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    Clinical Trial Results:
    Oxidative stress and Circulating Nuclear DNA (cfDNA) in critically ill patients with acute kidney failure treated with continuous renal replacement therapies. Effect of two anticoagulation strategies of the extracorporeal purification system in renal function recovery.

    Summary
    EudraCT number
    		 2016-004361-12
    Trial protocol
    		 ES  
    Global end of trial date
    30 May 2022

    Results information
    Results version number
    		 v1(current)
    This version publication date
    06 Nov 2024
    First version publication date
    06 Nov 2024
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    FER-CIT-2016-01
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT06646328
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Fernando Sánchez
    Sponsor organisation address
    Carrer de Sanz de Bremond, 8, 1, Castelló de la Plana, Spain, 12004
    Public contact
    Fernando Sánchez, Fernando Sánchez, 34 625978412, sanchez_fermor@gva.es
    Scientific contact
    Fernando Sánchez, Fernando Sánchez, 34 625978412, sanchez_fermor@gva.es
    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
    01 Oct 2024
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    30 May 2022
    Global end of trial reached?
    Yes
    Global end of trial date
    30 May 2022
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    1. To compare the effect on bio-incompatibility induced oxidative stress and systemic oxidative stress in critically ill patients with ARF using two anticoagulation strategies of the extracorporeal system in continuous renal replacement therapies (CRRT) (heparin vs citrate). 2. To compare the effect on extracellular levels of circulating nucleosomes in critically ill patients with ARF employing two anticoagulation strategies of the extracorporeal system CRRT (heparin vs citrate). 3. To evaluate the clinical impact in terms of recovery of renal function in critically ill patients with ARF when two anticoagulation strategies of the extracorporeal system CRRT (heparin vs citrate) are used.
    Protection of trial subjects
    Patients who are able to provide consent can participate in the study by signing the Informed Consent (IC) form. If a patient is unable to provide consent, we will seek consent from their family. If there is no family available, we will consider the opinion of the person the patient trusts or their designated decision-maker. If none of these options are available, deferred consent will not be considered and the patient will not be included in the study.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    03 Apr 2017
    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
    Spain: 20
    Worldwide total number of subjects
    20
    EEA total number of subjects
    20
    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)
    12
    From 65 to 84 years
    8
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 Inclusion criteria: Adult patients in the intensive care unit with acute kidney injury requiring continuous renal replacement therapy. Patients or their families must sign the Informed Consent (IC) form before randomization to participate in the study. Randomization by sealed envelopes.

    Pre-assignment
    Screening details
    		 Exclusion Criteria: < 18 years old. Pregnancy or lactation. Terminal disease or life expectancy < 48 hours. Increased risk of bleeding. Systemic anticoagulation therapy. Contraindication for heparin. Heparin-induced thrombocytopenia. Dialysis before inclusion. Hypercalcemia. Severe Hepatitis. Cirrhosis. Inclusion in another protocol.

    Period 1
    Period 1 title
    T0
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Heparin
    Arm description
    		 Anticoagulation with heparin during continuous renal replacement therapies
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Heparin
    Investigational medicinal product code
    Other name
    Unfractionated heparin
    Pharmaceutical forms
    Concentrate for solution for haemodialysis
    Routes of administration
    Extracorporeal use
    Dosage and administration details
    Initial dose of 500–1000 IU/hour with adaptation of the infusion to the patient and the clotting time.

    Arm title
    		 Citrate
    Arm description
    		 Citrate anticoagulation during continuous renal replacement therapies
    Arm type
    		 Experimental

    Investigational medicinal product name
    Trisodium citrate
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for haemodialysis
    Routes of administration
    Extracorporeal use
    Dosage and administration details
    Regional citrate anticoagulation was used at an initial dose of 4 mmol/L and with a calcium reinfusion solution at an initial dose of 1.7 mmol/L, with adaptation of both infusions to the patient ionic calcium levels.

    Number of subjects in period 1
    		Heparin Citrate
    Started
    10
    10
    Completed
    10
    10
    Period 2
    Period 2 title
    T1 prefilter (60 minutes)
    Is this the baseline period?
    		 No
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Heparin
    Arm description
    		 Anticoagulation with heparin during continuous renal replacement therapies
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Heparin
    Investigational medicinal product code
    Other name
    Unfractionated heparin
    Pharmaceutical forms
    Concentrate for solution for haemodialysis
    Routes of administration
    Extracorporeal use
    Dosage and administration details
    Initial dose of 500–1000 IU/hour with adaptation of the infusion to the patient and the clotting time.

    Arm title
    		 Citrate
    Arm description
    		 Citrate anticoagulation during continuous renal replacement therapies
    Arm type
    		 Experimental

    Investigational medicinal product name
    Trisodium citrate
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for haemodialysis
    Routes of administration
    Extracorporeal use
    Dosage and administration details
    Regional citrate anticoagulation was used at an initial dose of 4 mmol/L and with a calcium reinfusion solution at an initial dose of 1.7 mmol/L, with adaptation of both infusions to the patient ionic calcium levels.

    Number of subjects in period 2
    		Heparin Citrate
    Started
    10
    10
    Completed
    10
    10
    Period 3
    Period 3 title
    T1 postfilter (60 minutes)
    Is this the baseline period?
    		 No
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Heparin
    Arm description
    		 Anticoagulation with heparin during continuous renal replacement therapies
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Heparin
    Investigational medicinal product code
    Other name
    Unfractionated heparin
    Pharmaceutical forms
    Concentrate for solution for haemodialysis
    Routes of administration
    Extracorporeal use
    Dosage and administration details
    Initial dose of 500–1000 IU/hour with adaptation of the infusion to the patient and the clotting time.

    Arm title
    		 Citrate
    Arm description
    		 Citrate anticoagulation during continuous renal replacement therapies
    Arm type
    		 Experimental

    Investigational medicinal product name
    Trisodium citrate
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for haemodialysis
    Routes of administration
    Extracorporeal use
    Dosage and administration details
    Regional citrate anticoagulation was used at an initial dose of 4 mmol/L and with a calcium reinfusion solution at an initial dose of 1.7 mmol/L, with adaptation of both infusions to the patient ionic calcium levels.

    Number of subjects in period 3
    		Heparin Citrate
    Started
    10
    10
    Completed
    10
    10
    Period 4
    Period 4 title
    T2 prefilter (24 hours)
    Is this the baseline period?
    		 No
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Heparin
    Arm description
    		 Anticoagulation with heparin during continuous renal replacement therapies
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Heparin
    Investigational medicinal product code
    Other name
    Unfractionated heparin
    Pharmaceutical forms
    Concentrate for solution for haemodialysis
    Routes of administration
    Extracorporeal use
    Dosage and administration details
    Initial dose of 500–1000 IU/hour with adaptation of the infusion to the patient and the clotting time.

    Arm title
    		 Citrate
    Arm description
    		 Citrate anticoagulation during continuous renal replacement therapies
    Arm type
    		 Experimental

    Investigational medicinal product name
    Trisodium citrate
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for haemodialysis
    Routes of administration
    Extracorporeal use
    Dosage and administration details
    Regional citrate anticoagulation was used at an initial dose of 4 mmol/L and with a calcium reinfusion solution at an initial dose of 1.7 mmol/L, with adaptation of both infusions to the patient ionic calcium levels.

    Number of subjects in period 4 [1]
    		Heparin Citrate
    Started
    9
    8
    Completed
    9
    8
    Notes
    [1] - 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: One patient in the heparin arm and two in the citrate arm died between periods 3 and 4.
    Period 5
    Period 5 title
    T2 postfilter (24 hours)
    Is this the baseline period?
    		 No
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Heparin
    Arm description
    		 Anticoagulation with heparin during continuous renal replacement therapies
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Heparin
    Investigational medicinal product code
    Other name
    Unfractionated heparin
    Pharmaceutical forms
    Concentrate for solution for haemodialysis
    Routes of administration
    Extracorporeal use
    Dosage and administration details
    Initial dose of 500–1000 IU/hour with adaptation of the infusion to the patient and the clotting time.

    Arm title
    		 Citrate
    Arm description
    		 Citrate anticoagulation during continuous renal replacement therapies
    Arm type
    		 Experimental

    Investigational medicinal product name
    Trisodium citrate
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for haemodialysis
    Routes of administration
    Extracorporeal use
    Dosage and administration details
    Regional citrate anticoagulation was used at an initial dose of 4 mmol/L and with a calcium reinfusion solution at an initial dose of 1.7 mmol/L, with adaptation of both infusions to the patient ionic calcium levels.

    Number of subjects in period 5
    		Heparin Citrate
    Started
    9
    8
    Completed
    9
    8

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Heparin
    Reporting group description
    		 Anticoagulation with heparin during continuous renal replacement therapies

    Reporting group title
    Citrate
    Reporting group description
    		 Citrate anticoagulation during continuous renal replacement therapies

    Reporting group values
    		 Heparin Citrate Total
    Number of subjects
    		 10 10 20
    Age categorical
    Units: Subjects
        Adults (18-64 years)
    		 3 7 10
        From 65-84 years
    		 7 3 10
        85 years and over
    		 0 0 0
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 60.87 ( 11.11 ) 68.55 ( 7.32 ) -
    Gender categorical
    Units: Subjects
        Female
    		 3 0 3
        Male
    		 7 10 17
    Mechanical ventilation
    Units: Subjects
        Yes
    		 5 5 10
        No
    		 5 5 10
    Vasoactive support
    Units: Subjects
        Yes
    		 8 9 17
        No
    		 2 1 3
    Personal history: ischemic heart disease
    Units: Subjects
        Yes
    		 1 2 3
        No
    		 9 8 17
    Personal history: dyslipidemia
    Units: Subjects
        Yes
    		 5 5 10
        No
    		 5 5 10
    Personal histiry: diabete mellitus
    Units: Subjects
        Yes
    		 3 2 5
        No
    		 7 8 15
    Personal history: hypertension
    Units: Subjects
        Yes
    		 6 7 13
        No
    		 4 3 7
    Personal history: obesity
    Units: Subjects
        Yes
    		 4 2 6
        No
    		 6 8 14
    Personal history: CPOD
    Units: Subjects
        Yes
    		 1 2 3
        No
    		 9 8 17
    Personal history:chronic kidney disease without dialysis treatment
    Units: Subjects
        Yes
    		 2 1 3
        No
    		 8 9 17
    APACHE II score
    Units: Points
        arithmetic mean (standard deviation)
    		 18.40 ( 7.63 ) 19.40 ( 3.72 ) -
    SAPS 3 score
    Units: Points
        arithmetic mean (standard deviation)
    		 62.30 ( 16.25 ) 66.00 ( 13.24 ) -
    SOFA score
    Units: Points
        median (inter-quartile range (Q1-Q3))
    		 8.00 (6.75 to 12.25) 9.00 (7.00 to 9.00) -
    Noradrenaline
    Units: microgram(s)/kilogram/minute
        arithmetic mean (standard deviation)
    		 0.30 ( 0.32 ) 0.44 ( 0.25 ) -
    Lactate
    Units: mmol/L
        median (inter-quartile range (Q1-Q3))
    		 2.30 (1.35 to 4.10) 1.90 (1.20 to 6.90) -
    Urea
    Units: mg/dl
        arithmetic mean (standard deviation)
    		 122.33 ( 91.92 ) 127.90 ( 98.41 ) -
    Creatinine
    Units: mg/dl
        arithmetic mean (standard deviation)
    		 3.70 ( 2.14 ) 3.48 ( 2.38 ) -
    Bilirrubine
    Units: mg/dl
        median (inter-quartile range (Q1-Q3))
    		 1.33 (0.92 to 2.48) 0.54 (0.34 to 2.54) -
    Leukocytes
    Units: *10^3/microL
        median (inter-quartile range (Q1-Q3))
    		 12.80 (8.25 to 14.78) 11.69 (7.88 to 28.18) -
    Platelets
    Units: *10^3/mm3
        median (inter-quartile range (Q1-Q3))
    		 179.00 (134.50 to 221.25) 228.50 (160.50 to 332.50) -
    Baseline creatinine
    Units: mg/dl
        median (standard deviation)
    		 1.16 ( 0.95 ) 1.36 ( 1.16 ) -

    End points

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    End points reporting groups
    Reporting group title
    Heparin
    Reporting group description
    		 Anticoagulation with heparin during continuous renal replacement therapies

    Reporting group title
    Citrate
    Reporting group description
    		 Citrate anticoagulation during continuous renal replacement therapies
    Reporting group title
    Heparin
    Reporting group description
    		 Anticoagulation with heparin during continuous renal replacement therapies

    Reporting group title
    Citrate
    Reporting group description
    		 Citrate anticoagulation during continuous renal replacement therapies
    Reporting group title
    Heparin
    Reporting group description
    		 Anticoagulation with heparin during continuous renal replacement therapies

    Reporting group title
    Citrate
    Reporting group description
    		 Citrate anticoagulation during continuous renal replacement therapies
    Reporting group title
    Heparin
    Reporting group description
    		 Anticoagulation with heparin during continuous renal replacement therapies

    Reporting group title
    Citrate
    Reporting group description
    		 Citrate anticoagulation during continuous renal replacement therapies
    Reporting group title
    Heparin
    Reporting group description
    		 Anticoagulation with heparin during continuous renal replacement therapies

    Reporting group title
    Citrate
    Reporting group description
    		 Citrate anticoagulation during continuous renal replacement therapies

    Primary: Recovery of renal function

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    End point title
    		 Recovery of renal function
    End point description
    Duration of RRT
    End point type
    Primary
    End point timeframe
    Through study completion, an average of 20 days
    End point values
    		 Heparin Citrate
    Number of subjects analysed
    10
    10
    Units: Days
        median (inter-quartile range (Q1-Q3))
    3.50 (2.00 to 8.00)
    2.00 (1.00 to 3.50)
    Statistical analysis title
    		 Duration of renal replacement therapy
    Comparison groups
    Heparin v Citrate
    Number of subjects included in analysis
    20
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.05 [1]
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval
    Notes
    [1] - 0.114

    Primary: Recovery of renal function

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    End point title
    		 Recovery of renal function
    End point description
    Recovery of renal function and dialysis dependency at ICU discharge
    End point type
    Primary
    End point timeframe
    Through study completion, an average of 20 days
    End point values
    		 Heparin Citrate
    Number of subjects analysed
    6
    7
    Units: Total
        Creatinine recovered up to previous values
    2
    5
        Creatinine values >50% from baseline
    3
    2
        Dialysys dependent
    1
    0
    Statistical analysis title
    		 Recovery of renal function
    Comparison groups
    Heparin v Citrate
    Number of subjects included in analysis
    13
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.05 [2]
    Method
    		 Fisher exact
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    2.333
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.635
         upper limit
    		 8.569
    Notes
    [2] - 0.286

    Primary: Recovery of renal function

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    End point title
    		 Recovery of renal function
    End point description
    Recovery of renal function and dialysis dependency at hospital discharge
    End point type
    Primary
    End point timeframe
    Through study completion, an average of 20 days
    End point values
    		 Heparin Citrate
    Number of subjects analysed
    6
    6
    Units: Total
        Creatinine recovered up to previous values
    5
    6
        Creatinine values >50% from baseline
    0
    0
        Dialysys dependent
    1
    0
    Statistical analysis title
    		 Recovery of renal function
    Comparison groups
    Heparin v Citrate
    Number of subjects included in analysis
    12
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.05 [3]
    Method
    		 Fisher exact
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    0.833
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.583
         upper limit
    		 1.192
    Notes
    [3] - 1.00

    Secondary: Activation and elimination of free radicals

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    End point title
    		 Activation and elimination of free radicals
    End point description
    GSH at the beginning of RRT
    End point type
    Secondary
    End point timeframe
    At the beginning of RRT
    End point values
    		 Heparin Citrate
    Number of subjects analysed
    10
    10
    Units: micromole(s)/millilitre
        arithmetic mean (standard deviation)
    0.102 ( 0.045 )
    0.120 ( 0.036 )
    Statistical analysis title
    		 GSH at the beginning of RRT
    Comparison groups
    Heparin v Citrate
    Number of subjects included in analysis
    20
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.05 [4]
    Method
    		 t-test, 2-sided
    Confidence interval
    Notes
    [4] - 0.322

    Secondary: Activation and elimination of free radicals

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    End point title
    		 Activation and elimination of free radicals
    End point description
    GSH prefilter 60 minutes after initiation of RRT
    End point type
    Secondary
    End point timeframe
    60 minutes after initiation of RRT
    End point values
    		 Heparin Citrate
    Number of subjects analysed
    10
    10
    Units: micromole(s)/millilitre
        median (standard deviation)
    0.125 ( 0.029 )
    0.135 ( 0.026 )
    Statistical analysis title
    		 GSH prefilter 60 minutes after initiation RRT
    Comparison groups
    Heparin v Citrate
    Number of subjects included in analysis
    20
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.05 [5]
    Method
    		 t-test, 2-sided
    Confidence interval
    Notes
    [5] - 0.409

    Secondary: Activation and elimination of free radicals

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    End point title
    		 Activation and elimination of free radicals
    End point description
    GSH postfilter 60 minutes after initiation of RRT
    End point type
    Secondary
    End point timeframe
    60 minutes after initiation of RRT
    End point values
    		 Heparin Citrate
    Number of subjects analysed
    10
    10
    Units: micromole(s)/millilitre
        arithmetic mean (standard deviation)
    0.102 ( 0.043 )
    0.149 ( 0.050 )
    Statistical analysis title
    		 GSH postfilter 60 minutes after initiation
    Comparison groups
    Heparin v Citrate
    Number of subjects included in analysis
    20
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.05 [6]
    Method
    		 t-test, 2-sided
    Parameter type
    		 d Cohen
    Point estimate
    -0.986
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.907
         upper limit
    		 -0.041
    Notes
    [6] - 0.041

    Secondary: Activation and elimination of free radicals

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    End point title
    		 Activation and elimination of free radicals
    End point description
    Change in GSH prefilter/postfilter 60 minutes after initiation RRT heparin
    End point type
    Secondary
    End point timeframe
    60 minutes after initiation RRT
    End point values
    		 Heparin Heparin
    Number of subjects analysed
    10
    10
    Units: micromole(s)/millilitre
        arithmetic mean (standard deviation)
    0.125 ( 0.029 )
    0.102 ( 0.043 )
    Statistical analysis title
    		 GSH prefilter/postfilter 60 minutes heparin
    Comparison groups
    Heparin v Heparin
    Number of subjects included in analysis
    20
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.05 [7]
    Method
    		 t-test, 2-sided
    Parameter type
    		 d Cohen
    Point estimate
    0.903
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.142
         upper limit
    		 1.63
    Notes
    [7] - 0.019

    Secondary: Activation and elimination of free radicals

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    End point title
    		 Activation and elimination of free radicals
    End point description
    Change in GSH prefilter/postfilter 60 minutes after initiation RRT citrate
    End point type
    Secondary
    End point timeframe
    60 minutes after initiation RRT
    End point values
    		 Citrate Citrate
    Number of subjects analysed
    10
    10
    Units: micromole(s)/millilitre
        arithmetic mean (standard deviation)
    0.135 ( 0.026 )
    0.149 ( 0.050 )
    Statistical analysis title
    		 GSH prefilter/postfilter 60 minutes citrate
    Comparison groups
    Citrate v Citrate
    Number of subjects included in analysis
    20
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.05 [8]
    Method
    		 t-test, 2-sided
    Confidence interval
    Notes
    [8] - 0.193

    Secondary: Activation and elimination of free radicals

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    End point title
    		 Activation and elimination of free radicals
    End point description
    GSH prefilter 24 hours after initiation RRT
    End point type
    Secondary
    End point timeframe
    24 hours after initiation RRT
    End point values
    		 Heparin Citrate
    Number of subjects analysed
    9
    8
    Units: micromole(s)/millilitre
        arithmetic mean (standard deviation)
    0.109 ( 0.055 )
    0.151 ( 0.044 )
    Statistical analysis title
    		 GSH 24 hours after initiation RRT
    Comparison groups
    Heparin v Citrate
    Number of subjects included in analysis
    17
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.05 [9]
    Method
    		 t-test, 2-sided
    Confidence interval
    Notes
    [9] - 0.109

    Secondary: Activation and elimination of free radicals

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    End point title
    		 Activation and elimination of free radicals
    End point description
    GSH postfilter 24 hours after initiation RRT
    End point type
    Secondary
    End point timeframe
    24 hours after initiation RRT
    End point values
    		 Heparin Citrate
    Number of subjects analysed
    9
    8
    Units: micromole(s)/millilitre
        arithmetic mean (standard deviation)
    0.105 ( 0.056 )
    0.150 ( 0.038 )
    Statistical analysis title
    		 GSH postfilter 24 hours after initiation RRT
    Comparison groups
    Heparin v Citrate
    Number of subjects included in analysis
    17
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.05 [10]
    Method
    		 t-test, 2-sided
    Confidence interval
    Notes
    [10] - 0.072

    Secondary: Activation and elimination of free radicals

    		 Close Top of page
    End point title
    		 Activation and elimination of free radicals
    End point description
    Change in GSH prefilter/postfilter 24 hours after initiation RRT heparin
    End point type
    Secondary
    End point timeframe
    24 hours after initiation RRT
    End point values
    		 Heparin Heparin
    Number of subjects analysed
    9
    9
    Units: micromole(s)/millilitre
        arithmetic mean (standard deviation)
    0.109 ( 0.055 )
    0.105 ( 0.056 )
    Statistical analysis title
    		 GSH prefilter/postfilter 24 hours heparin
    Comparison groups
    Heparin v Heparin
    Number of subjects included in analysis
    18
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.05 [11]
    Method
    		 t-test, 2-sided
    Confidence interval
    Notes
    [11] - 0.582

    Secondary: Activation and elimination of free radicals

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    End point title
    		 Activation and elimination of free radicals
    End point description
    Change in GSH prefilter/postfilter 24 hours after initiation RRT citrate
    End point type
    Secondary
    End point timeframe
    24 hours after initiation RRT
    End point values
    		 Citrate Citrate
    Number of subjects analysed
    8
    8
    Units: micromole(s)/millilitre
        arithmetic mean (standard deviation)
    0.151 ( 0.044 )
    0.150 ( 0.038 )
    Statistical analysis title
    		 GSH prefilter/postfilter 24 hours citrate
    Comparison groups
    Citrate v Citrate
    Number of subjects included in analysis
    16
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.05 [12]
    Method
    		 t-test, 2-sided
    Confidence interval
    Notes
    [12] - 0.872

    Secondary: Activation and elimination of free radicals

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    End point title
    		 Activation and elimination of free radicals
    End point description
    GSSG at the beginning of RRT
    End point type
    Secondary
    End point timeframe
    At the beginning of RRT
    End point values
    		 Heparin Citrate
    Number of subjects analysed
    10
    9
    Units: micromole(s)/millilitre
        median (inter-quartile range (Q1-Q3))
    0.289 (0.184 to 0.410)
    0.290 (0.192 to 0.592)
    Statistical analysis title
    		 GSSG at the beginning of RRT
    Comparison groups
    Citrate v Heparin
    Number of subjects included in analysis
    19
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.05 [13]
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval
    Notes
    [13] - 1.00

    Secondary: Activation and elimination of free radicals

    		 Close Top of page
    End point title
    		 Activation and elimination of free radicals
    End point description
    GSSG prefilter 60 minutes after initiation of RRT
    End point type
    Secondary
    End point timeframe
    60 minutes after initiation of RRT
    End point values
    		 Heparin Citrate
    Number of subjects analysed
    10
    9
    Units: micromole(s)/millilitre
        median (inter-quartile range (Q1-Q3))
    0.370 (0.191 to 0.407)
    0.247 (0.215 to 0.338)
    Statistical analysis title
    		 GSSG prefilter 60 minutes
    Comparison groups
    Heparin v Citrate
    Number of subjects included in analysis
    19
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.05 [14]
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval
    Notes
    [14] - 0.315

    Secondary: Activation and elimination of free radicals

    		 Close Top of page
    End point title
    		 Activation and elimination of free radicals
    End point description
    GSSG postfilter 60 minutes after initiation of RRT
    End point type
    Secondary
    End point timeframe
    60 minutes after initiation of RRT
    End point values
    		 Heparin Citrate
    Number of subjects analysed
    9
    10
    Units: micromole(s)/millilitre
        median (inter-quartile range (Q1-Q3))
    0.370 (0.176 to 0.543)
    0.335 (0.240 to 0.388)
    Statistical analysis title
    		 GSSG postfilter 60 minutes
    Comparison groups
    Heparin v Citrate
    Number of subjects included in analysis
    19
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.05 [15]
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval
    Notes
    [15] - 0.720

    Secondary: Activation and elimination of free radicals

    		 Close Top of page
    End point title
    		 Activation and elimination of free radicals
    End point description
    Change in GSSG prefilter/postfilter 60 minutes after initiation RRT heparin
    End point type
    Secondary
    End point timeframe
    60 minutes after initiation of RRT
    End point values
    		 Heparin Heparin
    Number of subjects analysed
    10
    10
    Units: micromole(s)/millilitre
        median (inter-quartile range (Q1-Q3))
    0.370 (0.191 to 0.407)
    0.370 (0.176 to 0.543)
    Statistical analysis title
    		 GSSG prefilter/postfilter 60 minutes heparin
    Comparison groups
    Heparin v Heparin
    Number of subjects included in analysis
    20
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.05 [16]
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval
    Notes
    [16] - 0.678

    Secondary: Activation and elimination of free radicals

    		 Close Top of page
    End point title
    		 Activation and elimination of free radicals
    End point description
    Chancge in GSSG prefilter/postfilter 60 minutes citrate
    End point type
    Secondary
    End point timeframe
    60 minutes after initiation RRT
    End point values
    		 Citrate Citrate
    Number of subjects analysed
    9
    9
    Units: micromole(s)/millilitre
        median (inter-quartile range (Q1-Q3))
    0.247 (0.215 to 0.338)
    0.335 (0.240 to 0.388)
    Statistical analysis title
    		 GSSG prefilter/postfilter 60 minutes citrate
    Comparison groups
    Citrate v Citrate
    Number of subjects included in analysis
    18
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.05 [17]
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval
    Notes
    [17] - 0.515

    Secondary: Activation and elimination of free radicals

    		 Close Top of page
    End point title
    		 Activation and elimination of free radicals
    End point description
    GSSG prefilter 24 hours after initiation RRT
    End point type
    Secondary
    End point timeframe
    24 hours after initiation RRT
    End point values
    		 Heparin Citrate
    Number of subjects analysed
    8
    8
    Units: micromole(s)/millilitre
        median (inter-quartile range (Q1-Q3))
    0.349 (0.223 to 0.676)
    0.211 (0.170 to 0.270)
    Statistical analysis title
    		 GSSG 24 hours after initiation RRT
    Comparison groups
    Heparin v Citrate
    Number of subjects included in analysis
    16
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.05 [18]
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval
    Notes
    [18] - 0.105

    Secondary: Activation and elimination of free radicals

    		 Close Top of page
    End point title
    		 Activation and elimination of free radicals
    End point description
    GSSG postfilter 24 hours after initiation RRT
    End point type
    Secondary
    End point timeframe
    24 hours after initiation RRT
    End point values
    		 Heparin Citrate
    Number of subjects analysed
    8
    8
    Units: micromole(s)/millilitre
        arithmetic mean (standard error)
    0.410 ( 0.269 )
    0.238 ( 0.067 )
    Statistical analysis title
    		 GSSG postfilter 24 hours after initiation RRT
    Comparison groups
    Heparin v Citrate
    Number of subjects included in analysis
    16
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.05 [19]
    Method
    		 t-test, 2-sided
    Confidence interval
    Notes
    [19] - 0.118

    Secondary: Activation and elimination of free radicals

    		 Close Top of page
    End point title
    		 Activation and elimination of free radicals
    End point description
    Change in GSSG prefilter/postfilter 24 hours after initiation RRT heparin
    End point type
    Secondary
    End point timeframe
    24 hours after initiation RRT
    End point values
    		 Heparin Heparin
    Number of subjects analysed
    8
    8
    Units: microcurie(s)/microlitre
        median (inter-quartile range (Q1-Q3))
    0.349 (0.223 to 0.676)
    0.335 (0.206 to 0.535)
    Statistical analysis title
    		 GSSG prefilter/postfilter 24 hours heparin
    Comparison groups
    Heparin v Heparin
    Number of subjects included in analysis
    16
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.05 [20]
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval
    Notes
    [20] - 0.674

    Secondary: Activation and elimination of free radicals

    		 Close Top of page
    End point title
    		 Activation and elimination of free radicals
    End point description
    Change in GSSG prefilter/postfilter 24 hours after initiation RRT citrate
    End point type
    Secondary
    End point timeframe
    24 hours after initiation RRT
    End point values
    		 Citrate Citrate
    Number of subjects analysed
    8
    8
    Units: micromole(s)/millilitre
        median (inter-quartile range (Q1-Q3))
    0.211 (0.170 to 0.270)
    0.271 (0.181 to 0.282)
    Statistical analysis title
    		 GSSG prefilter/postfilter 24 hours citrate
    Comparison groups
    Citrate v Citrate
    Number of subjects included in analysis
    16
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.05 [21]
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval
    Notes
    [21] - 0.401

    Secondary: Activation and elimination of free radicals

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    End point title
    		 Activation and elimination of free radicals
    End point description
    GSSG/GSH at the beginning of RRT
    End point type
    Secondary
    End point timeframe
    At the beginning of RRT
    End point values
    		 Heparin Citrate
    Number of subjects analysed
    9
    9
    Units: non unit
        median (inter-quartile range (Q1-Q3))
    2.288 (1.965 to 3.909)
    2.379 (1.834 to 4.855)
    Statistical analysis title
    		 GSSG/GSH at the beginning of RRT
    Comparison groups
    Heparin v Citrate
    Number of subjects included in analysis
    18
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 ≤ 0.05 [22]
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval
    Notes
    [22] - 0.796

    Secondary: Activation and elimination of free radicals

    		 Close Top of page
    End point title
    		 Activation and elimination of free radicals
    End point description
    GSSG/GSH prefilter 60 minutes after initiation of RRT
    End point type
    Secondary
    End point timeframe
    60 minutes after initiation of RRT
    End point values
    		 Heparin Citrate
    Number of subjects analysed
    10
    9
    Units: non unit
        median (inter-quartile range (Q1-Q3))
    2.514 (1.941 to 3.973)
    2.056 (1.531 to 3.043)
    Statistical analysis title
    		 GSSG/GSH prefilter 60 minutes after initiation RRT
    Comparison groups
    Heparin v Citrate
    Number of subjects included in analysis
    19
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.05 [23]
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval
    Notes
    [23] - 0.278

    Secondary: Activation and elimination of free radicals

    		 Close Top of page
    End point title
    		 Activation and elimination of free radicals
    End point description
    GSSG/GSH postfilter 60 minutes after initiation of RRT
    End point type
    Secondary
    End point timeframe
    60 minutes after initiation of RRT
    End point values
    		 Heparin Citrate
    Number of subjects analysed
    9
    10
    Units: non unit
        median (inter-quartile range (Q1-Q3))
    3.988 (2.359 to 8.000)
    2.474 (1.302 to 4.282)
    Statistical analysis title
    		 GSSG/GSH postfilter 60 minutes after initiation
    Comparison groups
    Heparin v Citrate
    Number of subjects included in analysis
    19
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.05 [24]
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval
    Notes
    [24] - 0.278

    Secondary: Activation and elimination of free radicals

    		 Close Top of page
    End point title
    		 Activation and elimination of free radicals
    End point description
    Change in GSSG/GSH prefilter/postfilter 60 minutes after initiation RRT heparin
    End point type
    Secondary
    End point timeframe
    60 minutes after initiation RRT
    End point values
    		 Heparin Heparin
    Number of subjects analysed
    9
    9
    Units: non unit
        median (inter-quartile range (Q1-Q3))
    2.514 (1.941 to 3.973)
    3.988 (2.359 to 8.000)
    Statistical analysis title
    		 GSSG/GSH prefilter/postfilter 60 minutes heparin
    Comparison groups
    Heparin v Heparin
    Number of subjects included in analysis
    18
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.05 [25]
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval
    Notes
    [25] - 0.086

    Secondary: Activation and elimination of free radicals

    		 Close Top of page
    End point title
    		 Activation and elimination of free radicals
    End point description
    Change in GSSG/GSH prefilter/postfilter 60 minutes after initiation RRT citrate
    End point type
    Secondary
    End point timeframe
    60 minutes after initiation RRT
    End point values
    		 Citrate Citrate
    Number of subjects analysed
    9
    9
    Units: non unit
        median (inter-quartile range (Q1-Q3))
    2.056 (1.531 to 3.043)
    2.474 (1.302 to 4.282)
    Statistical analysis title
    		 GSSG/GSH prefilter/postfilter 60 minutes citrate
    Comparison groups
    Citrate v Citrate
    Number of subjects included in analysis
    18
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.05 [26]
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval
    Notes
    [26] - 0.441

    Secondary: Activation and elimination of free radicals

    		 Close Top of page
    End point title
    		 Activation and elimination of free radicals
    End point description
    GSSG/GSH GSSG prefilter 24 hours after initiation RRT
    End point type
    Secondary
    End point timeframe
    24 hours after initiation RRT
    End point values
    		 Heparin Citrate
    Number of subjects analysed
    7
    8
    Units: Non unit
        arithmetic mean (standard deviation)
    3.069 ( 1.320 )
    1.495 ( 0.421 )
    Statistical analysis title
    		 GSSG/GSH prefilter 24 hours after initiation
    Comparison groups
    Heparin v Citrate
    Number of subjects included in analysis
    15
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.05 [27]
    Method
    		 t-test, 2-sided
    Parameter type
    		 d Cohen
    Point estimate
    1.659
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.484
         upper limit
    		 2.835
    Notes
    [27] - 0.007

    Secondary: Activation and elimination of free radicals

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    End point title
    		 Activation and elimination of free radicals
    End point description
    GSSG/GSH postfilter 24 hours after initiation RRT
    End point type
    Secondary
    End point timeframe
    24 hours after initiation RRT
    End point values
    		 Heparin Citrate
    Number of subjects analysed
    7
    8
    Units: Non unit
        arithmetic mean (standard deviation)
    3.125 ( 1.487 )
    1.667 ( 0.699 )
    Statistical analysis title
    		 GSSG/GSH postfilter 24 hours after initiation
    Comparison groups
    Heparin v Citrate
    Number of subjects included in analysis
    15
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.05 [28]
    Method
    		 t-test, 2-sided
    Parameter type
    		 d Cohen
    Point estimate
    -1.278
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.391
         upper limit
    		 -0.165
    Notes
    [28] - 0.028

    Secondary: Activation and elimination of free radicals

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    End point title
    		 Activation and elimination of free radicals
    End point description
    Change in GSSG/GSH prefilter/postfilter 24 hours after initiation RRT heparin
    End point type
    Secondary
    End point timeframe
    24 hours after initiation RRT
    End point values
    		 Heparin Heparin
    Number of subjects analysed
    6
    6
    Units: Non unit
        arithmetic mean (standard deviation)
    2.738 ( 1.081 )
    2.860 ( 1.436 )
    Statistical analysis title
    		 GSSG/GSH prefilter/postfilter 24 hours heparin
    Comparison groups
    Heparin v Heparin
    Number of subjects included in analysis
    12
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.05 [29]
    Method
    		 t-test, 2-sided
    Confidence interval
    Notes
    [29] - 0.543

    Secondary: Activation and elimination of free radicals

    		 Close Top of page
    End point title
    		 Activation and elimination of free radicals
    End point description
    Change in GSSG/GSH prefilter/postfilter 24 hours after initiation RRT citrate
    End point type
    Secondary
    End point timeframe
    24 hours citrate
    End point values
    		 Citrate Citrate
    Number of subjects analysed
    8
    8
    Units: Non unit
        arithmetic mean (standard deviation)
    1.495 ( 0.421 )
    1.677 ( 0.699 )
    Statistical analysis title
    		 GSSG/GSH prefilter/postfilter 24 hours after
    Comparison groups
    Citrate v Citrate
    Number of subjects included in analysis
    16
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.05 [30]
    Method
    		 t-test, 2-sided
    Confidence interval
    Notes
    [30] - 0.409

    Secondary: Activation and elimination of biomarkers of inflammation

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    End point title
    		 Activation and elimination of biomarkers of inflammation
    End point description
    MPO at the beginning of RRT
    End point type
    Secondary
    End point timeframe
    At the beginning of RRT
    End point values
    		 Heparin Citrate
    Number of subjects analysed
    10
    9
    Units: mU/ml
        median (inter-quartile range (Q1-Q3))
    125.673 (95.176 to 147.835)
    63.386 (52.239 to 112.167)
    Statistical analysis title
    		 MPO at the beginning of RRT
    Comparison groups
    Heparin v Citrate
    Number of subjects included in analysis
    19
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.05 [31]
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval
    Notes
    [31] - 0.010

    Secondary: Activation and elimination of biomarkers of inflammation

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    End point title
    		 Activation and elimination of biomarkers of inflammation
    End point description
    MPO prefilter 60 minutes after initiation of RRT
    End point type
    Secondary
    End point timeframe
    60 minutes after initiation of RRT
    End point values
    		 Heparin Citrate
    Number of subjects analysed
    10
    9
    Units: mU/ml
        arithmetic mean (standard deviation)
    96.691 ( 24.051 )
    83.726 ( 36.693 )
    Statistical analysis title
    		 MPO prefilter 60 minutes
    Comparison groups
    Heparin v Citrate
    Number of subjects included in analysis
    19
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.05 [32]
    Method
    		 t-test, 2-sided
    Confidence interval
    Notes
    [32] - 0.370

    Secondary: Activation and elimination of biomarkers of inflammation

    		 Close Top of page
    End point title
    		 Activation and elimination of biomarkers of inflammation
    End point description
    MPO postfilter 60 minutes after initiation of RRT
    End point type
    Secondary
    End point timeframe
    60 minutes after initiation of RRT
    End point values
    		 Heparin Citrate
    Number of subjects analysed
    10
    9
    Units: mU/ml
        arithmetic mean (standard deviation)
    121.892 ( 30.815 )
    87.577 ( 28.093 )
    Statistical analysis title
    		 MPO postfilter 60 minutes
    Comparison groups
    Heparin v Citrate
    Number of subjects included in analysis
    19
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.05 [33]
    Method
    		 t-test, 2-sided
    Parameter type
    		 d Cohen
    Point estimate
    -1.161
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.14
         upper limit
    		 -0.192
    Notes
    [33] - 0.022

    Secondary: Activation and elimination of biomarkers of inflammation

    		 Close Top of page
    End point title
    		 Activation and elimination of biomarkers of inflammation
    End point description
    Change in MPO prefilter/postfilter 60 minutes after initiation RRT heparin
    End point type
    Secondary
    End point timeframe
    60 minutes after initiation of RRT
    End point values
    		 Heparin Heparin
    Number of subjects analysed
    9
    9
    Units: mU/ml
        arithmetic mean (standard deviation)
    96.691 ( 24.051 )
    121.892 ( 30.815 )
    Statistical analysis title
    		 MPO prefilter/postfilter 60 minutes heparin
    Comparison groups
    Heparin v Heparin
    Number of subjects included in analysis
    18
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.05 [34]
    Method
    		 t-test, 2-sided
    Parameter type
    		 d Cohen
    Point estimate
    1.122
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.032
         upper limit
    		 2.02
    Notes
    [34] - 0.014

    Secondary: Activation and elimination of biomarkers of inflammation

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    End point title
    		 Activation and elimination of biomarkers of inflammation
    End point description
    MPO prefilter/postfilter 60 minutes citrate
    End point type
    Secondary
    End point timeframe
    60 minutes after initiation of RRT
    End point values
    		 Citrate Citrate
    Number of subjects analysed
    9
    9
    Units: mU/ml
        arithmetic mean (standard deviation)
    83.726 ( 36.693 )
    87.577 ( 28.093 )
    Statistical analysis title
    		 MPO prefilter/postfilter 60 minutes citrate
    Comparison groups
    Citrate v Citrate
    Number of subjects included in analysis
    18
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.05 [35]
    Method
    		 t-test, 2-sided
    Confidence interval
    Notes
    [35] - 0.680

    Secondary: Activation and elimination of biomarkers of inflammation

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    End point title
    		 Activation and elimination of biomarkers of inflammation
    End point description
    MPO prefilter 24 hours after initiation RRT
    End point type
    Secondary
    End point timeframe
    24 hours after initiation RRT
    End point values
    		 Heparin Citrate
    Number of subjects analysed
    9
    8
    Units: mU/ml
        median (inter-quartile range (Q1-Q3))
    88.925 (78.249 to 127.644)
    87.323 (69.137 to 111.738)
    Statistical analysis title
    		 GSSG 24 hours after initiation RRT
    Comparison groups
    Heparin v Citrate
    Number of subjects included in analysis
    17
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.05 [36]
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval
    Notes
    [36] - 0.743

    Secondary: Activation and elimination of biomarkers of inflammation

    		 Close Top of page
    End point title
    		 Activation and elimination of biomarkers of inflammation
    End point description
    MPO postfilter 24 hours after initiation RRT
    End point type
    Secondary
    End point timeframe
    24 hours after initiation RRT
    End point values
    		 Heparin Citrate
    Number of subjects analysed
    9
    8
    Units: mU/ml
        arithmetic mean (standard deviation)
    119.323 ( 45.117 )
    86.616 ( 22.675 )
    Statistical analysis title
    		 MPO postfilter 24 hours after initiation RRT
    Comparison groups
    Heparin v Citrate
    Number of subjects included in analysis
    17
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.05 [37]
    Method
    		 t-test, 2-sided
    Confidence interval
    Notes
    [37] - 0.084

    Secondary: Activation and elimination of biomarkers of inflammation

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    End point title
    		 Activation and elimination of biomarkers of inflammation
    End point description
    Change in MPO prefilter/postfilter 24 hours after initiation RRT heparin
    End point type
    Secondary
    End point timeframe
    24 hours after initiation RRT
    End point values
    		 Heparin Heparin
    Number of subjects analysed
    9
    9
    Units: mU/ml
        median (standard deviation)
    103.144 ( 35.376 )
    119.323 ( 45.117 )
    Statistical analysis title
    		 MPO prefilter/postfilter 24 hours heparin
    Comparison groups
    Heparin v Heparin
    Number of subjects included in analysis
    18
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.05 [38]
    Method
    		 t-test, 2-sided
    Confidence interval
    Notes
    [38] - 0.216

    Secondary: Activation and elimination of biomarkers of inflammation

    		 Close Top of page
    End point title
    		 Activation and elimination of biomarkers of inflammation
    End point description
    Change in MPO prefilter/postfilter 24 hours after initiation RRT citrate
    End point type
    Secondary
    End point timeframe
    24 hours after initiation RRT
    End point values
    		 Citrate Citrate
    Number of subjects analysed
    8
    8
    Units: mU/ml
        median (inter-quartile range (Q1-Q3))
    87.323 (69.137 to 111.738)
    84.620 (69.136 to 104.009)
    Statistical analysis title
    		 MPO prefilter/postfilter 24 hours citrate
    Comparison groups
    Citrate v Citrate
    Number of subjects included in analysis
    16
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.05 [39]
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval
    Notes
    [39] - 0.263

    Secondary: Activation and elimination of biomarkers of cell damage

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    End point title
    		 Activation and elimination of biomarkers of cell damage
    End point description
    Circulating cell-free DNA (cfDNA) at the beginning of RRT
    End point type
    Secondary
    End point timeframe
    At the beginning of RRT
    End point values
    		 Heparin Citrate
    Number of subjects analysed
    10
    10
    Units: nanogram(s)/millilitre
        arithmetic mean (standard deviation)
    1247.467 ( 732.377 )
    853.569 ( 526.755 )
    Statistical analysis title
    		 cfDNA at the beginning of RRT
    Comparison groups
    Heparin v Citrate
    Number of subjects included in analysis
    20
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.05 [40]
    Method
    		 t-test, 2-sided
    Confidence interval
    Notes
    [40] - 0.184

    Secondary: Activation and elimination of biomarkers of cell damage

    		 Close Top of page
    End point title
    		 Activation and elimination of biomarkers of cell damage
    End point description
    cfDNA prefilter 60 minutes after initiation of RRT
    End point type
    Secondary
    End point timeframe
    60 minutes after initiation of RRT
    End point values
    		 Heparin Citrate
    Number of subjects analysed
    10
    10
    Units: nanogram(s)/millilitre
        arithmetic mean (standard deviation)
    1416.767 ( 813.978 )
    894.022 ( 551.939 )
    Statistical analysis title
    		 cfDNA prefilter 60 minutes after initiation RRT
    Comparison groups
    Heparin v Citrate
    Number of subjects included in analysis
    20
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.05 [41]
    Method
    		 t-test, 2-sided
    Confidence interval
    Notes
    [41] - 0.110

    Secondary: Activation and elimination of biomarkers of cell damage

    		 Close Top of page
    End point title
    		 Activation and elimination of biomarkers of cell damage
    End point description
    cfDNA postfilter 60 minutes after initiation of RRT
    End point type
    Secondary
    End point timeframe
    60 minutes after initiation of RRT
    End point values
    		 Heparin Citrate
    Number of subjects analysed
    10
    10
    Units: nanogram(s)/millilitre
        arithmetic mean (standard deviation)
    1299.040 ( 643.126 )
    941.419 ( 603.344 )
    Statistical analysis title
    		 cfDNA postfilter 60 minutes after initiation RRT
    Comparison groups
    Heparin v Citrate
    Number of subjects included in analysis
    20
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.05 [42]
    Method
    		 t-test, 2-sided
    Confidence interval
    Notes
    [42] - 0.216

    Secondary: Activation and elimination of biomarkers of cell damage

    		 Close Top of page
    End point title
    		 Activation and elimination of biomarkers of cell damage
    End point description
    Change in cfDNA prefilter/postfilter 60 minutes after initiation RRT heparin
    End point type
    Secondary
    End point timeframe
    60 minutes after initiation RRT
    End point values
    		 Heparin Heparin
    Number of subjects analysed
    10
    10
    Units: nanogram(s)/millilitre
        arithmetic mean (standard deviation)
    1416.767 ( 813.978 )
    1299.040 ( 643.126 )
    Statistical analysis title
    		 cfDNA prefilter/postfilter 60 minutes heparin
    Comparison groups
    Heparin v Heparin
    Number of subjects included in analysis
    20
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.05 [43]
    Method
    		 t-test, 2-sided
    Confidence interval
    Notes
    [43] - 0.524

    Secondary: Activation and elimination of biomarkers of cell damage

    		 Close Top of page
    End point title
    		 Activation and elimination of biomarkers of cell damage
    End point description
    Change in cfDNA prefilter/postfilter 60 minutes after initiation RRT citrate
    End point type
    Secondary
    End point timeframe
    60 minutes after initiation RRT
    End point values
    		 Citrate Citrate
    Number of subjects analysed
    10
    10
    Units: nanogram(s)/millilitre
        arithmetic mean (standard deviation)
    894.022 ( 551.939 )
    941.419 ( 603.344 )
    Statistical analysis title
    		 cfDNA prefilter/postfilter 60 minutes citrate
    Comparison groups
    Citrate v Citrate
    Number of subjects included in analysis
    20
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.05 [44]
    Method
    		 t-test, 2-sided
    Confidence interval
    Notes
    [44] - 0.448

    Secondary: Activation and elimination of biomarkers of cell damage

    		 Close Top of page
    End point title
    		 Activation and elimination of biomarkers of cell damage
    End point description
    cfDNA prefilter 24 hours after initiation RRT
    End point type
    Secondary
    End point timeframe
    24 hours after initiation RRT
    End point values
    		 Heparin Citrate
    Number of subjects analysed
    8
    8
    Units: nanogram(s)/millilitre
        arithmetic mean (standard deviation)
    1675.836 ( 882.759 )
    1234.318 ( 508.296 )
    Statistical analysis title
    		 cfDNA prefilter 24 hours after initiation RRT
    Comparison groups
    Heparin v Citrate
    Number of subjects included in analysis
    16
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.05 [45]
    Method
    		 t-test, 2-sided
    Confidence interval
    Notes
    [45] - 0.240

    Secondary: Activation and elimination of biomarkers of cell damage

    		 Close Top of page
    End point title
    		 Activation and elimination of biomarkers of cell damage
    End point description
    cfDNA postfilter 24 hours after initiation RRT
    End point type
    Secondary
    End point timeframe
    24 hours after initiation RRT
    End point values
    		 Heparin Citrate
    Number of subjects analysed
    8
    8
    Units: nanogram(s)/millilitre
        arithmetic mean (standard deviation)
    1921.533 ( 779.795 )
    1184.161 ( 670.064 )
    Statistical analysis title
    		 cfDNA postfilter 24 hours after initiation RRT
    Comparison groups
    Heparin v Citrate
    Number of subjects included in analysis
    16
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.05 [46]
    Method
    		 t-test, 2-sided
    Confidence interval
    Notes
    [46] - 0.062

    Secondary: Activation and elimination of biomarkers of cell damage

    		 Close Top of page
    End point title
    		 Activation and elimination of biomarkers of cell damage
    End point description
    Change in cfDNA prefilter/postfilter 24 hours after initiation RRT heparin
    End point type
    Secondary
    End point timeframe
    24 hours after initiation RRT
    End point values
    		 Heparin Heparin
    Number of subjects analysed
    8
    8
    Units: nanogram(s)/millilitre
        arithmetic mean (standard deviation)
    1675.836 ( 882.759 )
    1921.533 ( 779.795 )
    Statistical analysis title
    		 cfDNA prefilter/postfilter 24 hours heparin
    Comparison groups
    Heparin v Heparin
    Number of subjects included in analysis
    16
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.05 [47]
    Method
    		 t-test, 2-sided
    Confidence interval
    Notes
    [47] - 0.075

    Secondary: Activation and elimination of biomarkers of cell damage

    		 Close Top of page
    End point title
    		 Activation and elimination of biomarkers of cell damage
    End point description
    Change in cfDNA prefilter/postfilter 24 hours after initiation RRT citrate
    End point type
    Secondary
    End point timeframe
    24 hours after initiation RRT
    End point values
    		 Citrate Citrate
    Number of subjects analysed
    8
    8
    Units: nanogram(s)/millilitre
        arithmetic mean (standard deviation)
    1234.318 ( 508.296 )
    1184.161 ( 670.064 )
    Statistical analysis title
    		 cfDNA prefilter/postfilter 24 hours citrate
    Comparison groups
    Citrate v Citrate
    Number of subjects included in analysis
    16
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.05 [48]
    Method
    		 t-test, 2-sided
    Confidence interval
    Notes
    [48] - 0.805

    Secondary: Mass transfer of free radicals

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    End point title
    		 Mass transfer of free radicals
    End point description
    Median levels of total amount of GSH mass removed expressed as a percentage of the filter inlet GSH mass
    End point type
    Secondary
    End point timeframe
    60 minutes after initiation of RRT
    End point values
    		 Heparin Citrate
    Number of subjects analysed
    10
    10
    Units: percent
        arithmetic mean (standard deviation)
    20.903 ( 21.998 )
    -1.829 ( 21.074 )
    Statistical analysis title
    		 GSH mass transfer 60 minutes
    Comparison groups
    Heparin v Citrate
    Number of subjects included in analysis
    20
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.05 [49]
    Method
    		 t-test, 2-sided
    Parameter type
    		 d Cohen
    Point estimate
    1.055
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.102
         upper limit
    		 1.984
    Notes
    [49] - 0.030

    Secondary: Mass transfer of free radicals

    		 Close Top of page
    End point title
    		 Mass transfer of free radicals
    End point description
    Median levels of total amount of GSH mass removed expressed as a percentage of the filter inlet GSH mass
    End point type
    Secondary
    End point timeframe
    24 hours after initiation of RRT
    End point values
    		 Heparin Citrate
    Number of subjects analysed
    9
    8
    Units: percent
        arithmetic mean (standard error)
    -4.798 ( 33.667 )
    4.765 ( 12.786 )
    Statistical analysis title
    		 GSH mass transfer 24 hours
    Comparison groups
    Heparin v Citrate
    Number of subjects included in analysis
    17
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.05 [50]
    Method
    		 t-test, 2-sided
    Confidence interval
    Notes
    [50] - 0.462

    Secondary: Mass transfer of free radicals

    		 Close Top of page
    End point title
    		 Mass transfer of free radicals
    End point description
    Median levels of total amount of GSSG mass removed expressed as a percentage of the filter inlet GSSG mass
    End point type
    Secondary
    End point timeframe
    60 minutes after initiation of RRT
    End point values
    		 Heparin Citrate
    Number of subjects analysed
    9
    9
    Units: percent
        arithmetic mean (standard deviation)
    -8.903 ( 33.062 )
    -15.543 ( 39.779 )
    Statistical analysis title
    		 GSSG mass transfer 60 minutes
    Comparison groups
    Heparin v Citrate
    Number of subjects included in analysis
    18
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.05 [51]
    Method
    		 t-test, 2-sided
    Confidence interval
    Notes
    [51] - 0.705

    Secondary: Mass transfer of free radicals

    		 Close Top of page
    End point title
    		 Mass transfer of free radicals
    End point description
    Median levels of total amount of GSSG mass removed expressed as a percentage of the filter inlet GSSG mass
    End point type
    Secondary
    End point timeframe
    24 hours after initiation of RRT
    End point values
    		 Heparin Citrate
    Number of subjects analysed
    8
    8
    Units: percent
        arithmetic mean (standard deviation)
    2.198 ( 33.644 )
    -6.713 ( 32.103 )
    Statistical analysis title
    		 GSSG mass transfer 24 hours
    Comparison groups
    Heparin v Citrate
    Number of subjects included in analysis
    16
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.05 [52]
    Method
    		 t-test, 2-sided
    Confidence interval
    Notes
    [52] - 0.591

    Secondary: Mass transfer of biomarkers of inflammation

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    End point title
    		 Mass transfer of biomarkers of inflammation
    End point description
    Median levels of total amount of MPO mass removed expressed as a percentage of the filter inlet MPO mass
    End point type
    Secondary
    End point timeframe
    60 minutes after initiation RRT
    End point values
    		 Heparin Citrate
    Number of subjects analysed
    10
    8
    Units: percent
        arithmetic mean (standard deviation)
    -28.197 ( 31.545 )
    5.483 ( 18.628 )
    Statistical analysis title
    		 MPO mass transfer 60 minutes
    Comparison groups
    Heparin v Citrate
    Number of subjects included in analysis
    18
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.05 [53]
    Method
    		 t-test, 2-sided
    Parameter type
    		 d Cohen
    Point estimate
    -1.263
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.272
         upper limit
    		 -0.221
    Notes
    [53] - 0.017

    Secondary: Mass transfer of biomarkers of inflammation

    		 Close Top of page
    End point title
    		 Mass transfer of biomarkers of inflammation
    End point description
    Median levels of total amount of MPO mass removed expressed as a percentage of the filter inlet MPO mass
    End point type
    Secondary
    End point timeframe
    24 hours after initiation of RRT
    End point values
    		 Heparin Citrate
    Number of subjects analysed
    9
    8
    Units: percent
        arithmetic mean (standard deviation)
    -16.824 ( 40.049 )
    11.725 ( 19.926 )
    Statistical analysis title
    		 MPO mass transfer 24 hours
    Comparison groups
    Heparin v Citrate
    Number of subjects included in analysis
    17
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.05 [54]
    Method
    		 t-test, 2-sided
    Confidence interval
    Notes
    [54] - 0.089

    Secondary: Mass transfer of biomarkers of inflammation

    		 Close Top of page
    End point title
    		 Mass transfer of biomarkers of inflammation
    End point description
    Median levels of total amount of CRP mass removed expressed as a percentage of the filter inlet CRP mass
    End point type
    Secondary
    End point timeframe
    60 minutes after initiation RRT
    End point values
    		 Heparin Citrate
    Number of subjects analysed
    10
    10
    Units: percent
        median (inter-quartile range (Q1-Q3))
    -3.095 (-5.260 to 0.275)
    1.790 (-0.658 to 3.420)
    Statistical analysis title
    		 CRP mass transfer 60 minutes
    Comparison groups
    Heparin v Citrate
    Number of subjects included in analysis
    20
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.05 [55]
    Method
    		 Wilcoxon (Mann-Whitney)
    Parameter type
    		 g Hedges
    Point estimate
    -0.964
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.848
         upper limit
    		 -0.056
    Notes
    [55] - 0.023

    Secondary: Mass transfer of biomarkers of inflammation

    		 Close Top of page
    End point title
    		 Mass transfer of biomarkers of inflammation
    End point description
    Median levels of total amount of CRP mass removed expressed as a percentage of the filter inlet CRP mass
    End point type
    Secondary
    End point timeframe
    24 hours after initiation of RRT
    End point values
    		 Heparin Citrate
    Number of subjects analysed
    7
    8
    Units: percent
        arithmetic mean (standard deviation)
    -1.206 ( 2.622 )
    3.131 ( 2.735 )
    Statistical analysis title
    		 CRP mass transfer 24 hours
    Comparison groups
    Heparin v Citrate
    Number of subjects included in analysis
    15
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.05 [56]
    Method
    		 Wilcoxon (Mann-Whitney)
    Parameter type
    		 g Hedges
    Point estimate
    -1.521
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.616
         upper limit
    		 -0.383
    Notes
    [56] - 0.021

    Secondary: Mass transfer of biomarkers of cell damage

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    End point title
    		 Mass transfer of biomarkers of cell damage
    End point description
    Median levels of total amount of cfDNA mass removed expressed as a percentage of the filter inlet cfDNA mass
    End point type
    Secondary
    End point timeframe
    60 minutes after initiation RRT
    End point values
    		 Heparin Citrate
    Number of subjects analysed
    10
    10
    Units: percent
        arithmetic mean (standard deviation)
    -3.310 ( 37.482 )
    -5.094 ( 40.809 )
    Statistical analysis title
    		 DNA mass transfer 60 minutes
    Comparison groups
    Heparin v Citrate
    Number of subjects included in analysis
    20
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.05 [57]
    Method
    		 t-test, 2-sided
    Confidence interval
    Notes
    [57] - 0.920

    Secondary: Mass transfer of biomarkers of cell damage

    		 Close Top of page
    End point title
    		 Mass transfer of biomarkers of cell damage
    End point description
    Median levels of total amount of cfDNA mass removed expressed as a percentage of the filter inlet cfDNA mass
    End point type
    Secondary
    End point timeframe
    24 hours after initiation of RRT
    End point values
    		 Heparin Citrate
    Number of subjects analysed
    8
    8
    Units: percent
        median (inter-quartile range (Q1-Q3))
    -3.115 (-56.169 to 0.285)
    8.240 (-10.390 to 19.463)
    Statistical analysis title
    		 cfDNA mass transfer 24 hours
    Comparison groups
    Heparin v Citrate
    Number of subjects included in analysis
    16
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.05
    Method
    		 Wilcoxon (Mann-Whitney)
    Parameter type
    		 g Hedges
    Point estimate
    -0.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.86
         upper limit
    		 0.196

    Secondary: Clearance rate of free radicals

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    End point title
    		 Clearance rate of free radicals
    End point description
    GSH clearance rate 60 minutes after initiation RRT
    End point type
    Secondary
    End point timeframe
    60 minutes after initiation RRT
    End point values
    		 Heparin Citrate
    Number of subjects analysed
    10
    10
    Units: millilitre(s)/minute
        arithmetic mean (standard deviation)
    17.286 ( 17.332 )
    -2.792 ( 16.303 )
    Statistical analysis title
    		 GSH clearance rate 60 minutes
    Comparison groups
    Heparin v Citrate
    Number of subjects included in analysis
    20
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.05 [58]
    Method
    		 t-test, 2-sided
    Parameter type
    		 d Cohen
    Point estimate
    1.193
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.221
         upper limit
    		 2.138
    Notes
    [58] - 0.016

    Secondary: Clearance rate of free radicals

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    End point title
    		 Clearance rate of free radicals
    End point description
    GSH clearance 24 hours after initiation of RRT
    End point type
    Secondary
    End point timeframe
    24 hours after initiation of RRT
    End point values
    		 Heparin Citrate
    Number of subjects analysed
    9
    8
    Units: millilitre(s)/minute
        arithmetic mean (standard error)
    -3.108 ( 23.930 )
    5.630 ( 9.530 )
    Statistical analysis title
    		 GSH clearance rate 24 hours
    Comparison groups
    Heparin v Citrate
    Number of subjects included in analysis
    17
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.05 [59]
    Method
    		 t-test, 2-sided
    Confidence interval
    Notes
    [59] - 0.350

    Secondary: Clearance rate of free radicals

    		 Close Top of page
    End point title
    		 Clearance rate of free radicals
    End point description
    GSH mean clearance 24 hours after initiation of RRT
    End point type
    Secondary
    End point timeframe
    24 hours after initiation of RRT
    End point values
    		 Heparin Citrate
    Number of subjects analysed
    8
    7
    Units: millilitre(s)/minute
        arithmetic mean (standard error)
    8.741 ( 9.256 )
    2.626 ( 9.492 )
    Statistical analysis title
    		 GSH mean clearance rate
    Comparison groups
    Heparin v Citrate
    Number of subjects included in analysis
    15
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.05 [60]
    Method
    		 t-test, 2-sided
    Confidence interval
    Notes
    [60] - 0.230

    Secondary: Clearance rate of free radicals

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    End point title
    		 Clearance rate of free radicals
    End point description
    GSSG clearance 60 minutes after initiation of RRT
    End point type
    Secondary
    End point timeframe
    60 minutes after initiation of RRT
    End point values
    		 Heparin Citrate
    Number of subjects analysed
    9
    9
    Units: millilitre(s)/minute
        arithmetic mean (standard deviation)
    -2.164 ( 30.707 )
    5.630 ( 9.530 )
    Statistical analysis title
    		 GSSG clearance rate 60 minutes
    Comparison groups
    Heparin v Citrate
    Number of subjects included in analysis
    18
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.05 [61]
    Method
    		 t-test, 2-sided
    Confidence interval
    Notes
    [61] - 0.554

    Secondary: Clearance rate of free radicals

    		 Close Top of page
    End point title
    		 Clearance rate of free radicals
    End point description
    GSSG clearance 24 hours after initiation of RRT
    End point type
    Secondary
    End point timeframe
    24 hours after initiation of RRT
    End point values
    		 Heparin Citrate
    Number of subjects analysed
    8
    8
    Units: millilitre(s)/minute
        arithmetic mean (standard deviation)
    4.449 ( 27.735 )
    -1.705 ( 26.713 )
    Statistical analysis title
    		 GSSG clearance rate 24 hours
    Comparison groups
    Heparin v Citrate
    Number of subjects included in analysis
    16
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.05 [62]
    Method
    		 t-test, 2-sided
    Confidence interval
    Notes
    [62] - 0.658

    Secondary: Clearance rate of free radicals

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    End point title
    		 Clearance rate of free radicals
    End point description
    GSSG mean clearance 24 hours after initiation of RRT
    End point type
    Secondary
    End point timeframe
    24 hours after initiation of RRT
    End point values
    		 Heparin Citrate
    Number of subjects analysed
    9
    8
    Units: millilitre(s)/minuyte
        arithmetic mean (standard deviation)
    2.360 ( 25.713 )
    -9.245 ( 17.104 )
    Statistical analysis title
    		 GSSG mean clearance rate
    Comparison groups
    Heparin v Citrate
    Number of subjects included in analysis
    17
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.05 [63]
    Method
    		 t-test, 2-sided
    Confidence interval
    Notes
    [63] - 0.297

    Secondary: Clearance of biomarkers of inflammation

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    End point title
    		 Clearance of biomarkers of inflammation
    End point description
    MPO clearance 60 minutes after initiation RRT
    End point type
    Secondary
    End point timeframe
    60 minutes after initiation RRT
    End point values
    		 Heparin Citrate
    Number of subjects analysed
    10
    9
    Units: millilitre(s)/minute
        median (inter-quartile range (Q1-Q3))
    -12.635 (-47.103 to -3.178)
    -4.810 (-9.915 to 14.200)
    Statistical analysis title
    		 MPO clearance rate 60 minutes
    Comparison groups
    Heparin v Citrate
    Number of subjects included in analysis
    19
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.05 [64]
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval
    Notes
    [64] - 0.133

    Secondary: Clearance of biomarkers of inflammation

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    End point title
    		 Clearance of biomarkers of inflammation
    End point description
    MPO clearance 24 hours after initiation of RRT
    End point type
    Secondary
    End point timeframe
    24 hours after initiation of RRT
    End point values
    		 Heparin Citrate
    Number of subjects analysed
    9
    8
    Units: millilitre(s)/min
        arithmetic mean (standard deviation)
    -8.833 ( 34.858 )
    6.516 ( 12.095 )
    Statistical analysis title
    		 MPO clearance rate 24 hours
    Comparison groups
    Heparin v Citrate
    Number of subjects included in analysis
    17
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.05 [65]
    Method
    		 t-test, 2-sided
    Confidence interval
    Notes
    [65] - 0.256

    Secondary: Clearance of biomarkers of inflammation

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    End point title
    		 Clearance of biomarkers of inflammation
    End point description
    MPO mean clearance 24 hours after initiation of RRT
    End point type
    Secondary
    End point timeframe
    24 hours after initiation of RRT
    End point values
    		 Heparin Citrate
    Number of subjects analysed
    9
    8
    Units: millilitre(s)/min
        median (inter-quartile range (Q1-Q3))
    -16.110 (-29.760 to -10.355)
    1.415 (-9.678 to 12.645)
    Statistical analysis title
    		 MPO mean clearance rate
    Comparison groups
    Citrate v Heparin
    Number of subjects included in analysis
    17
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.05 [66]
    Method
    		 Wilcoxon (Mann-Whitney)
    Parameter type
    		 g Hedges
    Point estimate
    -0.685
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.611
         upper limit
    		 0.261
    Notes
    [66] - 0.046

    Secondary: Clearance of biomarkers of inflammation

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    End point title
    		 Clearance of biomarkers of inflammation
    End point description
    CRP clearance 60 minutes after initiation of RRT
    End point type
    Secondary
    End point timeframe
    60 minutes after initiation of RRT
    End point values
    		 Heparin Citrate
    Number of subjects analysed
    10
    10
    Units: millilitre(s)/minute
        median (inter-quartile range (Q1-Q3))
    -2.185 (-4.863 to 0.225)
    1.670 (-0.410 to 2.375)
    Statistical analysis title
    		 CRP clearance rate 60 minutes
    Comparison groups
    Heparin v Citrate
    Number of subjects included in analysis
    20
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.05 [67]
    Method
    		 Wilcoxon (Mann-Whitney)
    Parameter type
    		 g Hedges
    Point estimate
    -0.692
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.552
         upper limit
    		 0.186
    Notes
    [67] - 0.019

    Secondary: Clearance of biomarkers of inflammation

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    End point title
    		 Clearance of biomarkers of inflammation
    End point description
    CRP clearance 24 hours after initiation of RRT
    End point type
    Secondary
    End point timeframe
    24 hours after initiation of RRT
    End point values
    		 Heparin Citrate
    Number of subjects analysed
    8
    8
    Units: millilitre(s)/minute
        median (inter-quartile range (Q1-Q3))
    -2.120 (-2.623 to -0.113)
    2.060 (1.543 to 4.580)
    Statistical analysis title
    		 CRP clearance rate 24 hours
    Comparison groups
    Heparin v Citrate
    Number of subjects included in analysis
    16
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.05 [68]
    Method
    		 Wilcoxon (Mann-Whitney)
    Parameter type
    		 g Hedges
    Point estimate
    -1.015
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.998
         upper limit
    		 -0.001
    Notes
    [68] - 0.010

    Secondary: Clearance of biomarkers of inflammation

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    End point title
    		 Clearance of biomarkers of inflammation
    End point description
    CRP mean clearance 24 hours after initiation of RRT
    End point type
    Secondary
    End point timeframe
    24 hours after initiation of RRT
    End point values
    		 Heparin Citrate
    Number of subjects analysed
    8
    8
    Units: millilitre(s)/minute
        median (inter-quartile range (Q1-Q3))
    -0.058 (-6.064 to 0.837)
    0.224 (-3.085 to 1.183)
    Statistical analysis title
    		 CRP mean clearance rate
    Comparison groups
    Citrate v Heparin
    Number of subjects included in analysis
    16
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.05 [69]
    Method
    		 Wilcoxon (Mann-Whitney)
    Parameter type
    		 g Hedges
    Point estimate
    -1.25
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.265
         upper limit
    		 -0.198
    Notes
    [69] - 0.015

    Secondary: Clearance of biomarkers of cell damage

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    End point title
    		 Clearance of biomarkers of cell damage
    End point description
    cfDNA clearance 60 minutes after initiation of RRT
    End point type
    Secondary
    End point timeframe
    60 minutes after initiation of RRT
    End point values
    		 Heparin Citrate
    Number of subjects analysed
    10
    10
    Units: millilitre(s)/minute
        median (inter-quartile range (Q1-Q3))
    2.120 (-24.108 to 10.485)
    3.525 (-13.073 to 17.500)
    Statistical analysis title
    		 cfDNA clearance rate 60 minutes
    Comparison groups
    Heparin v Citrate
    Number of subjects included in analysis
    20
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.05 [70]
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval
    Notes
    [70] - 0.853

    Secondary: Clearance of biomarkers of cell damage

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    End point title
    		 Clearance of biomarkers of cell damage
    End point description
    cfDNA clearance 24 hours after initiation of RRT
    End point type
    Secondary
    End point timeframe
    24 hours after initiation of RRT
    End point values
    		 Heparin Citrate
    Number of subjects analysed
    8
    8
    Units: millilitre(s)/minute
        median (inter-quartile range (Q1-Q3))
    -2.230 (-57.878 to -0.440)
    8.495 (-9.388 to 13.783)
    Statistical analysis title
    		 cfDNA clearance rate 24 hours
    Comparison groups
    Heparin v Citrate
    Number of subjects included in analysis
    16
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.05 [71]
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval
    Notes
    [71] - 0.050

    Secondary: Clearance of biomarkers of cell damage

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    End point title
    		 Clearance of biomarkers of cell damage
    End point description
    cfDNA mean clearance 24 hours after initiation of RRT
    End point type
    Secondary
    End point timeframe
    24 hours after initiation of RRT
    End point values
    		 Heparin Citrate
    Number of subjects analysed
    7
    8
    Units: millilitre(s)/minute
        median (inter-quartile range (Q1-Q3))
    -0.390 (-10.760 to 0.000)
    9.895 (-5.728 to 19.633)
    Statistical analysis title
    		 cfDNA mean clearance rate
    Comparison groups
    Heparin v Citrate
    Number of subjects included in analysis
    15
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.05 [72]
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval
    Notes
    [72] - 0.054

    Secondary: Length of stay

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    End point title
    		 Length of stay
    End point description
    ICU length of stay from ICU admission until the date of ICU discharge or date of death from any cause, whichever came first, assessed up to 90 days
    End point type
    Secondary
    End point timeframe
    From ICU admission until the date of ICU discharge or date of death from any cause, whichever came first, assessed up to 90 days
    End point values
    		 Heparin Citrate
    Number of subjects analysed
    10
    10
    Units: day
        median (inter-quartile range (Q1-Q3))
    8.50 (3.75 to 12.25)
    4.50 (1.75 to 7.75)
    Statistical analysis title
    		 ICU length of stay
    Comparison groups
    Heparin v Citrate
    Number of subjects included in analysis
    20
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.05 [73]
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval
    Notes
    [73] - 0.165

    Secondary: Length of stay

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    End point title
    		 Length of stay
    End point description
    Hospital length of stay
    End point type
    Secondary
    End point timeframe
    From hospital admission until the date of documented hospital discharge or date of death from any cause, whichever came first, assessed up to 90 days
    End point values
    		 Heparin Citrate
    Number of subjects analysed
    10
    10
    Units: day
        median (inter-quartile range (Q1-Q3))
    18.50 (12.00 to 48.75)
    19.50 (12.75 to 30.75)
    Statistical analysis title
    		 Hospital length of stay
    Comparison groups
    Heparin v Citrate
    Number of subjects included in analysis
    20
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.05 [74]
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval
    Notes
    [74] - 0.853

    Secondary: Mortality

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    End point title
    		 Mortality
    End point description
    ICU mortality
    End point type
    Secondary
    End point timeframe
    Through study completion, an average of 20 days
    End point values
    		 Heparin Citrate
    Number of subjects analysed
    10
    10
    Units: percent
        number (not applicable)
    40
    30
    Statistical analysis title
    		 ICU mortality
    Comparison groups
    Heparin v Citrate
    Number of subjects included in analysis
    20
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.05 [75]
    Method
    		 Chi-squared corrected
    Confidence interval
    Notes
    [75] - 1.000

    Secondary: Mortality

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    End point title
    		 Mortality
    End point description
    Hospital mortality
    End point type
    Secondary
    End point timeframe
    Day 90 after ICU admission
    End point values
    		 Heparin Citrate
    Number of subjects analysed
    10
    10
    Units: percent
        number (not applicable)
    40
    40
    Statistical analysis title
    		 Hospital mortality
    Comparison groups
    Heparin v Citrate
    Number of subjects included in analysis
    20
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.05 [76]
    Method
    		 Chi-squared corrected
    Confidence interval
    Notes
    [76] - 1.000

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    24 hours
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    5.0
    Reporting groups
    Reporting group title
    Active Comparator : Heparin
    Reporting group description
    		 -

    Reporting group title
    Experimental : Citrate
    Reporting group description
    		 -

    Serious adverse events
    		 Active Comparator : Heparin Experimental : Citrate
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 10 (0.00%)
         number of deaths (all causes)
    4
    4
         number of deaths resulting from adverse events
    0
    0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    		 Active Comparator : Heparin Experimental : Citrate
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    5 / 10 (50.00%)
    1 / 10 (10.00%)
    Investigations
    Platelet count decreased
         subjects affected / exposed
    5 / 10 (50.00%)
    1 / 10 (10.00%)
         occurrences all number
    5
    1

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    15 Jul 2019
    Addition of research center and designated researcher

    Interruptions (globally)
    Were there any global interruptions to the trial? Yes
    Date
    Interruption
    Restart date
    21 Mar 2020
    COVID pandemic.
    11 Jan 2021

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    Early termination leading to a small number of subjects analysed
    For support, Contact us.
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