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    Clinical Trial Results:
    A 2x2 factorial randomised examiner blind open label trial to determine the CLinical and cost- Effectiveness of hypertonic saline (HTS 6%) and carbocisteine for Airway cleaRance versus usual care over 52 weeks in bronchiectasis

    Summary
    EudraCT number
    		 2017-000664-14
    Trial protocol
    		 GB  
    Global end of trial date
    24 Sep 2024

    Results information
    Results version number
    		 v1(current)
    This version publication date
    01 Jan 2026
    First version publication date
    01 Jan 2026
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    16178SE-AS
    Additional study identifiers
    ISRCTN number
    		 ISRCTN89040295
    US NCT number
    		 NCT04140214
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Belfast Health and Social Care Trust
    Sponsor organisation address
    Non Clinical Support Building, Royal Victoria Hospital, 274 Grosvenor Road, Belfast, Belfast, United Kingdom, BT9 7AB
    Public contact
    Professor Judy Bradley, Queens University Belfast, 00 44 2895047973, judy.bradley@qub.ac.uk
    Scientific contact
    Professor Judy Bradley, Queens University Belfast, 00 44 2895047973, judy.bradley@qub.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
    18 Dec 2024
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    24 Sep 2024
    Global end of trial reached?
    Yes
    Global end of trial date
    24 Sep 2024
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    This study aims to find out if hypertonic saline (salty water) or carbocisteine or a combination of both is most effective at reducing the number of exacerbations in people with bronchiectasis following 52 weeks of treatment. People with bronchiectasis have chronic sputum production and both hypertonic saline and carbocisteine can help people with bronchiectasis clear their chest. Research has shown that these agents can make it easier for patients to cough up sputum resulting in potentially fewer exacerbations requiring antibiotics and hospital admissions.
    Protection of trial subjects
    A small number of this patient population experience small side effects from nebulising hypertonic saline (HTS) e.g. wheeze. The likelihood of this will be minimised by all patients assigned hypertonic saline completing a drug response assessment on entry into the study. A small number of patients experience some minimal side effects (stomach discomfort, vomiting, skin rashes and allergies) associated with carbocisteine. The PI or designee recorded all directly observed Adverse Events and all Adverse Events spontaneously reported by the patient. Any complications were treated as per the standard procedure for the treating clinician. A Data Monitoring and Ethics Committee (DMEC) was also convened will containing experts in respiratory medicine.
    Background therapy
    		 None
    Evidence for comparator
    		 -
    Actual start date of recruitment
    01 Jan 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: 288
    Worldwide total number of subjects
    288
    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)
    0
    Adults (18-64 years)
    103
    From 65 to 84 years
    181
    85 years and over
    4

    Subject disposition

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    Recruitment
    Recruitment details
    		 288 patients were recruited between 27/06/2018 and 28/09/2023 from UK based centres.

    Pre-assignment
    Screening details
    		 Overall 2804 patients were assessed for eligibility for the CLEAR Trial. Of these 288 were recruited to the study. Of those 288 patients recruited, 46 patients completed a 30-day washout of mucoactive treatment prior to recruitment.

    Pre-assignment period milestones
    Number of subjects started
    		 288
    Number of subjects completed
    		 288

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Intervention 1: HTS (6%)
    Arm description
    		 Standard care and twice daily nebulised HTS (6%) over 52 weeks
    Arm type
    		 Experimental

    Investigational medicinal product name
    Mucoclear Hypertonic Saline (6%)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Inhalation solution
    Routes of administration
    Inhalation use
    Dosage and administration details
    Administer a 1 x 4 mL ampoule twice daily for 52 weeks using the e-Flow nebuliser.

    Arm title
    		 Intervention 2: Carbocisteine
    Arm description
    		 Standard care and carbocisteine (750 mg three times per day until visit 3 reducing to 750 mg two times per day) over 52 weeks.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Carbocisteine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    2 x 375 mg oral capsules three times daily until visit 3. At visit 3 patients were instructed to reduce their dose to 2 x 375 mg capsules twice daily for the remainder of the 52 weeks.

    Arm title
    		 Intervention 3: Mucoclear Hypertonic Saline and Carbocisteine
    Arm description
    		 Standard care and combination of twice daily nebulised HTS (6%) and carbocisteine (750 mg of three times per day until visit 3 reducing to 750 mg twice per day) over 52 weeks.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Mucoclear Hypertonic Saline (6%)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Inhalation solution
    Routes of administration
    Inhalation use
    Dosage and administration details
    Administer a 1 x 4 mL ampoule twice daily for 52 weeks using the e-Flow nebuliser.

    Investigational medicinal product name
    Carbocisteine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    2 x 375 mg oral capsules three times daily until visit 3. At visit 3 patients were instructed to reduce their dose to 2 x 375 mg capsules twice daily for the remainder of the 52 weeks.

    Arm title
    		 Control: Standard Care
    Arm description
    		 Standard care over 52 weeks
    Arm type
    		 No intervention

    Investigational medicinal product name
    No investigational medicinal product assigned in this arm
    Number of subjects in period 1
    		Intervention 1: HTS (6%) Intervention 2: Carbocisteine Intervention 3: Mucoclear Hypertonic Saline and Carbocisteine Control: Standard Care
    Started
    73
    71
    73
    71
    Completed
    67
    70
    59
    71
    Not completed
    6
    1
    14
    0
         did not reach week 8 as per mITT definition
    6
    1
    14
    -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Intervention 1: HTS (6%)
    Reporting group description
    		 Standard care and twice daily nebulised HTS (6%) over 52 weeks

    Reporting group title
    Intervention 2: Carbocisteine
    Reporting group description
    		 Standard care and carbocisteine (750 mg three times per day until visit 3 reducing to 750 mg two times per day) over 52 weeks.

    Reporting group title
    Intervention 3: Mucoclear Hypertonic Saline and Carbocisteine
    Reporting group description
    		 Standard care and combination of twice daily nebulised HTS (6%) and carbocisteine (750 mg of three times per day until visit 3 reducing to 750 mg twice per day) over 52 weeks.

    Reporting group title
    Control: Standard Care
    Reporting group description
    		 Standard care over 52 weeks

    Reporting group values
    		 Intervention 1: HTS (6%) Intervention 2: Carbocisteine Intervention 3: Mucoclear Hypertonic Saline and Carbocisteine Control: Standard Care Total
    Number of subjects
    		 73 71 73 71 288
    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
        arithmetic mean (standard deviation)
    		 63.5 ( 14.0 ) 66.0 ( 13.2 ) 67.2 ( 13.0 ) 66.3 ( 11.5 ) -
    Gender categorical
    Units: Subjects
        Female
    		 38 47 48 38 171
        Male
    		 35 24 25 33 117
    Ethnicity
    Units: Subjects
        White
    		 72 67 70 69 278
        Asian/Asian British
    		 1 1 1 0 3
        Indian
    		 0 1 0 1 2
        Chinese
    		 0 1 0 1 2
        Black/African/Caribbean/Black British
    		 0 1 1 0 2
        African
    		 0 0 1 0 1
    Height
    Units: metre
        arithmetic mean (standard deviation)
    		 168.5 ( 7.9 ) 164.6 ( 9.9 ) 163.6 ( 9.5 ) 166.7 ( 9.8 ) -
    Weight
    Units: kilogram(s)
        arithmetic mean (standard deviation)
    		 79.6 ( 16.4 ) 71.1 ( 16.9 ) 75.2 ( 17.8 ) 80.3 ( 16.6 ) -
    Temperature
    Units: celsius temperature
        arithmetic mean (standard deviation)
    		 36.4 ( 0.6 ) 36.5 ( 0.4 ) 36.5 ( 0.4 ) 36.4 ( 0.5 ) -
    Systolic BP
    Units: mmHg
        arithmetic mean (standard deviation)
    		 136.4 ( 18.3 ) 135.7 ( 18.1 ) 135.1 ( 14.0 ) 136.3 ( 18.6 ) -
    Diastolic BP
    Units: mmHg
        arithmetic mean (standard deviation)
    		 77.8 ( 10.0 ) 76.0 ( 9.1 ) 77.3 ( 8.4 ) 77.9 ( 9.0 ) -
    Pulse
    Units: BPM
        arithmetic mean (standard deviation)
    		 72.1 ( 14.0 ) 71.7 ( 10.3 ) 72.7 ( 10.7 ) 72.9 ( 10.9 ) -
    Respiratory Rate
    Units: per minute
        arithmetic mean (standard deviation)
    		 16.7 ( 2.8 ) 16.9 ( 2.3 ) 16.8 ( 2.5 ) 16.8 ( 2.1 ) -
    SpO2
    Units: Percentage
        arithmetic mean (standard deviation)
    		 96.5 ( 1.3 ) 96.2 ( 1.9 ) 96.2 ( 1.7 ) 96.4 ( 1.4 ) -
    BSI Score
    Units: Number
        arithmetic mean (standard deviation)
    		 6.8 ( 3.3 ) 7.9 ( 2.8 ) 7.1 ( 3.3 ) 7.7 ( 3.5 ) -
    FACED Score
    Units: Number
        arithmetic mean (standard deviation)
    		 1.9 ( 1.6 ) 2.4 ( 1.4 ) 2.0 ( 1.4 ) 2.2 ( 1.4 ) -

    End points

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    End points reporting groups
    Reporting group title
    Intervention 1: HTS (6%)
    Reporting group description
    		 Standard care and twice daily nebulised HTS (6%) over 52 weeks

    Reporting group title
    Intervention 2: Carbocisteine
    Reporting group description
    		 Standard care and carbocisteine (750 mg three times per day until visit 3 reducing to 750 mg two times per day) over 52 weeks.

    Reporting group title
    Intervention 3: Mucoclear Hypertonic Saline and Carbocisteine
    Reporting group description
    		 Standard care and combination of twice daily nebulised HTS (6%) and carbocisteine (750 mg of three times per day until visit 3 reducing to 750 mg twice per day) over 52 weeks.

    Reporting group title
    Control: Standard Care
    Reporting group description
    		 Standard care over 52 weeks

    Primary: Mean number of exacerbations over 52 weeks

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    End point title
    		 Mean number of exacerbations over 52 weeks
    End point description
    Mean number of exacerbations over 52 weeks
    End point type
    Primary
    End point timeframe
    Randomisation (Baseline) until week 52
    End point values
    		 Intervention 1: HTS (6%) Intervention 2: Carbocisteine Intervention 3: Mucoclear Hypertonic Saline and Carbocisteine Control: Standard Care
    Number of subjects analysed
    67
    70
    59
    71
    Units: Number
        arithmetic mean (standard deviation)
    0.75 ( 1.08 )
    0.93 ( 0.94 )
    0.78 ( 1.18 )
    1.04 ( 1.54 )
    Statistical analysis title
    		 Primary Outcome: HTS vs No
    Statistical analysis description
    HTS vs No i.e. Group 1&3 vs Group 2&4 Mean number of exacerbations over 52 weeks
    Comparison groups
    Intervention 1: HTS (6%) v Intervention 2: Carbocisteine v Intervention 3: Mucoclear Hypertonic Saline and Carbocisteine v Control: Standard Care
    Number of subjects included in analysis
    267
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [1]
    P-value
    		 = 0.119
    Method
    		 Negative Binomial Regression
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -0.26
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.58
         upper limit
    		 0.07
    Notes
    [1] - Unadjusted
    Statistical analysis title
    		 Primary Outcome: CARB vs No
    Statistical analysis description
    CARB vs No i.e. Group 2&3 vs Group 1&4 Mean number of exacerbations over 52 weeks
    Comparison groups
    Intervention 1: HTS (6%) v Intervention 2: Carbocisteine v Intervention 3: Mucoclear Hypertonic Saline and Carbocisteine v Control: Standard Care
    Number of subjects included in analysis
    267
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [2]
    P-value
    		 = 0.792
    Method
    		 Negative Binomial Regression
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -0.04
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.37
         upper limit
    		 0.28
    Notes
    [2] - Unadjusted

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    The AE reporting period for the trial begins upon enrolment into the trial and ends 30 days following the last administration of the study drug.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    4
    Reporting groups
    Reporting group title
    Intervention 1: HTS (6%)
    Reporting group description
    		 Standard care and twice daily nebulised HTS (6%) over 52 weeks

    Reporting group title
    Intervention 2: Carbocisteine
    Reporting group description
    		 Standard care and carbocisteine (750 mg three times per day until visit 3 reducing to 750 mg two times per day) over 52 weeks.

    Reporting group title
    Intervention 3: Mucoclear Hypertonic Saline and Carbocisteine
    Reporting group description
    		 Standard care and combination of twice daily nebulised HTS (6%) and carbocisteine (750 mg of three times per day until visit 3 reducing to 750 mg twice per day) over 52 weeks.

    Reporting group title
    Control: Standard Care
    Reporting group description
    		 Standard care over 52 weeks

    Serious adverse events
    		 Intervention 1: HTS (6%) Intervention 2: Carbocisteine Intervention 3: Mucoclear Hypertonic Saline and Carbocisteine Control: Standard Care
    Total subjects affected by serious adverse events
         subjects affected / exposed
    6 / 72 (8.33%)
    10 / 72 (13.89%)
    10 / 69 (14.49%)
    9 / 71 (12.68%)
         number of deaths (all causes)
    0
    1
    0
    1
         number of deaths resulting from adverse events
    0
    0
    0
    0
    Injury, poisoning and procedural complications
    Fall
         subjects affected / exposed
    0 / 72 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pelvic fracture
         subjects affected / exposed
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
    1 / 71 (1.41%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Fracture
         subjects affected / exposed
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
    2 / 71 (2.82%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    Fall
         subjects affected / exposed
    0 / 72 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Myasthenia gravis
         subjects affected / exposed
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Acute coronary syndrome
         subjects affected / exposed
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Myocardial Infarction
         subjects affected / exposed
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
    2 / 71 (2.82%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Palpitations
         subjects affected / exposed
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
    1 / 71 (1.41%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ventricular Tachycardia
         subjects affected / exposed
    0 / 72 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Surgical and medical procedures
    Cholecystectomy
         subjects affected / exposed
    0 / 72 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hip surgery
         subjects affected / exposed
    0 / 72 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Thrombophlebitis
         subjects affected / exposed
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Vertigo postional
         subjects affected / exposed
    0 / 72 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    Vertigo
         subjects affected / exposed
    1 / 72 (1.39%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Appendicitis
         subjects affected / exposed
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
    1 / 71 (1.41%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bleeding Duodenal Ulcer
         subjects affected / exposed
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
    1 / 71 (1.41%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Chest pain
         subjects affected / exposed
    1 / 72 (1.39%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Colecystitis
         subjects affected / exposed
    0 / 72 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Colitis Ischaemic
         subjects affected / exposed
    1 / 72 (1.39%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haemorrhage
         subjects affected / exposed
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intestinal Obstruction
         subjects affected / exposed
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
    1 / 71 (1.41%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Oesophagitis
         subjects affected / exposed
    0 / 72 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Atrial Fibrillation
         subjects affected / exposed
    1 / 72 (1.39%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dyspnoea
         subjects affected / exposed
    0 / 72 (0.00%)
    1 / 72 (1.39%)
    1 / 69 (1.45%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lower respiratory tract infection
         subjects affected / exposed
    0 / 72 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    0 / 72 (0.00%)
    1 / 72 (1.39%)
    1 / 69 (1.45%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Sebacious Cyst
         subjects affected / exposed
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Pyelonephritis
         subjects affected / exposed
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Joint effusion
         subjects affected / exposed
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Influenza
         subjects affected / exposed
    1 / 72 (1.39%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lower respiratory tract infection
         subjects affected / exposed
    1 / 72 (1.39%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    0 / 72 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Intervention 1: HTS (6%) Intervention 2: Carbocisteine Intervention 3: Mucoclear Hypertonic Saline and Carbocisteine Control: Standard Care
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    50 / 72 (69.44%)
    53 / 72 (73.61%)
    50 / 69 (72.46%)
    41 / 71 (57.75%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Large intestine polyp
         subjects affected / exposed
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
    1 / 71 (1.41%)
         occurrences all number
    0
    0
    0
    1
    Lipoma
         subjects affected / exposed
    0 / 72 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
    0 / 71 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Prostate cancer
         subjects affected / exposed
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
    1 / 71 (1.41%)
         occurrences all number
    0
    0
    0
    1
    Headache
         subjects affected / exposed
    3 / 72 (4.17%)
    3 / 72 (4.17%)
    2 / 69 (2.90%)
    0 / 71 (0.00%)
         occurrences all number
    3
    3
    2
    0
    Vascular disorders
    Aortic aneurysm
         subjects affected / exposed
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
    0 / 71 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Circulatory collapse
         subjects affected / exposed
    0 / 72 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
    0 / 71 (0.00%)
         occurrences all number
    0
    2
    0
    0
    Dizziness
         subjects affected / exposed
    3 / 72 (4.17%)
    3 / 72 (4.17%)
    2 / 69 (2.90%)
    1 / 71 (1.41%)
         occurrences all number
    3
    3
    2
    1
    Dyspnoea
         subjects affected / exposed
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
    0 / 71 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Haematuria
         subjects affected / exposed
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
    1 / 71 (1.41%)
         occurrences all number
    0
    0
    0
    1
    Peripheral swelling
         subjects affected / exposed
    0 / 72 (0.00%)
    1 / 72 (1.39%)
    1 / 69 (1.45%)
    0 / 71 (0.00%)
         occurrences all number
    0
    1
    1
    0
    Pulmonary embolism
         subjects affected / exposed
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
    0 / 71 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Syncope
         subjects affected / exposed
    1 / 72 (1.39%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
    0 / 71 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Thrombophlebitis
         subjects affected / exposed
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
    0 / 71 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Varicose vein
         subjects affected / exposed
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
    0 / 71 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Surgical and medical procedures
    Cataract Operation
         subjects affected / exposed
    0 / 72 (0.00%)
    3 / 72 (4.17%)
    1 / 69 (1.45%)
    0 / 71 (0.00%)
         occurrences all number
    0
    4
    2
    0
    Cholecystectomy
         subjects affected / exposed
    0 / 72 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
    0 / 71 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Wisdom teeth removal
         subjects affected / exposed
    0 / 72 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
    0 / 71 (0.00%)
         occurrences all number
    0
    1
    0
    0
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    0 / 72 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
    1 / 71 (1.41%)
         occurrences all number
    0
    1
    0
    1
    Chills
         subjects affected / exposed
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
    1 / 71 (1.41%)
         occurrences all number
    0
    0
    0
    1
    Cold sweat
         subjects affected / exposed
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
    1 / 71 (1.41%)
         occurrences all number
    0
    0
    0
    1
    Drug withdrawal syndrome
         subjects affected / exposed
    1 / 72 (1.39%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
    0 / 71 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Facial pain
         subjects affected / exposed
    1 / 72 (1.39%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
    0 / 71 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Fatigue
         subjects affected / exposed
    1 / 72 (1.39%)
    4 / 72 (5.56%)
    2 / 69 (2.90%)
    1 / 71 (1.41%)
         occurrences all number
    1
    4
    2
    1
    Feeling jittery
         subjects affected / exposed
    1 / 72 (1.39%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
    0 / 71 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Injection site reaction
         subjects affected / exposed
    1 / 72 (1.39%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
    0 / 71 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Lethargy
         subjects affected / exposed
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
    1 / 71 (1.41%)
         occurrences all number
    0
    0
    0
    1
    Night sweats
         subjects affected / exposed
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
    0 / 71 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Nodule
         subjects affected / exposed
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
    0 / 71 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Pyrexia
         subjects affected / exposed
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
    1 / 71 (1.41%)
         occurrences all number
    0
    0
    0
    1
    Thirst
         subjects affected / exposed
    1 / 72 (1.39%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
    0 / 71 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Immune system disorders
    Hypersensitivity
         subjects affected / exposed
    0 / 72 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
    0 / 71 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Urticaria
         subjects affected / exposed
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
    1 / 71 (1.41%)
         occurrences all number
    0
    0
    0
    1
    Reproductive system and breast disorders
    Batholin's abscess
         subjects affected / exposed
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
    1 / 71 (1.41%)
         occurrences all number
    0
    0
    0
    1
    Breast mass
         subjects affected / exposed
    0 / 72 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
    0 / 71 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Breast pain
         subjects affected / exposed
    1 / 72 (1.39%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
    0 / 71 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Metrorrhagia
         subjects affected / exposed
    0 / 72 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
    0 / 71 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Penis disorder
         subjects affected / exposed
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
    0 / 71 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Prostatomegaly
         subjects affected / exposed
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
    1 / 71 (1.41%)
         occurrences all number
    0
    0
    0
    1
    Vaginal haemorrhage
         subjects affected / exposed
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
    1 / 71 (1.41%)
         occurrences all number
    0
    0
    0
    1
    Respiratory, thoracic and mediastinal disorders
    Aphonia
         subjects affected / exposed
    0 / 72 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
    0 / 71 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Asthma
         subjects affected / exposed
    0 / 72 (0.00%)
    3 / 72 (4.17%)
    0 / 69 (0.00%)
    1 / 71 (1.41%)
         occurrences all number
    0
    3
    0
    1
    Bronchospasm
         subjects affected / exposed
    2 / 72 (2.78%)
    0 / 72 (0.00%)
    2 / 69 (2.90%)
    0 / 71 (0.00%)
         occurrences all number
    2
    0
    2
    0
    Chest discomfort
         subjects affected / exposed
    3 / 72 (4.17%)
    0 / 72 (0.00%)
    2 / 69 (2.90%)
    1 / 71 (1.41%)
         occurrences all number
    3
    0
    2
    1
    Chest pain
         subjects affected / exposed
    1 / 72 (1.39%)
    1 / 72 (1.39%)
    1 / 69 (1.45%)
    1 / 71 (1.41%)
         occurrences all number
    1
    1
    1
    1
    Chest tightness
         subjects affected / exposed
    1 / 72 (1.39%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
    1 / 71 (1.41%)
         occurrences all number
    1
    0
    0
    1
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
    0 / 71 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Chronic rhinosinusitis without nasal polyps
         subjects affected / exposed
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
    1 / 71 (1.41%)
         occurrences all number
    0
    0
    0
    1
    Cough
         subjects affected / exposed
    5 / 72 (6.94%)
    3 / 72 (4.17%)
    2 / 69 (2.90%)
    1 / 71 (1.41%)
         occurrences all number
    5
    3
    2
    1
    Darker sputum
         subjects affected / exposed
    0 / 72 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
    0 / 71 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Dry throat
         subjects affected / exposed
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
    0 / 71 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Dysphonia
         subjects affected / exposed
    0 / 72 (0.00%)
    1 / 72 (1.39%)
    1 / 69 (1.45%)
    0 / 71 (0.00%)
         occurrences all number
    0
    1
    2
    0
    Dyspnoea
         subjects affected / exposed
    1 / 72 (1.39%)
    4 / 72 (5.56%)
    4 / 69 (5.80%)
    2 / 71 (2.82%)
         occurrences all number
    3
    5
    5
    3
    Epistaxis
         subjects affected / exposed
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
    2 / 71 (2.82%)
         occurrences all number
    0
    0
    1
    2
    Haemoptysis
         subjects affected / exposed
    2 / 72 (2.78%)
    0 / 72 (0.00%)
    2 / 69 (2.90%)
    2 / 71 (2.82%)
         occurrences all number
    2
    0
    2
    2
    Infective exacerbation of bronchiectasis
         subjects affected / exposed
    0 / 72 (0.00%)
    3 / 72 (4.17%)
    1 / 69 (1.45%)
    1 / 71 (1.41%)
         occurrences all number
    0
    3
    1
    1
    Lower Respiratory Tract Infection
         subjects affected / exposed
    1 / 72 (1.39%)
    2 / 72 (2.78%)
    0 / 69 (0.00%)
    1 / 71 (1.41%)
         occurrences all number
    1
    2
    0
    1
    Nasal congestion and inflammation
         subjects affected / exposed
    0 / 72 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
    0 / 71 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Non cardiac chest pain
         subjects affected / exposed
    2 / 72 (2.78%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
    0 / 71 (0.00%)
         occurrences all number
    2
    0
    0
    0
    Oropharyngeal pain
         subjects affected / exposed
    4 / 72 (5.56%)
    1 / 72 (1.39%)
    2 / 69 (2.90%)
    4 / 71 (5.63%)
         occurrences all number
    4
    1
    2
    4
    Painful respiration
         subjects affected / exposed
    1 / 72 (1.39%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
    0 / 71 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Pneumonia
         subjects affected / exposed
    0 / 72 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
    0 / 71 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Pulmonary congestion
         subjects affected / exposed
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
    0 / 71 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Pulmonary pain
         subjects affected / exposed
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
    1 / 71 (1.41%)
         occurrences all number
    0
    0
    0
    1
    Respiratory tract congestion
         subjects affected / exposed
    0 / 72 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
    1 / 71 (1.41%)
         occurrences all number
    0
    1
    0
    1
    Rhinitis
         subjects affected / exposed
    0 / 72 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
    0 / 71 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Rhinitus allergic
         subjects affected / exposed
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
    0 / 71 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Rhinorrhoea
         subjects affected / exposed
    1 / 72 (1.39%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
    1 / 71 (1.41%)
         occurrences all number
    1
    0
    1
    1
    Sinus pain
         subjects affected / exposed
    1 / 72 (1.39%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
    0 / 71 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Sneezing
         subjects affected / exposed
    1 / 72 (1.39%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
    0 / 71 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Sputum Increased
         subjects affected / exposed
    1 / 72 (1.39%)
    2 / 72 (2.78%)
    0 / 69 (0.00%)
    0 / 71 (0.00%)
         occurrences all number
    1
    2
    0
    0
    Syncope
         subjects affected / exposed
    0 / 72 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
    0 / 71 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Throat irritation
         subjects affected / exposed
    1 / 72 (1.39%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
    0 / 71 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Virus
         subjects affected / exposed
    1 / 72 (1.39%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
    0 / 71 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Wheezing
         subjects affected / exposed
    1 / 72 (1.39%)
    2 / 72 (2.78%)
    3 / 69 (4.35%)
    2 / 71 (2.82%)
         occurrences all number
    1
    2
    3
    2
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
    1 / 71 (1.41%)
         occurrences all number
    0
    0
    0
    1
    Depressed mood
         subjects affected / exposed
    2 / 72 (2.78%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
    0 / 71 (0.00%)
         occurrences all number
    2
    1
    0
    0
    Nightmare
         subjects affected / exposed
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
    0 / 71 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Panic attack
         subjects affected / exposed
    1 / 72 (1.39%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
    0 / 71 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Investigations
    Blood cholesterol increased
         subjects affected / exposed
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
    1 / 71 (1.41%)
         occurrences all number
    0
    0
    1
    1
    Blood abnormal
         subjects affected / exposed
    1 / 72 (1.39%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
    1 / 71 (1.41%)
         occurrences all number
    1
    0
    0
    1
    Blood urine present
         subjects affected / exposed
    1 / 72 (1.39%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
    0 / 71 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Colonoscopy
         subjects affected / exposed
    1 / 72 (1.39%)
    0 / 72 (0.00%)
    2 / 69 (2.90%)
    0 / 71 (0.00%)
         occurrences all number
    1
    0
    3
    0
    Cystoscopy
         subjects affected / exposed
    1 / 72 (1.39%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
    0 / 71 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Escherichia test positive
         subjects affected / exposed
    0 / 72 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
    0 / 71 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Oesophagogastroduodenoscopy
         subjects affected / exposed
    1 / 72 (1.39%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
    0 / 71 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Serum ferritin decreased
         subjects affected / exposed
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
    0 / 71 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Weight decreased
         subjects affected / exposed
    0 / 72 (0.00%)
    1 / 72 (1.39%)
    1 / 69 (1.45%)
    1 / 71 (1.41%)
         occurrences all number
    0
    1
    1
    1
    Injury, poisoning and procedural complications
    Ankle Fracture
         subjects affected / exposed
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
    1 / 71 (1.41%)
         occurrences all number
    0
    0
    1
    1
    Fall
         subjects affected / exposed
    1 / 72 (1.39%)
    2 / 72 (2.78%)
    3 / 69 (4.35%)
    3 / 71 (4.23%)
         occurrences all number
    1
    3
    3
    3
    Head injury
         subjects affected / exposed
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
    0 / 71 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Ligament sprain
         subjects affected / exposed
    1 / 72 (1.39%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
    0 / 71 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Limb injury
         subjects affected / exposed
    1 / 72 (1.39%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
    0 / 71 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Pelvic Fracture
         subjects affected / exposed
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
    1 / 71 (1.41%)
         occurrences all number
    0
    0
    0
    1
    Pulled muscle
         subjects affected / exposed
    0 / 72 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
    0 / 71 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Road traffic accident
         subjects affected / exposed
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
    0 / 71 (0.00%)
         occurrences all number
    0
    0
    2
    0
    Skin laceration
         subjects affected / exposed
    0 / 72 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
    0 / 71 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Cardiac disorders
    Hypertrophic cardiomyopathy
         subjects affected / exposed
    0 / 72 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
    0 / 71 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Arterial fibrosis
         subjects affected / exposed
    1 / 72 (1.39%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
    0 / 71 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Myocardial infarction
         subjects affected / exposed
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
    2 / 71 (2.82%)
         occurrences all number
    0
    0
    1
    2
    Tachycardia
         subjects affected / exposed
    2 / 72 (2.78%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
    0 / 71 (0.00%)
         occurrences all number
    2
    0
    0
    0
    Bundle branch block left
         subjects affected / exposed
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
    1 / 71 (1.41%)
         occurrences all number
    0
    0
    0
    1
    Palpitations
         subjects affected / exposed
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
    3 / 71 (4.23%)
         occurrences all number
    0
    0
    0
    3
    Acute coronary syndrome
         subjects affected / exposed
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
    0 / 71 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Atrial fibrillation
         subjects affected / exposed
    1 / 72 (1.39%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
    0 / 71 (0.00%)
         occurrences all number
    1
    1
    0
    0
    Nervous system disorders
    Bell's palsy
         subjects affected / exposed
    0 / 72 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
    0 / 71 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Gait disturbance
         subjects affected / exposed
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
    1 / 71 (1.41%)
         occurrences all number
    0
    0
    0
    1
    Hypoaesthesia
         subjects affected / exposed
    0 / 72 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
    0 / 71 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Loss of consciousness
         subjects affected / exposed
    0 / 72 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
    0 / 71 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Nerve compression
         subjects affected / exposed
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
    1 / 71 (1.41%)
         occurrences all number
    0
    0
    0
    1
    Ophthalmic migraine
         subjects affected / exposed
    1 / 72 (1.39%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
    0 / 71 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Taste disorder
         subjects affected / exposed
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
    0 / 71 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Trigeminal neuralgia
         subjects affected / exposed
    1 / 72 (1.39%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
    0 / 71 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Vertigo positional
         subjects affected / exposed
    0 / 72 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
    0 / 71 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    1 / 72 (1.39%)
    0 / 72 (0.00%)
    2 / 69 (2.90%)
    0 / 71 (0.00%)
         occurrences all number
    1
    0
    2
    0
    Lymphadenopathy
         subjects affected / exposed
    0 / 72 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
    0 / 71 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Ear and labyrinth disorders
    Ear infection
         subjects affected / exposed
    0 / 72 (0.00%)
    2 / 72 (2.78%)
    0 / 69 (0.00%)
    0 / 71 (0.00%)
         occurrences all number
    0
    2
    0
    0
    Excessive cerumen production
         subjects affected / exposed
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
    0 / 71 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Otorrhoea
         subjects affected / exposed
    0 / 72 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
    0 / 71 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Tinnitus
         subjects affected / exposed
    0 / 72 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
    0 / 71 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Vertigo
         subjects affected / exposed
    1 / 72 (1.39%)
    0 / 72 (0.00%)
    2 / 69 (2.90%)
    0 / 71 (0.00%)
         occurrences all number
    1
    0
    2
    0
    Eye disorders
    Conjunctivitis
         subjects affected / exposed
    0 / 72 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
    0 / 71 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Cataract
         subjects affected / exposed
    0 / 72 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
    1 / 71 (1.41%)
         occurrences all number
    0
    1
    0
    1
    Eye Swelling
         subjects affected / exposed
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    2 / 69 (2.90%)
    0 / 71 (0.00%)
         occurrences all number
    0
    0
    2
    0
    Eye irritation
         subjects affected / exposed
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
    0 / 71 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Eye pruritis
         subjects affected / exposed
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
    0 / 71 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Hordeolum
         subjects affected / exposed
    1 / 72 (1.39%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
    0 / 71 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Ocular hyperaemia
         subjects affected / exposed
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
    0 / 71 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Swelling of eyelid
         subjects affected / exposed
    1 / 72 (1.39%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
    0 / 71 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Gastrointestinal disorders
    Abdominal discomfort
         subjects affected / exposed
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
    0 / 71 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Abdominal distension
         subjects affected / exposed
    1 / 72 (1.39%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
    0 / 71 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Abdominal pain
         subjects affected / exposed
    2 / 72 (2.78%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
    1 / 71 (1.41%)
         occurrences all number
    3
    0
    1
    1
    Abdominal pain upper
         subjects affected / exposed
    2 / 72 (2.78%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
    0 / 71 (0.00%)
         occurrences all number
    2
    0
    1
    0
    Anal pruritus
         subjects affected / exposed
    0 / 72 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
    0 / 71 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Appendicitis
         subjects affected / exposed
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
    1 / 71 (1.41%)
         occurrences all number
    0
    0
    0
    1
    Chapped lips
         subjects affected / exposed
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
    0 / 71 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Chest pain
         subjects affected / exposed
    1 / 72 (1.39%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
    0 / 71 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Colitis ischaemic
         subjects affected / exposed
    1 / 72 (1.39%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
    0 / 71 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Constipation
         subjects affected / exposed
    1 / 72 (1.39%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
    0 / 71 (0.00%)
         occurrences all number
    1
    1
    0
    0
    Diarrhoea
         subjects affected / exposed
    1 / 72 (1.39%)
    6 / 72 (8.33%)
    3 / 69 (4.35%)
    3 / 71 (4.23%)
         occurrences all number
    1
    6
    3
    4
    Diverticulitis
         subjects affected / exposed
    0 / 72 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
    1 / 71 (1.41%)
         occurrences all number
    0
    1
    0
    2
    Dry mouth
         subjects affected / exposed
    2 / 72 (2.78%)
    0 / 72 (0.00%)
    2 / 69 (2.90%)
    1 / 71 (1.41%)
         occurrences all number
    2
    0
    2
    1
    Duodenal ulcer perforation
         subjects affected / exposed
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
    1 / 71 (1.41%)
         occurrences all number
    0
    0
    0
    1
    Faeces discoloured
         subjects affected / exposed
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
    0 / 71 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Gastritis
         subjects affected / exposed
    0 / 72 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
    0 / 71 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Gastrointestinal haemorrhage
         subjects affected / exposed
    1 / 72 (1.39%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
    0 / 71 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Gastrooesophageal reflux disease
         subjects affected / exposed
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
    0 / 71 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Haematochezia
         subjects affected / exposed
    1 / 72 (1.39%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
    0 / 71 (0.00%)
         occurrences all number
    1
    1
    0
    0
    Haemorrhoids
         subjects affected / exposed
    0 / 72 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
    0 / 71 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Heartburn
         subjects affected / exposed
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
    0 / 71 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Hernia
         subjects affected / exposed
    0 / 72 (0.00%)
    1 / 72 (1.39%)
    1 / 69 (1.45%)
    0 / 71 (0.00%)
         occurrences all number
    0
    1
    1
    0
    Intestinal obstruction
         subjects affected / exposed
    0 / 72 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
    1 / 71 (1.41%)
         occurrences all number
    0
    1
    0
    1
    Irritable bowel syndrome
         subjects affected / exposed
    0 / 72 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
    0 / 71 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Mouth ulceration
         subjects affected / exposed
    1 / 72 (1.39%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
    0 / 71 (0.00%)
         occurrences all number
    1
    1
    0
    0
    Nausea
         subjects affected / exposed
    1 / 72 (1.39%)
    6 / 72 (8.33%)
    7 / 69 (10.14%)
    0 / 71 (0.00%)
         occurrences all number
    1
    6
    7
    0
    Oesophagitis
         subjects affected / exposed
    0 / 72 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
    0 / 71 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Oral disorder
         subjects affected / exposed
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
    1 / 71 (1.41%)
         occurrences all number
    0
    0
    0
    1
    Upper gastrointestinal haemorrhage
         subjects affected / exposed
    1 / 72 (1.39%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
    0 / 71 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Vomiting
         subjects affected / exposed
    4 / 72 (5.56%)
    2 / 72 (2.78%)
    4 / 69 (5.80%)
    1 / 71 (1.41%)
         occurrences all number
    4
    2
    6
    1
    Skin and subcutaneous tissue disorders
    Contusion
         subjects affected / exposed
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
    1 / 71 (1.41%)
         occurrences all number
    0
    0
    0
    1
    Dry skin
         subjects affected / exposed
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
    1 / 71 (1.41%)
         occurrences all number
    0
    0
    1
    1
    Eczema infected
         subjects affected / exposed
    1 / 72 (1.39%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
    0 / 71 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Erythema
         subjects affected / exposed
    1 / 72 (1.39%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
    0 / 71 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Flushing
         subjects affected / exposed
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
    1 / 71 (1.41%)
         occurrences all number
    0
    0
    0
    1
    Nail disorder
         subjects affected / exposed
    0 / 72 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
    0 / 71 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Photodermatosis
         subjects affected / exposed
    1 / 72 (1.39%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
    0 / 71 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Rash
         subjects affected / exposed
    0 / 72 (0.00%)
    5 / 72 (6.94%)
    3 / 69 (4.35%)
    2 / 71 (2.82%)
         occurrences all number
    0
    5
    3
    2
    Skin infection
         subjects affected / exposed
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
    0 / 71 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Hernia repair
         subjects affected / exposed
    1 / 72 (1.39%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
    0 / 71 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Hip surgery
         subjects affected / exposed
    0 / 72 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
    0 / 71 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Limb operation
         subjects affected / exposed
    1 / 72 (1.39%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
    0 / 71 (0.00%)
         occurrences all number
    2
    0
    0
    0
    Renal and urinary disorders
    Chromaturia
         subjects affected / exposed
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
    1 / 71 (1.41%)
         occurrences all number
    0
    0
    0
    2
    Pyelonephritis
         subjects affected / exposed
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
    0 / 71 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Renal mass
         subjects affected / exposed
    1 / 72 (1.39%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
    0 / 71 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Unstable bladder
         subjects affected / exposed
    0 / 72 (0.00%)
    1 / 72 (1.39%)
    1 / 69 (1.45%)
    0 / 71 (0.00%)
         occurrences all number
    0
    1
    1
    0
    Urinary Tract Infection
         subjects affected / exposed
    0 / 72 (0.00%)
    4 / 72 (5.56%)
    5 / 69 (7.25%)
    3 / 71 (4.23%)
         occurrences all number
    0
    7
    8
    3
    Endocrine disorders
    Hypercalcaemia
         subjects affected / exposed
    0 / 72 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
    0 / 71 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    2 / 72 (2.78%)
    0 / 72 (0.00%)
    2 / 69 (2.90%)
    3 / 71 (4.23%)
         occurrences all number
    2
    0
    2
    3
    Back pain
         subjects affected / exposed
    0 / 72 (0.00%)
    2 / 72 (2.78%)
    1 / 69 (1.45%)
    2 / 71 (2.82%)
         occurrences all number
    0
    2
    1
    3
    Fall
         subjects affected / exposed
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
    0 / 71 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Joint swelling
         subjects affected / exposed
    0 / 72 (0.00%)
    2 / 72 (2.78%)
    0 / 69 (0.00%)
    1 / 71 (1.41%)
         occurrences all number
    0
    2
    0
    2
    Musculoskeletal chest pain
         subjects affected / exposed
    1 / 72 (1.39%)
    1 / 72 (1.39%)
    1 / 69 (1.45%)
    1 / 71 (1.41%)
         occurrences all number
    1
    1
    1
    1
    Musculoskeletal knee pain
         subjects affected / exposed
    1 / 72 (1.39%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
    0 / 71 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Myalgia
         subjects affected / exposed
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
    2 / 71 (2.82%)
         occurrences all number
    0
    0
    0
    2
    Neck pain
         subjects affected / exposed
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
    0 / 71 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Pain in extremity
         subjects affected / exposed
    1 / 72 (1.39%)
    0 / 72 (0.00%)
    2 / 69 (2.90%)
    0 / 71 (0.00%)
         occurrences all number
    1
    0
    2
    0
    Radius fracture
         subjects affected / exposed
    0 / 72 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
    1 / 71 (1.41%)
         occurrences all number
    0
    1
    0
    1
    Spinal stenosis
         subjects affected / exposed
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
    1 / 71 (1.41%)
         occurrences all number
    0
    0
    0
    1
    Infections and infestations
    Aspergillus infection
         subjects affected / exposed
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
    0 / 71 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Boil
         subjects affected / exposed
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
    0 / 71 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Candida infection
         subjects affected / exposed
    0 / 72 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
    0 / 71 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Covid-19
         subjects affected / exposed
    3 / 72 (4.17%)
    5 / 72 (6.94%)
    5 / 69 (7.25%)
    3 / 71 (4.23%)
         occurrences all number
    3
    5
    5
    3
    Escherichia infection
         subjects affected / exposed
    1 / 72 (1.39%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
    0 / 71 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Eye infection
         subjects affected / exposed
    1 / 72 (1.39%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
    0 / 71 (0.00%)
         occurrences all number
    2
    0
    0
    0
    Fungal infections
         subjects affected / exposed
    0 / 72 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
    0 / 71 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Furuncle
         subjects affected / exposed
    0 / 72 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
    0 / 71 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Helicobacter infection
         subjects affected / exposed
    2 / 72 (2.78%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
    0 / 71 (0.00%)
         occurrences all number
    2
    0
    1
    0
    Hepes zoster
         subjects affected / exposed
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
    0 / 71 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Influenza
         subjects affected / exposed
    2 / 72 (2.78%)
    0 / 72 (0.00%)
    3 / 69 (4.35%)
    2 / 71 (2.82%)
         occurrences all number
    2
    0
    3
    2
    Kidney infection
         subjects affected / exposed
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
    1 / 71 (1.41%)
         occurrences all number
    0
    0
    1
    1
    Lower respiratory tract infection
         subjects affected / exposed
    1 / 72 (1.39%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
    0 / 71 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Nasopharyngitis
         subjects affected / exposed
    1 / 72 (1.39%)
    1 / 72 (1.39%)
    2 / 69 (2.90%)
    3 / 71 (4.23%)
         occurrences all number
    1
    1
    3
    3
    Onychomycosis
         subjects affected / exposed
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
    0 / 71 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Parotitis
         subjects affected / exposed
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
    0 / 71 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Pseudomonas infection
         subjects affected / exposed
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
    0 / 71 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Respiratory syncytial virus infection
         subjects affected / exposed
    0 / 72 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
    0 / 71 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Sinus infection
         subjects affected / exposed
    0 / 72 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
    0 / 71 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Sinusitis
         subjects affected / exposed
    3 / 72 (4.17%)
    1 / 72 (1.39%)
    2 / 69 (2.90%)
    2 / 71 (2.82%)
         occurrences all number
    9
    1
    3
    2
    Tooth abscess
         subjects affected / exposed
    1 / 72 (1.39%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
    0 / 71 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Upper respiratory tract infection
         subjects affected / exposed
    1 / 72 (1.39%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
    2 / 71 (2.82%)
         occurrences all number
    1
    0
    1
    2
    Viral infection
         subjects affected / exposed
    0 / 72 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
    0 / 71 (0.00%)
         occurrences all number
    0
    2
    0
    0
    Metabolism and nutrition disorders
    Folate deficiency
         subjects affected / exposed
    1 / 72 (1.39%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
    0 / 71 (0.00%)
         occurrences all number
    1
    0
    0
    0

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    01 Mar 2018
    Addition of a new site: University Hospitals of Morecombe Bay NHS Foundation Trust – Royal Lancaster Infirmary
    26 Mar 2018
    1. Protocol, patient information sheet, RSSQ_since last visit, RSSQ_symptoms of exacerbation, RSSQ_end of exacerbation, and GP letter updated to remove aspects of examiner blinding 2. Protocol amended to include more information on DRA, exacerbation management and re-order the inclusion.exclusion criteria 3. PIS to include the DRA and instructions re management of exacerbation 4. Informed consent changed to reflect the change in version of the PIS 5. Inclusion of the Ethics Reference Number
    22 Aug 2018
    Application updated to include a new site: Southern Health & Social Care Trust_Craigavon Area Hospital
    25 Feb 2019
    Application updated to include a new site: North Tees and Hartlepool NHS Foundation Trust_North Tees University Hospital
    12 Mar 2019
    Addition of a participant Newsletter
    29 Aug 2019
    eporting section to remove the timeline and that these will be reported to CTU. 2. Updates to the current versions of the Patient Information Sheet and consent form: • Cover sheet page numbers corrected. • Add information about addition of spirometry sub-study • Add information about requirement for salbutamol during study being assessed by study doctor. • Addition to calendar lung function at home on day of study visit. • Removal of information about prescription data being reviewed from information sheet and consent form. • Addition of a standalone Data Transparency Statement with an accompanying cover letter. 3. Update to the GP Letter to allow sites to highlight that a Drug Response Assessment will be completed for patients allocated to the MucoClear treatment groups and to allow the inclusion of text about the patient being prescribed a bronchodilator if required.
    14 Oct 2019
    Update to application to add the following site: Imperial College Healthcare NHS Trust_St Mary’s Hospital
    14 Nov 2019
    Update to application to add the following site: County Durham and Darlington Foundation Trust_Darlington Memorial Hospital
    13 Feb 2020
    Update to application to add the following sites: • Blackpool Teaching Hospitals NHS Foundation Trust_Blackpool Victoria Hospital, with PI Dr Tarek Saba • NHS Great Glasgow and Clyde_Glasgow Royal Infirmary, with PI Dr Eric Livingstone
    27 Mar 2020
    Update to application to add the following sites: > Bradford Teaching Hospitals NHS Foundation Trust _Bradford Royal Infirmary > Swansea Bay University Health Board_Morriston Hospital Swansea > Northumbria Healthcare NHS Foundation Trust_North Tyneside General Hospital
    13 May 2020
    Update to application to add the following sites: • Stoke Mandeville Hospital, Buckinghamshire Healthcare NHS Trust, with PI Dr Mitra Shahidi
    14 Jul 2020
    A Belfast team, as representatives of the CI/QUB team, can support CLEAR trial sites across the UK to deliver follow-up visits by phone if local site resources are unable to deliver.
    13 Oct 2021
    Extension to study recruitment until September 2022, reduction in sample size (288) to 80% power, removal of 2nd year follow up - leaving a 12-month study period, update of inclusion criteria from"Two or more pulmonary exacerbations in the last year requiring antibiotics to " Two or more pulmonary exacerbations in a 1 year period in the past 2 years requiring antibiotics"
    27 Oct 2021
    Update to Mucodyne SPC & Mucoclear Info Leaflet
    17 Dec 2021
    Addition of Patient Information Sheet/Consent Form document for the CLEAR EME Sputum Sample Sub-study.
    03 Aug 2022
    • A Change to inclusion criteria - Changed from “2 or more pulmonary exacerbations in a 1 year period in the past 2 years requiring antibiotics” to “One or more pulmonary exacerbations in the last year requiring antibiotics. • The removal of SWATs A and B • The addition of the collection of data from patient’s electronic records at 104 weeks post randomisation (for patients recruited prior to the implementation of protocol v5.0) • Removal of the stipulation of 14 EME sites (to have no limit on the number of EME sites) • 3 G.P surgeries to be added as P.I.C. sites within the primary care setting

    Interruptions (globally)
    Were there any global interruptions to the trial? Yes
    Date
    Interruption
    Restart date
    12 Mar 2020
    Pause to recruitment due to Covid-19 pandemic.
    01 Nov 2021

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