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    Clinical Trial Results:
    Immediate oral, immediate topical or delayed oral antibiotics for acute otitis media with discharge (the Runny Ear STudy: REST)

    Summary
    EudraCT number
    		 2017-003635-10
    Trial protocol
    		 GB  
    Global end of trial date
    25 Sep 2020

    Results information
    Results version number
    		 v1(current)
    This version publication date
    25 Apr 2021
    First version publication date
    25 Apr 2021
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    2814
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 -
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    University of Bristol
    Sponsor organisation address
    Beacon House, Queens Road, Bristol, United Kingdom,
    Public contact
    Centre for Academic Primary Care, University of Bristol, +44 01179287350, rest-study@bristol.ac.uk
    Scientific contact
    Centre for Academic Primary Care, University of Bristol, +44 01179287350, rest-study@bristol.ac.uk
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    25 Aug 2020
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    31 Oct 2019
    Global end of trial reached?
    Yes
    Global end of trial date
    25 Sep 2020
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To determine whether either ciprofloxacin 0.3% drops, or delayed oral amoxicillin (clarithromycin if penicillin allergic or other suitable oral antibiotic as chosen by the GP), is non-inferior to current usual care (immediate oral antibiotics) for overall illness duration in children with AOMd presenting to primary care.
    Protection of trial subjects
    Details of adverse events were reported via parent completed questionnaire and collected by the study team.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    01 Sep 2018
    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: 22
    Worldwide total number of subjects
    22
    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)
    4
    Children (2-11 years)
    16
    Adolescents (12-17 years)
    2
    Adults (18-64 years)
    0
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 Screening was automated by the TRANSFORM software when a child with ear discharge presented (with parent/guardian) to a recruiting practice. Participant eligibility was then confirmed by the recruiting clinician.

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Immediate topical ear drops
    Arm description
    		 -
    Arm type
    		 Experimental

    Investigational medicinal product name
    Immediate ciprofloxacin (0.3%) ear drop solution
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Ear drops
    Routes of administration
    Auricular use
    Dosage and administration details
    Immediate ciprofloxacin (0.3%) ear drop solution, four drops given three times a day for 7 days, with an advice sheet on how to administer the ear drops and standardised symptom management advice.

    Arm title
    		 Delayed oral amoxicillin
    Arm description
    		 -
    Arm type
    		 Experimental

    Investigational medicinal product name
    Delayed oral amoxicillin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Oral liquid
    Routes of administration
    Oral use
    Dosage and administration details
    Delayed dose-by-age oral amoxicillin suspension given three times a day for 7 days, and an advice sheet containing structured delaying advice and standardised symptom management advice.

    Arm title
    		 Immediate oral amoxicillin
    Arm description
    		 -
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Immediate oral amoxicillin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Oral liquid
    Routes of administration
    Oral use
    Dosage and administration details
    Immediate dose-by-age oral amoxicillin given three times a day for 7 days, and standardised symptom management advice.

    Number of subjects in period 1
    		Immediate topical ear drops Delayed oral amoxicillin Immediate oral amoxicillin
    Started
    10
    7
    5
    Completed
    10
    7
    5

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Immediate topical ear drops
    Reporting group description
    		 -

    Reporting group title
    Delayed oral amoxicillin
    Reporting group description
    		 -

    Reporting group title
    Immediate oral amoxicillin
    Reporting group description
    		 -

    Reporting group values
    		 Immediate topical ear drops Delayed oral amoxicillin Immediate oral amoxicillin Total
    Number of subjects
    		 10 7 5 22
    Age categorical
    Units: Subjects
        In utero
    		 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0
        Newborns (0-27 days)
    		 0
        Infants and toddlers (28 days-23 months)
    		 0
        Children (2-11 years)
    		 0
        Adolescents (12-17 years)
    		 0
        Adults (18-64 years)
    		 0
        From 65-84 years
    		 0
        85 years and over
    		 0
    Age continuous
    Units: years
        median (inter-quartile range (Q1-Q3))
    		 5 (2 to 6) 5 (3 to 11) 6 (2 to 7) -
    Gender categorical
    Units: Subjects
        Female
    		 6 2 0 8
        Male
    		 4 5 5 14

    End points

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    End points reporting groups
    Reporting group title
    Immediate topical ear drops
    Reporting group description
    		 -

    Reporting group title
    Delayed oral amoxicillin
    Reporting group description
    		 -

    Reporting group title
    Immediate oral amoxicillin
    Reporting group description
    		 -

    Primary: Primary Outcome: Duration of symptoms

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    End point title
    		 Primary Outcome: Duration of symptoms [1]
    End point description
    End point type
    Primary
    End point timeframe
    From baseline up to 14 days
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: The trial was stopped early due to lack of recruitment, as such no formal between group statistical analyses were performed.
    End point values
    		 Immediate topical ear drops Delayed oral amoxicillin Immediate oral amoxicillin
    Number of subjects analysed
    7
    6
    4
    Units: Days
        median (inter-quartile range (Q1-Q3))
    4 (3 to 6)
    4 (3 to 7)
    6 (4 to 9)
    No statistical analyses for this end point

    Secondary: Secondary Outcome: N with symptoms resolved by day 3

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    End point title
    		 Secondary Outcome: N with symptoms resolved by day 3
    End point description
    End point type
    Secondary
    End point timeframe
    Baseline to 3 days
    End point values
    		 Immediate topical ear drops Delayed oral amoxicillin Immediate oral amoxicillin
    Number of subjects analysed
    7
    6
    4
    Units: Participants
        number (not applicable)
    3
    3
    1
    No statistical analyses for this end point

    Secondary: Secondary Outcome: Time to symptoms rated as 'slight problem' or better

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    End point title
    		 Secondary Outcome: Time to symptoms rated as 'slight problem' or better
    End point description
    End point type
    Secondary
    End point timeframe
    Baseline up to 14 days
    End point values
    		 Immediate topical ear drops Delayed oral amoxicillin Immediate oral amoxicillin
    Number of subjects analysed
    7
    6
    4
    Units: Days
        median (inter-quartile range (Q1-Q3))
    3 (2 to 5)
    4 (2 to 6)
    3 (3 to 4)
    No statistical analyses for this end point

    Secondary: Secondary Outcome: N with symptoms rated "slight problem" or better by day 3

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    End point title
    		 Secondary Outcome: N with symptoms rated "slight problem" or better by day 3
    End point description
    End point type
    Secondary
    End point timeframe
    Baseline to day 3
    End point values
    		 Immediate topical ear drops Delayed oral amoxicillin Immediate oral amoxicillin
    Number of subjects analysed
    7
    6
    4
    Units: Participants
        number (not applicable)
    5
    3
    3
    No statistical analyses for this end point

    Secondary: Secondary Outcome: Duration of moderate or worse pain

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    End point title
    		 Secondary Outcome: Duration of moderate or worse pain
    End point description
    End point type
    Secondary
    End point timeframe
    Baseline to 14 days
    End point values
    		 Immediate topical ear drops Delayed oral amoxicillin Immediate oral amoxicillin
    Number of subjects analysed
    7
    6
    4
    Units: Days
        median (inter-quartile range (Q1-Q3))
    1 (1 to 3)
    2 (1 to 4)
    3 (2 to 3)
    No statistical analyses for this end point

    Secondary: Secondary Outcome: Duration of moderate or worse fever

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    End point title
    		 Secondary Outcome: Duration of moderate or worse fever
    End point description
    End point type
    Secondary
    End point timeframe
    Baseline up to 14 days
    End point values
    		 Immediate topical ear drops Delayed oral amoxicillin Immediate oral amoxicillin
    Number of subjects analysed
    7
    6
    4
    Units: Days
        median (inter-quartile range (Q1-Q3))
    1 (1 to 1)
    1 (1 to 1)
    1 (1 to 2)
    No statistical analyses for this end point

    Secondary: Secondary Outcome: Duration of moderate or worse ear discharge

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    End point title
    		 Secondary Outcome: Duration of moderate or worse ear discharge
    End point description
    End point type
    Secondary
    End point timeframe
    Baseline up to 14 days
    End point values
    		 Immediate topical ear drops Delayed oral amoxicillin Immediate oral amoxicillin
    Number of subjects analysed
    7
    6
    4
    Units: Days
        median (inter-quartile range (Q1-Q3))
    2 (1 to 3)
    3 (2 to 3)
    3 (2 to 3)
    No statistical analyses for this end point

    Secondary: Secondary Outcome: Duration of moderate or worse unwell

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    End point title
    		 Secondary Outcome: Duration of moderate or worse unwell
    End point description
    End point type
    Secondary
    End point timeframe
    Baseline up to 14 days
    End point values
    		 Immediate topical ear drops Delayed oral amoxicillin Immediate oral amoxicillin
    Number of subjects analysed
    7
    6
    4
    Units: Days
        median (inter-quartile range (Q1-Q3))
    1 (1 to 1)
    2 (1 to 3)
    2 (2 to 2)
    No statistical analyses for this end point

    Secondary: Secondary Outcome: Duration of moderate or worse sleep

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    End point title
    		 Secondary Outcome: Duration of moderate or worse sleep
    End point description
    End point type
    Secondary
    End point timeframe
    Baseline up to 14 days.
    End point values
    		 Immediate topical ear drops Delayed oral amoxicillin Immediate oral amoxicillin
    Number of subjects analysed
    7
    6
    4
    Units: Days
        median (inter-quartile range (Q1-Q3))
    1 (1 to 4)
    2 (1 to 2)
    2 (2 to 2)
    No statistical analyses for this end point

    Secondary: Secondary Outcome: Duration of moderate or worse crying

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    End point title
    		 Secondary Outcome: Duration of moderate or worse crying
    End point description
    End point type
    Secondary
    End point timeframe
    Baseline up to 14 days
    End point values
    		 Immediate topical ear drops Delayed oral amoxicillin Immediate oral amoxicillin
    Number of subjects analysed
    7
    6
    4
    Units: Days
        median (inter-quartile range (Q1-Q3))
    1 (1 to 3)
    2 (1 to 3)
    3 (2 to 3)
    No statistical analyses for this end point

    Secondary: Secondary Outcome: Duration of moderate or worse eating/ drinking

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    End point title
    		 Secondary Outcome: Duration of moderate or worse eating/ drinking
    End point description
    End point type
    Secondary
    End point timeframe
    Baseline up to 14 days.
    End point values
    		 Immediate topical ear drops Delayed oral amoxicillin Immediate oral amoxicillin
    Number of subjects analysed
    7
    6
    4
    Units: Days
        median (inter-quartile range (Q1-Q3))
    1 (1 to 2)
    1 (1 to 1)
    2 (2 to 2)
    No statistical analyses for this end point

    Secondary: Secondary Outcome: Duration of moderate or worse activities

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    End point title
    		 Secondary Outcome: Duration of moderate or worse activities
    End point description
    End point type
    Secondary
    End point timeframe
    Baseline up to 14 days
    End point values
    		 Immediate topical ear drops Delayed oral amoxicillin Immediate oral amoxicillin
    Number of subjects analysed
    7
    6
    4
    Units: Days
        median (inter-quartile range (Q1-Q3))
    1 (1 to 1)
    2 (1 to 2)
    2 (2 to 2)
    No statistical analyses for this end point

    Secondary: Secondary Outcome: Satisfaction with treatment at day 14

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    End point title
    		 Secondary Outcome: Satisfaction with treatment at day 14
    End point description
    End point type
    Secondary
    End point timeframe
    Day 14
    End point values
    		 Immediate topical ear drops Delayed oral amoxicillin Immediate oral amoxicillin
    Number of subjects analysed
    7
    6
    4
    Units: Counts
        Extremely satisfied
    4
    1
    2
        Satisfied
    3
    4
    1
        Neither satisfied nor dissatisfied
    0
    1
    0
        Not satisfied
    0
    0
    1
        Extremely dissatisfied
    0
    0
    0
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    At Day 7 participants were asked to report on the previous 7 days. At Day 14 participants were asked to report on the previous 7 days.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 NA
    Dictionary version
    NA
    Reporting groups
    Reporting group title
    Immediate topical ear drops
    Reporting group description
    		 -

    Reporting group title
    Delayed oral amoxicillin
    Reporting group description
    		 -

    Reporting group title
    Immediate oral amoxicillin
    Reporting group description
    		 -

    Serious adverse events
    		 Immediate topical ear drops Delayed oral amoxicillin Immediate oral amoxicillin
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
         number of deaths (all causes)
    0
    0
    0
         number of deaths resulting from adverse events
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    		 Immediate topical ear drops Delayed oral amoxicillin Immediate oral amoxicillin
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    2 / 10 (20.00%)
    1 / 7 (14.29%)
    1 / 6 (16.67%)
    Infections and infestations
    New or worsening symptoms of infection
         subjects affected / exposed
    2 / 10 (20.00%)
    1 / 7 (14.29%)
    1 / 6 (16.67%)
         occurrences all number
    2
    1
    1

    More information

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

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

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

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