.76%)
         occurrences all number
    0
    1
    falls
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 21 (0.00%)
         occurrences all number
    1
    0
    fatigue
         subjects affected / exposed
    1 / 24 (4.17%)
    2 / 21 (9.52%)
         occurrences all number
    2
    3
    Fibromyalgia
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 21 (0.00%)
         occurrences all number
    1
    0
    generalized stabbing pain and ache from left ankle up to the left hip.
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 21 (0.00%)
         occurrences all number
    1
    0
    gout
         subjects affected / exposed
    0 / 24 (0.00%)
    1 / 21 (4.76%)
         occurrences all number
    0
    2
    Haematuria
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 21 (0.00%)
         occurrences all number
    2
    0
    headaches
         subjects affected / exposed
    2 / 24 (8.33%)
    6 / 21 (28.57%)
         occurrences all number
    2
    14
    herniated lumbar disc
         subjects affected / exposed
    0 / 24 (0.00%)
    1 / 21 (4.76%)
         occurrences all number
    0
    1
    hot and cold sweats
         subjects affected / exposed
    0 / 24 (0.00%)
    1 / 21 (4.76%)
         occurrences all number
    0
    1
    Hyperglycaemia
         subjects affected / exposed
    1 / 24 (4.17%)
    4 / 21 (19.05%)
         occurrences all number
    1
    6
    hypertension
         subjects affected / exposed
    2 / 24 (8.33%)
    2 / 21 (9.52%)
         occurrences all number
    2
    2
    Influenza
         subjects affected / exposed
    0 / 24 (0.00%)
    2 / 21 (9.52%)
         occurrences all number
    0
    2
    insomnia
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 21 (0.00%)
         occurrences all number
    1
    0
    left ankle pain
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 21 (0.00%)
         occurrences all number
    1
    0
    left knee pain
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 21 (0.00%)
         occurrences all number
    1
    0
    left lower leg - hot tender and tight at night
         subjects affected / exposed
    0 / 24 (0.00%)
    1 / 21 (4.76%)
         occurrences all number
    0
    1
    left shoulder pain
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 21 (0.00%)
         occurrences all number
    1
    0
    leg cramps
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 21 (0.00%)
         occurrences all number
    1
    0
    leg pain
         subjects affected / exposed
    1 / 24 (4.17%)
    1 / 21 (4.76%)
         occurrences all number
    1
    1
    light headed
         subjects affected / exposed
    0 / 24 (0.00%)
    1 / 21 (4.76%)
         occurrences all number
    0
    4
    loin pain
         subjects affected / exposed
    0 / 24 (0.00%)
    1 / 21 (4.76%)
         occurrences all number
    0
    1
    lower respiratory tract infection
         subjects affected / exposed
    3 / 24 (12.50%)
    4 / 21 (19.05%)
         occurrences all number
    4
    5
    Malaise
         subjects affected / exposed
    0 / 24 (0.00%)
    1 / 21 (4.76%)
         occurrences all number
    0
    1
    memory impairment
         subjects affected / exposed
    2 / 24 (8.33%)
    0 / 21 (0.00%)
         occurrences all number
    3
    0
    Migraine
         subjects affected / exposed
    0 / 24 (0.00%)
    1 / 21 (4.76%)
         occurrences all number
    0
    2
    muscle spasm
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 21 (0.00%)
         occurrences all number
    1
    0
    myalgia
         subjects affected / exposed
    2 / 24 (8.33%)
    2 / 21 (9.52%)
         occurrences all number
    2
    2
    nausea
         subjects affected / exposed
    2 / 24 (8.33%)
    3 / 21 (14.29%)
         occurrences all number
    3
    6
    oesteoarthritis both knees
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 21 (0.00%)
         occurrences all number
    1
    0
    pain in left ankle
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 21 (0.00%)
         occurrences all number
    1
    0
    pain in tongue when eating or drinking since taking 1 week of antibiotics.
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 21 (0.00%)
         occurrences all number
    1
    0
    painful eye after laser eye treatment
         subjects affected / exposed
    0 / 24 (0.00%)
    1 / 21 (4.76%)
         occurrences all number
    0
    1
    painful wisdom tooth
         subjects affected / exposed
    0 / 24 (0.00%)
    1 / 21 (4.76%)
         occurrences all number
    0
    1
    palella ligament injury
         subjects affected / exposed
    0 / 24 (0.00%)
    1 / 21 (4.76%)
         occurrences all number
    0
    1
    palpitations
         subjects affected / exposed
    0 / 24 (0.00%)
    1 / 21 (4.76%)
         occurrences all number
    0
    1
    parasthesia
         subjects affected / exposed
    1 / 24 (4.17%)
    1 / 21 (4.76%)
         occurrences all number
    2
    1
    post liver biopsy pain
         subjects affected / exposed
    2 / 24 (8.33%)
    1 / 21 (4.76%)
         occurrences all number
    4
    2
    Pruritus
         subjects affected / exposed
    3 / 24 (12.50%)
    0 / 21 (0.00%)
         occurrences all number
    6
    0
    rectal polyps removed
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 21 (0.00%)
         occurrences all number
    1
    0
    right knee pain
         subjects affected / exposed
    0 / 24 (0.00%)
    1 / 21 (4.76%)
         occurrences all number
    0
    1
    severe trigonitis
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 21 (0.00%)
         occurrences all number
    1
    0
    shoulder pain
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 21 (0.00%)
         occurrences all number
    1
    0
    sleep apnoea
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 21 (0.00%)
         occurrences all number
    1
    0
    sore throat
         subjects affected / exposed
    1 / 24 (4.17%)
    1 / 21 (4.76%)
         occurrences all number
    1
    1
    tonsilitis
         subjects affected / exposed
    1 / 24 (4.17%)
    1 / 21 (4.76%)
         occurrences all number
    1
    1
    toothache and subsequent tooth extraction
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 21 (0.00%)
         occurrences all number
    1
    0
    viral illness
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 21 (0.00%)
         occurrences all number
    1
    0
    viral upper respiratory infection
         subjects affected / exposed
    4 / 24 (16.67%)
    3 / 21 (14.29%)
         occurrences all number
    5
    6
    vitamin d deficiency
         subjects affected / exposed
    0 / 24 (0.00%)
    1 / 21 (4.76%)
         occurrences all number
    0
    1
    vomiting
         subjects affected / exposed
    1 / 24 (4.17%)
    1 / 21 (4.76%)
         occurrences all number
    2
    1
    whiplash following rta
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 21 (0.00%)
         occurrences all number
    1
    0
    whiplash/back pain
         subjects affected / exposed
    0 / 24 (0.00%)
    1 / 21 (4.76%)
         occurrences all number
    0
    1
    Social circumstances
    depression
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 21 (0.00%)
         occurrences all number
    1
    0
    Eye disorders
    scratch on left cornea
         subjects affected / exposed
    0 / 24 (0.00%)
    1 / 21 (4.76%)
         occurrences all number
    0
    2
    Reproductive system and breast disorders
    Hysterectomy
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 21 (0.00%)
         occurrences all number
    1
    0
    Gastrointestinal disorders
    Irritable bowel syndrome
         subjects affected / exposed
    1 / 24 (4.17%)
    1 / 21 (4.76%)
         occurrences all number
    1
    1
    Respiratory, thoracic and mediastinal disorders
    asthma
         subjects affected / exposed
    0 / 24 (0.00%)
    1 / 21 (4.76%)
         occurrences all number
    0
    1
    Skin and subcutaneous tissue disorders
    skin erthema
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 21 (0.00%)
         occurrences all number
    1
    0
    skin rash
         subjects affected / exposed
    0 / 24 (0.00%)
    1 / 21 (4.76%)
         occurrences all number
    0
    1
    soft tissue facial injuries
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 21 (0.00%)
         occurrences all number
    1
    0
    Renal and urinary disorders
    kidney stone
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 21 (0.00%)
         occurrences all number
    1
    0
    Renal colic
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 21 (0.00%)
         occurrences all number
    1
    0
    Infections and infestations
    ear infection
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 21 (0.00%)
         occurrences all number
    1
    0
    skin infection
         subjects affected / exposed
    1 / 24 (4.17%)
    1 / 21 (4.76%)
         occurrences all number
    1
    1

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    16 Dec 2010
    Updated in line with feedback from the MHRA: - Description of concomitant medications to be avoided by participants and potential drug interactions added - Biochemistry profile has been expanded to include urea and electrolytes - The dose of Losartan has been justified as being a standard dose and the dose which has been used in previous studies - extra visit (visit three) added to the study schedule in which participants will revisit the clinic/research centre for measurement of urea, electrolytes, blood pressure and waist circumference - electrolyte disturbance included as an exclusion criteria
    25 Nov 2011
    - Amendment to study schedule to remove and add assessments - Clarification of number of tablets/capsules in each bottle - Correction of visit numbers throughout the protocol (to coincide with information in earlier amendment).
    20 Dec 2011
    - Amendment to protocol and study schedule to add assessments (GSK biomarker analysis) - Patients to be fasted prior to all visits, apart from visit three (week one) - Clarification re Fibroscan and patient’s BMI - Review of compliance of medication added to schedule at visit three (week one) - “Tablets” amended to “Capsules” in the protocol for accuracy - Code break list to be used instead of code break envelopes - Updated web address for online randomisation - Change in fax number for reporting SAEs - Co-Investigator added to protocol contacts - Membership of Trial Management Group amended - Addition of three new sites (and Principal Investigator details)
    14 May 2012
    - Exclusion criteria (HBA1C >15.0 and amendment to diabetes treatment) - Ultrasound may be carried out +/- 1 month from screening visit date - Amendment to number of centres participating
    14 Aug 2012
    - Clarification of when local serum samples and samples for GSK Biomarker analysis are to be taken. - The serum sample for assessment of GSK Biomarkers no longer be collected at both screening and baseline visits, only at the baseline visit. - Clarification that patients may opt out of having samples taken for GSK Biomarker analysis, but continue in the main part of the study. - Clarification that Fibroscan to be carried out when facilities are available. - Amendment to number of centres participating. More sites are currently being invited to participate.
    18 Feb 2013
    Protocol amended in order to reflect changes in the funding arrangements and the changes in statistical analysis due to the reduced recruitment figures.
    09 Jul 2013
    Amendment made to the assessments carried out if patients withdraw early from the study as a liver biopsy for those who wish to withdraw early from the study would not help to assess a change in fibrosis of the liver. Therefore for those who wished to withdraw early a liver biopsy would not be requested. All other tests remained the same.

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

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