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    Clinical Trial Results:
    Preoperative Volume Replacement vs. usual care in Diabetic patients having CABG surgery: a randomised controlled Trial

    Summary
    EudraCT number
    		 2009-013159-31
    Trial protocol
    		 GB  
    Global end of trial date
    23 Aug 2019

    Results information
    Results version number
    		 v1(current)
    This version publication date
    15 Apr 2020
    First version publication date
    15 Apr 2020
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    CS/2009/3292
    Additional study identifiers
    ISRCTN number
    		 ISRCTN02159606
    US NCT number
    		 -
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    University Hospitals Bristol NHS Foundation Trust
    Sponsor organisation address
    Research & Innovation Dept, Level 3, UH Bristol Education Centre, Upper Maudlin Street, Bristol, United Kingdom, BS2 8AE
    Public contact
    University Hospitals Bristol NHS Foundation Trust, Research and Development Department, 0117 342 0233, R&DSponsorship@UHBristol.nhs.uk
    Scientific contact
    University of Bristol, Clinical Trials Evaluation Unit, 0117 342 3151, btc-mailbox@bristol.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
    22 Oct 2018
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    13 Nov 2014
    Global end of trial reached?
    Yes
    Global end of trial date
    23 Aug 2019
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The VeRDiCT Trial is proposed to test the hypothesis that the postoperative incidence of renal insufficiency will be lower, and post-operative recovery faster, if diabetic patients are treated with volume replacement therapy prior to surgery. This treatment has already been shown to prevent acute kidney injury in certain clinical scenarios. Our principal objective is to compare the time from surgery until the patient is 'fit for discharge' in diabetics having coronary artery bypass surgery, randomly assigned to either receive preoperative volume replacement therapy, or to not (i.e. routine care).
    Protection of trial subjects
    All potential participants were sent or given an invitation letter and patient information sheet (PIS) (approved by the local Research Ethics Committee,(REC)) describing the study. The patient had time to read the PIS and to discuss their participation with others outside the research team (e.g. relatives or friends) if they wished. Most patients had at least 24 hours to consider whether to participate. Full informed consent was obtained for every trial participant. The patient's GP was informed of their participation in the trial. All members of the direct healthcare team are contractually bound to abide by standard NHS conditions of confidentiality and the need to access medical records will be explained to each patient during the process of obtaining consent.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    15 Jul 2010
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    United Kingdom: 122
    Worldwide total number of subjects
    122
    EEA total number of subjects
    122
    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)
    56
    From 65 to 84 years
    66
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 Of the 331 eligible patients screened, 128 provided written informed consent and agreed to take part in the study.

    Pre-assignment
    Screening details
    		 Between July 2010 and July 2014, a total of 444 patients were screened for inclusion in the trial, 113 of whom were ineligible.

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Volume replacement therapy
    Arm description
    		 CABG with or without cardiopulmonary bypass (CPB), with preoperative volume replacement therapy (1 ml/kg/hr of Hartmann’s solution for 12 consecutive hours prior to surgery).
    Arm type
    		 Experimental

    Investigational medicinal product name
    Hartmann’s Solution (Compound Sodium Lactate Intravenous Infusion BP)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection/infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    The dosage is dependant on body mass as follows: 1ml/kg/hr for 12 hours, therefore, maximum dose (ml) = body mass x12 If for some reason there is less than 12 hours for administration of the IMP, such as a delay in admission to hospital until later than the normal start time for the infusion, or an event that occurs overnight (e.g. patient has a shower) resulting in the infusion being disconnected for a short period, the rate will be increased so that the full dose could be given. The dose will still be equivalent to 1ml/kg/hr for 12 hours, and therefore the maximum dose will stay the same. The minimum time that the IMP can be administered over is 8 hours.

    Arm title
    		 Usual care
    Arm description
    		 CABG with or without CPB with conventional preoperative management (no preoperative fluids).
    Arm type
    		 No intervention

    Investigational medicinal product name
    No investigational medicinal product assigned in this arm
    Number of subjects in period 1 [1]
    		Volume replacement therapy Usual care
    Started
    60
    61
    Completed
    60
    61
    Notes
    [1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
    Justification: One patient allocated to the volume replacement therapy group was withdrawn post-randomisation, pre-operatively as they had AVR added to their CABG surgery and were therefore ineligible.

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Volume replacement therapy
    Reporting group description
    		 CABG with or without cardiopulmonary bypass (CPB), with preoperative volume replacement therapy (1 ml/kg/hr of Hartmann’s solution for 12 consecutive hours prior to surgery).

    Reporting group title
    Usual care
    Reporting group description
    		 CABG with or without CPB with conventional preoperative management (no preoperative fluids).

    Reporting group values
    		 Volume replacement therapy Usual care Total
    Number of subjects
    		 60 61 121
    Age categorical
    Units: Subjects
        In utero
    		 0
        Preterm newborn infants (gestational age < 37 wks)
    		 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)
    		 0
        From 65-84 years
    		 0
        85 years and over
    		 0
    Age continuous
    Units: years
        median (inter-quartile range (Q1-Q3))
    		 67 (59.4 to 71.4) 66 (60.6 to 70.7) -
    Gender categorical
    Units: Subjects
        Female
    		 9 10 19
        Male
    		 51 51 102
    Pre-operative creatine > 160μmol/l
    Units: Subjects
        Yes
    		 4 3 7
        No
    		 56 58 114
    Ejection fraction < 50%
    Units: Subjects
        Yes
    		 11 12 23
        No
    		 49 49 98
    Age >= 70 years
    Units: Subjects
        Yes
    		 17 17 34
        No
    		 43 44 87
    Cardiac angiogram in last 5 days
    Units: Subjects
        Yes
    		 7 5 12
        No
    		 53 56 109
    Chronic pulmonary disease
    Units: Subjects
        Yes
    		 6 8 14
        No
    		 54 53 107
    Extracardiac arteriopathy
    Units: Subjects
        Yes
    		 6 5 11
        No
    		 54 56 110
    Neurological dysfunction
    Units: Subjects
        Yes
    		 2 3 5
        No
    		 58 58 116
    Unstable angina
    Units: Subjects
        Yes
    		 2 3 5
        No
    		 58 58 116
    Myocardial infarction within 90 days
    Units: Subjects
        Yes
    		 19 13 32
        No
    		 41 48 89
    NYHA class
    Units: Subjects
        Class I
    		 17 9 26
        Class II
    		 28 36 64
        Class III
    		 15 14 29
        Class IV
    		 0 2 2
    CCS class
    Units: Subjects
        Asymptomatic
    		 10 7 17
        Class I
    		 9 3 12
        Class II
    		 15 28 43
        Class III
    		 21 18 39
        Class IV
    		 5 5 10
    >50% disease in left main stem
    Units: Subjects
        Yes
    		 14 9 23
        No
    		 46 52 98
    Number of diseased vessels
    Units: Subjects
        Single
    		 0 2 2
        Double
    		 17 15 32
        Triple
    		 42 44 86
        Unrecorded
    		 1 0 1
    Previous PCI
    Units: Subjects
        Yes
    		 13 7 20
        No
    		 47 54 101
    Previous MI
    Units: Subjects
        Yes
    		 33 28 61
        No
    		 27 33 60
    Diabetes
    Units: Subjects
        Type I
    		 1 7 8
        Type 2 insulin
    		 24 24 48
        Type 2 oral
    		 35 30 65
    Smoking
    Units: Subjects
        Current
    		 7 5 12
        Ex (>1 month)
    		 31 36 67
        Never
    		 22 20 42
    Hypertension requiring treatment
    Units: Subjects
        Yes
    		 55 55 110
        No
    		 5 6 11
    Hypercholesterolaemia
    Units: Subjects
        Yes
    		 57 52 109
        No
    		 3 9 12
    Neurological disease
    Units: Subjects
        Yes
    		 3 2 5
        No
    		 57 58 115
        Not recorded
    		 0 1 1
    Peptic ulceration
    Units: Subjects
        Yes
    		 0 2 2
        No
    		 60 59 119
    Heart rhythm
    Units: Subjects
        Sinus
    		 55 56 111
        AF
    		 3 3 6
        Block
    		 1 2 3
        Unrecorded
    		 1 0 1
    Pacemaker
    Units: Subjects
        Permanent
    		 2 1 3
        None
    		 58 60 118
    Operative priority
    Units: Subjects
        Elective
    		 41 46 87
        Urgent
    		 19 15 34
    Family history (cardiac)
    Units: Subjects
        Yes
    		 36 37 73
        No
    		 24 23 47
        Unrecorded
    		 0 1 1
    CPB used (intra-operative)
    Units: Subjects
        Yes
    		 20 19 39
        No
    		 40 42 82
    Number of distal coronary anastomoses (intra-operative)
    Units: Subjects
        One
    		 7 7 14
        Two
    		 21 21 42
        Three
    		 25 29 54
        Four
    		 6 3 9
        Five
    		 1 1 2
    Number of arterial conduits (intra-operative)
    Units: Subjects
        None
    		 2 0 2
        One
    		 47 57 104
        Two
    		 9 4 13
        Three
    		 2 0 2
    Tranexamic used (intra-operative)
    Units: Subjects
        Yes
    		 50 55 105
        No
    		 10 6 16
    Cell saver set up (intra-operative)
    Units: Subjects
        Yes
    		 9 11 20
        No
    		 51 50 101
    Intra-operative insulin infusion
    Units: Subjects
        Yes
    		 36 36 72
        No
    		 24 25 49
    Intra-operative inotropes
    Excluding noradrenaline
    Units: Subjects
        Yes
    		 3 3 6
        No
    		 57 57 114
        Unrecorded
    		 0 1 1
    Intra-operative noradrenaline
    Units: Subjects
        Yes
    		 7 9 16
        No
    		 53 52 105
    Intra-operative pacing
    Excluding patients with pacing beforehand
    Units: Subjects
        Yes
    		 3 8 11
        No
    		 54 52 106
        Unrecorded
    		 3 1 4
    Intra-operative IABP
    Units: Subjects
        Yes
    		 1 0 1
        No
    		 59 61 120
    Need for defibrillation (intra-operative and post-operative)
    Units: Subjects
        Yes
    		 2 2 4
        No
    		 58 59 117
    Arrhythmias on chest closure
    Excluding patients with permanent pacemaker beforehand
    Units: Subjects
        AF
    		 2 4 6
        Other
    		 0 2 2
        None, sinus rhythm
    		 56 54 110
        Unrecorded
    		 2 1 3
    BMI
    Units: kg/m2
        median (inter-quartile range (Q1-Q3))
    		 30 (27.0 to 33.8) 31 (28.2 to 33.9) -
    EuroSCORE (additive)
    Units: N/A
        median (inter-quartile range (Q1-Q3))
    		 3 (2 to 4) 2 (2 to 4) -
    Logistic EuroSCORE
    Units: N/A
        median (inter-quartile range (Q1-Q3))
    		 2.3 (1.4 to 3.4) 1.8 (1.3 to 3.4) -
    Haemoglobin
    Units: g/dL
        median (inter-quartile range (Q1-Q3))
    		 14 (12.7 to 14.9) 14 (12.4 to 15.1) -
    Platelets
    Units: 10^9/L
        arithmetic mean (standard deviation)
    		 251 ± 63.9 241 ± 59.2 -
    Creatinine
    Units: μmol/l
        median (inter-quartile range (Q1-Q3))
    		 86 (76.5 to 108.5) 87 (75.0 to 100.0) -
    Total bypass time (intra-operative)
    Units: minute
        median (inter-quartile range (Q1-Q3))
    		 80 (64.5 to 95.0) 79 (64.0 to 103.0) -
    Cumulative cross-clamp time (intra-operative)
    Units: minute
        arithmetic mean (standard deviation)
    		 48 ± 13.0 49 ± 17.7 -
    Dose of tranexamic acid (intra-operative)
    Units: gram(s)
        median (inter-quartile range (Q1-Q3))
    		 2 (2 to 2) 2 (2 to 2) -
    Volume of cell saver infused (intra-operative)
    Units: millilitre(s)
        median (inter-quartile range (Q1-Q3))
    		 240 (100 to 400) 238 (0 to 1000) -
    Lowest haematocrit (intra-operative)
    Units: percent
        median (inter-quartile range (Q1-Q3))
    		 31 (28.0 to 35.9) 31 (27.5 to 36.0) -
    Dose/weight of VRT
    Units: N/A
        median (inter-quartile range (Q1-Q3))
    		 12 (11.7 to 12.0) 0 (0 to 0) -
    Duration of VRT
    Units: hours
        median (inter-quartile range (Q1-Q3))
    		 12 (11.4 to 12.5) 0 (0 to 0) -

    End points

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    End points reporting groups
    Reporting group title
    Volume replacement therapy
    Reporting group description
    		 CABG with or without cardiopulmonary bypass (CPB), with preoperative volume replacement therapy (1 ml/kg/hr of Hartmann’s solution for 12 consecutive hours prior to surgery).

    Reporting group title
    Usual care
    Reporting group description
    		 CABG with or without CPB with conventional preoperative management (no preoperative fluids).

    Subject analysis set title
    High risk - VRT group
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Subgroup of patients with high risk - VRT group

    Subject analysis set title
    Low risk - VRT group
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Subgroup of patients with low risk - VRT group

    Subject analysis set title
    High risk - usual care group
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Subgroup of patients with high risk - usual care group

    Subject analysis set title
    Low risk - usual care group
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Subgroup of patients with low risk - usual care group

    Subject analysis set title
    Oral treatment only - VRT group
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Subgroup of patients receiving oral treatment only - VRT group

    Subject analysis set title
    Oral treatment only - usual care group
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Subgroup of patients receiving oral treatment only - usual care group

    Subject analysis set title
    Insulin +/- oral treatment - VRT group
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Subgroup of patients receiving insulin +/- oral treatment - VRT group

    Subject analysis set title
    Insulin +/- oral treatment - usual care group
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Subgroup of patients receiving insulin +/- oral treatment - usual care group

    Primary: Time to fitness for discharge

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    End point title
    		 Time to fitness for discharge
    End point description
    Time until patients first classified as fit for 'discharge'
    End point type
    Primary
    End point timeframe
    Post-op in-hospital
    End point values
    		 Volume replacement therapy Usual care High risk - VRT group Low risk - VRT group High risk - usual care group Low risk - usual care group Oral treatment only - VRT group Oral treatment only - usual care group Insulin +/- oral treatment - VRT group Insulin +/- oral treatment - usual care group
    Number of subjects analysed
    60
    61
    22
    38
    23
    37
    35
    30
    25 [1]
    31
    Units: Days
        median (inter-quartile range (Q1-Q3))
    7 (5 to 12)
    7 (5 to 12)
    9 (5 to 13)
    7 (5 to 9)
    7 (5 to 12)
    7 (5 to 9)
    7 (5 to 12)
    7 (5 to 12)
    7 (5 to 999)
    7 (5 to 12)
    Notes
    [1] - 75th percentile (Q3) is undefined. 999 entered
    Statistical analysis title
    		 Time to fitness for discharge
    Comparison groups
    Volume replacement therapy v Usual care
    Number of subjects included in analysis
    121
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.7867
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.07
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.67
         upper limit
    		 1.7
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.25
    Statistical analysis title
    		 Time to fitness for discharge - high risk
    Statistical analysis description
    Comparing time to fitness for discharge between VRT and usual care groups in high risk patients only
    Comparison groups
    High risk - VRT group v High risk - usual care group
    Number of subjects included in analysis
    45
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.83
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.32
         upper limit
    		 2.13
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.4
    Statistical analysis title
    		 Time to fitness for discharge - low risk
    Statistical analysis description
    Comparing time to fitness for discharge between VRT and usual care groups in low risk patients only
    Comparison groups
    Low risk - VRT group v Low risk - usual care group
    Number of subjects included in analysis
    75
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.14
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.63
         upper limit
    		 2.08
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.35
    Statistical analysis title
    		 Time to fitness for discharge - oral treatment
    Statistical analysis description
    Comparing time to fitness for discharge between VRT and usual care groups for patients receiving oral treatment only for their diabetes
    Comparison groups
    Oral treatment only - VRT group v Oral treatment only - usual care group
    Number of subjects included in analysis
    65
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.11
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.6
         upper limit
    		 2.07
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.35
    Statistical analysis title
    		 Time to fitness for discharge - insulin +/- oral
    Statistical analysis description
    Comparing time to fitness for discharge between VRT and usual care groups for patients receiving insulin +/- oral treatment only for their diabetes
    Comparison groups
    Insulin +/- oral treatment - VRT group v Insulin +/- oral treatment - usual care group
    Number of subjects included in analysis
    56
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.86
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.32
         upper limit
    		 2.28
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.43

    Secondary: Acute kidney injury

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    End point title
    		 Acute kidney injury
    End point description
    AKI = YES if any post-operative measurement ≥ 1.5 x baseline
    End point type
    Secondary
    End point timeframe
    Serum creatinine measured from blood samples collected preoperatively (baseline, pre-trial intervention) and at 0, 24, 48, 72, 96, and 120 hours
    End point values
    		 Volume replacement therapy Usual care Oral treatment only - VRT group Oral treatment only - usual care group Insulin +/- oral treatment - VRT group Insulin +/- oral treatment - usual care group
    Number of subjects analysed
    60
    61
    35
    30
    25
    31
    Units: Subjects
        Yes
    18
    13
    9
    7
    9
    6
        No
    42
    48
    26
    23
    16
    25
    Statistical analysis title
    		 Acute kidney injury
    Comparison groups
    Volume replacement therapy v Usual care
    Number of subjects included in analysis
    121
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.2377
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.65
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.72
         upper limit
    		 3.8
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.7
    Statistical analysis title
    		 Acute kidney injury - oral treatment only
    Statistical analysis description
    Comparing acute kidney injury between VRT and usual care groups in patients receiving oral treatment only for their diabetes
    Comparison groups
    Oral treatment only - usual care group v Oral treatment only - VRT group
    Number of subjects included in analysis
    65
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.08
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.34
         upper limit
    		 3.41
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.63
    Statistical analysis title
    		 Acute kidney injury - insulin +/- oral treatment
    Statistical analysis description
    Comparing acute kidney injury between VRT and usual care groups in patients receiving insulin +/- oral treatment for their diabetes
    Comparison groups
    Insulin +/- oral treatment - VRT group v Insulin +/- oral treatment - usual care group
    Number of subjects included in analysis
    56
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    2.69
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.48
         upper limit
    		 15.04
    Variability estimate
    Standard error of the mean
    Dispersion value
    2.36

    Secondary: Hospital morbidity

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    End point title
    		 Hospital morbidity
    End point description
    End point type
    Secondary
    End point timeframe
    Post-intervention to hospital discharge
    End point values
    		 Volume replacement therapy Usual care
    Number of subjects analysed
    60
    61
    Units: Subjects
        Yes
    51
    54
        No
    9
    7
    Statistical analysis title
    		 In-hospital morbidity
    Comparison groups
    Volume replacement therapy v Usual care
    Number of subjects included in analysis
    121
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.5547
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    0.72
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.25
         upper limit
    		 2.12
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.4

    Secondary: Participants with eGFR <60ml/min on at least 2 of the 8 post-operative times

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    End point title
    		 Participants with eGFR <60ml/min on at least 2 of the 8 post-operative times
    End point description
    Conditional mean imputation used to impute missing values of eGFR.
    End point type
    Secondary
    End point timeframe
    Estimated glomerular filtration rate (eGFR) from serum creatinine measured from blood samples collected preoperatively (baseline, pre-trial intervention), and at 0, 12, 24, 36, 48, 72, 96 and 120 hours after the operation
    End point values
    		 Volume replacement therapy Usual care
    Number of subjects analysed
    60
    61
    Units: Subjects
        Yes
    31
    28
        No
    29
    33
    Statistical analysis title
    		 eGFR<60 mL/min
    Comparison groups
    Volume replacement therapy v Usual care
    Number of subjects included in analysis
    121
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.4219
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.38
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.63
         upper limit
    		 3.01
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.55

    Secondary: Pre-operative post-intervention blood glucose

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    End point title
    		 Pre-operative post-intervention blood glucose
    End point description
    End point type
    Secondary
    End point timeframe
    Pre-op post-intervention
    End point values
    		 Volume replacement therapy Usual care
    Number of subjects analysed
    24
    28
    Units: mmol/L
        median (inter-quartile range (Q1-Q3))
    6.5 (5.5 to 8.1)
    6.9 (5.5 to 8.6)
    Statistical analysis title
    		 Pre-operative post-intervention blood glucose
    Comparison groups
    Volume replacement therapy v Usual care
    Number of subjects included in analysis
    52
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.759
    Method
    		 Regression, Linear
    Parameter type
    		 Geometric mean ratio
    Point estimate
    0.97
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.81
         upper limit
    		 1.17
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.09

    Secondary: Pre-operative post-intervention HbA1c

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    End point title
    		 Pre-operative post-intervention HbA1c
    End point description
    End point type
    Secondary
    End point timeframe
    Pre-op post-intervention
    End point values
    		 Volume replacement therapy Usual care
    Number of subjects analysed
    24
    28
    Units: mmol/L
        median (inter-quartile range (Q1-Q3))
    53.5 (47.5 to 60.5)
    54.5 (47.0 to 70.5)
    Statistical analysis title
    		 Pre-operative post-intervention HbA1c
    Comparison groups
    Usual care v Volume replacement therapy
    Number of subjects included in analysis
    52
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.162
    Method
    		 Regression, Linear
    Parameter type
    		 Geometric mean ratio
    Point estimate
    0.92
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.81
         upper limit
    		 1.04
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.06

    Secondary: eGFR

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    End point title
    		 eGFR
    End point description
    End point type
    Secondary
    End point timeframe
    Estimated glomerular filtration rate (eGFR) from serum creatinine measured from blood samples collected preoperatively (baseline, pre-trial intervention), and at 0, 12, 24, 36, 48, 72, 96 and 120 hours after the operation
    End point values
    		 Volume replacement therapy Usual care Oral treatment only - VRT group Oral treatment only - usual care group Insulin +/- oral treatment - VRT group Insulin +/- oral treatment - usual care group
    Number of subjects analysed
    60
    61
    35
    30
    25
    31
    Units: mmol/min
    arithmetic mean (standard deviation)
        Pre-operative
    70.5 ± 18.9
    69 ± 16
    74.2 ± 14.9
    73.9 ± 16.6
    63.5 ± 24.1
    63.7 ± 14.1
        Operation end
    76.0 ± 17.0
    75.7 ± 15.8
    78.9 ± 14.2
    78.9 ± 14.0
    71.5 ± 20.1
    72.7 ± 17.0
        Operation end + 12 hours
    69.7 ± 19.2
    69.7 ± 19.6
    73.7 ± 17.9
    75.7 ± 17.1
    63.6 ± 20.0
    62.9 ± 20.4
        Operation end + 24 hours
    60.7 ± 20.3
    62.5 ± 21.7
    64.7 ± 19.1
    66.6 ± 20.0
    55.1 ± 21.1
    58.2 ± 22.8
        Operation end + 36 hours
    59.5 ± 22.9
    60.5 ± 23.5
    63.2 ± 20.2
    63.1 ± 20.8
    54.9 ± 25.8
    57.9 ± 26.1
        Operation end + 48 hours
    59.4 ± 23.8
    58.7 ± 23
    60.8 ± 22.4
    62.8 ± 20.9
    57.7 ± 25.8
    55.6 ± 24.4
        Operation end + 72 hours
    62.2 ± 24.8
    63.3 ± 24.4
    66.2 ± 23.5
    66.9 ± 22.8
    56.1 ± 26.1
    59.9 ± 25.8
        Operation end + 96 hours
    64.9 ± 25.0
    66.7 ± 24.2
    66.6 ± 24.4
    72.3 ± 21.8
    62.5 ± 262
    61.1 ± 25.7
        Operation end + 120 hours
    65.0 ± 24.5
    71.0 ± 21.3
    67.7 ± 24.6
    74.3 ± 20.1
    62.0 ± 24.5
    67.3 ± 22.5
    Statistical analysis title
    		 eGFR
    Comparison groups
    Usual care v Volume replacement therapy
    Number of subjects included in analysis
    121
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.5799
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    -1.06
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.59
         upper limit
    		 2.48
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.8
    Statistical analysis title
    		 eGFR - oral treatment only
    Statistical analysis description
    Comparing eGFR between VRT and usual care groups in patients receiving oral treatment only for their diabetes
    Comparison groups
    Oral treatment only - VRT group v Oral treatment only - usual care group
    Number of subjects included in analysis
    65
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    -0.23
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.92
         upper limit
    		 4.46
    Variability estimate
    Standard error of the mean
    Dispersion value
    2.39
    Statistical analysis title
    		 eGFR - insulin +/- oral treatment
    Statistical analysis description
    Comparing eGFR between VRT and usual care groups in patients receiving insulin +/- oral treatment for their diabetes
    Comparison groups
    Insulin +/- oral treatment - VRT group v Insulin +/- oral treatment - usual care group
    Number of subjects included in analysis
    56
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    -2.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -9.46
         upper limit
    		 4.87
    Variability estimate
    Standard error of the mean
    Dispersion value
    3.65

    Secondary: Microalbumin/creatinine ratio

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    End point title
    		 Microalbumin/creatinine ratio
    End point description
    End point type
    Secondary
    End point timeframe
    Measured in urine samples collected preoperatively (baseline, pre-trial intervention) and at 0, 24, 48 and 120 hours
    End point values
    		 Volume replacement therapy Usual care Oral treatment only - VRT group Oral treatment only - usual care group Insulin +/- oral treatment - VRT group Insulin +/- oral treatment - usual care group
    Number of subjects analysed
    60
    61
    35
    30
    25
    31
    Units: mg/mmol
    median (inter-quartile range (Q1-Q3))
        Pre-operative
    1.2 (0.5 to 3.9)
    1.4 (0.8 to 2.9)
    1 (0.5 to 3.5)
    1.1 (0.6 to 2.3)
    2 (0.7 to 5.5)
    1.7 (1.1 to 4.1)
        Operation end
    3.4 (2.0 to 9.7)
    5.1 (2.1 to 8.7)
    2.9 (1.8 to 9.7)
    4.2 (1.2 to 8.5)
    3.9 (2.5 to 8.6)
    5.6 (2.8 to 9)
        Operation end + 24 hours
    2.9 (1.8 to 7.1)
    3.2 (2.0 to 6.1)
    2.9 (1.7 to 5.1)
    3.4 (1.9 to 6.6)
    3.4 (1.9 to 8.1)
    3.1 (2 to 5.8)
        Operation end + 48 hours
    5.1 (2.1 to 8.0)
    3.6 (2.1 to 6.7)
    4.4 (2.1 to 7.4)
    3.6 (2.2 to 5.3)
    5.2 (2.2 to 9.2)
    3.7 (2.1 to 6.9)
        Operation end + 120 hours
    1.6 (1.1 to 7.1)
    2.0 (1.4 to 4.1)
    1.6 (1.1 to 5)
    1.6 (0.6 to 2.9)
    2.2 (1.1 to 16.1)
    2.7 (2 to 6.1)
    Statistical analysis title
    		 Microalbumin/creatinine ratio
    Comparison groups
    Volume replacement therapy v Usual care
    Number of subjects included in analysis
    121
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.5604
    Method
    		 Mixed models analysis
    Parameter type
    		 Geometric mean ratio
    Point estimate
    1.07
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.85
         upper limit
    		 1.37
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.13
    Statistical analysis title
    		 Microalbumin/creatinine ratio - oral treatment
    Statistical analysis description
    Comparing microalbumin/creatinine ratio between VRT and usual care groups in patients receiving oral treatment only for their diabetes
    Comparison groups
    Oral treatment only - usual care group v Oral treatment only - VRT group
    Number of subjects included in analysis
    65
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    		 Mixed models analysis
    Parameter type
    		 Geometric mean ratio
    Point estimate
    1.01
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.73
         upper limit
    		 1.4
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.17
    Statistical analysis title
    		 Microalbumin/creatinine ratio - insulin +/- oral
    Statistical analysis description
    Comparing microalbumin/creatinine ratio between VRT and usual care groups in patients receiving insulin +/- oral treatment for their diabetes
    Comparison groups
    Insulin +/- oral treatment - VRT group v Insulin +/- oral treatment - usual care group
    Number of subjects included in analysis
    56
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    		 Mixed models analysis
    Parameter type
    		 Geometric mean ratio
    Point estimate
    1.17
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.71
         upper limit
    		 1.9
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.29

    Secondary: C-reactive protein

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    End point title
    		 C-reactive protein
    End point description
    End point type
    Secondary
    End point timeframe
    Measured preoperatively (baseline, pre-trial intervention) and at 0, 12, 24, 48, 72 and 120 hours after the operation.
    End point values
    		 Volume replacement therapy Usual care
    Number of subjects analysed
    26
    28
    Units: mg/L
    median (inter-quartile range (Q1-Q3))
        Pre-operative
    2 (1 to 4)
    2 (1 to 3)
        Operation end
    1 (1 to 3)
    1 (1 to 2)
        Operation end + 12 hours
    45 (36 to 58.5)
    44 (36.5 to 59.5)
        Operation end + 24 hours
    132 (123 to 183)
    167.5 (133.5 to 180)
        Operation end + 48 hours
    241.5 (199 to 287)
    249 (184 to 290)
        Operation end + 72 hours
    232 (174 to 295)
    249 (198 to 284)
        Operation end + 120 hours
    91.5 (61 to 124)
    97 (63 to 132)
    Statistical analysis title
    		 C-reactive protein
    Comparison groups
    Volume replacement therapy v Usual care
    Number of subjects included in analysis
    54
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.9353
    Method
    		 Regression, Linear
    Parameter type
    		 Geometric mean ratio
    Point estimate
    1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.89
         upper limit
    		 1.11
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.05

    Secondary: Troponin T

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    End point title
    		 Troponin T
    End point description
    End point type
    Secondary
    End point timeframe
    Measured preoperatively (baseline, pre-trial intervention) and at 0, 12, 24, 48, 72 and 120 hours after the operation.
    End point values
    		 Volume replacement therapy Usual care
    Number of subjects analysed
    26
    28
    Units: µg/L
    median (inter-quartile range (Q1-Q3))
        Pre-operative
    12 (9.5 to 13.5)
    9 (6 to 21)
        Operation end
    166 (86 to 267)
    129.5 (76.5 to 226.5)
        Operation end + 12 hours
    234.5 (130 to 364)
    197 (80 to 320)
        Operation end + 24 hours
    200 (103 to 258)
    177 (70 to 249)
        Operation end + 48 hours
    145 (87 to 193)
    142 (68 to 225)
        Operation end + 72 hours
    123 (75.5 to 189.5)
    132 (70 to 179)
        Operation end + 120 hours
    89.5 (54 to 158)
    66 (34 to 111)
    Statistical analysis title
    		 Troponin T
    Comparison groups
    Volume replacement therapy v Usual care
    Number of subjects included in analysis
    54
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.4923
    Method
    		 Regression, Linear
    Parameter type
    		 Geometric mean ratio
    Point estimate
    1.14
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.8
         upper limit
    		 1.64
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.21

    Secondary: N-acetyl glucosaminidase (NAG)

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    End point title
    		 N-acetyl glucosaminidase (NAG)
    End point description
    End point type
    Secondary
    End point timeframe
    Measured in urine samples collected preoperatively (baseline, pre-trial intervention) and at 0, 24, 48 and 120 hours
    End point values
    		 Volume replacement therapy Usual care Oral treatment only - VRT group Oral treatment only - usual care group Insulin +/- oral treatment - VRT group Insulin +/- oral treatment - usual care group
    Number of subjects analysed
    36
    37
    22
    18
    14
    19
    Units: U/g
    median (inter-quartile range (Q1-Q3))
        Pre-operative
    1.9 (1.3 to 3.6)
    2.4 (1.7 to 3.9)
    1.8 (1.1 to 2.9)
    2.1 (1.5 to 3.9)
    2.1 (1.7 to 6.7)
    3 (1.9 to 4.5)
        Operation end
    4.3 (2.2 to 7.7)
    4.6 (1.9 to 7.3)
    3.5 (2 to 6.7)
    4.1 (1.7 to 5.7)
    4.6 (2.8 to 9.8)
    5.9 (3.0 to 10.4)
        Operation end + 24 hours
    8.6 (5.9 to 15.1)
    6.8 (4.7 to 14.9)
    8.6 (6 to 13.5)
    6.2 (4.2 to 12.3)
    8.9 (5.9 to 19.2)
    10.5 (5.0 to 20.7)
        Operation end + 48 hours
    7.8 (3.3 to 19.4)
    8.4 (2.3 to 15.4)
    5.3 (2.9 to 12.1)
    6.0 (2.2 to 12.8)
    17.4 (6.5 to 26.4)
    9.7 (5.2 to 19.1)
        Operation end + 120 hours
    7 (4.1 to 9.4)
    6 (3.9 to 9.8)
    5.9 (3.8 to 8.6)
    4.8 (3.6 to 6.2)
    9.3 (7.3 to 13.4)
    9.3 (6.5 to 14.3)
    Statistical analysis title
    		 N-acetyl glucosaminidase (NAG)
    Comparison groups
    Volume replacement therapy v Usual care
    Number of subjects included in analysis
    73
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.4912
    Method
    		 Regression, Linear
    Parameter type
    		 Geometric mean ratio
    Point estimate
    1.09
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.85
         upper limit
    		 1.4
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.14
    Statistical analysis title
    		 NAG - oral treatment only
    Statistical analysis description
    Comparing NAG between VRT and usual care groups in patients receiving oral treatment only for their diabetes
    Comparison groups
    Oral treatment only - VRT group v Oral treatment only - usual care group
    Number of subjects included in analysis
    40
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    		 Mixed models analysis
    Parameter type
    		 Geometric mean ratio
    Point estimate
    1.25
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.91
         upper limit
    		 1.72
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.2
    Statistical analysis title
    		 NAG - insulin +/- oral treatment
    Statistical analysis description
    Comparing NAG between VRT and usual care groups in patients receiving insulin +/- oral treatment for their diabetes
    Comparison groups
    Insulin +/- oral treatment - VRT group v Insulin +/- oral treatment - usual care group
    Number of subjects included in analysis
    33
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    		 Mixed models analysis
    Parameter type
    		 Geometric mean ratio
    Point estimate
    0.78
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.48
         upper limit
    		 1.27
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.19

    Secondary: CROQ core total score

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    End point title
    		 CROQ core total score
    End point description
    End point type
    Secondary
    End point timeframe
    Pre-operatively and 3 months post-randomisation
    End point values
    		 Volume replacement therapy Usual care
    Number of subjects analysed
    60
    61
    Units: N/A
    median (inter-quartile range (Q1-Q3))
        Pre-operative
    47.2 (40.1 to 52)
    47.6 (42.1 to 52)
        3 months post-operative
    54 (48.3 to 56.6)
    53.6 (47.9 to 56.4)
    Statistical analysis title
    		 CROQ score total score
    Comparison groups
    Volume replacement therapy v Usual care
    Number of subjects included in analysis
    121
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.5967
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (final values)
    Point estimate
    0.66
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.78
         upper limit
    		 3.1
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.24

    Secondary: CROQ symptoms score

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    End point title
    		 CROQ symptoms score
    End point description
    End point type
    Secondary
    End point timeframe
    Pre-operative and 3 months post-operative
    End point values
    		 Volume replacement therapy Usual care
    Number of subjects analysed
    60
    61
    Units: N/A
    median (inter-quartile range (Q1-Q3))
        Pre-operative
    69 (50 to 85.7)
    68.8 (48.2 to 85.7)
        3 months post-operative
    92.9 (85.7 to 100)
    92.9 (79.1 to 96.4)
    Statistical analysis title
    		 CROQ symptoms score
    Comparison groups
    Volume replacement therapy v Usual care
    Number of subjects included in analysis
    121
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.5901
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (final values)
    Point estimate
    1.57
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.12
         upper limit
    		 7.26
    Variability estimate
    Standard error of the mean
    Dispersion value
    2.9

    Secondary: CROQ physical functioning score

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    End point title
    		 CROQ physical functioning score
    End point description
    End point type
    Secondary
    End point timeframe
    Pre-operative and 3 months post-operative
    End point values
    		 Volume replacement therapy Usual care
    Number of subjects analysed
    59
    61
    Units: N/A
    median (inter-quartile range (Q1-Q3))
        Pre-operative
    56.3 (31.3 to 91.7)
    56.3 (25 to 85.7)
        3 months post-operative
    90.7 (65.7 to 100)
    83.5 (62.5 to 93.8)
    Statistical analysis title
    		 CROQ physical functioning score
    Comparison groups
    Volume replacement therapy v Usual care
    Number of subjects included in analysis
    120
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.993
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -0.04
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -9.61
         upper limit
    		 9.52
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.88

    Secondary: CROQ cognitive functioning score

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    End point title
    		 CROQ cognitive functioning score
    End point description
    End point type
    Secondary
    End point timeframe
    Pre-operative and 3 months post-operative
    End point values
    		 Volume replacement therapy Usual care
    Number of subjects analysed
    60
    61
    Units: N/A
    median (inter-quartile range (Q1-Q3))
        Pre-operative
    80 (53.3 to 100)
    86.7 (60 to 100)
        3 months post-operative
    83.4 (63.4 to 100)
    90 (60 to 100)
    Statistical analysis title
    		 CROQ cognitive functioning score
    Comparison groups
    Volume replacement therapy v Usual care
    Number of subjects included in analysis
    121
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.6638
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (final values)
    Point estimate
    1.91
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -6.62
         upper limit
    		 10.45
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.35

    Secondary: CROQ psychosocial functioning score

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    End point title
    		 CROQ psychosocial functioning score
    End point description
    End point type
    Secondary
    End point timeframe
    Pre-operative and 3 months post-operative
    End point values
    		 Volume replacement therapy Usual care
    Number of subjects analysed
    60
    61
    Units: N/A
    median (inter-quartile range (Q1-Q3))
        Pre-operative
    62.5 (39.3 to 80.4)
    68.8 (47.3 to 82.1)
        3 months post-operative
    85.7 (62.5 to 92.9)
    85.7 (67.9 to 92.9)
    Statistical analysis title
    		 CROQ psychosocial functioning score
    Comparison groups
    Volume replacement therapy v Usual care
    Number of subjects included in analysis
    121
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.2563
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (final values)
    Point estimate
    4.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.31
         upper limit
    		 12.71
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.09

    Secondary: CROQ satisfaction score

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    End point title
    		 CROQ satisfaction score
    End point description
    End point type
    Secondary
    End point timeframe
    3 months post-operative
    End point values
    		 Volume replacement therapy Usual care
    Number of subjects analysed
    51
    53
    Units: N/A
        median (inter-quartile range (Q1-Q3))
    86.7 (75 to 100)
    79.2 (62.5 to 91.7)
    Statistical analysis title
    		 CROQ satisfaction score
    Statistical analysis description
    Comaparing CROQ satisfaction score between VRT and usual care groups at 3 months post-operation. Multiple imputation used to account for missing data.
    Comparison groups
    Usual care v Volume replacement therapy
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.123
    Method
    		 Regression, Linear
    Parameter type
    		 Mean difference (final values)
    Point estimate
    5.65
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.56
         upper limit
    		 12.86
    Variability estimate
    Standard error of the mean
    Dispersion value
    3.63

    Secondary: CROQ adverse effects score

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    End point title
    		 CROQ adverse effects score
    End point description
    Adverse effects score categorised into quartiles and summarised
    End point type
    Secondary
    End point timeframe
    3 months post-operative
    End point values
    		 Volume replacement therapy Usual care
    Number of subjects analysed
    51
    54
    Units: Subjects
        Quartile 1: <72.7
    8
    12
        Quartile 2: ≥ 72.7 & < 84.1
    13
    14
        Quartile 3: ≥ 84.1 & < 93.2
    14
    12
        Quartile 4: ≥ 93.2
    16
    16
    Statistical analysis title
    		 CROQ adverse effects score
    Statistical analysis description
    CROQ adverse effects score categorised into quartiles and compared between VRT and usual care groups
    Comparison groups
    Volume replacement therapy v Usual care
    Number of subjects included in analysis
    105
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.52
    Method
    		 Ordered logistic regression
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.27
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.38
         upper limit
    		 2.15
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.45

    Secondary: Cost of healthcare resources

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    End point title
    		 Cost of healthcare resources
    End point description
    Costs assessed included duration of operation, intensive care unit (ICU)/high dependency unit (HDU) and ward stay, additional interventions to treat complications, readmissions and re-operations.
    End point type
    Secondary
    End point timeframe
    During hospital stay
    End point values
    		 Volume replacement therapy Usual care
    Number of subjects analysed
    60
    60
    Units: Pounds
        median (inter-quartile range (Q1-Q3))
    11820.8 (10878.4 to 13798.1)
    11501.1 (10487 to 13815.2)
    Statistical analysis title
    		 Cost of healthcare resources
    Comparison groups
    Usual care v Volume replacement therapy
    Number of subjects included in analysis
    120
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.3703
    Method
    		 Regression, Linear
    Parameter type
    		 Geometric mean ratio
    Point estimate
    1.04
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.96
         upper limit
    		 1.12
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.04

    Other pre-specified: Duration of operation

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    End point title
    		 Duration of operation
    End point description
    End point type
    Other pre-specified
    End point timeframe
    Duration of operation
    End point values
    		 Volume replacement therapy Usual care
    Number of subjects analysed
    60
    61
    Units: hours
        arithmetic mean (standard deviation)
    3 ± 0.9
    4 ± 1.0
    No statistical analyses for this end point

    Other pre-specified: Duration of ICU/HDU stay

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    End point title
    		 Duration of ICU/HDU stay
    End point description
    End point type
    Other pre-specified
    End point timeframe
    Length of ICU/HDU stay
    End point values
    		 Volume replacement therapy Usual care
    Number of subjects analysed
    60
    60
    Units: hours
        median (inter-quartile range (Q1-Q3))
    93 (58 to 121.5)
    94 (66.8 to 123.4)
    No statistical analyses for this end point

    Other pre-specified: Duration of ward stay

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    End point title
    		 Duration of ward stay
    End point description
    End point type
    Other pre-specified
    End point timeframe
    Length of ward stay
    End point values
    		 Volume replacement therapy Usual care
    Number of subjects analysed
    60
    61
    Units: hours
        median (inter-quartile range (Q1-Q3))
    74 (49.9 to 112.4)
    72 (28 to 122.1)
    No statistical analyses for this end point

    Other pre-specified: Duration of ventilation

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    End point title
    		 Duration of ventilation
    End point description
    End point type
    Other pre-specified
    End point timeframe
    Duration of in-hospital ventilation
    End point values
    		 Volume replacement therapy Usual care
    Number of subjects analysed
    60
    61
    Units: hours
        median (inter-quartile range (Q1-Q3))
    6 (4.6 to 10)
    7 (4.8 to 9.6)
    No statistical analyses for this end point

    Other pre-specified: Any transfusion

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    End point title
    		 Any transfusion
    End point description
    End point type
    Other pre-specified
    End point timeframe
    In-hospital
    End point values
    		 Volume replacement therapy Usual care
    Number of subjects analysed
    60
    61
    Units: Subjects
        Yes
    20
    16
        No
    40
    45
    No statistical analyses for this end point

    Other pre-specified: If transfusion, units received

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    End point title
    		 If transfusion, units received
    End point description
    End point type
    Other pre-specified
    End point timeframe
    Units of blood received during transfusion
    End point values
    		 Volume replacement therapy Usual care
    Number of subjects analysed
    20
    16
    Units: units
        median (inter-quartile range (Q1-Q3))
    1 (1 to 2)
    3 (1 to 6)
    No statistical analyses for this end point

    Other pre-specified: Activated factor VII used

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    End point title
    		 Activated factor VII used
    End point description
    End point type
    Other pre-specified
    End point timeframe
    In-hospital
    End point values
    		 Volume replacement therapy Usual care
    Number of subjects analysed
    60
    61
    Units: Subjects
        Yes
    1
    0
        No
    59
    61
    No statistical analyses for this end point

    Other pre-specified: Colloid/crystalloid received

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    End point title
    		 Colloid/crystalloid received
    End point description
    End point type
    Other pre-specified
    End point timeframe
    In-hospital
    End point values
    		 Volume replacement therapy Usual care
    Number of subjects analysed
    60
    61
    Units: Subjects
        Yes
    60
    61
        No
    0
    0
    No statistical analyses for this end point

    Other pre-specified: Discharge destination

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    End point title
    		 Discharge destination
    End point description
    End point type
    Other pre-specified
    End point timeframe
    Hospital discharge
    End point values
    		 Volume replacement therapy Usual care
    Number of subjects analysed
    60
    61
    Units: Subjects
        Home
    57
    54
        Other ward within hospital
    0
    2
        Other hospital
    3
    2
        Other (e.g. nursing home)
    0
    2
        Patient died
    0
    1
    No statistical analyses for this end point

    Other pre-specified: Readmitted to hospital

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    End point title
    		 Readmitted to hospital
    End point description
    End point type
    Other pre-specified
    End point timeframe
    Any hospital readmission within 3 months post-operation
    End point values
    		 Volume replacement therapy Usual care
    Number of subjects analysed
    60
    60
    Units: Subjects
        Yes
    11
    8
        No
    49
    48
        Unknown
    0
    4
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    In-hospital and up to 3 months post-operatively
    Adverse event reporting additional description
    All expected adverse events reported as event names (not put through medical dictionary). Unexpected adverse events reported using MedDRA dictionary. For all events, 'non-serious adverse events' includes ALL events (serious and non-serious). This is consistent with the trial publication.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 Not used
    Dictionary version
    1
    Reporting groups
    Reporting group title
    Volume replacement therapy
    Reporting group description
    		 CABG with or without cardiopulmonary bypass (CPB), with preoperative volume replacement therapy (1 ml/kg/hr of Hartmann’s solution for 12 consecutive hours prior to surgery).

    Reporting group title
    Usual care
    Reporting group description
    		 CABG with or without CPB with conventional preoperative management (no preoperative fluids).

    Serious adverse events
    		 Volume replacement therapy Usual care
    Total subjects affected by serious adverse events
         subjects affected / exposed
    23 / 60 (38.33%)
    22 / 61 (36.07%)
         number of deaths (all causes)
    0
    2
         number of deaths resulting from adverse events
    0
    2
    Vascular disorders
    Haemorrhage
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 61 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Deep vein thrombosis
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 61 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Surgical and medical procedures
    Haemofiltration/dialysis
         subjects affected / exposed
    0 / 60 (0.00%)
    3 / 61 (4.92%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Reoperation
         subjects affected / exposed
    1 / 60 (1.67%)
    3 / 61 (4.92%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Re-intubation and ventilation
         subjects affected / exposed
    1 / 60 (1.67%)
    3 / 61 (4.92%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Inotropes
         subjects affected / exposed
    1 / 60 (1.67%)
    1 / 61 (1.64%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mask CPAP
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 61 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary artery catheter
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 61 (1.64%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Death - unknown cause
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 61 (1.64%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Reproductive system and breast disorders
    Tachypnoea
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 61 (1.64%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Acute respiratory distress syndrome
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 61 (1.64%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pleural effusion/pneumothorax
         subjects affected / exposed
    2 / 60 (3.33%)
    4 / 61 (6.56%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary embolus
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 61 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dyspnoea
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 61 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Epistaxis
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 61 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Investigations
    Blood potassium increased
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 61 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Fall
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 61 (1.64%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Cardiac arrest
         subjects affected / exposed
    1 / 60 (1.67%)
    1 / 61 (1.64%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Myocardial infarction
         subjects affected / exposed
    2 / 60 (3.33%)
    1 / 61 (1.64%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Supraventricular tachycardia/Atrial fibrillation
         subjects affected / exposed
    5 / 60 (8.33%)
    1 / 61 (1.64%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ventricular fibrillation/Ventricular tachycardia
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 61 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sinus tachycardia
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 61 (1.64%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pacing
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 61 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pericardial effusion/haemorrhage
         subjects affected / exposed
    2 / 60 (3.33%)
    1 / 61 (1.64%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac failure congestive
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 61 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chest pain
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 61 (1.64%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Transient ischaemic attack
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 61 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebrovascular accident
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 61 (1.64%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Seizure
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 61 (1.64%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Hiatus hernia
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 61 (1.64%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peptic ulcer/GI bleed/perforation
         subjects affected / exposed
    1 / 60 (1.67%)
    1 / 61 (1.64%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Skin ulcer
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 61 (1.64%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    Urinary retention
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 61 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acute kidney injury
         subjects affected / exposed
    18 / 60 (30.00%)
    13 / 61 (21.31%)
         occurrences causally related to treatment / all
    0 / 18
    0 / 13
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Endocrine disorders
    Hypoglycaemia
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 61 (1.64%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Musculoskeletal pain
         subjects affected / exposed
    2 / 60 (3.33%)
    0 / 61 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeketal chest pain
         subjects affected / exposed
    2 / 60 (3.33%)
    0 / 61 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Sepsis
         subjects affected / exposed
    2 / 60 (3.33%)
    6 / 61 (9.84%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 11
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory tract infection
         subjects affected / exposed
    5 / 60 (8.33%)
    4 / 61 (6.56%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chest infection
         subjects affected / exposed
    4 / 60 (6.67%)
    1 / 61 (1.64%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Wound infection
         subjects affected / exposed
    3 / 60 (5.00%)
    3 / 61 (4.92%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Wound dehiscence
         subjects affected / exposed
    2 / 60 (3.33%)
    3 / 61 (4.92%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Osteomyellitis
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 61 (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
    		 Volume replacement therapy Usual care
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    53 / 60 (88.33%)
    54 / 61 (88.52%)
    Vascular disorders
    Haemorrhage
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 61 (0.00%)
         occurrences all number
    1
    0
    Deep vein thrombosis
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 61 (0.00%)
         occurrences all number
    1
    0
    Surgical and medical procedures
    Haemofiltration/dialysis
         subjects affected / exposed
    0 / 60 (0.00%)
    3 / 61 (4.92%)
         occurrences all number
    0
    3
    Re-operation
         subjects affected / exposed
    1 / 60 (1.67%)
    3 / 61 (4.92%)
         occurrences all number
    1
    3
    Re-intubation and ventilation
         subjects affected / exposed
    1 / 60 (1.67%)
    3 / 61 (4.92%)
         occurrences all number
    1
    3
    Inotropes
         subjects affected / exposed
    19 / 60 (31.67%)
    32 / 61 (52.46%)
         occurrences all number
    20
    32
    Vasodilation procedure
         subjects affected / exposed
    21 / 60 (35.00%)
    15 / 61 (24.59%)
         occurrences all number
    21
    15
    IABP
         subjects affected / exposed
    1 / 60 (1.67%)
    1 / 61 (1.64%)
         occurrences all number
    1
    1
    Mask CPAP
         subjects affected / exposed
    7 / 60 (11.67%)
    12 / 61 (19.67%)
         occurrences all number
    7
    12
    Pulmonary artery catheter
         subjects affected / exposed
    1 / 60 (1.67%)
    1 / 61 (1.64%)
         occurrences all number
    1
    1
    General disorders and administration site conditions
    Oedema
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 61 (1.64%)
         occurrences all number
    0
    1
    Respiratory, thoracic and mediastinal disorders
    Acute respiratory distress syndrome
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 61 (1.64%)
         occurrences all number
    0
    1
    Pleural effusion/pneumothorax
         subjects affected / exposed
    4 / 60 (6.67%)
    4 / 61 (6.56%)
         occurrences all number
    4
    4
    Pulmonary embolism
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 61 (0.00%)
         occurrences all number
    1
    0
    Dyspnoea
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 61 (0.00%)
         occurrences all number
    1
    0
    Tachypnoea
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 61 (1.64%)
         occurrences all number
    0
    1
    Epistaxis
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 61 (0.00%)
         occurrences all number
    1
    0
    Investigations
    Blood potassium increased
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 61 (0.00%)
         occurrences all number
    1
    0
    Injury, poisoning and procedural complications
    Fall
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 61 (1.64%)
         occurrences all number
    0
    1
    Cardiac disorders
    Cardiac arrest
         subjects affected / exposed
    1 / 60 (1.67%)
    1 / 61 (1.64%)
         occurrences all number
    1
    1
    Myocardial infarction
         subjects affected / exposed
    7 / 60 (11.67%)
    6 / 61 (9.84%)
         occurrences all number
    7
    6
    Supraventricular tachycardia/Atrial fibrillation
         subjects affected / exposed
    23 / 60 (38.33%)
    20 / 61 (32.79%)
         occurrences all number
    23
    20
    Ventricular fibrillation/Ventricular tachycardia
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 61 (0.00%)
         occurrences all number
    1
    0
    Pacing
         subjects affected / exposed
    4 / 60 (6.67%)
    6 / 61 (9.84%)
         occurrences all number
    4
    6
    Pericardial effusion/haemorrhage
         subjects affected / exposed
    2 / 60 (3.33%)
    1 / 61 (1.64%)
         occurrences all number
    2
    1
    Cardiac failure congestive
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 61 (0.00%)
         occurrences all number
    1
    0
    Chest pain
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 61 (1.64%)
         occurrences all number
    0
    1
    Low cardiac output syndrome
         subjects affected / exposed
    1 / 60 (1.67%)
    2 / 61 (3.28%)
         occurrences all number
    1
    2
    Nervous system disorders
    Transient ischaemic attack
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 61 (0.00%)
         occurrences all number
    1
    0
    Cerebrovascular accident
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 61 (1.64%)
         occurrences all number
    0
    1
    Seizure
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 61 (1.64%)
         occurrences all number
    0
    1
    Gastrointestinal disorders
    Hiatus hernia
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 61 (1.64%)
         occurrences all number
    0
    1
    Peptic ulcer/GI bleed/perforation
         subjects affected / exposed
    1 / 60 (1.67%)
    2 / 61 (3.28%)
         occurrences all number
    1
    2
    Skin and subcutaneous tissue disorders
    Skin ulcer
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 61 (1.64%)
         occurrences all number
    0
    1
    Renal and urinary disorders
    Urinary retention
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 61 (0.00%)
         occurrences all number
    1
    0
    Acute kidney injury
         subjects affected / exposed
    18 / 60 (30.00%)
    13 / 61 (21.31%)
         occurrences all number
    18
    13
    Endocrine disorders
    Hypoglycaemia
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 61 (1.64%)
         occurrences all number
    0
    1
    Musculoskeletal and connective tissue disorders
    Musculoskeletal pain
         subjects affected / exposed
    2 / 60 (3.33%)
    0 / 61 (0.00%)
         occurrences all number
    2
    0
    Musculoskeletal chest pain
         subjects affected / exposed
    2 / 60 (3.33%)
    0 / 61 (0.00%)
         occurrences all number
    2
    0
    Infections and infestations
    Sepsis
         subjects affected / exposed
    13 / 60 (21.67%)
    24 / 61 (39.34%)
         occurrences all number
    12
    17
    Respiratory infection
         subjects affected / exposed
    17 / 60 (28.33%)
    19 / 61 (31.15%)
         occurrences all number
    14
    15
    Chest infection
         subjects affected / exposed
    4 / 60 (6.67%)
    1 / 61 (1.64%)
         occurrences all number
    4
    1
    Wound infection
         subjects affected / exposed
    3 / 60 (5.00%)
    3 / 61 (4.92%)
         occurrences all number
    3
    3
    Wound dehiscence
         subjects affected / exposed
    2 / 60 (3.33%)
    4 / 61 (6.56%)
         occurrences all number
    2
    3
    Osteomyelitis
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 61 (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
    24 Oct 2011
    Update to primary endpoint and to safety section
    16 Jan 2013
    Addition of new outcomes and timepoints for outcomes; sample size amended for tubular injury outcome; clarification added to the dosage and regimen section for the study medication; clarification of the end of trial definition; amendment of wording regarding collection, storage, labelling etc. of samples; amendment regarding documentation of drug administration; amendment regarding process for reporting SAEs; amendment of list of expected adverse events.
    04 Sep 2013
    Clarification that due to time restraints the pre-op CROQ can be completed alongside randomisation as long as the CROQ is completed prior to informing the patient of the treatment allocation. Clarification of the rule on randomisation if the pre-op creatinine result is not available in time. Sample size amended for tubular injury outcome and for secondary outcomes (i) to (l). MicroRNA and other biochemical predictors will also be measured in urine. Key data collection points table changed to include other biochemical predictors of health outcome for blood samples and to include microRNA and other biochemical predictors of health outcome in urine samples.

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

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

    Online references
    http://www.ncbi.nlm.nih.gov/pubmed/31539025
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