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 are conducted in the European Union (EU) and the European Economic Area (EEA);
  • clinical trials conducted outside the EU / EEA that are linked to European paediatric-medicine development.
  • Learn   more about the EU Clinical Trials Register   including the source of the information and the legal basis.


    The EU Clinical Trials Register currently displays   37978   clinical trials with a EudraCT protocol, of which   6230   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).
     
    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 to measure the effects and costs of a dental caries prevention regime for young children attending primary care dental services.

    Summary
    EudraCT number
    2009-010725-39
    Trial protocol
    GB  
    Global end of trial date
    22 Jun 2015

    Results information
    Results version number
    v1(current)
    This version publication date
    03 Mar 2018
    First version publication date
    03 Mar 2018
    Other versions

    Trial information

    Close Top of page
    Trial identification
    Sponsor protocol code
    08/14/19
    Additional study identifiers
    ISRCTN number
    ISRCTN36180119
    US NCT number
    -
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    Belfast Health and Social Care Trust
    Sponsor organisation address
    A Floor, Belfast City Hospital, Lisburn Road, Belfast, United Kingdom, BT9 7AB
    Public contact
    Professor Martin Tickle, University of Manchester, +44(0) 161 275 6610, martin.tickle@manchester.ac.uk
    Scientific contact
    Professor Martin Tickle, University of Manchester, +44(0) 161 275 6610, martin.tickle@manchester.ac.uk
    Sponsor organisation name
    University of Manchester
    Sponsor organisation address
    Oxford Road, Manchester, United Kingdom, M13 9PL
    Public contact
    Professor Martin Tickle, University of Manchester, +44(0) 1612756610, martin.tickle@manchester.ac.uk
    Scientific contact
    Professor Martin Tickle, University of Manchester, +44(0) 1612756610, martin.tickle@manchester.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
    28 Jul 2015
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    22 Jun 2015
    Global end of trial reached?
    Yes
    Global end of trial date
    22 Jun 2015
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To compare over a 3 year period the effectiveness of 22,600 ppm fluoride varnish, 1,450 ppm fluoride toothpaste, toothbrush and standardised health education, provided twice a year, as a preventive package, with standardised health education alone provided twice a year in: •preventing the conversion of children from caries−free to caries−active states in the primary dentition •reducing the number of carious surfaces (caries into dentine) in the primary dentition in children who convert from caries free to caries active states •preventing episodes of pain and extraction of primary teeth in 2 and 3 year−old children who are caries free at baseline and who attend primary care dental services. To compare over a 3 year period the costs of dental care in the group receiving 22,600 ppm fluoride varnish, 1,450 ppm fluoride toothpaste, toothbrush and standardised health education, provided twice a year as a preventive package, with the group receiving standardised health education alone.
    Protection of trial subjects
    The risks for children in the intervention group included allergic responses to the varnish, therefore children who had been hospitalised due to allergic reactions were excluded from the trial. There was also a risk of children in the intervention group developing fluorosis, however this risk was unlikely as the varnish was professionally applied and standardised advice on the safe use of toothpaste was given to all participants. An independent data monitoring and ethics committed was also convened for the trial.
    Background therapy
    Not Applicable
    Evidence for comparator
    The comparator was standardised health education advice.
    Actual start date of recruitment
    12 Apr 2011
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    United Kingdom: 1248
    Worldwide total number of subjects
    1248
    EEA total number of subjects
    1248
    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)
    1248
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    0
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

    Close Top of page
    Recruitment
    Recruitment details
    Recruitment took place between 12/04/2011 and 29/06/2012 from 22 general dental practices in Northern Ireland. 1248 children aged 2-3 years and who were caries free were recruited into the trial, exceeding the planned sample size of 1200.

    Pre-assignment
    Screening details
    A total of 2455 were screened by Community Dental Service dentists according to the trial inclusion/exclusion criteria. Children were excluded if they had a past history of fillings or extractions due to caries, fissure sealants on primary molar teeth, a history of severe allergic reactions requiring hospitalization or participating in an IMP study

    Period 1
    Period 1 title
    Overall trial (overall period)
    Is this the baseline period?
    Yes
    Allocation method
    Randomised - controlled
    Blinding used
    Single blind
    Roles blinded
    Assessor [1]
    Blinding implementation details
    The study was a two-arm, parallel-group, randomised controlled trial, with an allocation ratio of 1 : 1. Randomisation was undertaken by the clinical trials unit using randomised permuted blocks. Children/parents and general dental practice staff were not blinded; however, the Community Dental Service dentists who completed the outcome assessment were blinded to treatment allocation.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Intervention
    Arm description
    The intervention was composite in nature, comprising a varnish containing 22,600 parts per million (p.p.m.) fluoride, a toothbrush and a 50-ml tube of toothpaste containing 1450 p.p.m. fluoride; plus standardised, evidence-based prevention advice provided at 6-monthly intervals over 3 years.
    Arm type
    Experimental

    Investigational medicinal product name
    Duraphat
    Investigational medicinal product code
    PL 00049/0042
    Other name
    Pharmaceutical forms
    Dental suspension
    Routes of administration
    Dental use
    Dosage and administration details
    22,600 ppm of fluoride varnish was applied to the dried primary teeth of the children by a participating dentist following the product brochure, and a fluoride varnish application protocol which described the process of application for participating dentists. Up to 0.25 ml (=5.65 mg Fluoride) was applied twice a year at each 6 month visit and in total children would have received a maximum of 6 applications over the duration of the trial.

    Arm title
    Control
    Arm description
    The control group received standardised health education advice alone at 6-monthly intervals over 3 years.
    Arm type
    Advice Only

    Investigational medicinal product name
    No investigational medicinal product assigned in this arm
    Notes
    [1] - The roles blinded appear inconsistent with a simple blinded trial.
    Justification: Children, parents and the general dental practice staff were not blinded. However the Community Dental staff who completed the outcome assessment were blinded to treatment allocation.
    Number of subjects in period 1
    Intervention Control
    Started
    624
    624
    Completed
    549
    547
    Not completed
    75
    77
         Subject completed but no data chart available
    1
    -
         Lost to follow-up
    74
    77

    Baseline characteristics

    Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Intervention
    Reporting group description
    The intervention was composite in nature, comprising a varnish containing 22,600 parts per million (p.p.m.) fluoride, a toothbrush and a 50-ml tube of toothpaste containing 1450 p.p.m. fluoride; plus standardised, evidence-based prevention advice provided at 6-monthly intervals over 3 years.

    Reporting group title
    Control
    Reporting group description
    The control group received standardised health education advice alone at 6-monthly intervals over 3 years.

    Reporting group values
    Intervention Control Total
    Number of subjects
    624 624 1248
    Age categorical
    Units: Subjects
        In utero
    0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    0 0 0
        Newborns (0-27 days)
    0 0 0
        Infants and toddlers (28 days-23 months)
    0 0 0
        Children (2-11 years)
    624 624 1248
        Adolescents (12-17 years)
    0 0 0
        Adults (18-64 years)
    0 0 0
        From 65-84 years
    0 0 0
        85 years and over
    0 0 0
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    3.1 ± 0.53 3.1 ± 0.53 -
    Gender categorical
    Units: Subjects
        Female
    341 328 669
        Male
    283 296 579
    Socioeconomic Status - MDM 2010
    Units: Subjects
        Quintile 1 (most deprived)
    88 106 194
        Quintile 2
    141 134 275
        Quintile 3
    172 155 327
        Quintile 4
    148 155 303
        Quintile 5 (least deprived)
    74 73 147
        Missing
    1 1 2

    End points

    Close Top of page
    End points reporting groups
    Reporting group title
    Intervention
    Reporting group description
    The intervention was composite in nature, comprising a varnish containing 22,600 parts per million (p.p.m.) fluoride, a toothbrush and a 50-ml tube of toothpaste containing 1450 p.p.m. fluoride; plus standardised, evidence-based prevention advice provided at 6-monthly intervals over 3 years.

    Reporting group title
    Control
    Reporting group description
    The control group received standardised health education advice alone at 6-monthly intervals over 3 years.

    Primary: Conversion from caries free to caries active

    Close Top of page
    End point title
    Conversion from caries free to caries active
    End point description
    The primary outcome, the number (percentage) of children who converted to caries active over the trial.
    End point type
    Primary
    End point timeframe
    3 years
    End point values
    Intervention Control
    Number of subjects analysed
    549
    547
    Units: Subjects
    187
    213
    Statistical analysis title
    Conversion of caries free to caries active
    Statistical analysis description
    A logistic regression model was fitted adjusting for age and socioeconomic status measured by MDM 2010 quintiles.
    Comparison groups
    Intervention v Control
    Number of subjects included in analysis
    1096
    Analysis specification
    Pre-specified
    Analysis type
    equivalence
    P-value
    = 0.11
    Method
    Regression, Logistic
    Parameter type
    Odds ratio (OR)
    Point estimate
    0.81
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.64
         upper limit
    1.04
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.1

    Secondary: Number of decayed, missing, filled tooth surfaces in caries active children

    Close Top of page
    End point title
    Number of decayed, missing, filled tooth surfaces in caries active children
    End point description
    The number of decayed, missing, filled tooth surfaces was calculated for each child, who were caries active.
    End point type
    Secondary
    End point timeframe
    3 years
    End point values
    Intervention Control
    Number of subjects analysed
    187 [1]
    213 [2]
    Units: carious surfaces
        arithmetic mean (standard deviation)
    7.18 ± 7.99
    9.61 ± 8.75
    Notes
    [1] - Caries active children
    [2] - Caries active children
    Statistical analysis title
    Decayed, missing filled tooth surfaces
    Statistical analysis description
    A multiple linear regression analysis adjusted for age and socioeconomic status measured by MDM 2010 quintiles.
    Comparison groups
    Intervention v Control
    Number of subjects included in analysis
    400
    Analysis specification
    Pre-specified
    Analysis type
    equivalence
    P-value
    = 0.007
    Method
    Regression, Linear
    Parameter type
    Mean difference (final values)
    Point estimate
    -2.29
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -3.96
         upper limit
    -0.63
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.85

    Secondary: Number of extracted teeth in caries active children

    Close Top of page
    End point title
    Number of extracted teeth in caries active children
    End point description
    The number of extracted teeth was calculated for each child who was caries active.
    End point type
    Secondary
    End point timeframe
    3 years
    End point values
    Intervention Control
    Number of subjects analysed
    187 [3]
    213 [4]
    Units: Teeth
        arithmetic mean (standard deviation)
    0.45 ± 1.43
    0.46 ± 1.44
    Notes
    [3] - Caries active children
    [4] - Caries active children
    Statistical analysis title
    Number of extracted teeth
    Statistical analysis description
    A negative binomial model was fitted for the number of extracted teeth, which indicated significant overdispersion and was not statistically significant. A post hoc analysis on the number of children who had teeth extracted was undertaken for the children who were caries active.
    Comparison groups
    Intervention v Control
    Number of subjects included in analysis
    400
    Analysis specification
    Pre-specified
    Analysis type
    equivalence
    P-value
    = 0.95
    Method
    Negative binomial regression
    Parameter type
    Negative binomial regression coefficient
    Point estimate
    -0.03
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.88
         upper limit
    0.82
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.43

    Secondary: Number of caries active children with extracted teeth

    Close Top of page
    End point title
    Number of caries active children with extracted teeth
    End point description
    Number of caries active children with teeth extracted.
    End point type
    Secondary
    End point timeframe
    3 years
    End point values
    Intervention Control
    Number of subjects analysed
    187 [5]
    213 [6]
    Units: Subjects
    21
    28
    Notes
    [5] - Caries active children
    [6] - Caries active children
    Statistical analysis title
    Number of children with teeth extracted
    Statistical analysis description
    The planned negative binomial regression model indicated overdispersion. A logistic regression model was fitted adjusting for age and socioeconomic status measured by MDM 2010 quintiles.
    Comparison groups
    Intervention v Control
    Number of subjects included in analysis
    400
    Analysis specification
    Post-hoc
    Analysis type
    equivalence
    P-value
    = 0.56
    Method
    Regression, Logistic
    Parameter type
    Odds ratio (OR)
    Point estimate
    0.84
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.45
         upper limit
    1.54
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.26

    Secondary: Number of episodes of pain

    Close Top of page
    End point title
    Number of episodes of pain
    End point description
    Number of episodes of pain for all children.
    End point type
    Secondary
    End point timeframe
    3 years
    End point values
    Intervention Control
    Number of subjects analysed
    549 [7]
    547 [8]
    Units: Episode of pain
        arithmetic mean (standard deviation)
    0.37 ± 0.95
    0.47 ± 1.14
    Notes
    [7] - All children
    [8] - All children
    Statistical analysis title
    Number of episodes of pain
    Statistical analysis description
    A negative binomial regression model was fitted adjusting for caries status, age and socioeconomic status measured by MDM 2010 quintiles. There was significant overdispersion and this was not statistically significant. A post hoc analysis on the number of children having pain was also undertaken.
    Comparison groups
    Intervention v Control
    Number of subjects included in analysis
    1096
    Analysis specification
    Pre-specified
    Analysis type
    equivalence
    P-value
    = 0.81
    Method
    negative binomial regression
    Parameter type
    negative binomial regression coefficient
    Point estimate
    -0.03
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.32
         upper limit
    0.25
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.15

    Secondary: Number of children who had pain

    Close Top of page
    End point title
    Number of children who had pain
    End point description
    Number of children who had pain.
    End point type
    Secondary
    End point timeframe
    3 years
    End point values
    Intervention Control
    Number of subjects analysed
    549 [9]
    547 [10]
    Units: Subjects
    106
    120
    Notes
    [9] - All children
    [10] - All children
    Statistical analysis title
    Number of children who had pain
    Statistical analysis description
    A logistic regression adjusted for caries status, age and socioeconomic status measured by MDM 2010 quintiles was undertaken for the number of children with pain.
    Comparison groups
    Intervention v Control
    Number of subjects included in analysis
    1096
    Analysis specification
    Post-hoc
    Analysis type
    equivalence
    P-value
    = 0.74
    Method
    Regression, Logistic
    Parameter type
    Odds ratio (OR)
    Point estimate
    0.95
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.69
         upper limit
    1.3
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.15

    Secondary: Number of serious adverse events

    Close Top of page
    End point title
    Number of serious adverse events
    End point description
    Number of serious adverse events in all children, over 3 years.
    End point type
    Secondary
    End point timeframe
    Over 3 years
    End point values
    Intervention Control
    Number of subjects analysed
    624 [11]
    624 [12]
    Units: Serious Adverse Events
        arithmetic mean (standard deviation)
    0.09 ± 0.34
    0.072 ± 0.31
    Notes
    [11] - All children randomised
    [12] - All children randomised
    Statistical analysis title
    Number of Serious Adverse Events
    Statistical analysis description
    A negative binomial analysis was fitted, adjusting for age and socioeconomic status measured by MDM 2010 quintiles. There was significant overdispersion and a logistic regression model was fitted post hoc for whether a child had a SAE or not.
    Comparison groups
    Intervention v Control
    Number of subjects included in analysis
    1248
    Analysis specification
    Pre-specified
    Analysis type
    equivalence
    P-value
    = 0.42
    Method
    Negative binomial regression
    Parameter type
    Negative binomial regression coefficient
    Point estimate
    0.19
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.27
         upper limit
    0.65
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.24

    Secondary: Number of children having serious adverse events

    Close Top of page
    End point title
    Number of children having serious adverse events
    End point description
    Number of children randomized having a serious adverse event over 3 years.
    End point type
    Secondary
    End point timeframe
    Over 3 years
    End point values
    Intervention Control
    Number of subjects analysed
    624 [13]
    624 [14]
    Units: Subjects
    45
    37
    Notes
    [13] - All children randomised
    [14] - All children randomised
    Statistical analysis title
    Number of children who had SAEs
    Statistical analysis description
    A logistic regression model was fitted, adjusting for age and socioeconomic status measured by MDM 2010 quintiles. This was not statistically significant.
    Comparison groups
    Intervention v Control
    Number of subjects included in analysis
    1248
    Analysis specification
    Post-hoc
    Analysis type
    equivalence
    P-value
    = 0.36
    Method
    Regression, Logistic
    Parameter type
    Odds ratio (OR)
    Point estimate
    1.23
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.79
         upper limit
    1.94
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.28

    Secondary: Mean difference health service cost/mean difference in proportion caries free

    Close Top of page
    End point title
    Mean difference health service cost/mean difference in proportion caries free
    End point description
    Incremental cost-effectiveness as difference in health service costs divided by the proportion caries free intervention vs control.
    End point type
    Secondary
    End point timeframe
    3 Years
    End point values
    Intervention Control
    Number of subjects analysed
    549
    547
    Units: Cost per proportion caries free
        arithmetic mean (confidence interval 95%)
    -2092.59 (-30100.4 to 27921.8)
    -2092.59 (-30100.4 to 27921.8)
    Statistical analysis title
    Incremental cost-effectiveness
    Statistical analysis description
    Incremental cost-effectiveness. A sampling distribution for the incremental cost-effectiveness ratio was simulated based on a bootstrapped sample. The 2.5 and 97.5 percentiles for the ratio were used to establish the 95% confidence interval for the distribution.
    Comparison groups
    Intervention v Control
    Number of subjects included in analysis
    1096
    Analysis specification
    Pre-specified
    Analysis type
    equivalence
    P-value
    = 0.05
    Method
    Incremental cost-effectiveness ratio
    Parameter type
    Incremental cost-effectiveness ratio
    Point estimate
    -2092.59
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -30100.4
         upper limit
    27921.8

    Secondary: Mean difference in health service cost/mean difference in number of carious surfaces

    Close Top of page
    End point title
    Mean difference in health service cost/mean difference in number of carious surfaces
    End point description
    Incremental cost-effectiveness as difference in health service costs divided by the number of carious surfaces intervention vs control.
    End point type
    Secondary
    End point timeframe
    3 Years
    End point values
    Intervention Control
    Number of subjects analysed
    549
    547
    Units: Cost per number of carious surfaces
        arithmetic mean (confidence interval 95%)
    -250.58 (-454.39 to -79.52)
    -250.58 (-454.39 to -79.52)
    Statistical analysis title
    Incremental cost-effectiveness
    Statistical analysis description
    Incremental cost-effectiveness. A sampling distribution for the incremental cost-effectiveness ratio was simulated based on a bootstrapped sample. The 2.5 and 97.5 percentiles for the ratio were used to establish the 95% confidence interval for the distribution.
    Comparison groups
    Intervention v Control
    Number of subjects included in analysis
    1096
    Analysis specification
    Pre-specified
    Analysis type
    equivalence
    P-value
    = 0.05
    Method
    Incremental cost effectiveness ratio
    Parameter type
    Incremental cost effectiveness ratio
    Point estimate
    -250.58
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -454.39
         upper limit
    -79.52

    Secondary: Mean difference in health service cost/mean difference in number of episodes of pain

    Close Top of page
    End point title
    Mean difference in health service cost/mean difference in number of episodes of pain
    End point description
    Incremental cost-effectiveness as difference in health service costs divided by the number of episodes of pain intervention vs control.
    End point type
    Secondary
    End point timeframe
    3 Years
    End point values
    Intervention Control
    Number of subjects analysed
    549
    547
    Units: Cost per number of carious surfaces
        arithmetic mean (confidence interval 95%)
    -259.07 (-14644 to 14941.60)
    -259.07 (-14644 to 14941.60)
    Statistical analysis title
    Incremental cost-effectiveness
    Statistical analysis description
    Incremental cost-effectiveness. A sampling distribution for the incremental cost-effectiveness ratio was simulated based on a bootstrapped sample. The 2.5 and 97.5 percentiles for the ratio were used to establish the 95% confidence interval for the distribution.
    Comparison groups
    Intervention v Control
    Number of subjects included in analysis
    1096
    Analysis specification
    Pre-specified
    Analysis type
    equivalence
    P-value
    = 0.05
    Method
    Incremental cost-effectiveness ratio
    Parameter type
    Incremental cost-effectiveness ratio
    Point estimate
    -259.07
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -14664
         upper limit
    14941.6

    Adverse events

    Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    The adverse event (AE) reporting period for the trial began upon enrolment in to the study and ended at the 36 month visit. All SAEs were to be reported to the clinical trials unit within 24 hours of the local investigator becoming aware of the event.
    Adverse event reporting additional description
    All adverse events (AEs) were recorded and once causality was determined only adverse reactions (ARs) and SAEs were reported to the clinical trials unit. Due to small numbers a breakdown of term is not provided for serious and non-serious AEs.
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    NICTC
    Dictionary version
    4
    Reporting groups
    Reporting group title
    Intervention
    Reporting group description
    The intervention was composite in nature, comprising a varnish containing 22,600 parts per million (p.p.m.) fluoride, a toothbrush and a 50-ml tube of toothpaste containing 1450 p.p.m. fluoride; plus standardised, evidence-based prevention advice provided at 6-monthly intervals over 3 years.

    Reporting group title
    Control
    Reporting group description
    The control group received standardised caries prevention advice alone at 6-monthly intervals over 3 years.

    Serious adverse events
    Intervention Control
    Total subjects affected by serious adverse events
         subjects affected / exposed
    45 / 624 (7.21%)
    37 / 624 (5.93%)
         number of deaths (all causes)
    0
    0
         number of deaths resulting from adverse events
    0
    0
    Surgical and medical procedures
    Surgical and medical procedures
         subjects affected / exposed
    9 / 624 (1.44%)
    5 / 624 (0.80%)
         occurrences causally related to treatment / all
    0 / 9
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Cardiac disorders
         subjects affected / exposed
    1 / 624 (0.16%)
    1 / 624 (0.16%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Respiratory thoracic and mediastinal disorders
         subjects affected / exposed
    10 / 624 (1.60%)
    11 / 624 (1.76%)
         occurrences causally related to treatment / all
    0 / 10
    0 / 12
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    General disorders and administration site conditions
         subjects affected / exposed
    5 / 624 (0.80%)
    7 / 624 (1.12%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Gastrointestinal disorders
         subjects affected / exposed
    4 / 624 (0.64%)
    5 / 624 (0.80%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    Renal and urinary disorders
         subjects affected / exposed
    1 / 624 (0.16%)
    0 / 624 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Skin and subcutaneous tissue disorders
         subjects affected / exposed
    1 / 624 (0.16%)
    1 / 624 (0.16%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Musculoskeletal and connective tissue disorders
         subjects affected / exposed
    7 / 624 (1.12%)
    4 / 624 (0.64%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Metabolism and nutrition disorders
         subjects affected / exposed
    1 / 624 (0.16%)
    0 / 624 (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
    Infections and infestations
         subjects affected / exposed
    12 / 624 (1.92%)
    9 / 624 (1.44%)
         occurrences causally related to treatment / all
    0 / 13
    0 / 9
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 1%
    Non-serious adverse events
    Intervention Control
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    10 / 624 (1.60%)
    0 / 624 (0.00%)
    General disorders and administration site conditions
    General disorders and administration site conditions
         subjects affected / exposed
    5 / 624 (0.80%)
    0 / 624 (0.00%)
         occurrences all number
    5
    0
    Gastrointestinal disorders
    Gastrointestinal disorders
         subjects affected / exposed
    4 / 624 (0.64%)
    0 / 624 (0.00%)
         occurrences all number
    4
    0
    Skin and subcutaneous tissue disorders
    Skin and subcutaneous tissue disorders
         subjects affected / exposed
    1 / 624 (0.16%)
    0 / 624 (0.00%)
         occurrences all number
    1
    0

    More information

    Close Top of page

    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    16 Jul 2010
    Amendment 1 (substantial) was for the amendment of protocol version 12_12/05/2009 to protocol version 13_23/06/2010. This also included the delegation of signing authority for applications/submissions to MHRA and Ethics from Professor Martin Tickle as Chief Investigator to Dr Michael Donaldson the trial Principal Investigator.
    23 Mar 2011
    Amendment 2 (substantial) was submitted to ethics only. This was for the addition of a participant ID card.
    22 Dec 2011
    Amendment 3 (substantial) was for the amendment of protocol version 13_23/06/2010 to protocol version 14_19/08/2011.
    16 Jun 2014
    Amendment 5 (substantial) was submitted to ethics only. This was for the addition of a supplementary study to examine how being part of the trial impacted on oral health related parenting practices.
    21 Jul 2014
    Amendment 6 (substantial) was submitted to ethics only. This was for the addition of a letter to parents in advance of the 36 month visit.

    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/27685609
    http://www.ncbi.nlm.nih.gov/pubmed/28375708
    http://www.ncbi.nlm.nih.gov/pubmed/28521109
    As of 1.2.2020, the UK is no longer an EU Member State. However, EU law still applies to the UK during the transition period
    EU Clinical Trials Register Service Desk: https://servicedesk.ema.europa.eu
    European Medicines Agency © 1995-2020 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    Legal notice
    EMA HMA