Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   43871   clinical trials with a EudraCT protocol, of which   7290   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Download PDF

    Clinical Trial Results:
    A randomised controlled trial of a Synthetic Osmotic cervical dilator for induction of Labour in comparison to dinoprostone Vaginal insErt (SOLVE trial)

    Summary
    EudraCT number
    		 2016-004726-42
    Trial protocol
    		 GB  
    Global end of trial date
    06 Feb 2021

    Results information
    Results version number
    		 v1(current)
    This version publication date
    28 Oct 2021
    First version publication date
    28 Oct 2021
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    17/BW/MAT/PO14
    Additional study identifiers
    ISRCTN number
    		 ISRCTN20131893
    US NCT number
    		 NCT03001661
    WHO universal trial number (UTN)
    		 U1111-1189-2757
    Sponsors
    Sponsor organisation name
    Birmingham Women's and Children's NHS Foundation Trust
    Sponsor organisation address
    Steelhouse Lane, Birmingham, United Kingdom, B4 6NH
    Public contact
    Amanda Cotterill, Birmingham Clinical Trials Unit, University of Birmingham, +44 7795303779, a.cotterill.2@bham.ac.uk
    Scientific contact
    Amanda Cotterill, Birmingham Clinical Trials Unit, University of Birmingham, +44 7795303779, a.cotterill.2@bham.ac.uk
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    01 Apr 2021
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    06 Feb 2021
    Global end of trial reached?
    Yes
    Global end of trial date
    06 Feb 2021
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    To evaluate the effectiveness of the synthetic osmotic cervical dilator in cervical ripening, for IoL, in comparison to dinoprostone vaginal insert to achieve vaginal delivery.
    Protection of trial subjects
    Trial patients were treated as in normal clinical practice where the insertion of the Dilapan devices was done in a comfortable position, usually on labour ward and legs in lithotomy position. Entonox was given if required for relaxing the women. There was also the availability of analgesia if required.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    01 Feb 2017
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    United Kingdom: 674
    Worldwide total number of subjects
    674
    EEA total number of subjects
    0
    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)
    8
    Adults (18-64 years)
    666
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 Open to recruitment on 19th December 2017 Suspended 18th March 2020 Re-opened on 17th September 2020: after COVID lockdown restrictions were lifted Closed to recruitment on 27th January 2021: due to further COVID restrictions Study ended 6th February 2021 Recruitment target 860 Actual recruitment figure 674 Shortfall of 186 recruit

    Pre-assignment
    Screening details
    		 Any adult female who has a singleton pregnancy greater than 37 weeks and is deemed suitable for both mechanical and pharmacological induction of labour will be eligible for inclusion. 8364 were screened for the SOLVE trial, of these 674 were randomised.

    Period 1
    Period 1 title
    Baseline (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded
    Blinding implementation details
    N/A

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Dilapan-S
    Arm description
    		 DILAPAN-S® is a class IIa medical device. The device is CE marked and available on the market for use wherever cervical softening and dilation are desired.
    Arm type
    		 Experimental

    Investigational medicinal product name
    DILAPAN-S
    Investigational medicinal product code
    CO3_DSPlen-RevG_09_2019-03
    Other name
    Dilapan
    Pharmaceutical forms
    Endocervical gel
    Routes of administration
    Endocervical use
    Dosage and administration details
    First series of Dilapan-S inserted at Baseline. Removed and second series inserted up to a maximum of 24 hours after baseline. Second series removed up to a maximum of 24 hours after insertion i.e. each series was up to 24 hours duration

    Arm title
    		 Dinoprostone
    Arm description
    		 Slow release 10 mg vaginal drug delivery system (Prostaglandin E2)
    Arm type
    		 Active comparator

    Investigational medicinal product name
    DINOPROSTONE
    Investigational medicinal product code
    Product code 135 (taken from SmPc)?
    Other name
    Propess, Prostaglandin E2
    Pharmaceutical forms
    Pessary, Vaginal delivery system, Vaginal tablet
    Routes of administration
    Vaginal use
    Dosage and administration details
    First series of DINOPROSTONE (10mg) inserted at baseline. Removed up to a maximum of 24 hours after baseline. Second series inserted (10mg) + further 24 hours. This will include any timeframe given in local policies between the 1st and 2nd series for DINOPROSTONE as these may vary At least 30 minutes should elapse between removal of DINOPROSTONE vaginal insert and initiation of oxytocin therapy.

    Number of subjects in period 1
    		Dilapan-S Dinoprostone
    Started
    337
    337
    Have primary outcome data
    337
    335
    Completed
    337
    335
    Not completed
    0
    2
         Not eligible - randomised in error
    -
    2

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Dilapan-S
    Reporting group description
    		 DILAPAN-S® is a class IIa medical device. The device is CE marked and available on the market for use wherever cervical softening and dilation are desired.

    Reporting group title
    Dinoprostone
    Reporting group description
    		 Slow release 10 mg vaginal drug delivery system (Prostaglandin E2)

    Reporting group values
    		 Dilapan-S Dinoprostone Total
    Number of subjects
    		 337 337 674
    Age categorical
    Units: Subjects
        <20
    		 19 19 38
        20 to <30
    		 148 150 298
        30 to <40
    		 149 147 296
        40+
    		 21 21 42
    Age continuous
    Maternal age
    Units: years
        arithmetic mean (standard deviation)
    		 30.0 ( 6.1 ) 29.9 ( 6.2 ) -
    Gender categorical
    Units: Subjects
        Female
    		 337 337 674
        Male
    		 0 0 0
    Maternal obesity at first antenatal visit
    Units: Subjects
        BMI <30
    		 221 219 440
        BMI >= 30
    		 116 118 234
    Parity
    Units: Subjects
        Nulliparous
    		 269 272 541
        Multiparous
    		 68 65 133
    Ethnicity
    Units: Subjects
        White (British/Irish/other)
    		 223 228 451
        Black/Black British (Caribbean/African/other)
    		 33 19 52
        Asian/Asian British (Indian/Pakistani/other)
    		 60 63 123
        Mixed (White/Black/Asian/other)
    		 6 7 13
        Other
    		 14 16 30
        Declined to give information
    		 1 1 2
        Missing
    		 0 3 3
    Post-term pregnancy
    Units: Subjects
        Yes
    		 120 133 253
        No
    		 217 202 419
        Missing
    		 0 2 2
    Intrauterine growth restriction/oligohydramnios
    Units: Subjects
        Yes
    		 75 57 132
        No
    		 262 278 540
        Missing
    		 0 2 2
    Reduced fetal movement
    Units: Subjects
        Yes
    		 73 57 130
        No
    		 264 278 542
        Missing
    		 0 2 2
    Diabetes mellitus/ gestational diabetes
    Units: Subjects
        Yes
    		 52 45 97
        No
    		 285 290 575
        Missing
    		 0 2 2
    Large for gestational age
    Units: Subjects
        Yes
    		 42 44 86
        No
    		 295 291 586
        Missing
    		 0 2 2
    Pre-eclampsia
    Units: Subjects
        Yes
    		 13 18 31
        No
    		 324 317 641
        Missing
    		 0 2 2
    Gestational hypertension
    Units: Subjects
        Yes
    		 13 11 24
        No
    		 324 324 648
        Missing
    		 0 2 2
    Small for gestational age
    Units: Subjects
        Yes
    		 16 8 24
        No
    		 321 327 648
        Missing
    		 0 2 2
    Maternal age
    Units: Subjects
        Yes
    		 11 11 22
        No
    		 326 324 650
        Missing
    		 0 2 2
    Low PAPP-A
    Units: Subjects
        Yes
    		 10 7 17
        No
    		 327 328 655
        Missing
    		 0 2 2
    Maternal hepatic disease
    Units: Subjects
        Yes
    		 4 3 7
        No
    		 333 332 665
        Missing
    		 0 2 2
    Elected by mother
    Units: Subjects
        Yes
    		 3 4 7
        No
    		 334 331 665
        Missing
    		 0 2 2
    Rhesus isoimmunisation /increasing antibody titre
    Units: Subjects
        Yes
    		 4 1 5
        No
    		 333 334 667
        Missing
    		 0 2 2
    Maternal renal disease
    Units: Subjects
        Yes
    		 2 2 4
        No
    		 335 333 668
        Missing
    		 0 2 2
    Previous miscarriages
    Units: Subjects
        None
    		 248 254 502
        ≥ 1
    		 89 81 170
        Missing
    		 0 2 2
    Previous termination of pregnancies
    Units: Subjects
        None
    		 292 300 592
        ≥ 1
    		 45 35 80
        Missing
    		 0 2 2
    Previous deliveries >24 weeks
    Units: Subjects
        No
    		 268 270 538
        Yes
    		 69 65 134
        Missing
    		 0 2 2
    Presence of risk factor for GBS
    Units: Subjects
        Yes
    		 25 31 56
        No
    		 312 304 616
        Missing
    		 0 2 2
    Bishop score on initiation of cervical ripening ≥ 6
    Units: Subjects
        Yes
    		 53 49 102
        No
    		 284 287 571
        Missing
    		 0 1 1
    Randomising centre
    Units: Subjects
        Birmingham Women’s Hospital
    		 234 236 470
        City Hospital Birmingham
    		 30 33 63
        Heartlands
    		 35 34 69
        Princess Royal Hospital Telford
    		 38 34 72
    BMI
    BMI continous
    Units: kilogram(s)/square meter
        arithmetic mean (standard deviation)
    		 28.4 ( 6.6 ) 28.1 ( 6.6 ) -
    Weight at booking antenatal visit
    Units: kilogram(s)
        arithmetic mean (standard deviation)
    		 76.4 ( 19.3 ) 75.2 ( 18.5 ) -
    Height
    Units: centimeter
        arithmetic mean (standard deviation)
    		 164.0 ( 7.1 ) 163.6 ( 6.7 ) -

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Dilapan-S
    Reporting group description
    		 DILAPAN-S® is a class IIa medical device. The device is CE marked and available on the market for use wherever cervical softening and dilation are desired.

    Reporting group title
    Dinoprostone
    Reporting group description
    		 Slow release 10 mg vaginal drug delivery system (Prostaglandin E2)

    Primary: Primary: Failure to achieve vaginal delivery (caesarean section)

    		 Close Top of page
    End point title
    		 Primary: Failure to achieve vaginal delivery (caesarean section)
    End point description
    Where ‘Yes’ indicates a caesarean section or a vaginal delivery after the time frame specified
    End point type
    Primary
    End point timeframe
    Baseline / birth
    End point values
    		 Dilapan-S Dinoprostone
    Number of subjects analysed
    337
    335 [1]
    Units: Binary (Yes/ No)
        Yes
    126
    115
        No
    211
    220
    Notes
    [1] - 2 women are missing primary outcome data
    Statistical analysis title
    		 Failure to achieve vaginal delivery
    Statistical analysis description
    Risk ratio is estimated using a binomial model with a log link adjusting for age, BMI and parity as fixed effects, where DINOPROSTONE is the reference category and a risk ratio value <1 favours DILAPAN-S.
    Comparison groups
    Dilapan-S v Dinoprostone
    Number of subjects included in analysis
    672
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.33
    Method
    		 Regression, Logistic
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    1.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.9
         upper limit
    		 1.35

    Secondary: Secondary: Change in bishop score from baseline to completion of cervical ripening

    		 Close Top of page
    End point title
    		 Secondary: Change in bishop score from baseline to completion of cervical ripening
    End point description
    End point type
    Secondary
    End point timeframe
    Baseline / birth
    End point values
    		 Dilapan-S Dinoprostone
    Number of subjects analysed
    276 [2]
    282 [3]
    Units: Bishop score
        arithmetic mean (standard deviation)
    3.2 ( 2.3 )
    3.6 ( 2.7 )
    Notes
    [2] - 61 women were missing outcome data
    [3] - 55 women do not have outcome data
    Statistical analysis title
    		 Change in bishop score from baseline to completion
    Statistical analysis description
    Mean differences < 0 favour DILAPAN-S Mean difference is estimated using a mixed effects linear regression adjusted for Bishop score in addition to minimisation variables (age, BMI and parity) and randomising centre as a random effect.
    Comparison groups
    Dilapan-S v Dinoprostone
    Number of subjects included in analysis
    558
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.003
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -0.54
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.9
         upper limit
    		 -0.18

    Secondary: Secondary: Time between Bishop scores measured at baseline and completion of cervical ripening (hours)

    		 Close Top of page
    End point title
    		 Secondary: Time between Bishop scores measured at baseline and completion of cervical ripening (hours)
    End point description
    End point type
    Secondary
    End point timeframe
    Baseline / birth
    End point values
    		 Dilapan-S Dinoprostone
    Number of subjects analysed
    287 [4]
    282 [5]
    Units: hour
        arithmetic mean (standard deviation)
    30.5 ( 28.7 )
    30.6 ( 23.5 )
    Notes
    [4] - 50 missing outcome
    [5] - 45 missing outcome
    Statistical analysis title
    		 Time between Bishop scores
    Statistical analysis description
    The geometric mean indicates the central tendency or typical value of a set of numbers by using the product of their values (as opposed to the arithmetic mean which uses their sum) and is used for summarising skewed data. Comparative analysis uses a ratio of the geometric means. Geometric mean ratios <1 favour DILAPAN-S®. The geometric mean ratio is estimated using a mixed effect linear regression adjusted for minimisation variables and randomising centre as a random effect
    Comparison groups
    Dilapan-S v Dinoprostone
    Number of subjects included in analysis
    569
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.987
    Method
    		 Mixed models analysis
    Parameter type
    		 Geometric mean ratio
    Point estimate
    0.99
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.87
         upper limit
    		 1.15

    Secondary: Secondary: Use of analgesia during cervical ripening

    		 Close Top of page
    End point title
    		 Secondary: Use of analgesia during cervical ripening
    End point description
    End point type
    Secondary
    End point timeframe
    Baseline / birth
    End point values
    		 Dilapan-S Dinoprostone
    Number of subjects analysed
    332 [6]
    332 [7]
    Units: Binary (Yes/No)
        Yes
    170
    220
        No
    162
    112
    Notes
    [6] - 5 women are missing outcome data
    [7] - 5 women are missing outcome data
    Statistical analysis title
    		 Use of analgesia during cervical ripening
    Statistical analysis description
    DINOPROSTONE is the reference category and risk ratio values <1 favour DILAPAN-S. Risk ratio is estimated using a binomial model with a log link adjusting for age, BMI and parity as fixed effects.
    Comparison groups
    Dilapan-S v Dinoprostone
    Number of subjects included in analysis
    664
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Regression, Logistic
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    0.77
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.67
         upper limit
    		 0.87

    Secondary: Secondary: Time between randomisation and start of analgesia use for cervical ripening

    		 Close Top of page
    End point title
    		 Secondary: Time between randomisation and start of analgesia use for cervical ripening
    End point description
    End point type
    Secondary
    End point timeframe
    Baseline / birth
    End point values
    		 Dilapan-S Dinoprostone
    Number of subjects analysed
    167 [8]
    219 [9]
    Units: hour
        arithmetic mean (standard deviation)
    15.0 ( 24.5 )
    15.3 ( 14.1 )
    Notes
    [8] - 8 women are missing outcome data 162 women did not use analgesia
    [9] - 6 women are missing outcome data 112 women did not use analgesia
    Statistical analysis title
    		 Time between randomisation and start of analgesia
    Statistical analysis description
    The geometric mean indicates the central tendency or typical value of a set of numbers by using the product of their values (as opposed to the arithmetic mean which uses their sum) and is used for summarising skewed data. Comparative analysis uses a ratio of the geometric means. Geometric mean ratios <1 favour DILAPAN-S®. The geometric mean ratio is estimated using a mixed effect linear regression adjusted for minimisation variables and randomising centre as a random effect
    Comparison groups
    Dilapan-S v Dinoprostone
    Number of subjects included in analysis
    386
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001
    Method
    		 Mixed models analysis
    Parameter type
    		 Geometric mean ratio
    Point estimate
    0.49
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.38
         upper limit
    		 0.62

    Secondary: Secondary: Any complications during cervical ripening

    		 Close Top of page
    End point title
    		 Secondary: Any complications during cervical ripening
    End point description
    End point type
    Secondary
    End point timeframe
    Baseline / birth
    End point values
    		 Dilapan-S Dinoprostone
    Number of subjects analysed
    333 [10]
    327 [11]
    Units: Binary (Yes/No)
        Yes
    35
    66
        No
    298
    261
    Notes
    [10] - 4 women are missing outcome data
    [11] - 10 women are missing outcome data
    Statistical analysis title
    		 Any complications during cervical ripening
    Statistical analysis description
    DINOPROSTONE is the reference category and risk ratio values <1 favour DILAPAN-S. Risk ratio is estimated using a mixed poisson model with a log link adjusting for age, BMI and parity as fixed effects, and randomising centre as a random effect.
    Comparison groups
    Dinoprostone v Dilapan-S
    Number of subjects included in analysis
    660
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.002
    Method
    		 Mixed models analysis
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    0.52
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.35
         upper limit
    		 0.79

    Secondary: Secondary: Time between removal of last series of intervention to amniotomy

    		 Close Top of page
    End point title
    		 Secondary: Time between removal of last series of intervention to amniotomy
    End point description
    Amniotomy undertaken for induction of labour only.
    End point type
    Secondary
    End point timeframe
    Baseline / birth
    End point values
    		 Dilapan-S Dinoprostone
    Number of subjects analysed
    203 [12]
    118 [13]
    Units: hour
        arithmetic mean (standard deviation)
    30.3 ( 28.6 )
    30.9 ( 35.7 )
    Notes
    [12] - 34 women missing outcome data. 100 women did not have amniotomy for induction performed
    [13] - 29 women are missing outcome data 190 women did not have amniotomy for induction performed
    Statistical analysis title
    		 Time between removal of last series to amniotomy
    Statistical analysis description
    The geometric mean indicates the central tendency or typical value of a set of numbers by using the product of their values (as opposed to the arithmetic mean which uses their sum) and is used for summarising skewed data. Comparative analysis uses a ratio of the geometric means. Geometric mean ratios <1 favour DILAPAN-S®. The geometric mean ratio is estimated using a mixed effect linear regression adjusted for minimisation variables and randomising centre as a random effect
    Comparison groups
    Dilapan-S v Dinoprostone
    Number of subjects included in analysis
    321
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.633
    Method
    		 Mixed models analysis
    Parameter type
    		 Geometric mean ratio
    Point estimate
    1.08
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.78
         upper limit
    		 1.49

    Secondary: Secondary: Time between first insertion of intervention to when labour started

    		 Close Top of page
    End point title
    		 Secondary: Time between first insertion of intervention to when labour started
    End point description
    End point type
    Secondary
    End point timeframe
    Baseline / birth
    End point values
    		 Dilapan-S Dinoprostone
    Number of subjects analysed
    257 [14]
    258 [15]
    Units: hour
        arithmetic mean (standard deviation)
    54.8 ( 33.8 )
    48.1 ( 37.9 )
    Notes
    [14] - 80 women missing outcome data
    [15] - 79 women missing outcome data
    Statistical analysis title
    		 Time between insertion of intervention to labour
    Statistical analysis description
    The geometric mean indicates the central tendency or typical value of a set of numbers by using the product of their values (as opposed to the arithmetic mean which uses their sum) and is used for summarising skewed data. Comparative analysis uses a ratio of the geometric means. Geometric mean ratios <1 favour DILAPAN-S®. The geometric mean ratio is estimated using a mixed effect linear regression adjusted for minimisation variables and randomising centre as a random effect
    Comparison groups
    Dilapan-S v Dinoprostone
    Number of subjects included in analysis
    515
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001
    Method
    		 Mixed models analysis
    Parameter type
    		 Geometric mean ratio
    Point estimate
    1.34
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.19
         upper limit
    		 1.52

    Secondary: Secondary: Amniotomy undertaken for induction of labour

    		 Close Top of page
    End point title
    		 Secondary: Amniotomy undertaken for induction of labour
    End point description
    End point type
    Secondary
    End point timeframe
    Baseline / birth
    End point values
    		 Dilapan-S Dinoprostone
    Number of subjects analysed
    335 [16]
    331 [17]
    Units: Binary (Yes/No)
        Yes
    235
    141
        No
    100
    190
    Notes
    [16] - 2 women are missing outcome data
    [17] - 6 women are missing outcome data
    Statistical analysis title
    		 Amniotomy undertaken for induction of labour
    Statistical analysis description
    DINOPROSTONE is the reference category and risk ratio values <1 favour DILAPAN-S. Risk ratio is estimated using a binomial model with a log link adjusting for age, BMI and parity as fixed effects.
    Comparison groups
    Dilapan-S v Dinoprostone
    Number of subjects included in analysis
    666
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001
    Method
    		 Regression, Logistic
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    1.64
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.43
         upper limit
    		 1.89

    Secondary: Secondary: Amniotomy undertaken for augmentation of labour

    		 Close Top of page
    End point title
    		 Secondary: Amniotomy undertaken for augmentation of labour
    End point description
    End point type
    Secondary
    End point timeframe
    Induction of labour process
    End point values
    		 Dilapan-S Dinoprostone
    Number of subjects analysed
    336 [18]
    331 [19]
    Units: Binary (Yes/No)
        Yes
    15
    25
        No
    321
    306
    Notes
    [18] - 1 woman is missing outcome data
    [19] - 6 women are missing outcome data
    Statistical analysis title
    		 Amniotomy undertaken for augmentation of labour
    Statistical analysis description
    DINOPROSTONE is the reference category and risk ratio values <1 favour DILAPAN-S. Risk ratio is estimated using a mixed binomial model with a log link adjusting for age, BMI and parity and randomising centre as a random effect.
    Comparison groups
    Dilapan-S v Dinoprostone
    Number of subjects included in analysis
    667
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.088
    Method
    		 Mixed models analysis
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    0.58
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.31
         upper limit
    		 1.08

    Secondary: Secondary: Required oxytocin for induction of labour

    		 Close Top of page
    End point title
    		 Secondary: Required oxytocin for induction of labour
    End point description
    End point type
    Secondary
    End point timeframe
    Induction of labour process
    End point values
    		 Dilapan-S Dinoprostone
    Number of subjects analysed
    335 [20]
    331 [21]
    Units: Binary (Yes/No)
        Yes
    210
    130
        No
    125
    201
    Notes
    [20] - 2 women are missing outcome data
    [21] - 6 women are missing outcome data
    Statistical analysis title
    		 Required oxytocin for induction of labour
    Statistical analysis description
    DINOPROSTONE is the reference category and risk ratio values <1 favour DILAPAN-S. Risk ratio is estimated using a mixed binomial model with a log link adjusting for age, BMI and parity and randomising centre as a random effect.
    Comparison groups
    Dilapan-S v Dinoprostone
    Number of subjects included in analysis
    666
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001
    Method
    		 Mixed models analysis
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    1.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.28
         upper limit
    		 1.99

    Secondary: Secondary: Required oxytocin for augmentation of labour

    		 Close Top of page
    End point title
    		 Secondary: Required oxytocin for augmentation of labour
    End point description
    End point type
    Secondary
    End point timeframe
    Baseline / birth
    End point values
    		 Dilapan-S Dinoprostone
    Number of subjects analysed
    336 [22]
    331 [23]
    Units: Binary (Yes/No)
        Yes
    25
    43
        No
    311
    288
    Notes
    [22] - 1 women is missing outcome data
    [23] - 6 women are missing outcome data
    Statistical analysis title
    		 Required oxytocin for augmentation of labour
    Statistical analysis description
    DINOPROSTONE is the reference category and risk ratio values <1 favour DILAPAN-S. Risk ratio is estimated using a binomial model with a log link adjusting for age, BMI and parity as fixed effects.
    Comparison groups
    Dilapan-S v Dinoprostone
    Number of subjects included in analysis
    667
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.019
    Method
    		 Regression, Logistic
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    0.57
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.36
         upper limit
    		 0.91

    Secondary: Secondary: Use of analgesia/anaesthesia during labour

    		 Close Top of page
    End point title
    		 Secondary: Use of analgesia/anaesthesia during labour
    End point description
    End point type
    Secondary
    End point timeframe
    Baseline / birth
    End point values
    		 Dilapan-S Dinoprostone
    Number of subjects analysed
    334 [24]
    333 [25]
    Units: Binary (Yes/No)
        Yes
    299
    278
        No
    35
    55
    Notes
    [24] - 3 women are missing outcome data
    [25] - 4 women are missing outcome data
    Statistical analysis title
    		 Use of analgesia / anaesthesia during labour
    Statistical analysis description
    DINOPROSTONE is the reference category and risk ratio values <1 favour DILAPAN-S. Risk ratio is estimated using a binomial model with a log link adjusting for age, BMI and parity as fixed effects.
    Comparison groups
    Dilapan-S v Dinoprostone
    Number of subjects included in analysis
    667
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.021 [26]
    Method
    		 Regression, Logistic
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    1.07
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.01
         upper limit
    		 1.13
    Notes
    [26] - DINOPROSTONE is the reference category and risk differences < 0 favour DILAPAN-S®. Risk ratio is estimated using a binomial model with a log link adjusting for age, BMI and parity as fixed effects.

    Secondary: Secondary: Any complications during or after labour

    		 Close Top of page
    End point title
    		 Secondary: Any complications during or after labour
    End point description
    End point type
    Secondary
    End point timeframe
    Baseline / birth
    End point values
    		 Dilapan-S Dinoprostone
    Number of subjects analysed
    337
    335 [27]
    Units: Binary (Yes/No)
        Yes
    249
    244
        No
    88
    91
    Notes
    [27] - 2 women are missing outcome data
    Statistical analysis title
    		 Any complications during or after labour
    Statistical analysis description
    DINOPROSTONE is the reference category and risk ratio values <1 favour DILAPAN-S. Risk ratio is estimated using a binomial model with a log link adjusting for age, BMI and parity as fixed effects.
    Comparison groups
    Dilapan-S v Dinoprostone
    Number of subjects included in analysis
    672
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.931 [28]
    Method
    		 Regression, Logistic
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.92
         upper limit
    		 1.1
    Notes
    [28] - DINOPROSTONE is the reference category and risk differences < 0 favour DILAPAN-S®. Risk ratio is estimated using a binomial model with a log link adjusting for age, BMI and parity as fixed effects.

    Secondary: Secondary: Failure to achieve vaginal delivery within 24 hours from randomisation

    		 Close Top of page
    End point title
    		 Secondary: Failure to achieve vaginal delivery within 24 hours from randomisation
    End point description
    Where ‘Yes’ indicates a caesarean section or a vaginal delivery after the time frame specified
    End point type
    Secondary
    End point timeframe
    Baseline / birth
    End point values
    		 Dilapan-S Dinoprostone
    Number of subjects analysed
    337
    335 [29]
    Units: Binary (Yes/No)
        Yes
    306
    272
        No
    31
    63
    Notes
    [29] - 2 women are missing primary outcome data
    Statistical analysis title
    		 Failure to achieve vaginal delivery within 24hours
    Statistical analysis description
    DINOPROSTONE is the reference category and risk ratio values <1 favour DILAPAN-S. Risk ratio is estimated using a binomial model with a log link adjusting for age, BMI and parity as fixed effects.
    Comparison groups
    Dilapan-S v Dinoprostone
    Number of subjects included in analysis
    672
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [30]
    P-value
    		 = 0.0002
    Method
    		 Regression, Logistic
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    1.11
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.05
         upper limit
    		 1.18
    Notes
    [30] - DINOPROSTONE is the reference category and risk differences < 0 favour DILAPAN-S®. Risk ratio is estimated using a binomial model with a log link adjusting for age, BMI and parity as fixed effects.

    Secondary: Secondary: Failure to achieve vaginal delivery within 36 hours from randomisation

    		 Close Top of page
    End point title
    		 Secondary: Failure to achieve vaginal delivery within 36 hours from randomisation
    End point description
    Where 'Yes’ indicates a caesarean section or a vaginal delivery after the time frame specified
    End point type
    Secondary
    End point timeframe
    Baseline / birth
    End point values
    		 Dilapan-S Dinoprostone
    Number of subjects analysed
    337
    335 [31]
    Units: Binary (Yes/No)
        Yes
    273
    232
        No
    64
    103
    Notes
    [31] - 2 women are missing outcome data
    Statistical analysis title
    		 Failure to achieve vaginal delivery within 36hours
    Statistical analysis description
    DINOPROSTONE is the reference category and risk ratio values <1 favour DILAPAN-S. Risk ratio is estimated using a mixed poisson model with a log link adjusting for age, BMI and parity as fixed effects, and randomising centre as a random effect.
    Comparison groups
    Dilapan-S v Dinoprostone
    Number of subjects included in analysis
    672
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.082
    Method
    		 Mixed models analysis
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    1.17
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.98
         upper limit
    		 1.39

    Secondary: Secondary: Failure to achieve vaginal delivery within 48 hours from randomisation

    		 Close Top of page
    End point title
    		 Secondary: Failure to achieve vaginal delivery within 48 hours from randomisation
    End point description
    Where ‘Yes’ indicates a caesarean section or a vaginal delivery after the time frame specified
    End point type
    Secondary
    End point timeframe
    Baseline / birth
    End point values
    		 Dilapan-S Dinoprostone
    Number of subjects analysed
    337
    335 [32]
    Units: Binary (Yes/No)
        Yes
    232
    200
        No
    105
    135
    Notes
    [32] - 2 women are missing outcome data
    Statistical analysis title
    		 Failure to achieve vaginal delivery within 48hours
    Statistical analysis description
    DINOPROSTONE is the reference category and risk ratio values <1 favour DILAPAN-S. Risk ratio is estimated using a mixed poisson model with a log link adjusting for age, BMI and parity as fixed effects, and randomising centre as a random effect.
    Comparison groups
    Dilapan-S v Dinoprostone
    Number of subjects included in analysis
    672
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.14
    Method
    		 Mixed models analysis
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    1.15
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.95
         upper limit
    		 1.39

    Secondary: Secondary: Spontaneous vaginal delivery

    		 Close Top of page
    End point title
    		 Secondary: Spontaneous vaginal delivery
    End point description
    End point type
    Secondary
    End point timeframe
    Baseline/ birth
    End point values
    		 Dilapan-S Dinoprostone
    Number of subjects analysed
    337
    335 [33]
    Units: Binary (Yes/No)
        Yes
    129
    133
        No
    208
    202
    Notes
    [33] - 2 women are missing outcome data
    Statistical analysis title
    		 Spontaneous vaginal delivery
    Statistical analysis description
    DINOPROSTONE is the reference category and risk ratio values <1 favour DINOPROSTONE . Risk ratio is estimated using a binomial model with a log link adjusting for age, BMI and parity as fixed effects.
    Comparison groups
    Dinoprostone v Dilapan-S
    Number of subjects included in analysis
    672
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.505
    Method
    		 Regression, Logistic
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    0.94
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.79
         upper limit
    		 1.12

    Secondary: Secondary: Instrumental delivery due to delay in 2nd stage of labour and/or fetal heart rate abnormalities and/or abnormal FBS

    		 Close Top of page
    End point title
    		 Secondary: Instrumental delivery due to delay in 2nd stage of labour and/or fetal heart rate abnormalities and/or abnormal FBS
    End point description
    End point type
    Secondary
    End point timeframe
    Baseline/ birth
    End point values
    		 Dilapan-S Dinoprostone
    Number of subjects analysed
    337
    334 [34]
    Units: Binary (Yes/No)
        Yes
    71
    74
        No
    266
    260
    Notes
    [34] - 3 women are missing outcome data
    Statistical analysis title
    		 Instrumental delivery
    Statistical analysis description
    DINOPROSTONE is the reference category and risk ratio values <1 favour DILAPAN-S. Risk ratio is estimated using a mixed binomial model with a log link adjusting for age, BMI and parity and randomising centre as a random effect.
    Comparison groups
    Dilapan-S v Dinoprostone
    Number of subjects included in analysis
    671
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.858
    Method
    		 Mixed models analysis
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    0.97
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.74
         upper limit
    		 1.29

    Secondary: Secondary: Caesarean section delivery due to delay in 1st and/or 2nd stage of labour, and/or fetal heart rate abnormalities and/or abnormal FBS

    		 Close Top of page
    End point title
    		 Secondary: Caesarean section delivery due to delay in 1st and/or 2nd stage of labour, and/or fetal heart rate abnormalities and/or abnormal FBS
    End point description
    End point type
    Secondary
    End point timeframe
    Baseline / birth
    End point values
    		 Dilapan-S Dinoprostone
    Number of subjects analysed
    337
    335
    Units: Binary (Yes/No)
        Yes
    96
    74
        No
    241
    261
    Statistical analysis title
    		 Caesarean section delivery
    Statistical analysis description
    DINOPROSTONE is the reference category and risk ratio values <1 favour DILAPAN-S. Risk ratio is estimated using a mixed binomial model with a log link adjusting for age, BMI and parity and randomising centre as a random effect.
    Comparison groups
    Dilapan-S v Dinoprostone
    Number of subjects included in analysis
    672
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.039
    Method
    		 Mixed models analysis
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    1.31
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.01
         upper limit
    		 1.7

    Secondary: Secondary: Complications from delivery until discharge

    		 Close Top of page
    End point title
    		 Secondary: Complications from delivery until discharge
    End point description
    End point type
    Secondary
    End point timeframe
    Baseline / birth
    End point values
    		 Dilapan-S Dinoprostone
    Number of subjects analysed
    337
    335 [35]
    Units: Binary (Yes/No)
        Yes
    74
    69
        No
    263
    266
    Notes
    [35] - 2 women are missing outcome data
    Statistical analysis title
    		 Complications from delivery until discharge
    Statistical analysis description
    DINOPROSTONE is the reference category and risk ratio values <1 favour DILAPAN-S. Risk ratio is estimated using a binomial model with a log link adjusting for age, BMI and parity as fixed effects.
    Comparison groups
    Dilapan-S v Dinoprostone
    Number of subjects included in analysis
    672
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.648
    Method
    		 Regression, Logistic
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    1.07
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.8
         upper limit
    		 1.43

    Secondary: Secondary: Antibiotic use for pelvic infection

    		 Close Top of page
    End point title
    		 Secondary: Antibiotic use for pelvic infection
    End point description
    End point type
    Secondary
    End point timeframe
    Baseline / birth
    End point values
    		 Dilapan-S Dinoprostone
    Number of subjects analysed
    337
    335 [36]
    Units: Binary (Yes/No)
        Yes
    3
    2
        No
    334
    333
    Notes
    [36] - 2 women are missing outcome data
    Statistical analysis title
    		 Antibiotic use for pelvic infection
    Statistical analysis description
    DINOPROSTONE is the reference category and risk ratio values <1 favour DILAPAN-S. Risk ratio is estimated using a binomial model with a log link adjusting for age, BMI and parity as fixed effects.
    Comparison groups
    Dilapan-S v Dinoprostone
    Number of subjects included in analysis
    672
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.621
    Method
    		 Mixed models analysis
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    1.57
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.26
         upper limit
    		 9.37

    Secondary: Secondary: Duration of antibiotic use for pelvic infection

    		 Close Top of page
    End point title
    		 Secondary: Duration of antibiotic use for pelvic infection
    End point description
    No statistical analysis calculated as number of women with this outcome is so small.
    End point type
    Secondary
    End point timeframe
    Baseline / birth
    End point values
    		 Dilapan-S Dinoprostone
    Number of subjects analysed
    3 [37]
    2 [38]
    Units: day
        arithmetic mean (standard deviation)
    6.3 ( 4.6 )
    4.0 ( 2.8 )
    Notes
    [37] - Only 3 women have used antibiotics for pelvic infection
    [38] - Only 2 women have used antibiotics for pelvic infection
    No statistical analyses for this end point

    Secondary: Secondary: Length of stay from randomisation

    		 Close Top of page
    End point title
    		 Secondary: Length of stay from randomisation
    End point description
    End point type
    Secondary
    End point timeframe
    Baseline / birth
    End point values
    		 Dilapan-S Dinoprostone
    Number of subjects analysed
    337
    335 [39]
    Units: day
        arithmetic mean (standard deviation)
    4.7 ( 2.4 )
    4.7 ( 3.0 )
    Notes
    [39] - 2 women are missing outcome data
    Statistical analysis title
    		 Length of stay from randomisation
    Statistical analysis description
    The geometric mean indicates the central tendency or typical value of a set of numbers by using the product of their values (as opposed to the arithmetic mean which uses their sum) and is used for summarising skewed data. Comparative analysis uses a ratio of the geometric means. Geometric mean ratios <1 favour DILAPAN-S®. The geometric mean ratio is estimated using a mixed effect linear regression adjusted for minimisation variables and randomising centre as a random effect
    Comparison groups
    Dilapan-S v Dinoprostone
    Number of subjects included in analysis
    672
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.18
    Method
    		 Mixed models analysis
    Parameter type
    		 Geometric mean ratio
    Point estimate
    1.06
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.97
         upper limit
    		 1.15

    Secondary: Secondary: Baby born alive

    		 Close Top of page
    End point title
    		 Secondary: Baby born alive
    End point description
    No statistical analysis conducted as all babies were born alive.
    End point type
    Secondary
    End point timeframe
    Baseline / birth
    End point values
    		 Dilapan-S Dinoprostone
    Number of subjects analysed
    337
    335 [40]
    Units: Binary (Yes/No)
        Yes
    337
    335
        No
    0
    0
    Notes
    [40] - 2 women are missing outcome data
    No statistical analyses for this end point

    Secondary: Secondary: APGAR score at 1 minute

    		 Close Top of page
    End point title
    		 Secondary: APGAR score at 1 minute
    End point description
    End point type
    Secondary
    End point timeframe
    Baseline / birth
    End point values
    		 Dilapan-S Dinoprostone
    Number of subjects analysed
    336 [41]
    334 [42]
    Units: APGAR score
        arithmetic mean (standard deviation)
    8.4 ( 1.5 )
    8.3 ( 1.5 )
    Notes
    [41] - 1 women has no outcome data recorded
    [42] - 3 women have no outcome data recorded
    Statistical analysis title
    		 APGAR score at 1 minute
    Statistical analysis description
    Median differences < 0 favour DINOPROSTONE.
    Comparison groups
    Dilapan-S v Dinoprostone
    Number of subjects included in analysis
    670
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    		 Bootstrapping methods
    Parameter type
    		 Median difference (final values)
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0
         upper limit
    		 0

    Secondary: Secondary: APGAR score at 5 minutes

    		 Close Top of page
    End point title
    		 Secondary: APGAR score at 5 minutes
    End point description
    End point type
    Secondary
    End point timeframe
    Baseline / birth
    End point values
    		 Dilapan-S Dinoprostone
    Number of subjects analysed
    334 [43]
    333 [44]
    Units: APGAR score
        arithmetic mean (standard deviation)
    9.2 ( 0.7 )
    9.4 ( 1.5 )
    Notes
    [43] - 3 women are missing outcome data
    [44] - 4 woman have missing outcome data
    Statistical analysis title
    		 APGAR score at 5 minutes
    Statistical analysis description
    Median differences < 0 favour DINOPROSTONE
    Comparison groups
    Dilapan-S v Dinoprostone
    Number of subjects included in analysis
    667
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    		 Bootstrapping methods
    Parameter type
    		 Median difference (final values)
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0
         upper limit
    		 0

    Secondary: Secondary: APGAR score at 10 minutes

    		 Close Top of page
    End point title
    		 Secondary: APGAR score at 10 minutes
    End point description
    End point type
    Secondary
    End point timeframe
    Baseline / birth
    End point values
    		 Dilapan-S Dinoprostone
    Number of subjects analysed
    49 [45]
    57 [46]
    Units: APGAR score
        arithmetic mean (standard deviation)
    9.7 ( 0.7 )
    9.4 ( 1.5 )
    Notes
    [45] - 288 women have not recorded outcome data
    [46] - 280 women do not have outcome data recorded
    Statistical analysis title
    		 APGAR score at 10 minutes
    Statistical analysis description
    Median differences < 0 favour DINOPROSTONE
    Comparison groups
    Dilapan-S v Dinoprostone
    Number of subjects included in analysis
    106
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 1
    Method
    		 Bootstrapping methods
    Parameter type
    		 Median difference (final values)
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.17
         upper limit
    		 0.17

    Secondary: Secondary: Meconium staining noted

    		 Close Top of page
    End point title
    		 Secondary: Meconium staining noted
    End point description
    End point type
    Secondary
    End point timeframe
    Baseline / birth
    End point values
    		 Dilapan-S Dinoprostone
    Number of subjects analysed
    336 [47]
    335 [48]
    Units: Binary (Yes/ No)
        Yes
    46
    44
        No
    290
    291
    Notes
    [47] - 1 woman is missing outcome data
    [48] - 2 women are missing outcome data
    Statistical analysis title
    		 Meconium staining noted
    Statistical analysis description
    Where DINOPROSTONE is the reference category and risk ratio values <1 favour DILAPAN-S. Risk ratios are estimated using a mixed binomial model with a log link adjusting for age, BMI and parity and randomising centre as a random effect
    Comparison groups
    Dilapan-S v Dinoprostone
    Number of subjects included in analysis
    671
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.897
    Method
    		 Mixed models analysis
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    1.03
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.7
         upper limit
    		 1.5

    Secondary: Secondary: Metabolic acidosis

    		 Close Top of page
    End point title
    		 Secondary: Metabolic acidosis
    End point description
    End point type
    Secondary
    End point timeframe
    Baseline / birth
    End point values
    		 Dilapan-S Dinoprostone
    Number of subjects analysed
    147 [49]
    156 [50]
    Units: Binary (Yes/No)
        Yes
    14
    10
        No
    133
    146
    Notes
    [49] - 190 women are missing outcome data
    [50] - 181 women are missing outcome data
    Statistical analysis title
    		 Metabolic acidosis
    Statistical analysis description
    Where DINOPROSTONE is the reference category and risk ratio values <1 favour DILAPAN-S. Risk ratios are estimated using a mixed binomial model with a log link adjusting for age, BMI and parity and randomising centre as a random effect
    Comparison groups
    Dilapan-S v Dinoprostone
    Number of subjects included in analysis
    303
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.613
    Method
    		 Mixed models analysis
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    1.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.6
         upper limit
    		 2.39

    Secondary: Secondary: Requirement of review by doctor from neonatal team

    		 Close Top of page
    End point title
    		 Secondary: Requirement of review by doctor from neonatal team
    End point description
    End point type
    Secondary
    End point timeframe
    Baseline / birth
    End point values
    		 Dilapan-S Dinoprostone
    Number of subjects analysed
    337
    335 [51]
    Units: Binary (Yes/No)
        Yes
    123
    124
        No
    214
    211
    Notes
    [51] - 2 women are missing outcome data
    Statistical analysis title
    		 Requirement of review by doctor from neonatal team
    Statistical analysis description
    Where DINOPROSTONE is the reference category and risk ratio values <1 favour DILAPAN-S. Risk ratios are estimated using a mixed binomial model with a log link adjusting for age, BMI and parity and randomising centre as a random effect
    Comparison groups
    Dilapan-S v Dinoprostone
    Number of subjects included in analysis
    672
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.769
    Method
    		 Mixed models analysis
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    0.97
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.8
         upper limit
    		 1.18

    Secondary: Secondary: Duration of antibiotic use for neonatal

    		 Close Top of page
    End point title
    		 Secondary: Duration of antibiotic use for neonatal
    End point description
    End point type
    Secondary
    End point timeframe
    Baseline / birth
    End point values
    		 Dilapan-S Dinoprostone
    Number of subjects analysed
    60 [52]
    60 [53]
    Units: day
        arithmetic mean (standard deviation)
    3.6 ( 2.1 )
    4.3 ( 1.6 )
    Notes
    [52] - 1 woman is missing primary outcome data 276 women had no antibiotic use for neonatal infection
    [53] - 2 woman is missing primary outcome data 275 women had no antibiotic use for neonatal infection
    Statistical analysis title
    		 Duration of antibiotic use for neonatal infection
    Statistical analysis description
    The geometric mean indicates the central tendency or typical value of a set of numbers by using the product of their values (as opposed to the arithmetic mean which uses their sum) and is used for summarising skewed data. Comparative analysis uses a ratio of the geometric means. Geometric mean ratios <1 favour DILAPAN-S®. The geometric mean ratio is estimated using a mixed effect linear regression adjusted for minimisation variables and randomising centre as a random effect
    Comparison groups
    Dilapan-S v Dinoprostone
    Number of subjects included in analysis
    120
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.013
    Method
    		 Mixed models analysis
    Parameter type
    		 Geometric mean ratio
    Point estimate
    0.79
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.66
         upper limit
    		 0.95

    Secondary: Secondary: Admitted to neonatal unit

    		 Close Top of page
    End point title
    		 Secondary: Admitted to neonatal unit
    End point description
    End point type
    Secondary
    End point timeframe
    Baseline / birth
    End point values
    		 Dilapan-S Dinoprostone
    Number of subjects analysed
    337
    335 [54]
    Units: Binary (Yes/No)
        Yes
    45
    45
        No
    292
    290
    Notes
    [54] - 2 women missing outcome data
    Statistical analysis title
    		 Admitted to neonatal unit
    Statistical analysis description
    Where DINOPROSTONE is the reference category and risk ratio values <1 favour DILAPAN-S. Risk ratios are estimated using a mixed binomial model with a log link adjusting for age, BMI and parity and randomising centre as a random effect
    Comparison groups
    Dilapan-S v Dinoprostone
    Number of subjects included in analysis
    672
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.94
    Method
    		 Mixed models analysis
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    0.99
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.67
         upper limit
    		 1.44

    Secondary: Length of stay in neonatal unit

    		 Close Top of page
    End point title
    		 Length of stay in neonatal unit
    End point description
    End point type
    Secondary
    End point timeframe
    Baseline / birth
    End point values
    		 Dilapan-S Dinoprostone
    Number of subjects analysed
    45 [55]
    45 [56]
    Units: day
        arithmetic mean (standard deviation)
    5.2 ( 9.1 )
    3.5 ( 3.5 )
    Notes
    [55] - 292 women's babies were not admitted to the neonatal unit
    [56] - 290 women's babies were not admitted to the neonatal unit
    Statistical analysis title
    		 Length of stay in neonatal unit
    Statistical analysis description
    The geometric mean indicates the central tendency or typical value of a set of numbers by using the product of their values (as opposed to the arithmetic mean which uses their sum) and is used for summarising skewed data. Comparative analysis uses a ratio of the geometric means. Geometric mean ratios <1 favour DILAPAN-S®. The geometric mean ratio is estimated using a mixed effect linear regression adjusted for minimisation variables and randomising centre as a random effect
    Comparison groups
    Dilapan-S v Dinoprostone
    Number of subjects included in analysis
    90
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.146
    Method
    		 Mixed models analysis
    Parameter type
    		 Geometric mean ratio
    Point estimate
    1.36
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.9
         upper limit
    		 2.05

    Secondary: Secondary: Antibiotic use for neonatal infection

    		 Close Top of page
    End point title
    		 Secondary: Antibiotic use for neonatal infection
    End point description
    End point type
    Secondary
    End point timeframe
    Baseline / birth
    End point values
    		 Dilapan-S Dinoprostone
    Number of subjects analysed
    337
    335 [57]
    Units: Binary (Yes/No)
        Yes
    60
    60
        No
    277
    275
    Notes
    [57] - 2 women are missing outcome data
    Statistical analysis title
    		 Antibiotic use for neonatal infection
    Statistical analysis description
    Where DINOPROSTONE is the reference category and risk ratio values <1 favour DILAPAN-S. Risk ratios are estimated using a mixed binomial model with a log link adjusting for age, BMI and parity and randomising centre as a random effect
    Comparison groups
    Dilapan-S v Dinoprostone
    Number of subjects included in analysis
    672
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.889
    Method
    		 Mixed models analysis
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    0.98
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.71
         upper limit
    		 1.35

    Adverse events

    		 Close Top of page
    Adverse events information [1]
    Timeframe for reporting adverse events
    Adverse events will be collected from trial intervention to discharge with the exception of any ongoing adverse events post-discharge, which will be collected up to resolution of the event.
    Adverse event reporting additional description
    AEs are commonly encountered in participants receiving Dinoprostone vaginal insert and Dilapan-S. With the safety profiles for both interventions used in this trial being well characterised.
    Assessment type
    		 Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 CTCAE
    Dictionary version
    5
    Reporting groups
    Reporting group title
    Dilapan-S
    Reporting group description
    		 DILAPAN-S® is a class IIa medical device. The device is CE marked and available on the market for use wherever cervical softening and dilation are desired.

    Reporting group title
    Dinoprostone
    Reporting group description
    		 Slow release 10 mg vaginal drug delivery system (Prostaglandin E2)

    Notes
    [1] - There are no non-serious adverse events recorded for these results. It is expected that there will be at least one non-serious adverse event reported.
    Justification: All adverse events are reported as serious
    Serious adverse events
    		 Dilapan-S Dinoprostone
    Total subjects affected by serious adverse events
         subjects affected / exposed
    97 / 337 (28.78%)
    109 / 337 (32.34%)
         number of deaths (all causes)
    0
    1
         number of deaths resulting from adverse events
    0
    1
    Investigations
    Missing adverse event details
         subjects affected / exposed
    4 / 337 (1.19%)
    5 / 337 (1.48%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Raised CRP levels
         subjects affected / exposed
    0 / 337 (0.00%)
    1 / 337 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac arihythmias neonatal
         subjects affected / exposed
    1 / 337 (0.30%)
    0 / 337 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tricuspid and mitral regurgitation
         subjects affected / exposed
    1 / 337 (0.30%)
    0 / 337 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tachycardia neonatal
         subjects affected / exposed
    1 / 337 (0.30%)
    0 / 337 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pregnancy, puerperium and perinatal conditions
    Bowel injury caused at c-section
         subjects affected / exposed
    0 / 337 (0.00%)
    1 / 337 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chorioamnionitis
         subjects affected / exposed
    1 / 337 (0.30%)
    0 / 337 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Postpartum haemorrhage
         subjects affected / exposed
    32 / 337 (9.50%)
    25 / 337 (7.42%)
         occurrences causally related to treatment / all
    0 / 32
    0 / 25
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pelvic haematoma
         subjects affected / exposed
    0 / 337 (0.00%)
    1 / 337 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Placental abruption
         subjects affected / exposed
    1 / 337 (0.30%)
    1 / 337 (0.30%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pre-eclampsia
         subjects affected / exposed
    1 / 337 (0.30%)
    1 / 337 (0.30%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Raised temperature
         subjects affected / exposed
    1 / 337 (0.30%)
    4 / 337 (1.19%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tachycardia and raised temperature
         subjects affected / exposed
    3 / 337 (0.89%)
    1 / 337 (0.30%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bilicous vomit neonatal
         subjects affected / exposed
    0 / 337 (0.00%)
    1 / 337 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cleft lip
         subjects affected / exposed
    0 / 337 (0.00%)
    1 / 337 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fetal tachycardia and raised temperature
         subjects affected / exposed
    1 / 337 (0.30%)
    0 / 337 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypothermia neonatal
         subjects affected / exposed
    1 / 337 (0.30%)
    0 / 337 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypoxic-ischaemic encephalopathy
         subjects affected / exposed
    0 / 337 (0.00%)
    2 / 337 (0.59%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Meconium aspiration syndrome
         subjects affected / exposed
    0 / 337 (0.00%)
    1 / 337 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Prolonged hospital stay neonatal
         subjects affected / exposed
    0 / 337 (0.00%)
    3 / 337 (0.89%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Raised temperature neonatal
         subjects affected / exposed
    0 / 337 (0.00%)
    3 / 337 (0.89%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Baby lost more than 10% birthweight
         subjects affected / exposed
    0 / 337 (0.00%)
    1 / 337 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Severe asphyxia, sepsis, hypertension and hypoxic-ischaemic encephalopathy
         subjects affected / exposed
    0 / 337 (0.00%)
    1 / 337 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    Nervous system disorders
    Suspected Neuropraxia
         subjects affected / exposed
    1 / 337 (0.30%)
    0 / 337 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Seizures neonatal
         subjects affected / exposed
    0 / 337 (0.00%)
    1 / 337 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    1 / 337 (0.30%)
    0 / 337 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood loss
         subjects affected / exposed
    2 / 337 (0.59%)
    2 / 337 (0.59%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sepsis / suspected sepsis
         subjects affected / exposed
    20 / 337 (5.93%)
    21 / 337 (6.23%)
         occurrences causally related to treatment / all
    0 / 20
    0 / 21
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cyanotic episodes neonatal
         subjects affected / exposed
    0 / 337 (0.00%)
    1 / 337 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neonatal jaundice
         subjects affected / exposed
    1 / 337 (0.30%)
    0 / 337 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sepsis / suspected sepsis neonatal
         subjects affected / exposed
    11 / 337 (3.26%)
    17 / 337 (5.04%)
         occurrences causally related to treatment / all
    0 / 11
    0 / 17
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Social circumstances
    Prolonged hospital stay
         subjects affected / exposed
    2 / 337 (0.59%)
    0 / 337 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Transferred to NNU
         subjects affected / exposed
    1 / 337 (0.30%)
    0 / 337 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Pulmonary embolism
         subjects affected / exposed
    1 / 337 (0.30%)
    0 / 337 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Congenital pneumonia
         subjects affected / exposed
    0 / 337 (0.00%)
    1 / 337 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pnemothorax neonatal
         subjects affected / exposed
    1 / 337 (0.30%)
    0 / 337 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory disease neonatal
         subjects affected / exposed
    1 / 337 (0.30%)
    3 / 337 (0.89%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory distress neonatal
         subjects affected / exposed
    4 / 337 (1.19%)
    9 / 337 (2.67%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 9
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chest infection neonatal
         subjects affected / exposed
    0 / 337 (0.00%)
    1 / 337 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    Renal hypertension
         subjects affected / exposed
    0 / 337 (0.00%)
    1 / 337 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary retention
         subjects affected / exposed
    1 / 337 (0.30%)
    1 / 337 (0.30%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Uterine inversion
         subjects affected / exposed
    1 / 337 (0.30%)
    0 / 337 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Klebsiella Pneumoniae neonatal
         subjects affected / exposed
    1 / 337 (0.30%)
    0 / 337 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    		 Dilapan-S Dinoprostone
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    0 / 337 (0.00%)
    0 / 337 (0.00%)

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    17 Oct 2017
    Protocol 1) Change to inclusion and exclusion criteria 2) Change to outcomes 3) Changes to minimisation e.g. data to remove inpatient vs outpatient 4) Changes to adverse events and serious adverse events definitions 5) Update to Propess SmPC to January 2017 version 6) Removal of option for BCTU data entry 7) End of trial definition – extension of timeline 8) Changes to statistical considerations Patient Information Sheet 9) Addition of ‘or equivalent’ to the PALS details for those sites without a Patient Advice and Liaison Service 10) Explanation of when Propess is usually used 11) More information on the chance of receiving Oxytocin 12) Explicit mention of outpatient possibilities removed 13) Clarification on organisation of the study Maternal Satisfaction Questionnaire 14) Removal of allocation tick boxes 15) Addition of sentence requesting patient to complete the form for the first intervention received if they had both
    20 Apr 2018
    Protocol 1. Addition of email address for SAEs (administrative information) 2. Removal of bishop score in eligibility 3. Removal of USS dates in eligibility 4. Update of eligibility/ineligibility to schema 5. Addition of table of responsibilities
    02 Aug 2018
    The following modifications have been made to the protocol: Amendment to DILAPAN-S dosing schedule Removal of the need for CTG monitoring Removal of the use of iodine for cervical cleansing Amendment to Discontinuation of intervention Amendment to Withdrawal and re-confirmation of consent Addition of definitions of reportable SAEs and protocol-exempt SAEs not requiring reporting on a SAE form Removal of Sections 7.4-7.6 re CRF completion Inclusion of Investigators Brochure for Dilapan-S Minor typographical amendments and points of clarification
    04 Dec 2019
    The following modifications have been made to the Protocol:  Minor formatting and typographical changes  Change in Funder's organisational details  Change in Sponsor Representative details  Change in Trial Co-ordinator details  Addition of PI signature page  Removal of fax number and its use  Change in Team Management Leader and contact email  Change of primary objective and outcome to remove time limitation of 36 hours  Change of name for PROPESS TO DINOPROSTONE  Change of info collected on screening log from mothers hospital number and dob to mothers initials and age.  Addition of secondary outcome “Failure to achieve vaginal delivery within 36 hours of randomisation.  Clarification of Adverse Event reporting procedure and SAE definitions  None related protocol changes : o Extension to 31st December 2020 o Inclusion of Reference Safety Information

    Interruptions (globally)
    Were there any global interruptions to the trial? Yes
    Date
    Interruption
    Restart date
    06 Feb 2021
    Opened to recruitment 19th December 2017 Halted due to the Covid Pandemic 18th March 2021 Reopened to recruitment 17th September Recruitment ended 27th January 2021 Study Closure 6th February 2021
    -

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    Unable to meet the original recruitment target and ended the study earlier than expected due to funding issues and the impact of the pandemic.
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Thu May 02 21:52:31 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA