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    Clinical Trial Results:
    Effect of Combinations of Paracetamol, Ibuprofen, and Dexamethasone on Patient-Controlled Morphine Consumption in the First 24 Hours After Total Hip Arthroplasty. The RECIPE Randomized Clinical Trial

    Summary
    EudraCT number
    		 2019-002844-25
    Trial protocol
    		 DK  
    Global end of trial date
    15 Feb 2023

    Results information
    Results version number
    		 v1(current)
    This version publication date
    16 Oct 2024
    First version publication date
    16 Oct 2024
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    SM1-JOAST-2019
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT04123873
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    RCAI, Department of Anaethesiology, Næstved-Slagelse-Ringsted Hospitals
    Sponsor organisation address
    Ringstedgade 61, Næstved, Denmark, 4700
    Public contact
    Dept of Anaesthesiology, Næstved Hospital, 0045 56514002, anaestesisekretariat@regionsjaelland.dk
    Scientific contact
    Dept of Anaesthesiology, Næstved Hospital, 0045 56514002, anaestesisekretariat@regionsjaelland.dk
    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
    15 Feb 2023
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    15 Feb 2023
    Global end of trial reached?
    Yes
    Global end of trial date
    15 Feb 2023
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To investigate the analgesic effects, by differences in 24-hour morphine consumption, of different combinations of paracetamol, ibuprofen, and dexamethasone after total hip arthroplasty.
    Protection of trial subjects
    Subjects received a Patient Controlled Analgesia Pump with morphine, where they could steer their own pain treatment. Thus reducing patients discomfort in trial
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    01 Jan 2020
    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
    Denmark: 1060
    Worldwide total number of subjects
    1060
    EEA total number of subjects
    1060
    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)
    348
    From 65 to 84 years
    680
    85 years and over
    32

    Subject disposition

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    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 All participants scheduled for primary, unilateral total hip arthroplasty were screened for enrolment. 4468 patients were assessed for eleigibility.

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Paracetamol plus ibuprofen plus dexamthesone
    Arm description
    		 Oral paracetamol 1000 mg plus oral ibuprofen 400 mg plus single-dose intravenous dexamethasone 24 mg. The first dose of oral medication was given as premedication 1 h before surgery. The three remaining doses were continued postoperatively with 6 h intervals until 24 h postoperatively. The intravenous medication was given immediately after the onset of spinal anaesthesia or after the induction of general anaesthesia.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Paracetamol
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    The first dose of oral medication 1000 mg was given as premedication 1 h before surgery. The three remaining doses (1000 mg each) were continued postoperatively with 6 h intervals until 24 h postoperatively.

    Investigational medicinal product name
    Ibuprofen
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    The first dose of oral medication 400 mg was given as premedication 1 h before surgery. The three remaining doses (each 400 mg) were continued postoperatively with 6 h intervals until 24 h postoperatively.

    Investigational medicinal product name
    Dexamethasone
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    Dexamthasone 24 mg was given immediately after the onset of spinal anaesthesia or afterthe induction of general anaesthesia.

    Arm title
    		 Ibuprofen plus dexamthasone
    Arm description
    		 Oral ibuprofen 400 mg plus single-dose intravenous dexamethasone 24 mg plus placebo matching paracetamol.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Oral placebo 1000 mg. The first dose of oral medication was given as premedication 1 h before surgery. The three remaining doses were continued postoperatively with 6 h intervals until 24 h postoperatively.

    Investigational medicinal product name
    Ibuprofen
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    The first dose of oral medication 400 mg was given as premedication 1 h before surgery. The three remaining doses (each 400 mg) were continued postoperatively with 6 h intervals until 24 h postoperatively.

    Investigational medicinal product name
    Dexamethasone
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    Dexamthasone 24 mg was given immediately after the onset of spinal anaesthesia or afterthe induction of general anaesthesia.

    Arm title
    		 Paracetamol plus dexatmethasone
    Arm description
    		 Oral paracetamol 1000 mg plus single-dose intravenous dexamethasone 24 mg plus placebo matching ibuprofen.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Paracetamol
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    The first dose of oral medication 1000 mg was given as premedication 1 h before surgery. The three remaining doses (1000 mg each) were continued postoperatively with 6 h intervals until 24 h postoperatively.

    Investigational medicinal product name
    Dexamethasone
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    Dexamthasone 24 mg was given immediately after the onset of spinal anaesthesia or afterthe induction of general anaesthesia.

    Investigational medicinal product name
    Placebo to Ibuprofen
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Oral placebo 400 mg. The first dose of oral medication was given as premedication 1 h before surgery. The three remaining doses were continued postoperatively with 6 h intervals until 24 h postoperatively.

    Arm title
    		 Paracetamol plus Ibuprofen
    Arm description
    		 Oral paracetamol 1000 mg plus oral ibuprofen 400 mg plus placebo matching dexamethasone.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Paracetamol
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    The first dose of oral medication 1000 mg was given as premedication 1 h before surgery. The three remaining doses (1000 mg each) were continued postoperatively with 6 h intervals until 24 h postoperatively.

    Investigational medicinal product name
    Ibuprofen
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    The first dose of oral medication 400 mg was given as premedication 1 h before surgery. The three remaining doses (each 400 mg) were continued postoperatively with 6 h intervals until 24 h postoperatively.

    Investigational medicinal product name
    Placebo to Dexamethasone
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    The intravenous placebo (sodium chloride 6 ml) was given immediately after the onset of spinal anaesthesia or after the induction of general anaesthesia.

    Number of subjects in period 1
    		Paracetamol plus ibuprofen plus dexamthesone Ibuprofen plus dexamthasone Paracetamol plus dexatmethasone Paracetamol plus Ibuprofen
    Started
    265
    265
    265
    265
    Completed
    258
    262
    262
    261
    Not completed
    7
    3
    3
    4
         Consent withdrawn by subject
    -
    -
    1
    2
         Physician decision
    -
    -
    2
    1
         Expiration of interventional drugs
    1
    1
    -
    -
         Surgery cancelled
    5
    2
    -
    1
         Trial personnel overlooked surgery
    1
    -
    -
    -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Paracetamol plus ibuprofen plus dexamthesone
    Reporting group description
    		 Oral paracetamol 1000 mg plus oral ibuprofen 400 mg plus single-dose intravenous dexamethasone 24 mg. The first dose of oral medication was given as premedication 1 h before surgery. The three remaining doses were continued postoperatively with 6 h intervals until 24 h postoperatively. The intravenous medication was given immediately after the onset of spinal anaesthesia or after the induction of general anaesthesia.

    Reporting group title
    Ibuprofen plus dexamthasone
    Reporting group description
    		 Oral ibuprofen 400 mg plus single-dose intravenous dexamethasone 24 mg plus placebo matching paracetamol.

    Reporting group title
    Paracetamol plus dexatmethasone
    Reporting group description
    		 Oral paracetamol 1000 mg plus single-dose intravenous dexamethasone 24 mg plus placebo matching ibuprofen.

    Reporting group title
    Paracetamol plus Ibuprofen
    Reporting group description
    		 Oral paracetamol 1000 mg plus oral ibuprofen 400 mg plus placebo matching dexamethasone.

    Reporting group values
    		 Paracetamol plus ibuprofen plus dexamthesone Ibuprofen plus dexamthasone Paracetamol plus dexatmethasone Paracetamol plus Ibuprofen Total
    Number of subjects
    		 265 265 265 265 1060
    Age categorical
    Units: Subjects
        In utero
    		 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0
        Newborns (0-27 days)
    		 0
        Infants and toddlers (28 days-23 months)
    		 0
        Children (2-11 years)
    		 0
        Adolescents (12-17 years)
    		 0
        Adults (18-64 years)
    		 0
        From 65-84 years
    		 0
        85 years and over
    		 0
    Age continuous
    Units: years
        median (inter-quartile range (Q1-Q3))
    		 69 (62 to 74) 69 (60 to 75) 69 (61 to 76) 70 (62 to 76) -
    Gender categorical
    Units: Subjects
        Female
    		 148 141 153 156 598
        Male
    		 117 124 112 109 462
    American Society of Anesthesiologists score
    Units: Subjects
        Healthy
    		 64 67 58 56 245
        Mild systemic disease
    		 171 168 179 182 700
        Severe systemic disease
    		 30 30 28 27 115
    Diabetes
    Units: Subjects
        Type 2 diabetes
    		 16 8 18 12 54
        No diabetes
    		 249 257 247 253 1006
    Use of paracetamol before surgery
    Units: Subjects
        None
    		 40 39 36 45 160
        As needed
    		 111 101 105 94 411
        Daily use
    		 114 125 124 126 489
    Use of NSAID before surgery
    Units: Subjects
        None
    		 117 131 128 123 499
        As needed
    		 96 79 79 76 330
        Daily use
    		 52 55 58 66 231
    Daily opioid users: type of opioid
    Units: Subjects
        Morphine
    		 6 8 4 7 25
        Oxycodone
    		 4 4 6 6 20
        Tramadol
    		 6 5 7 7 25
        None
    		 249 248 248 245 990
    Use of gabapentinoids before surgery
    Units: Subjects
        None
    		 255 252 255 255 1017
        As needed
    		 0 4 3 2 9
        Daily use
    		 10 9 7 8 34
    Use of antidepressants before surgery
    Units: Subjects
        None
    		 245 251 253 252 1001
        As needed
    		 0 0 0 1 1
        Daily use
    		 13 11 9 8 41
        Unknown
    		 7 3 3 4 17
    Surgery type
    Units: Subjects
        Uncemented
    		 206 204 204 209 823
        Hybrid
    		 35 36 33 32 136
        Cemented
    		 21 21 23 18 83
        Not registred
    		 3 4 5 6 18
    Anaesthesia method
    Units: Subjects
        Spinal
    		 194 202 203 187 786
        General anaesthesia
    		 58 48 49 59 214
        Conversion from spinal to general anaesthesia
    		 13 15 13 19 60
    Spinal type plain
    Units: Subjects
        Spinal type plain
    		 202 214 213 203 832
        No spinal
    		 63 51 52 62 228
    Sufentanil administrated
    Sufentanil administrated for participants in general anaesthesia (planned or converted from spinal)
    Units: Subjects
        Sufentanil administrated
    		 54 48 53 61 216
        No sufentanil administrated
    		 211 217 212 204 844
    Ondansetron administrated
    Ondansetron 4 mg administrated
    Units: Subjects
        Ondansetron administrated
    		 252 254 251 250 1007
        No ondansetron adminstrated
    		 13 11 14 15 53
    Perioperative local infiltration analgesia
    Units: Subjects
        Perioperative local infiltration analgesia
    		 0 0 0 1 1
        None
    		 265 265 265 264 1059
    Height
    Units: centimetre
        arithmetic mean (standard deviation)
    		 172.1 ( 8.9 ) 172.2 ( 8.1 ) 171.6 ( 9.2 ) 171.7 ( 9.4 ) -
    Weigth
    Units: kilogram(s)
        arithmetic mean (standard deviation)
    		 82 ( 17.4 ) 79.8 ( 15.5 ) 80.9 ( 15.5 ) 81.6 ( 17.0 ) -
    BMI
    Units: kilogram(s)/square metre
        arithmetic mean (standard deviation)
    		 27.4 ( 4.6 ) 26.8 ( 4.2 ) 27.4 ( 4.2 ) 27.6 ( 4.5 ) -
    Morphine users: daily dose, mg
    Units: milligram(s)
        median (inter-quartile range (Q1-Q3))
    		 10.0 (10.0 to 11.5) 10.0 (10.0 to 16.3) 20.0 (20.0 to 22.5) 10.0 (10.0 to 15.0) -
    Oxycodone users: daily dose, mg
    Units: milligram(s)
        median (inter-quartile range (Q1-Q3))
    		 20.0 (16.3 to 22.5) 10.0 (8.8 to 15.0) 20.0 (12.5 to 20.0) 10.0 (6.3 to 13.8) -
    Tramadol users: daily dose, mg
    Units: milligram(s)
        median (inter-quartile range (Q1-Q3))
    		 75.0 (50.0 to 100.0) 100.0 (100.00 to 100.00) 100.0 (50.0 to 125.0) 100.0 (100.0 to 100.0) -
    Pain at rest VAS
    Units: millimetre(s)
        median (inter-quartile range (Q1-Q3))
    		 20.0 (1.5 to 40.0) 20.0 (4.8 to 35.0) 17.0 (2.5 to 35.0) 19.0 (0.0 to 40.0) -
    Pain during mobilisation VAS
    Units: millimetre
        median (inter-quartile range (Q1-Q3))
    		 45.5 (21.0 to 70.0) 44.0 (20.0 to 65.5) 41.0 (20.0 to 64.0) 46.0 (20.0 to 69.0) -
    Surgery duration
    Units: minute
        median (inter-quartile range (Q1-Q3))
    		 55 (45 to 68) 55 (45 to 69) 55 (45 to 69) 55 (45 to 70) -
    Bupivacaine dose
    Units: milligram(s)
        median (inter-quartile range (Q1-Q3))
    		 12.0 (11.0 to 12.5) 12.5 (11.0 to 12.5) 12.5 (11.0 to 12.5) 12.5 (11.0 to 12.5) -
    Sufentanil dose
    Sufentanil administrated for participants in general anaesthesia (planned or converted from spinal) Sufentanil dose
    Units: microgram(s)
        median (inter-quartile range (Q1-Q3))
    		 22.5 (19.0 to 27.3) 22.8 (20.0 to 26.4) 22.5 (20.0 to 26.9) 25.0 (20.0 to 27.0) -
    Blood loss
    Units: millilitre(s)
        median (inter-quartile range (Q1-Q3))
    		 300 (200 to 443) 300 (200 to 440) 250 (175 to 400) 300 (200 to 494) -

    End points

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    End points reporting groups
    Reporting group title
    Paracetamol plus ibuprofen plus dexamthesone
    Reporting group description
    		 Oral paracetamol 1000 mg plus oral ibuprofen 400 mg plus single-dose intravenous dexamethasone 24 mg. The first dose of oral medication was given as premedication 1 h before surgery. The three remaining doses were continued postoperatively with 6 h intervals until 24 h postoperatively. The intravenous medication was given immediately after the onset of spinal anaesthesia or after the induction of general anaesthesia.

    Reporting group title
    Ibuprofen plus dexamthasone
    Reporting group description
    		 Oral ibuprofen 400 mg plus single-dose intravenous dexamethasone 24 mg plus placebo matching paracetamol.

    Reporting group title
    Paracetamol plus dexatmethasone
    Reporting group description
    		 Oral paracetamol 1000 mg plus single-dose intravenous dexamethasone 24 mg plus placebo matching ibuprofen.

    Reporting group title
    Paracetamol plus Ibuprofen
    Reporting group description
    		 Oral paracetamol 1000 mg plus oral ibuprofen 400 mg plus placebo matching dexamethasone.

    Primary: 24-h morphine consumption

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    End point title
    		 24-h morphine consumption
    End point description
    End point type
    Primary
    End point timeframe
    Morphine consumption from last suture to 24 hours after last suture
    End point values
    		 Paracetamol plus ibuprofen plus dexamthesone Ibuprofen plus dexamthasone Paracetamol plus dexatmethasone Paracetamol plus Ibuprofen
    Number of subjects analysed
    258
    262
    262
    261
    Units: milligram(s)
        median (inter-quartile range (Q1-Q3))
    15 (8 to 26)
    16 (10 to 30)
    20 (12 to 32)
    24 (12 to 38)
    Statistical analysis title
    		 Median difference
    Comparison groups
    Ibuprofen plus dexamthasone v Paracetamol plus ibuprofen plus dexamthesone
    Number of subjects included in analysis
    520
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.14
    Method
    		 Hodges-Lehmann
    Parameter type
    		 Median difference (final values)
    Point estimate
    -2
    Confidence interval
         level
    		 99%
         sides
    2-sided
         lower limit
    		 -4
         upper limit
    		 2
    Statistical analysis title
    		 Median difference
    Comparison groups
    Paracetamol plus ibuprofen plus dexamthesone v Paracetamol plus dexatmethasone
    Number of subjects included in analysis
    520
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0013
    Method
    		 Hodges-Lehmann
    Parameter type
    		 Median difference (final values)
    Point estimate
    -4
    Confidence interval
         level
    		 99%
         sides
    2-sided
         lower limit
    		 -8
         upper limit
    		 -1
    Statistical analysis title
    		 Median difference
    Comparison groups
    Paracetamol plus ibuprofen plus dexamthesone v Paracetamol plus Ibuprofen
    Number of subjects included in analysis
    519
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001
    Method
    		 Hodges-Lehmann
    Parameter type
    		 Median difference (final values)
    Point estimate
    -6
    Confidence interval
         level
    		 99%
         sides
    2-sided
         lower limit
    		 -10
         upper limit
    		 -3
    Statistical analysis title
    		 Median difference
    Comparison groups
    Ibuprofen plus dexamthasone v Paracetamol plus dexatmethasone
    Number of subjects included in analysis
    524
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.033
    Method
    		 Hodges-Lehmann
    Parameter type
    		 Median difference (final values)
    Point estimate
    -2
    Confidence interval
         level
    		 99%
         sides
    2-sided
         lower limit
    		 -6
         upper limit
    		 0
    Statistical analysis title
    		 Median difference
    Comparison groups
    Ibuprofen plus dexamthasone v Paracetamol plus Ibuprofen
    Number of subjects included in analysis
    523
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001
    Method
    		 Hodges-Lehmann
    Parameter type
    		 Median difference (final values)
    Point estimate
    -4.5
    Confidence interval
         level
    		 99%
         sides
    2-sided
         lower limit
    		 -8
         upper limit
    		 -2
    Statistical analysis title
    		 Median difference
    Comparison groups
    Paracetamol plus dexatmethasone v Paracetamol plus Ibuprofen
    Number of subjects included in analysis
    523
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.13
    Method
    		 Hodges-Lehmann
    Parameter type
    		 Median difference (final values)
    Point estimate
    -2
    Confidence interval
         level
    		 99%
         sides
    2-sided
         lower limit
    		 -6
         upper limit
    		 2

    Secondary: Adverse events, 0 to 24 h postoperatively

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    End point title
    		 Adverse events, 0 to 24 h postoperatively
    End point description
    End point type
    Secondary
    End point timeframe
    0 to 24 hours postoperatively
    End point values
    		 Paracetamol plus ibuprofen plus dexamthesone Ibuprofen plus dexamthasone Paracetamol plus dexatmethasone Paracetamol plus Ibuprofen
    Number of subjects analysed
    258
    262
    262
    261
    Units: events
    91
    99
    103
    165
    Statistical analysis title
    		 Relative Risk
    Comparison groups
    Paracetamol plus ibuprofen plus dexamthesone v Ibuprofen plus dexamthasone
    Number of subjects included in analysis
    520
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.55
    Method
    		 Regression, Linear
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    0.93
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.73
         upper limit
    		 1.14
    Statistical analysis title
    		 Relative Risk
    Comparison groups
    Paracetamol plus ibuprofen plus dexamthesone v Paracetamol plus dexatmethasone
    Number of subjects included in analysis
    520
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.34
    Method
    		 Regression, Linear
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    0.89
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.73
         upper limit
    		 1.15
    Statistical analysis title
    		 Relative Risk
    Comparison groups
    Paracetamol plus ibuprofen plus dexamthesone v Paracetamol plus Ibuprofen
    Number of subjects included in analysis
    519
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001
    Method
    		 Regression, Linear
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    0.56
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.45
         upper limit
    		 0.66
    Statistical analysis title
    		 Relative Risk
    Comparison groups
    Ibuprofen plus dexamthasone v Paracetamol plus dexatmethasone
    Number of subjects included in analysis
    524
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.73
    Method
    		 Regression, Linear
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    0.96
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.79
         upper limit
    		 1.22
    Statistical analysis title
    		 Relative Risk
    Comparison groups
    Ibuprofen plus dexamthasone v Paracetamol plus Ibuprofen
    Number of subjects included in analysis
    523
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001
    Method
    		 Regression, Linear
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    0.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.5
         upper limit
    		 0.7
    Statistical analysis title
    		 Relative Risk
    Comparison groups
    Paracetamol plus Ibuprofen v Paracetamol plus dexatmethasone
    Number of subjects included in analysis
    523
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.13
    Method
    		 Regression, Linear
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    0.62
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.51
         upper limit
    		 0.73

    Secondary: Pain at rest 24 hours postoperatively

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    End point title
    		 Pain at rest 24 hours postoperatively
    End point description
    End point type
    Secondary
    End point timeframe
    24 hours postoperatively
    End point values
    		 Paracetamol plus ibuprofen plus dexamthesone Ibuprofen plus dexamthasone Paracetamol plus dexatmethasone Paracetamol plus Ibuprofen
    Number of subjects analysed
    258
    262
    262
    261
    Units: millimetre(s)
        median (inter-quartile range (Q1-Q3))
    10 (1 to 20)
    12 (0 to 28)
    13 (1 to 25)
    12 (1 to 25)
    Statistical analysis title
    		 Pairwise comparisons between the median pain score
    Comparison groups
    Paracetamol plus ibuprofen plus dexamthesone v Ibuprofen plus dexamthasone
    Number of subjects included in analysis
    520
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.2
    Method
    		 Hodges-Lehmann
    Parameter type
    		 Median difference (final values)
    Point estimate
    0
    Confidence interval
         level
    		 99%
         sides
    2-sided
         lower limit
    		 -5
         upper limit
    		 0
    Statistical analysis title
    		 Pairwise comparisons between the median pain score
    Comparison groups
    Paracetamol plus ibuprofen plus dexamthesone v Paracetamol plus dexatmethasone
    Number of subjects included in analysis
    520
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.1
    Method
    		 Hodges-Lehmann
    Parameter type
    		 Median difference (final values)
    Point estimate
    0
    Confidence interval
         level
    		 99%
         sides
    2-sided
         lower limit
    		 -5
         upper limit
    		 0
    Statistical analysis title
    		 Pairwise comparisons between the median pain score
    Comparison groups
    Paracetamol plus ibuprofen plus dexamthesone v Paracetamol plus Ibuprofen
    Number of subjects included in analysis
    519
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.14
    Method
    		 Hodges-Lehmann
    Parameter type
    		 Median difference (final values)
    Point estimate
    0
    Confidence interval
         level
    		 99%
         sides
    2-sided
         lower limit
    		 -5
         upper limit
    		 0
    Statistical analysis title
    		 Pairwise comparisons between the median pain score
    Comparison groups
    Paracetamol plus dexatmethasone v Ibuprofen plus dexamthasone
    Number of subjects included in analysis
    524
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.72
    Method
    		 Hodges-Lehmann
    Parameter type
    		 Median difference (final values)
    Point estimate
    0
    Confidence interval
         level
    		 99%
         sides
    2-sided
         lower limit
    		 -2
         upper limit
    		 1
    Statistical analysis title
    		 Pairwise comparisons between the median pain score
    Comparison groups
    Ibuprofen plus dexamthasone v Paracetamol plus Ibuprofen
    Number of subjects included in analysis
    523
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.72
    Method
    		 Hodges-Lehmann
    Parameter type
    		 Median difference (final values)
    Point estimate
    0
    Confidence interval
         level
    		 99%
         sides
    2-sided
         lower limit
    		 -2
         upper limit
    		 1
    Statistical analysis title
    		 Pairwise comparisons between the median
    Comparison groups
    Paracetamol plus Ibuprofen v Paracetamol plus dexatmethasone
    Number of subjects included in analysis
    523
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.92
    Method
    		 Hodges-Lehmann
    Parameter type
    		 Median difference (final values)
    Point estimate
    0
    Confidence interval
         level
    		 99%
         sides
    2-sided
         lower limit
    		 -2
         upper limit
    		 2

    Secondary: Pain during mobilisation at 24 h postoperatively

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    End point title
    		 Pain during mobilisation at 24 h postoperatively
    End point description
    End point type
    Secondary
    End point timeframe
    24 hours postoperatively
    End point values
    		 Paracetamol plus ibuprofen plus dexamthesone Ibuprofen plus dexamthasone Paracetamol plus dexatmethasone Paracetamol plus Ibuprofen
    Number of subjects analysed
    258
    262
    262
    261
    Units: millimetre(s)
        median (inter-quartile range (Q1-Q3))
    31 (18 to 50)
    32 (18 to 50)
    40 (20 to 60)
    43 (27 to 65)
    Statistical analysis title
    		 Pairwise comparisons pain score mobilisation
    Comparison groups
    Paracetamol plus ibuprofen plus dexamthesone v Ibuprofen plus dexamthasone
    Number of subjects included in analysis
    520
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.5
    Method
    		 Hodges-Lehmann
    Parameter type
    		 Median difference (final values)
    Point estimate
    0
    Confidence interval
         level
    		 99%
         sides
    2-sided
         lower limit
    		 -6
         upper limit
    		 5
    Statistical analysis title
    		 Pairwise comparisons pain score mobilisation
    Comparison groups
    Paracetamol plus ibuprofen plus dexamthesone v Paracetamol plus dexatmethasone
    Number of subjects included in analysis
    520
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0031
    Method
    		 Hodges-Lehmann
    Parameter type
    		 Median difference (final values)
    Point estimate
    -6
    Confidence interval
         level
    		 99%
         sides
    2-sided
         lower limit
    		 -12
         upper limit
    		 0
    Statistical analysis title
    		 Pairwise comparisons pain score mobilisation
    Comparison groups
    Paracetamol plus ibuprofen plus dexamthesone v Paracetamol plus Ibuprofen
    Number of subjects included in analysis
    519
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001
    Method
    		 Hodges-Lehmann
    Parameter type
    		 Median difference (final values)
    Point estimate
    -10
    Confidence interval
         level
    		 99%
         sides
    2-sided
         lower limit
    		 -16
         upper limit
    		 -5
    Statistical analysis title
    		 Pairwise comparisons pain score mobilisation
    Comparison groups
    Ibuprofen plus dexamthasone v Paracetamol plus dexatmethasone
    Number of subjects included in analysis
    524
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.016
    Method
    		 Hodges-Lehmann
    Parameter type
    		 Median difference (final values)
    Point estimate
    -5
    Confidence interval
         level
    		 99%
         sides
    2-sided
         lower limit
    		 -10
         upper limit
    		 0
    Statistical analysis title
    		 Pairwise comparisons pain score mobilisation
    Comparison groups
    Ibuprofen plus dexamthasone v Paracetamol plus Ibuprofen
    Number of subjects included in analysis
    523
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001
    Method
    		 Hodges-Lehmann
    Parameter type
    		 Median difference (final values)
    Point estimate
    -10
    Confidence interval
         level
    		 99%
         sides
    2-sided
         lower limit
    		 -15
         upper limit
    		 -4
    Statistical analysis title
    		 Pairwise comparisons pain score mobilisation
    Comparison groups
    Paracetamol plus Ibuprofen v Paracetamol plus dexatmethasone
    Number of subjects included in analysis
    523
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.058
    Method
    		 Hodges-Lehmann
    Parameter type
    		 Median difference (final values)
    Point estimate
    -5
    Confidence interval
         level
    		 99%
         sides
    2-sided
         lower limit
    		 -10
         upper limit
    		 2

    Secondary: Maximum pain during 5 m walk

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    End point title
    		 Maximum pain during 5 m walk
    End point description
    End point type
    Secondary
    End point timeframe
    24 h postoperatively
    End point values
    		 Paracetamol plus ibuprofen plus dexamthesone Ibuprofen plus dexamthasone Paracetamol plus dexatmethasone Paracetamol plus Ibuprofen
    Number of subjects analysed
    258
    262
    262
    261
    Units: millimetre(s)
        median (inter-quartile range (Q1-Q3))
    27 (15 to 41)
    30 (16 to 46)
    35 (20 to 50)
    35 (20 to 51)
    Statistical analysis title
    		 Pairwise comparisons max pain score walk
    Comparison groups
    Paracetamol plus ibuprofen plus dexamthesone v Ibuprofen plus dexamthasone
    Number of subjects included in analysis
    520
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.13
    Method
    		 Hodges-Lehmann
    Parameter type
    		 Median difference (final values)
    Point estimate
    -3
    Confidence interval
         level
    		 99%
         sides
    2-sided
         lower limit
    		 -8
         upper limit
    		 2
    Statistical analysis title
    		 Pairwise comparisons max pain score walk
    Comparison groups
    Paracetamol plus ibuprofen plus dexamthesone v Paracetamol plus dexatmethasone
    Number of subjects included in analysis
    520
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.002
    Method
    		 Hodges-Lehmann
    Parameter type
    		 Median difference (final values)
    Point estimate
    -6
    Confidence interval
         level
    		 99%
         sides
    2-sided
         lower limit
    		 -12
         upper limit
    		 -1
    Statistical analysis title
    		 Pairwise comparisons max pain score walk
    Comparison groups
    Paracetamol plus ibuprofen plus dexamthesone v Paracetamol plus Ibuprofen
    Number of subjects included in analysis
    519
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001
    Method
    		 Hodges-Lehmann
    Parameter type
    		 Median difference (final values)
    Point estimate
    -9
    Confidence interval
         level
    		 99%
         sides
    2-sided
         lower limit
    		 -14
         upper limit
    		 3
    Statistical analysis title
    		 Pairwise comparisons max pain score walk
    Comparison groups
    Ibuprofen plus dexamthasone v Paracetamol plus dexatmethasone
    Number of subjects included in analysis
    524
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.078
    Method
    		 Hodges-Lehmann
    Parameter type
    		 Median difference (final values)
    Point estimate
    -3
    Confidence interval
         level
    		 99%
         sides
    2-sided
         lower limit
    		 -9
         upper limit
    		 2
    Statistical analysis title
    		 Pairwise comparisons max pain score walk
    Comparison groups
    Ibuprofen plus dexamthasone v Paracetamol plus Ibuprofen
    Number of subjects included in analysis
    523
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.016
    Method
    		 Hodges-Lehmann
    Parameter type
    		 Median difference (final values)
    Point estimate
    -5
    Confidence interval
         level
    		 99%
         sides
    2-sided
         lower limit
    		 -10
         upper limit
    		 0
    Statistical analysis title
    		 Copy of Pairwise comparisons max pain score walk
    Comparison groups
    Paracetamol plus Ibuprofen v Paracetamol plus dexatmethasone
    Number of subjects included in analysis
    523
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.37
    Method
    		 Hodges-Lehmann
    Parameter type
    		 Median difference (final values)
    Point estimate
    -2
    Confidence interval
         level
    		 99%
         sides
    2-sided
         lower limit
    		 -8
         upper limit
    		 4

    Other pre-specified: Pain at rest 6h

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    End point title
    		 Pain at rest 6h
    End point description
    End point type
    Other pre-specified
    End point timeframe
    6 hours postoperatively
    End point values
    		 Paracetamol plus ibuprofen plus dexamthesone Ibuprofen plus dexamthasone Paracetamol plus dexatmethasone Paracetamol plus Ibuprofen
    Number of subjects analysed
    258
    262
    262
    261
    Units: millimetre(s)
        median (inter-quartile range (Q1-Q3))
    16 (10 to 31)
    20 (8 to 30)
    25 (10 to 40)
    29 (11 to 48)
    Statistical analysis title
    		 Pairwise comparisons pain rest 6h
    Comparison groups
    Paracetamol plus ibuprofen plus dexamthesone v Ibuprofen plus dexamthasone
    Number of subjects included in analysis
    520
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.73
    Method
    		 Hodges-Lehmann
    Parameter type
    		 Median difference (final values)
    Point estimate
    0
    Confidence interval
         level
    		 99%
         sides
    2-sided
         lower limit
    		 -4
         upper limit
    		 3
    Statistical analysis title
    		 Pairwise comparisons pain rest 6h
    Comparison groups
    Paracetamol plus ibuprofen plus dexamthesone v Paracetamol plus dexatmethasone
    Number of subjects included in analysis
    520
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0076
    Method
    		 Hodges-Lehmann
    Parameter type
    		 Median difference (final values)
    Point estimate
    -5
    Confidence interval
         level
    		 99%
         sides
    2-sided
         lower limit
    		 -10
         upper limit
    		 0
    Statistical analysis title
    		 Pairwise comparisons pain rest 6h
    Comparison groups
    Paracetamol plus ibuprofen plus dexamthesone v Paracetamol plus Ibuprofen
    Number of subjects included in analysis
    519
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001
    Method
    		 Hodges-Lehmann
    Parameter type
    		 Median difference (final values)
    Point estimate
    -10
    Confidence interval
         level
    		 99%
         sides
    2-sided
         lower limit
    		 -14
         upper limit
    		 -4
    Statistical analysis title
    		 Pairwise comparisons pain rest 6h
    Comparison groups
    Ibuprofen plus dexamthasone v Paracetamol plus dexatmethasone
    Number of subjects included in analysis
    524
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0048
    Method
    		 Hodges-Lehmann
    Parameter type
    		 Median difference (final values)
    Point estimate
    -5
    Confidence interval
         level
    		 99%
         sides
    2-sided
         lower limit
    		 -10
         upper limit
    		 0
    Statistical analysis title
    		 Pairwise comparisons pain rest 6h
    Comparison groups
    Ibuprofen plus dexamthasone v Paracetamol plus Ibuprofen
    Number of subjects included in analysis
    523
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001
    Method
    		 Hodges-Lehmann
    Parameter type
    		 Median difference (final values)
    Point estimate
    -10
    Confidence interval
         level
    		 99%
         sides
    2-sided
         lower limit
    		 -14
         upper limit
    		 -4
    Statistical analysis title
    		 Pairwise comparisons pain rest 6h
    Comparison groups
    Paracetamol plus Ibuprofen v Paracetamol plus dexatmethasone
    Number of subjects included in analysis
    523
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.032
    Method
    		 Hodges-Lehmann
    Parameter type
    		 Median difference (final values)
    Point estimate
    -4
    Confidence interval
         level
    		 99%
         sides
    2-sided
         lower limit
    		 -10
         upper limit
    		 0

    Other pre-specified: Pain during mobilisation, 6 h

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    End point title
    		 Pain during mobilisation, 6 h
    End point description
    End point type
    Other pre-specified
    End point timeframe
    6 hours postoperatively
    End point values
    		 Paracetamol plus ibuprofen plus dexamthesone Ibuprofen plus dexamthasone Paracetamol plus dexatmethasone Paracetamol plus Ibuprofen
    Number of subjects analysed
    258
    262
    262
    261
    Units: millimetre(s)
        median (inter-quartile range (Q1-Q3))
    30 (15 to 51)
    30 (15 to 50)
    37 (20 to 55)
    48 (25 to 69)
    Statistical analysis title
    		 Pairwise comparisons pain mobilisation 6h
    Comparison groups
    Paracetamol plus ibuprofen plus dexamthesone v Ibuprofen plus dexamthasone
    Number of subjects included in analysis
    520
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.32
    Method
    		 Hodges-Lehmann
    Parameter type
    		 Median difference (final values)
    Point estimate
    0
    Confidence interval
         level
    		 99%
         sides
    2-sided
         lower limit
    		 -5
         upper limit
    		 7
    Statistical analysis title
    		 Pairwise comparisons pain mobilisation 6h
    Comparison groups
    Paracetamol plus ibuprofen plus dexamthesone v Paracetamol plus dexatmethasone
    Number of subjects included in analysis
    520
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.1
    Method
    		 Hodges-Lehmann
    Parameter type
    		 Median difference (final values)
    Point estimate
    -5
    Confidence interval
         level
    		 99%
         sides
    2-sided
         lower limit
    		 -10
         upper limit
    		 1
    Statistical analysis title
    		 Pairwise comparisons pain mobilisation 6h
    Comparison groups
    Paracetamol plus ibuprofen plus dexamthesone v Paracetamol plus Ibuprofen
    Number of subjects included in analysis
    519
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001
    Method
    		 Hodges-Lehmann
    Parameter type
    		 Median difference (final values)
    Point estimate
    -13
    Confidence interval
         level
    		 99%
         sides
    2-sided
         lower limit
    		 -20
         upper limit
    		 -6
    Statistical analysis title
    		 Pairwise comparisons pain mobilisation 6h
    Comparison groups
    Ibuprofen plus dexamthasone v Paracetamol plus dexatmethasone
    Number of subjects included in analysis
    524
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.02
    Method
    		 Hodges-Lehmann
    Parameter type
    		 Median difference (final values)
    Point estimate
    -5
    Confidence interval
         level
    		 99%
         sides
    2-sided
         lower limit
    		 -11
         upper limit
    		 0
    Statistical analysis title
    		 Pairwise comparisons pain mobilisation 6h
    Comparison groups
    Ibuprofen plus dexamthasone v Paracetamol plus Ibuprofen
    Number of subjects included in analysis
    523
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001
    Method
    		 Hodges-Lehmann
    Parameter type
    		 Median difference (final values)
    Point estimate
    -15
    Confidence interval
         level
    		 99%
         sides
    2-sided
         lower limit
    		 -20
         upper limit
    		 -8
    Statistical analysis title
    		 Pairwise comparisons pain mobilisation 6h
    Comparison groups
    Paracetamol plus Ibuprofen v Paracetamol plus dexatmethasone
    Number of subjects included in analysis
    523
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001
    Method
    		 Hodges-Lehmann
    Parameter type
    		 Median difference (final values)
    Point estimate
    -9
    Confidence interval
         level
    		 99%
         sides
    2-sided
         lower limit
    		 -15
         upper limit
    		 -2

    Other pre-specified: Nausea, 6 h

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    End point title
    		 Nausea, 6 h
    End point description
    End point type
    Other pre-specified
    End point timeframe
    6 hours postoperatively
    End point values
    		 Paracetamol plus ibuprofen plus dexamthesone Ibuprofen plus dexamthasone Paracetamol plus dexatmethasone Paracetamol plus Ibuprofen
    Number of subjects analysed
    248
    251
    244
    243
    Units: patients
    21
    19
    23
    49
    Statistical analysis title
    		 Relative Risk Nausea 6h
    Comparison groups
    Paracetamol plus ibuprofen plus dexamthesone v Ibuprofen plus dexamthasone
    Number of subjects included in analysis
    499
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.71
    Method
    		 Regression, Linear
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    1.11
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.46
         upper limit
    		 1.78
    Statistical analysis title
    		 Relative Risk Nausea 6h
    Comparison groups
    Paracetamol plus ibuprofen plus dexamthesone v Paracetamol plus dexatmethasone
    Number of subjects included in analysis
    492
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.68
    Method
    		 Regression, Linear
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    0.89
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.56
         upper limit
    		 2.02
    Statistical analysis title
    		 Relative Risk Nausea 6h
    Comparison groups
    Paracetamol plus ibuprofen plus dexamthesone v Paracetamol plus Ibuprofen
    Number of subjects included in analysis
    491
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001
    Method
    		 Regression, Linear
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    0.43
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.23
         upper limit
    		 0.63
    Statistical analysis title
    		 Relative Risk Nausea 6h
    Comparison groups
    Ibuprofen plus dexamthasone v Paracetamol plus dexatmethasone
    Number of subjects included in analysis
    495
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.041
    Method
    		 Regression, Linear
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    0.79
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.5
         upper limit
    		 1.83
    Statistical analysis title
    		 Relative Risk Nausea 6h
    Comparison groups
    Ibuprofen plus dexamthasone v Paracetamol plus Ibuprofen
    Number of subjects included in analysis
    494
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001
    Method
    		 Regression, Linear
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    0.38
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.19
         upper limit
    		 0.57
    Statistical analysis title
    		 Relative Risk Nausea 6h
    Comparison groups
    Paracetamol plus Ibuprofen v Paracetamol plus dexatmethasone
    Number of subjects included in analysis
    487
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0012
    Method
    		 Regression, Linear
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    0.47
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.26
         upper limit
    		 0.69

    Other pre-specified: Nausea 24 h

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    End point title
    		 Nausea 24 h
    End point description
    End point type
    Other pre-specified
    End point timeframe
    24 hours postoperatively
    End point values
    		 Paracetamol plus ibuprofen plus dexamthesone Ibuprofen plus dexamthasone Paracetamol plus dexatmethasone Paracetamol plus Ibuprofen
    Number of subjects analysed
    256
    261
    257
    257
    Units: patients
    49
    68
    70
    125
    Statistical analysis title
    		 Relative Risk Nausea 24h
    Comparison groups
    Paracetamol plus ibuprofen plus dexamthesone v Ibuprofen plus dexamthasone
    Number of subjects included in analysis
    517
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.058
    Method
    		 Regression, Linear
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    0.74
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.5
         upper limit
    		 0.97
    Statistical analysis title
    		 Relative Risk Nausea 24h
    Comparison groups
    Paracetamol plus ibuprofen plus dexamthesone v Paracetamol plus dexatmethasone
    Number of subjects included in analysis
    513
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.03
    Method
    		 Regression, Linear
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    0.71
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.54
         upper limit
    		 1.02
    Statistical analysis title
    		 Relative Risk Nausea 24h
    Comparison groups
    Paracetamol plus ibuprofen plus dexamthesone v Paracetamol plus Ibuprofen
    Number of subjects included in analysis
    513
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001
    Method
    		 Regression, Linear
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    0.39
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.28
         upper limit
    		 0.5
    Statistical analysis title
    		 Relative Risk Nausea 24h
    Comparison groups
    Ibuprofen plus dexamthasone v Paracetamol plus dexatmethasone
    Number of subjects included in analysis
    518
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.76
    Method
    		 Regression, Linear
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    0.96
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.75
         upper limit
    		 1.33
    Statistical analysis title
    		 Relative Risk Nausea 24h
    Comparison groups
    Ibuprofen plus dexamthasone v Paracetamol plus Ibuprofen
    Number of subjects included in analysis
    518
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001
    Method
    		 Regression, Linear
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    0.54
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.41
         upper limit
    		 0.67
    Statistical analysis title
    		 Relative Risk Nausea 24h
    Comparison groups
    Paracetamol plus Ibuprofen v Paracetamol plus dexatmethasone
    Number of subjects included in analysis
    514
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001
    Method
    		 Regression, Linear
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    0.56
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.43
         upper limit
    		 0.69

    Other pre-specified: Vomiting 0-24 h

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    End point title
    		 Vomiting 0-24 h
    End point description
    End point type
    Other pre-specified
    End point timeframe
    0 to 24 hours postoperatively
    End point values
    		 Paracetamol plus ibuprofen plus dexamthesone Ibuprofen plus dexamthasone Paracetamol plus dexatmethasone Paracetamol plus Ibuprofen
    Number of subjects analysed
    256
    261
    255
    257
    Units: patients
    23
    29
    33
    81
    Statistical analysis title
    		 Relative Risk Vomiting 0-24h
    Comparison groups
    Paracetamol plus ibuprofen plus dexamthesone v Ibuprofen plus dexamthasone
    Number of subjects included in analysis
    517
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.42
    Method
    		 Regression, Linear
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    0.81
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.39
         upper limit
    		 1.22
    Statistical analysis title
    		 Relative Risk Vomiting 0-24h
    Comparison groups
    Paracetamol plus ibuprofen plus dexamthesone v Paracetamol plus dexatmethasone
    Number of subjects included in analysis
    511
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.16
    Method
    		 Regression, Linear
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    0.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.47
         upper limit
    		 1.39
    Statistical analysis title
    		 Relative Risk Vomiting 0-24h
    Comparison groups
    Paracetamol plus ibuprofen plus dexamthesone v Paracetamol plus Ibuprofen
    Number of subjects included in analysis
    513
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001
    Method
    		 Regression, Linear
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    0.28
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.16
         upper limit
    		 0.41
    Statistical analysis title
    		 Relative Risk Vomiting 0-24h
    Comparison groups
    Ibuprofen plus dexamthasone v Paracetamol plus dexatmethasone
    Number of subjects included in analysis
    516
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.52
    Method
    		 Regression, Linear
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    0.86
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.59
         upper limit
    		 1.6
    Statistical analysis title
    		 Relative Risk Vomiting 0-24h
    Comparison groups
    Ibuprofen plus dexamthasone v Paracetamol plus Ibuprofen
    Number of subjects included in analysis
    518
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001
    Method
    		 Regression, Linear
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    0.35
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.22
         upper limit
    		 0.49
    Statistical analysis title
    		 Relative Risk Vomiting 0-24h
    Comparison groups
    Paracetamol plus Ibuprofen v Paracetamol plus dexatmethasone
    Number of subjects included in analysis
    512
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001
    Method
    		 Regression, Linear
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    0.41
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.26
         upper limit
    		 0.56

    Other pre-specified: Dizziness walk test, 24 h

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    End point title
    		 Dizziness walk test, 24 h
    End point description
    End point type
    Other pre-specified
    End point timeframe
    24 hours postoperatively
    End point values
    		 Paracetamol plus ibuprofen plus dexamthesone Ibuprofen plus dexamthasone Paracetamol plus dexatmethasone Paracetamol plus Ibuprofen
    Number of subjects analysed
    233
    237
    230
    221
    Units: Patients
    27
    33
    25
    48
    Statistical analysis title
    		 Relative Risk Dizziness walk test 24h
    Comparison groups
    Paracetamol plus ibuprofen plus dexamthesone v Ibuprofen plus dexamthasone
    Number of subjects included in analysis
    470
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.47
    Method
    		 Regression, Linear
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    0.84
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.45
         upper limit
    		 1.23
    Statistical analysis title
    		 Relative Risk Dizziness walk test 24h
    Comparison groups
    Paracetamol plus ibuprofen plus dexamthesone v Paracetamol plus dexatmethasone
    Number of subjects included in analysis
    463
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.78
    Method
    		 Regression, Linear
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    1.07
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.71
         upper limit
    		 2.18
    Statistical analysis title
    		 Relative Risk Dizziness walk test 24h
    Comparison groups
    Paracetamol plus ibuprofen plus dexamthesone v Paracetamol plus Ibuprofen
    Number of subjects included in analysis
    454
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0042
    Method
    		 Regression, Linear
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    0.54
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.31
         upper limit
    		 0.77
    Statistical analysis title
    		 Relative Risk Dizziness walk test 24h
    Comparison groups
    Ibuprofen plus dexamthasone v Paracetamol plus dexatmethasone
    Number of subjects included in analysis
    467
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.34
    Method
    		 Regression, Linear
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    1.27
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.85
         upper limit
    		 2.46
    Statistical analysis title
    		 Relative Risk Dizziness walk test 24h
    Comparison groups
    Ibuprofen plus dexamthasone v Paracetamol plus Ibuprofen
    Number of subjects included in analysis
    458
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.029
    Method
    		 Regression, Linear
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    0.64
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.39
         upper limit
    		 0.9
    Statistical analysis title
    		 Relative Risk Dizziness walk test 24h
    Comparison groups
    Paracetamol plus Ibuprofen v Paracetamol plus dexatmethasone
    Number of subjects included in analysis
    451
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0023
    Method
    		 Regression, Linear
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    0.51
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.29
         upper limit
    		 0.73

    Other pre-specified: Anti–emetic use, 0–24 h

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    End point title
    		 Anti–emetic use, 0–24 h
    End point description
    End point type
    Other pre-specified
    End point timeframe
    0 to 24 hours postoperatively
    End point values
    		 Paracetamol plus ibuprofen plus dexamthesone Ibuprofen plus dexamthasone Paracetamol plus dexatmethasone Paracetamol plus Ibuprofen
    Number of subjects analysed
    257
    261
    261
    263
    Units: patients
    36
    49
    65
    95
    Statistical analysis title
    		 Relative Risk Anti-emetic use
    Comparison groups
    Paracetamol plus ibuprofen plus dexamthesone v Ibuprofen plus dexamthasone
    Number of subjects included in analysis
    518
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.13
    Method
    		 Regression, Linear
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    0.74
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.45
         upper limit
    		 1.03
    Statistical analysis title
    		 Relative Risk Anti-emetic use
    Comparison groups
    Paracetamol plus ibuprofen plus dexamthesone v Paracetamol plus dexatmethasone
    Number of subjects included in analysis
    518
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0017
    Method
    		 Regression, Linear
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    0.56
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.41
         upper limit
    		 0.89
    Statistical analysis title
    		 Relative Risk Anti-emetic use
    Comparison groups
    Paracetamol plus ibuprofen plus dexamthesone v Paracetamol plus Ibuprofen
    Number of subjects included in analysis
    520
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001
    Method
    		 Regression, Linear
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    0.38
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.25
         upper limit
    		 0.51
    Statistical analysis title
    		 Relative Risk Anti-emetic use
    Comparison groups
    Ibuprofen plus dexamthasone v Paracetamol plus dexatmethasone
    Number of subjects included in analysis
    522
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.089
    Method
    		 Regression, Linear
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    0.76
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.57
         upper limit
    		 1.12
    Statistical analysis title
    		 Relative Risk Anti-emetic use
    Comparison groups
    Ibuprofen plus dexamthasone v Paracetamol plus Ibuprofen
    Number of subjects included in analysis
    524
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001
    Method
    		 Regression, Linear
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    0.52
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.37
         upper limit
    		 0.67
    Statistical analysis title
    		 Relative Risk Anti-emetic use
    Comparison groups
    Paracetamol plus Ibuprofen v Paracetamol plus dexatmethasone
    Number of subjects included in analysis
    524
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0037
    Method
    		 Regression, Linear
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    0.68
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.5
         upper limit
    		 0.86

    Other pre-specified: Sleep quality

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    End point title
    		 Sleep quality
    End point description
    VAS 0-100, 0 worst to 100 best.
    End point type
    Other pre-specified
    End point timeframe
    24 hours postoperatively
    End point values
    		 Paracetamol plus ibuprofen plus dexamthesone Ibuprofen plus dexamthasone Paracetamol plus dexatmethasone Paracetamol plus Ibuprofen
    Number of subjects analysed
    258
    262
    262
    261
    Units: millimetre(s)
        median (inter-quartile range (Q1-Q3))
    50 (30 to 79)
    50 (30 to 80)
    50 (30 to 75)
    58 (40 to 80)
    Statistical analysis title
    		 Median difference sleep quality
    Comparison groups
    Paracetamol plus ibuprofen plus dexamthesone v Ibuprofen plus dexamthasone
    Number of subjects included in analysis
    520
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.65
    Method
    		 Hodges-Lehmann
    Parameter type
    		 Median difference (final values)
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -5
         upper limit
    		 4
    Statistical analysis title
    		 Median difference sleep quality
    Comparison groups
    Paracetamol plus ibuprofen plus dexamthesone v Paracetamol plus dexatmethasone
    Number of subjects included in analysis
    520
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.5
    Method
    		 Hodges-Lehmann
    Parameter type
    		 Median difference (final values)
    Point estimate
    1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3
         upper limit
    		 6
    Statistical analysis title
    		 Median difference sleep quality
    Comparison groups
    Paracetamol plus ibuprofen plus dexamthesone v Paracetamol plus Ibuprofen
    Number of subjects included in analysis
    519
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.51
    Method
    		 Hodges-Lehmann
    Parameter type
    		 Median difference (final values)
    Point estimate
    -5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -10
         upper limit
    		 0
    Statistical analysis title
    		 Median difference sleep quality
    Comparison groups
    Ibuprofen plus dexamthasone v Paracetamol plus dexatmethasone
    Number of subjects included in analysis
    524
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.27
    Method
    		 Hodges-Lehmann
    Parameter type
    		 Median difference (final values)
    Point estimate
    2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2
         upper limit
    		 8
    Statistical analysis title
    		 Median difference sleep quality
    Comparison groups
    Ibuprofen plus dexamthasone v Paracetamol plus Ibuprofen
    Number of subjects included in analysis
    523
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.1
    Method
    		 Hodges-Lehmann
    Parameter type
    		 Median difference (final values)
    Point estimate
    -4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -10
         upper limit
    		 0
    Statistical analysis title
    		 Median difference sleep quality
    Comparison groups
    Paracetamol plus Ibuprofen v Paracetamol plus dexatmethasone
    Number of subjects included in analysis
    523
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0073
    Method
    		 Hodges-Lehmann
    Parameter type
    		 Median difference (final values)
    Point estimate
    -6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -11
         upper limit
    		 -1

    Other pre-specified: Intra–operative blood loss

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    End point title
    		 Intra–operative blood loss
    End point description
    End point type
    Other pre-specified
    End point timeframe
    Intra-operative blood loss
    End point values
    		 Paracetamol plus ibuprofen plus dexamthesone Ibuprofen plus dexamthasone Paracetamol plus dexatmethasone Paracetamol plus Ibuprofen
    Number of subjects analysed
    258
    262
    262
    261
    Units: millilitre(s)
        median (inter-quartile range (Q1-Q3))
    300 (200 to 450)
    300 (200 to 440)
    250 (175 to 400)
    300 (200 to 500)
    Statistical analysis title
    		 Median difference blood loss
    Comparison groups
    Paracetamol plus ibuprofen plus dexamthesone v Ibuprofen plus dexamthasone
    Number of subjects included in analysis
    520
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.77
    Method
    		 Hodges-Lehmann
    Parameter type
    		 Median difference (net)
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -10
         upper limit
    		 50
    Statistical analysis title
    		 Median difference blood loss
    Comparison groups
    Paracetamol plus ibuprofen plus dexamthesone v Paracetamol plus dexatmethasone
    Number of subjects included in analysis
    520
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.13
    Method
    		 Hodges-Lehmann
    Parameter type
    		 Median difference (net)
    Point estimate
    20
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0
         upper limit
    		 50
    Statistical analysis title
    		 Median difference blood loss
    Comparison groups
    Paracetamol plus ibuprofen plus dexamthesone v Paracetamol plus Ibuprofen
    Number of subjects included in analysis
    519
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.26
    Method
    		 Hodges-Lehmann
    Parameter type
    		 Median difference (net)
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -50
         upper limit
    		 0
    Statistical analysis title
    		 Median difference blood loss
    Comparison groups
    Ibuprofen plus dexamthasone v Paracetamol plus dexatmethasone
    Number of subjects included in analysis
    524
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.044
    Method
    		 Hodges-Lehmann
    Parameter type
    		 Median difference (net)
    Point estimate
    40
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0
         upper limit
    		 60
    Statistical analysis title
    		 Median difference blood loss
    Comparison groups
    Ibuprofen plus dexamthasone v Paracetamol plus Ibuprofen
    Number of subjects included in analysis
    523
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.46
    Method
    		 Hodges-Lehmann
    Parameter type
    		 Median difference (net)
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -50
         upper limit
    		 25
    Statistical analysis title
    		 Median difference blood loss
    Comparison groups
    Paracetamol plus Ibuprofen v Paracetamol plus dexatmethasone
    Number of subjects included in analysis
    523
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.011
    Method
    		 Hodges-Lehmann
    Parameter type
    		 Median difference (net)
    Point estimate
    -50
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -75
         upper limit
    		 0

    Other pre-specified: Serious adverse events within 90 days

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    End point title
    		 Serious adverse events within 90 days
    End point description
    End point type
    Other pre-specified
    End point timeframe
    Within 90 days postoperatively.
    End point values
    		 Paracetamol plus ibuprofen plus dexamthesone Ibuprofen plus dexamthasone Paracetamol plus dexatmethasone Paracetamol plus Ibuprofen
    Number of subjects analysed
    258
    262
    262
    261
    Units: patients
    20
    24
    31
    35
    Statistical analysis title
    		 Relative Risk Adverse events 90 days
    Comparison groups
    Paracetamol plus ibuprofen plus dexamthesone v Ibuprofen plus dexamthasone
    Number of subjects included in analysis
    520
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.58
    Method
    		 Regression, Linear
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    0.85
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.37
         upper limit
    		 1.33
    Statistical analysis title
    		 Relative Risk Adverse events 90 days
    Comparison groups
    Paracetamol plus ibuprofen plus dexamthesone v Paracetamol plus dexatmethasone
    Number of subjects included in analysis
    520
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.12
    Method
    		 Regression, Linear
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    0.66
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.43
         upper limit
    		 1.38
    Statistical analysis title
    		 Relative Risk Adverse events 90 days
    Comparison groups
    Paracetamol plus ibuprofen plus dexamthesone v Paracetamol plus Ibuprofen
    Number of subjects included in analysis
    519
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.036
    Method
    		 Regression, Linear
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    0.58
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.28
         upper limit
    		 0.88
    Statistical analysis title
    		 Relative Risk Adverse events 90 days
    Comparison groups
    Ibuprofen plus dexamthasone v Paracetamol plus dexatmethasone
    Number of subjects included in analysis
    524
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.32
    Method
    		 Regression, Linear
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    0.78
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.52
         upper limit
    		 1.54
    Statistical analysis title
    		 Relative Risk Adverse events 90 days
    Comparison groups
    Ibuprofen plus dexamthasone v Paracetamol plus Ibuprofen
    Number of subjects included in analysis
    523
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.12
    Method
    		 Regression, Linear
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    0.68
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.35
         upper limit
    		 1.01
    Statistical analysis title
    		 Relative Risk Adverse events 90 days
    Comparison groups
    Paracetamol plus Ibuprofen v Paracetamol plus dexatmethasone
    Number of subjects included in analysis
    523
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.55
    Method
    		 Regression, Linear
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    0.87
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.48
         upper limit
    		 1.26

    Other pre-specified: Oxford Hip Score at 90 days

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    End point title
    		 Oxford Hip Score at 90 days
    End point description
    End point type
    Other pre-specified
    End point timeframe
    90 days postoperatively
    End point values
    		 Paracetamol plus ibuprofen plus dexamthesone Ibuprofen plus dexamthasone Paracetamol plus dexatmethasone Paracetamol plus Ibuprofen
    Number of subjects analysed
    258
    262
    262
    261
    Units: points
        median (inter-quartile range (Q1-Q3))
    41 (36 to 450)
    41 (36 to 45)
    41 (34 to 45)
    42 (36 to 45)
    Statistical analysis title
    		 Median difference Oxford Hip Score
    Comparison groups
    Paracetamol plus ibuprofen plus dexamthesone v Ibuprofen plus dexamthasone
    Number of subjects included in analysis
    520
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.52
    Method
    		 Hodges-Lehmann
    Parameter type
    		 Median difference (final values)
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1
         upper limit
    		 1
    Statistical analysis title
    		 Median difference Oxford Hip Score
    Comparison groups
    Paracetamol plus ibuprofen plus dexamthesone v Paracetamol plus dexatmethasone
    Number of subjects included in analysis
    520
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.14
    Method
    		 Hodges-Lehmann
    Parameter type
    		 Median difference (final values)
    Point estimate
    1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0
         upper limit
    		 2
    Statistical analysis title
    		 Median difference Oxford Hip Score
    Comparison groups
    Paracetamol plus ibuprofen plus dexamthesone v Paracetamol plus Ibuprofen
    Number of subjects included in analysis
    519
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.99
    Method
    		 Hodges-Lehmann
    Parameter type
    		 Median difference (final values)
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1
         upper limit
    		 1
    Statistical analysis title
    		 Median difference Oxford Hip Score
    Comparison groups
    Ibuprofen plus dexamthasone v Paracetamol plus dexatmethasone
    Number of subjects included in analysis
    524
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.49
    Method
    		 Hodges-Lehmann
    Parameter type
    		 Median difference (final values)
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1
         upper limit
    		 2
    Statistical analysis title
    		 Median difference Oxford Hip Score
    Comparison groups
    Ibuprofen plus dexamthasone v Paracetamol plus Ibuprofen
    Number of subjects included in analysis
    523
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.74
    Method
    		 Hodges-Lehmann
    Parameter type
    		 Median difference (final values)
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1
         upper limit
    		 1
    Statistical analysis title
    		 Median difference Oxford Hip Score
    Comparison groups
    Paracetamol plus Ibuprofen v Paracetamol plus dexatmethasone
    Number of subjects included in analysis
    523
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.34
    Method
    		 Hodges-Lehmann
    Parameter type
    		 Median difference (final values)
    Point estimate
    -1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2
         upper limit
    		 0

    Other pre-specified: EQ5D5L index score

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    End point title
    		 EQ5D5L index score
    End point description
    End point type
    Other pre-specified
    End point timeframe
    90 days postoperatively
    End point values
    		 Paracetamol plus ibuprofen plus dexamthesone Ibuprofen plus dexamthasone Paracetamol plus dexatmethasone Paracetamol plus Ibuprofen
    Number of subjects analysed
    258
    262
    262
    261
    Units: score
        median (inter-quartile range (Q1-Q3))
    0.93 (0.87 to 1)
    0.93 (0.88 to 1)
    0.93 (0.87 to 1)
    0.93 (0.87 to 1)
    Statistical analysis title
    		 Median difference EQ5D5L index score
    Comparison groups
    Paracetamol plus ibuprofen plus dexamthesone v Ibuprofen plus dexamthasone
    Number of subjects included in analysis
    520
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.78
    Method
    		 Hodges-Lehmann
    Parameter type
    		 Median difference (final values)
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.004
         upper limit
    		 0
    Statistical analysis title
    		 Median difference EQ5D5L index score
    Comparison groups
    Paracetamol plus ibuprofen plus dexamthesone v Paracetamol plus dexatmethasone
    Number of subjects included in analysis
    520
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.68
    Method
    		 Hodges-Lehmann
    Parameter type
    		 Median difference (final values)
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0
         upper limit
    		 0.005
    Statistical analysis title
    		 Median difference EQ5D5L index score
    Comparison groups
    Paracetamol plus ibuprofen plus dexamthesone v Paracetamol plus Ibuprofen
    Number of subjects included in analysis
    519
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.77
    Method
    		 Hodges-Lehmann
    Parameter type
    		 Median difference (final values)
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0
         upper limit
    		 0
    Statistical analysis title
    		 Median difference EQ5D5L index score
    Comparison groups
    Ibuprofen plus dexamthasone v Paracetamol plus dexatmethasone
    Number of subjects included in analysis
    524
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.56
    Method
    		 Hodges-Lehmann
    Parameter type
    		 Median difference (final values)
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0
         upper limit
    		 0.008
    Statistical analysis title
    		 Median difference EQ5D5L index score
    Comparison groups
    Ibuprofen plus dexamthasone v Paracetamol plus Ibuprofen
    Number of subjects included in analysis
    523
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.58
    Method
    		 Hodges-Lehmann
    Parameter type
    		 Median difference (final values)
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0
         upper limit
    		 0.004
    Statistical analysis title
    		 Median difference EQ5D5L index score
    Comparison groups
    Paracetamol plus Ibuprofen v Paracetamol plus dexatmethasone
    Number of subjects included in analysis
    523
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.91
    Method
    		 Hodges-Lehmann
    Parameter type
    		 Median difference (final values)
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0
         upper limit
    		 0.002

    Other pre-specified: EQ5D5L VAS score 90 days

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    End point title
    		 EQ5D5L VAS score 90 days
    End point description
    End point type
    Other pre-specified
    End point timeframe
    90 days postoperatively
    End point values
    		 Paracetamol plus ibuprofen plus dexamthesone Ibuprofen plus dexamthasone Paracetamol plus dexatmethasone Paracetamol plus Ibuprofen
    Number of subjects analysed
    258
    262
    262
    261
    Units: millimetre(s)
        median (inter-quartile range (Q1-Q3))
    85 (75 to 90)
    85 (75 to 90)
    85 (75 to 90)
    85 (75 to 90)
    Statistical analysis title
    		 Median difference EQ5D5L VAS score
    Comparison groups
    Paracetamol plus ibuprofen plus dexamthesone v Ibuprofen plus dexamthasone
    Number of subjects included in analysis
    520
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.71
    Method
    		 Hodges-Lehmann
    Parameter type
    		 Median difference (final values)
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0
         upper limit
    		 3
    Statistical analysis title
    		 Median difference EQ5D5L VAS score
    Comparison groups
    Paracetamol plus ibuprofen plus dexamthesone v Paracetamol plus dexatmethasone
    Number of subjects included in analysis
    520
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.75
    Method
    		 Hodges-Lehmann
    Parameter type
    		 Median difference (final values)
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0
         upper limit
    		 2
    Statistical analysis title
    		 Median difference EQ5D5L VAS score
    Comparison groups
    Paracetamol plus ibuprofen plus dexamthesone v Paracetamol plus Ibuprofen
    Number of subjects included in analysis
    519
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.59
    Method
    		 Hodges-Lehmann
    Parameter type
    		 Median difference (final values)
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0
         upper limit
    		 3
    Statistical analysis title
    		 Median difference EQ5D5L VAS score
    Comparison groups
    Ibuprofen plus dexamthasone v Paracetamol plus dexatmethasone
    Number of subjects included in analysis
    524
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.48
    Method
    		 Hodges-Lehmann
    Parameter type
    		 Median difference (final values)
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0
         upper limit
    		 5
    Statistical analysis title
    		 Median difference EQ5D5L VAS score
    Comparison groups
    Ibuprofen plus dexamthasone v Paracetamol plus Ibuprofen
    Number of subjects included in analysis
    523
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.86
    Method
    		 Hodges-Lehmann
    Parameter type
    		 Median difference (final values)
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0
         upper limit
    		 0
    Statistical analysis title
    		 Median difference EQ5D5L VAS score
    Comparison groups
    Paracetamol plus Ibuprofen v Paracetamol plus dexatmethasone
    Number of subjects included in analysis
    523
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.46
    Method
    		 Hodges-Lehmann
    Parameter type
    		 Median difference (final values)
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -5
         upper limit
    		 0

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    0 to 24 hours postoperatively
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 ICH-GCP
    Dictionary version
    Revision 2
    Reporting groups
    Reporting group title
    Paracetamol plus ibuprofen plus dexamthesone
    Reporting group description
    		 Oral paracetamol 1000 mg plus oral ibuprofen 400 mg plus single-dose intravenous dexamethasone 24 mg. The first dose of oral medication was given as premedication 1 h before surgery. The three remaining doses were continued postoperatively with 6 h intervals until 24 h postoperatively. The intravenous medication was given immediately after the onset of spinal anaesthesia or after the induction of general anaesthesia.

    Reporting group title
    Ibuprofen plus dexamthasone
    Reporting group description
    		 Oral ibuprofen 400 mg plus single-dose intravenous dexamethasone 24 mg plus placebo matching paracetamol.

    Reporting group title
    Paracetamol plus dexatmethasone
    Reporting group description
    		 Oral paracetamol 1000 mg plus single-dose intravenous dexamethasone 24 mg plus placebo matching ibuprofen.

    Reporting group title
    Paracetamol plus Ibuprofen
    Reporting group description
    		 Oral paracetamol 1000 mg plus oral ibuprofen 400 mg plus placebo matching dexamethasone.

    Serious adverse events
    		 Paracetamol plus ibuprofen plus dexamthesone Ibuprofen plus dexamthasone Paracetamol plus dexatmethasone Paracetamol plus Ibuprofen
    Total subjects affected by serious adverse events
         subjects affected / exposed
    6 / 258 (2.33%)
    5 / 262 (1.91%)
    3 / 262 (1.15%)
    13 / 261 (4.98%)
         number of deaths (all causes)
    0
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    0
    Cardiac disorders
    Cardiac arrhythmia
         subjects affected / exposed
    0 / 258 (0.00%)
    0 / 262 (0.00%)
    1 / 262 (0.38%)
    0 / 261 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haemodynamic instability
         subjects affected / exposed
    1 / 258 (0.39%)
    0 / 262 (0.00%)
    0 / 262 (0.00%)
    1 / 261 (0.38%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Surgical and medical procedures
    Complete and incomplete prosthetic dislocation
         subjects affected / exposed
    1 / 258 (0.39%)
    1 / 262 (0.38%)
    1 / 262 (0.38%)
    1 / 261 (0.38%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Neuropathic pain
         subjects affected / exposed
    0 / 258 (0.00%)
    0 / 262 (0.00%)
    0 / 262 (0.00%)
    1 / 261 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Drop foot
         subjects affected / exposed
    0 / 258 (0.00%)
    1 / 262 (0.38%)
    0 / 262 (0.00%)
    1 / 261 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Worsening of known symptoms from previous critical illness
         subjects affected / exposed
    0 / 258 (0.00%)
    0 / 262 (0.00%)
    0 / 262 (0.00%)
    1 / 261 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hospitalisation 4 or more days
         subjects affected / exposed
    3 / 258 (1.16%)
    3 / 262 (1.15%)
    1 / 262 (0.38%)
    7 / 261 (2.68%)
         occurrences causally related to treatment / all
    3 / 3
    3 / 3
    1 / 1
    7 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Respiratory failure
         subjects affected / exposed
    1 / 258 (0.39%)
    0 / 262 (0.00%)
    0 / 262 (0.00%)
    0 / 261 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Renal failure
         subjects affected / exposed
    0 / 258 (0.00%)
    0 / 262 (0.00%)
    0 / 262 (0.00%)
    1 / 261 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 1%
    Non-serious adverse events
    		 Paracetamol plus ibuprofen plus dexamthesone Ibuprofen plus dexamthasone Paracetamol plus dexatmethasone Paracetamol plus Ibuprofen
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    122 / 258 (47.29%)
    150 / 262 (57.25%)
    167 / 262 (63.74%)
    248 / 261 (95.02%)
    Cardiac disorders
    Vasovagal episode or syncope
         subjects affected / exposed
    8 / 258 (3.10%)
    1 / 262 (0.38%)
    5 / 262 (1.91%)
    5 / 261 (1.92%)
         occurrences all number
    8
    1
    5
    5
    Cardiac arrhythmia
         subjects affected / exposed
    1 / 258 (0.39%)
    0 / 262 (0.00%)
    1 / 262 (0.38%)
    1 / 261 (0.38%)
         occurrences all number
    1
    0
    1
    1
    Hypotensive episode
         subjects affected / exposed
    0 / 258 (0.00%)
    1 / 262 (0.38%)
    1 / 262 (0.38%)
    3 / 261 (1.15%)
         occurrences all number
    0
    1
    1
    3
    Surgical and medical procedures
    Blood transfusion
         subjects affected / exposed
    0 / 258 (0.00%)
    2 / 262 (0.76%)
    4 / 262 (1.53%)
    1 / 261 (0.38%)
         occurrences all number
    0
    2
    4
    1
    Blood oozing from surgical wound
         subjects affected / exposed
    0 / 258 (0.00%)
    1 / 262 (0.38%)
    2 / 262 (0.76%)
    0 / 261 (0.00%)
         occurrences all number
    0
    1
    2
    0
    Perioperative fracture
         subjects affected / exposed
    1 / 258 (0.39%)
    0 / 262 (0.00%)
    2 / 262 (0.76%)
    3 / 261 (1.15%)
         occurrences all number
    1
    0
    2
    3
    Haematoma
         subjects affected / exposed
    1 / 258 (0.39%)
    0 / 262 (0.00%)
    0 / 262 (0.00%)
    0 / 261 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Nervous system disorders
    Dizziness during 5 m walk
         subjects affected / exposed
    27 / 258 (10.47%)
    33 / 262 (12.60%)
    25 / 262 (9.54%)
    48 / 261 (18.39%)
         occurrences all number
    27
    33
    25
    48
    Confusion
         subjects affected / exposed
    1 / 258 (0.39%)
    1 / 262 (0.38%)
    1 / 262 (0.38%)
    1 / 261 (0.38%)
         occurrences all number
    1
    1
    1
    1
    Delirium
         subjects affected / exposed
    0 / 258 (0.00%)
    0 / 262 (0.00%)
    0 / 262 (0.00%)
    1 / 261 (0.38%)
         occurrences all number
    0
    0
    0
    1
    Worsening of known neurologic symptoms
         subjects affected / exposed
    0 / 258 (0.00%)
    1 / 262 (0.38%)
    0 / 262 (0.00%)
    0 / 261 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Pain and logistics
         subjects affected / exposed
    0 / 258 (0.00%)
    0 / 262 (0.00%)
    0 / 262 (0.00%)
    1 / 261 (0.38%)
         occurrences all number
    0
    0
    0
    1
    Paraesthesia
         subjects affected / exposed
    0 / 258 (0.00%)
    0 / 262 (0.00%)
    1 / 262 (0.38%)
    0 / 261 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Blood and lymphatic system disorders
    Non-surgical drop in hemoglobin level
         subjects affected / exposed
    0 / 258 (0.00%)
    0 / 262 (0.00%)
    1 / 262 (0.38%)
    0 / 261 (0.00%)
         occurrences all number
    0
    0
    0
    0
    General disorders and administration site conditions
    Delayed mobilisation or discharge
         subjects affected / exposed
    2 / 258 (0.78%)
    7 / 262 (2.67%)
    8 / 262 (3.05%)
    9 / 261 (3.45%)
         occurrences all number
    2
    7
    8
    9
    Immune system disorders
    Urticaria
         subjects affected / exposed
    0 / 258 (0.00%)
    0 / 262 (0.00%)
    4 / 262 (1.53%)
    1 / 261 (0.38%)
         occurrences all number
    0
    0
    4
    1
    Gastrointestinal disorders
    Nausea
         subjects affected / exposed
    57 / 258 (22.09%)
    70 / 262 (26.72%)
    75 / 262 (28.63%)
    133 / 261 (50.96%)
         occurrences all number
    57
    70
    75
    133
    Vomiting
         subjects affected / exposed
    23 / 258 (8.91%)
    29 / 262 (11.07%)
    34 / 262 (12.98%)
    81 / 261 (31.03%)
         occurrences all number
    23
    29
    34
    81
    Stomach discomfort or pain
         subjects affected / exposed
    0 / 258 (0.00%)
    1 / 262 (0.38%)
    0 / 262 (0.00%)
    2 / 261 (0.77%)
         occurrences all number
    0
    1
    0
    2
    Respiratory, thoracic and mediastinal disorders
    Pneumonia
         subjects affected / exposed
    0 / 258 (0.00%)
    1 / 262 (0.38%)
    0 / 262 (0.00%)
    0 / 261 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Desaturation
         subjects affected / exposed
    0 / 258 (0.00%)
    1 / 262 (0.38%)
    0 / 262 (0.00%)
    0 / 261 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Renal and urinary disorders
    Impaired kidney function
         subjects affected / exposed
    1 / 258 (0.39%)
    0 / 262 (0.00%)
    2 / 262 (0.76%)
    2 / 261 (0.77%)
         occurrences all number
    1
    0
    2
    2
    Urinary infection
         subjects affected / exposed
    0 / 258 (0.00%)
    1 / 262 (0.38%)
    1 / 262 (0.38%)
    0 / 261 (0.00%)
         occurrences all number
    0
    1
    1
    0
    Urinary retention
         subjects affected / exposed
    0 / 258 (0.00%)
    0 / 262 (0.00%)
    0 / 262 (0.00%)
    1 / 261 (0.38%)
         occurrences all number
    0
    0
    0
    1

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? No

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

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

    Online references
    http://www.ncbi.nlm.nih.gov/pubmed/38458208
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