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    Clinical Trial Results:
    Efficacy, safety and tolerability of Influcid tablets in patients (1 to 65 years old) suffering from upper respiratory tract infections with flu-like symptoms. A randomized, international, multicenter, controlled clinical trial.

    Summary
    EudraCT number
    2010-021422-35
    Trial protocol
    DE  
    Global end of trial date
    02 Aug 2011

    Results information
    Results version number
    v1(current)
    This version publication date
    05 Jul 2016
    First version publication date
    02 Aug 2015
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    09-NI-EP-001
    Additional study identifiers
    ISRCTN number
    ISRCTN60440500
    US NCT number
    -
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    Deutsche Homöopathie-Union, DHU-Arzneimittel GmbH & Co. KG
    Sponsor organisation address
    Ottostraße 24, Karlsruhe, Germany, D-76227
    Public contact
    Deutsche Homöopathie-Union, DHU-Arzneimittel GmbH & Co. KG, Ottostrasse 24, D-76227 Karlsruhe, + 49 (0)721 409301, info@dhu.com
    Scientific contact
    Deutsche Homöopathie-Union, DHU-Arzneimittel GmbH & Co. KG, Ottostrasse 24, D-76227 Karlsruhe , + 49 (0)721 409301, info@dhu.com
    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?
    Yes
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    02 Aug 2011
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    02 Aug 2011
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The actual study has been set up to evaluate systematically the efficacy and tolerability of Influcid. Patients received standard symptomatic medication, which was taken on demand (ST group) or Influcid for 7 days in addition to the same on demand symptomatic treatment (IFC group). Response at day 4, defined as absence of fever and absence or very mild degree of upper respiratory tract infection symptoms, was the primary outcome measure.
    Protection of trial subjects
    All patients received standard symptomatic medication on demand. One half of the patients received additionally Influcid. Examinations performed consisted mainly of a physical examination including evaluation of upper respiratory tract infection complaints and the assessment of upper respiratory tract infection symptoms via a questionnaire. Apart from this questionnaire, physical examination did not differ significantly from routine physical examination, neither did it involve any particular risk for the patient. At inclusion a throat swab (for a group A beta-hemolytic streptococci rapid test) and a nasopharyngeal swab (for an influenza test) were taken. Patients were informed about a possible slight discomfort caused by these tests via the patient informed consent form.
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    23 Nov 2010
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Ukraine: 300
    Country: Number of subjects enrolled
    Germany: 223
    Worldwide total number of subjects
    523
    EEA total number of subjects
    223
    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)
    24
    Children (2-11 years)
    240
    Adolescents (12-17 years)
    40
    Adults (18-64 years)
    219
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    Patients were recruited during one cold season going from end of November 2010 until beginning of April 2011. In Ukraine, patients were recruited at 4 general practitioner sites and 8 pediatric sites located mostly in polyclinics. In Germany, patients were recruited at 4 general practitioners practices and 6 pediatric practices.

    Pre-assignment
    Screening details
    A total of 533 patients gave their informed consent to participate in the trial. 10 of these 533 patients were screening failures due to a postive rapid test for group A beta-hemolytic streptococci at enrolment. A total of 523 patients were randomised.

    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
    ST [SAF]
    Arm description
    The control group "ST" was treated only with symptomatic medication on-demand.
    Arm type
    Active comparator

    Investigational medicinal product name
    Paracetamol
    Investigational medicinal product code
    IMP N° PR02
    Other name
    ben-u-ron®
    Pharmaceutical forms
    Syrup
    Routes of administration
    Oral use
    Dosage and administration details
    ben-u-ron® syrup [IMP N° PR02] was offered to all patients of both arms. 5 ml syrup contained 200 mg paracetamol. The prescribed dosage of paracetamol was dependent on age and body weight. Generally 10-15 mg paracetamol per kg body weight as individual dose, up to 60 mg / kg body weight as total daily dose were recommended. The respective dose interval was dependent on symptoms and maximum daily dose, and was not to fall below 6 hours.

    Investigational medicinal product name
    Oxymetazoline hydrochloride 0.05%
    Investigational medicinal product code
    IMP N° PR04
    Other name
    Nasivin®
    Pharmaceutical forms
    Nasal spray
    Routes of administration
    Nasal use
    Dosage and administration details
    Nasivin® syrup [IMP N° PR04] was offered to patients aged 6 years or older of both arms. 1 spray squirt with 45 µl solution contained 22.5 µg of oxymetazoline hydrochloride. The solution was to be squirted 2-3 times per day into every nostril. The individual dose was not to be administered more than 3 times per day. The spray was not to be used for more than 7 days.

    Investigational medicinal product name
    Oxymetazoline hydrochloride 0.025%
    Investigational medicinal product code
    IMP N° PR05
    Other name
    Nasivin®
    Pharmaceutical forms
    Nasal spray
    Routes of administration
    Nasal use
    Dosage and administration details
    Nasivin® syrup [IMP N° PR05] was offered to patients aged 1-5 years or older of both arms. 1 spray squirt with 45 µl solution contained 11.25 µg of oxymetazoline hydrochloride. The solution was to be squirted 2-3 times per day into every nostril. The individual dose was not to be administered more than 3 times per day. The spray was not to be used for more than 7 days.

    Investigational medicinal product name
    Ambroxol hydrochloride
    Investigational medicinal product code
    IMP N° PR03
    Other name
    Mucosolvan®
    Pharmaceutical forms
    Syrup
    Routes of administration
    Oral use
    Dosage and administration details
    Mucosolvan® syrup [IMP N° PR03] was offered to all patients of both arms. 5 ml syrup contained 30 mg ambroxol hydrochloride. Children up to 2 years old were to take 1.25 ml of syrup twice a day. For this age group, the syrup was only to be given according to the direction of the investigator. Children from 2 to 5 years were to take 1.25 ml of syrup three times a day. Children from 6 to 12 years were to take 2.5 ml of syrup 2-3 times a day. Adults and adolescents of 12 years and old were to take 5 ml of syrup 3 times a day during the first 2-3 days, thereafter 5 ml solution twice a day. When dosing for adults - adolescents, an increase of efficacy could be achieved by giving 10 ml of syrup twice a day.

    Arm title
    IFC [SAF]
    Arm description
    The test group “IFC” received 7 days of treatment with Influcid tablets (day 1 - day 7) additionally to on-demand symptomatic treatment
    Arm type
    Experimental

    Investigational medicinal product name
    Paracetamol
    Investigational medicinal product code
    IMP N° PR02
    Other name
    ben-u-ron®
    Pharmaceutical forms
    Syrup
    Routes of administration
    Oral use
    Dosage and administration details
    ben-u-ron® syrup [IMP N° PR02] was offered to all patients of both arms. 5 ml syrup contained 200 mg paracetamol. The prescribed dosage of paracetamol was dependent on age and body weight. Generally 10-15 mg paracetamol per kg body weight as individual dose, up to 60 mg / kg body weight as total daily dose were recommended. The respective dose interval was dependent on symptoms and maximum daily dose, and was not to fall below 6 hours.

    Investigational medicinal product name
    Ambroxol hydrochloride
    Investigational medicinal product code
    IMP N° PR03
    Other name
    Mucosolvan®
    Pharmaceutical forms
    Syrup
    Routes of administration
    Oral use
    Dosage and administration details
    Mucosolvan® syrup [IMP N° PR03] was offered to all patients of both arms. 5 ml syrup contained 30 mg ambroxol hydrochloride. Children up to 2 years old were to take 1.25 ml of syrup twice a day. For this age group, the syrup was only to be given according to the direction of the investigator. Children from 2 to 5 years were to take 1.25 ml of syrup three times a day. Children from 6 to 12 years were to take 2.5 ml of syrup 2-3 times a day. Adults and adolescents of 12 years and old were to take 5 ml of syrup 3 times a day during the first 2-3 days, thereafter 5 ml solution twice a day. When dosing for adults - adolescents, an increase of efficacy could be achieved by giving 10 ml of syrup twice a day.

    Investigational medicinal product name
    Aconitum D3, Bryonia D2, Eupatorium perfoliatum D1, Gelsemium D3, Ipecacuanha D3 and Phosphorus D5
    Investigational medicinal product code
    IMP N° PR01
    Other name
    Influcid®
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Test drug was provided to patients of IFC arm only . Separate blisters for children ( <12 years) and adolescents, adults (≥12 years) were provided. Acute dosage (first 72 hours) comprised intake of 1 tablet every 2 hours (8 tablets per day) for children and 1 tablet every hour (12 tablets per day) for adolescents, adults. Maintenance dosage (following 96 hours) comprised intake of 1 tablet 3 times a day (3 tablets per day) for children and 2 tablets 3 times a day (6 tablets per day) for adolescents, adults. [Note: Patients, who were randomised until noon at baseline, took the complete acute dosage on study days 1-3 and started with the maintenance dosage on study day 4. Patients, who were randomised at baseline after noon, took half of the acute dosage on study day 1. These patients took the complete acute dosage on study days 2-4 and started with the maintenance dosage on study day 5.]

    Investigational medicinal product name
    Oxymetazoline hydrochloride 0.05%
    Investigational medicinal product code
    IMP N° PR04
    Other name
    Nasivin®
    Pharmaceutical forms
    Nasal spray
    Routes of administration
    Nasal use
    Dosage and administration details
    Nasivin® syrup [IMP N° PR04] was offered to patients aged 6 years or older of both arms. 1 spray squirt with 45 µl solution contained 22.5 µg of oxymetazoline hydrochloride. The solution was to be squirted 2-3 times per day into every nostril. The individual dose was not to be administered more than 3 times per day. The spray was not to be used for more than 7 days.

    Investigational medicinal product name
    Oxymetazoline hydrochloride 0.025%
    Investigational medicinal product code
    IMP N° PR05
    Other name
    Nasivin®
    Pharmaceutical forms
    Nasal spray
    Routes of administration
    Nasal use
    Dosage and administration details
    Nasivin® syrup [IMP N° PR05] was offered to patients aged 1-5 years or older of both arms. 1 spray squirt with 45 µl solution contained 11.25 µg of oxymetazoline hydrochloride. The solution was to be squirted 2-3 times per day into every nostril. The individual dose was not to be administered more than 3 times per day. The spray was not to be used for more than 7 days.

    Number of subjects in period 1
    ST [SAF] IFC [SAF]
    Started
    258
    265
    1st FU visit completed (day 4±1)
    258
    264
    Termination visit completed (day 15±2)
    246
    256
    2nd FU visit completed (day 8±1)
    256
    262
    Completed
    246
    256
    Not completed
    12
    9
         Protocol deviation
    11
    5
         Non compliance/Parents incompliance
    -
    2
         Lack of efficacy
    -
    1
         Lost to follow-up
    1
    1

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    ST [SAF]
    Reporting group description
    The control group "ST" was treated only with symptomatic medication on-demand.

    Reporting group title
    IFC [SAF]
    Reporting group description
    The test group “IFC” received 7 days of treatment with Influcid tablets (day 1 - day 7) additionally to on-demand symptomatic treatment

    Reporting group values
    ST [SAF] IFC [SAF] Total
    Number of subjects
    258 265 523
    Age categorical
    Units: Subjects
        < 12 years
    133 131 264
        ≥ 12 years
    125 134 259
    Age continuous
    Units: years
        median (inter-quartile range (Q1-Q3))
    10 (5 to 32) 12 (5 to 33) -
    Gender categorical
    Units: Subjects
        Male
    120 106 226
        Female
    138 159 297
    Influenza A and B test results
    Units: Subjects
        Influenza A and B negative
    219 229 448
        Influenza A positive
    33 21 54
        Influenza B positive
    6 12 18
        Not recorded
    0 3 3
    Fever
    Assessment of axillary measurement of body temperature [°C] at physicians office.
    Units: Subjects
        no ( ≤37.2°C)
    2 0 2
        mild (>37.2°C but <37.5°C)
    0 0 0
        moderate (≥37.5°C but <38.5°C)
    224 226 450
        high ( ≥38.5°C)
    32 39 71
    Presence of hyperemia of mucosa
    Units: Subjects
        no
    28 24 52
        yes
    230 241 471
    Presence of nasal breathing impairment
    Units: Subjects
        no
    27 38 65
        yes
    231 227 458
    Ability to perform daily activities
    Units: Subjects
        no
    211 198 409
        yes
    47 67 114
    Presence of nasal symptoms [URTI symptom 1]
    Units: Subjects
        no
    16 30 46
        yes
    242 235 477
    Presence of Pharyngeal symptoms [URTI symptom 2]
    Units: Subjects
        no
    24 21 45
        yes
    234 244 478
    Presence of Cough [URTI symptom 3]
    Units: Subjects
        no
    48 67 115
        yes
    210 198 408
    Presence of Feeling tired [URTI symptom 4]
    Units: Subjects
        no
    7 4 11
        yes
    251 261 512
    Presence of Weakness [URTI symptom 5]
    Units: Subjects
        no
    8 9 17
        yes
    250 256 506
    Presence of Body aches [URTI symptom 6]
    Units: Subjects
        no
    50 53 103
        yes
    208 212 420
    Presence of Irritable/whiny [URTI symptom 7]
    This symptom has been assessed for chidren [patients <12 years] only.
    Units: Subjects
        no
    17 16 33
        yes
    116 115 231
        Not applicable [patients >12 years]
    125 134 259
    Presence of Less active [URTI symptom 8]
    This symptom has been assessed for chidren [patients <12 years] only.
    Units: Subjects
        no
    5 5 10
        yes
    128 126 254
        Not applicable [patients >12 years]
    125 134 259
    Body temperature
    Axillary measurement of body temperature [°C] at physicians office.
    Units: [°C]
        median (inter-quartile range (Q1-Q3))
    37.9 (37.8 to 38.2) 37.9 (37.8 to 38.2) -
    WURSS-21 total sum score
    The WURSS-21 total sum score is calculated as sum of items 2 to 20 of the Wisconsin Upper Respiratory Symptom Survey 21 (WURSS-21) which is a 21-item illness-specific health-related quality of life questionnaire. [Note: Available diary WURSS-21 questionnaire data at baseline was recorded for: N=230 (ST [SAF]); N=240 (IFC [SAF]); N=208 (ST arm [PP analysis set]); N=230 (ST arm [ITT analysis set]); N=238 (IFC arm [ITT analysis set]) and N=209 (IFC arm [PP analysis set]) patients.]
    Units: SCORE
        median (inter-quartile range (Q1-Q3))
    75 (59 to 92) 72 (53 to 92.5) -
    Subject analysis sets

    Subject analysis set title
    IFC arm [PP analysis set]
    Subject analysis set type
    Per protocol
    Subject analysis set description
    This subject analysis set consists of all patients of IFC arm without major protocol violations. N=41 out of N=265 IFC patients have been excluded from 'IFC arm [PP analysis set]' due to relevant protocol violations.

    Subject analysis set title
    ST arm [PP analysis set]
    Subject analysis set type
    Per protocol
    Subject analysis set description
    This subject analysis set consists of all patients of ST arm without major protocol violations. N=37 out of N=258 ST patients have been excluded from 'ST arm [PP analysis set]' due to relevant protocol violations.

    Subject analysis set title
    ST arm [ITT analysis set]
    Subject analysis set type
    Intention-to-treat
    Subject analysis set description
    This subject analysis set consists of all patients of ST arm who contributed post-baseline efficacy data. N=2 out of N=258 ST patients have been excluded from 'ST arm [ITT analysis set]' due to missing post-baseline efficacy data.

    Subject analysis set title
    IFC arm [ITT analysis set]
    Subject analysis set type
    Intention-to-treat
    Subject analysis set description
    This subject analysis set consists of all patients of IFC arm who contributed post-baseline efficacy data. N=4 out of N=265 IFC patients have been excluded from 'IFC arm [ITT analysis set]' due to missing post-baseline efficacy data.

    Subject analysis sets values
    IFC arm [PP analysis set] ST arm [PP analysis set] ST arm [ITT analysis set] IFC arm [ITT analysis set]
    Number of subjects
    224
    221
    256
    261
    Age categorical
    Units: Subjects
        < 12 years
    117
    110
    131
    130
        ≥ 12 years
    107
    111
    125
    131
    Age continuous
    Units: years
        median (inter-quartile range (Q1-Q3))
    10 (4 to 33)
    12 (5 to 33)
    10.5 (5 to 32.5)
    12 (4 to 33)
    Gender categorical
    Units: Subjects
        Male
    88
    102
    118
    104
        Female
    136
    119
    138
    157
    Influenza A and B test results
    Units: Subjects
        Influenza A and B negative
    198
    196
    219
    227
        Influenza A positive
    12
    20
    31
    19
        Influenza B positive
    11
    5
    6
    12
        Not recorded
    3
    0
    0
    3
    Fever
    Assessment of axillary measurement of body temperature [°C] at physicians office.
    Units: Subjects
        no ( ≤37.2°C)
    0
    0
    2
    0
        mild (>37.2°C but <37.5°C)
    0
    0
    0
    0
        moderate (≥37.5°C but <38.5°C)
    191
    195
    222
    222
        high ( ≥38.5°C)
    33
    26
    32
    39
    Presence of hyperemia of mucosa
    Units: Subjects
        no
    23
    18
    28
    24
        yes
    201
    203
    228
    237
    Presence of nasal breathing impairment
    Units: Subjects
        no
    36
    24
    27
    38
        yes
    188
    197
    229
    223
    Ability to perform daily activities
    Units: Subjects
        no
    172
    182
    209
    196
        yes
    52
    39
    47
    65
    Presence of nasal symptoms [URTI symptom 1]
    Units: Subjects
        no
    29
    14
    16
    30
        yes
    195
    207
    240
    231
    Presence of Pharyngeal symptoms [URTI symptom 2]
    Units: Subjects
        no
    19
    17
    24
    21
        yes
    205
    204
    232
    240
    Presence of Cough [URTI symptom 3]
    Units: Subjects
        no
    60
    44
    48
    67
        yes
    164
    177
    208
    194
    Presence of Feeling tired [URTI symptom 4]
    Units: Subjects
        no
    3
    7
    7
    4
        yes
    221
    214
    249
    257
    Presence of Weakness [URTI symptom 5]
    Units: Subjects
        no
    8
    7
    8
    9
        yes
    216
    214
    248
    252
    Presence of Body aches [URTI symptom 6]
    Units: Subjects
        no
    45
    37
    48
    53
        yes
    179
    184
    208
    208
    Presence of Irritable/whiny [URTI symptom 7]
    This symptom has been assessed for chidren [patients <12 years] only.
    Units: Subjects
        no
    14
    11
    17
    16
        yes
    103
    99
    114
    114
        Not applicable [patients >12 years]
    107
    111
    125
    131
    Presence of Less active [URTI symptom 8]
    This symptom has been assessed for chidren [patients <12 years] only.
    Units: Subjects
        no
    5
    3
    5
    5
        yes
    112
    107
    126
    125
        Not applicable [patients >12 years]
    107
    111
    125
    131
    Body temperature
    Axillary measurement of body temperature [°C] at physicians office.
    Units: [°C]
        median (inter-quartile range (Q1-Q3))
    37.9 (37.8 to 38.2)
    37.9 (37.8 to 38.2)
    37.9 (37.8 to 38.2)
    37.9 (37.8 to 38.2)
    WURSS-21 total sum score
    The WURSS-21 total sum score is calculated as sum of items 2 to 20 of the Wisconsin Upper Respiratory Symptom Survey 21 (WURSS-21) which is a 21-item illness-specific health-related quality of life questionnaire. [Note: Available diary WURSS-21 questionnaire data at baseline was recorded for: N=230 (ST [SAF]); N=240 (IFC [SAF]); N=208 (ST arm [PP analysis set]); N=230 (ST arm [ITT analysis set]); N=238 (IFC arm [ITT analysis set]) and N=209 (IFC arm [PP analysis set]) patients.]
    Units: SCORE
        median (inter-quartile range (Q1-Q3))
    70 (54 to 92)
    77 (60 to 93.5)
    75 (59 to 92)
    72 (54 to 93)

    End points

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    End points reporting groups
    Reporting group title
    ST [SAF]
    Reporting group description
    The control group "ST" was treated only with symptomatic medication on-demand.

    Reporting group title
    IFC [SAF]
    Reporting group description
    The test group “IFC” received 7 days of treatment with Influcid tablets (day 1 - day 7) additionally to on-demand symptomatic treatment

    Subject analysis set title
    IFC arm [PP analysis set]
    Subject analysis set type
    Per protocol
    Subject analysis set description
    This subject analysis set consists of all patients of IFC arm without major protocol violations. N=41 out of N=265 IFC patients have been excluded from 'IFC arm [PP analysis set]' due to relevant protocol violations.

    Subject analysis set title
    ST arm [PP analysis set]
    Subject analysis set type
    Per protocol
    Subject analysis set description
    This subject analysis set consists of all patients of ST arm without major protocol violations. N=37 out of N=258 ST patients have been excluded from 'ST arm [PP analysis set]' due to relevant protocol violations.

    Subject analysis set title
    ST arm [ITT analysis set]
    Subject analysis set type
    Intention-to-treat
    Subject analysis set description
    This subject analysis set consists of all patients of ST arm who contributed post-baseline efficacy data. N=2 out of N=258 ST patients have been excluded from 'ST arm [ITT analysis set]' due to missing post-baseline efficacy data.

    Subject analysis set title
    IFC arm [ITT analysis set]
    Subject analysis set type
    Intention-to-treat
    Subject analysis set description
    This subject analysis set consists of all patients of IFC arm who contributed post-baseline efficacy data. N=4 out of N=265 IFC patients have been excluded from 'IFC arm [ITT analysis set]' due to missing post-baseline efficacy data.

    Primary: Fraction of patients with symptom alleviation at day 4 of the study

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    End point title
    Fraction of patients with symptom alleviation at day 4 of the study
    End point description
    Symptoms alleviation is defined as: - Absence of fever (axillary temperature ≤ 37.2°C) and - Absence or very mild degree of the symptoms assessed by Wisconsin Upper Respiratory Symptom Survey 21 (WURSS-21) which is a 21-item illness-specific health-related quality of life questionnaire. Fever was measured 3-times daily by the patient (or in case of children by their parents) at home. Mean value covering last 24 hours was basis for this definition. Absence or very mild degree of symptoms is defined as answer to question “How sick do you feel today?” with “0” (not sick) or “1” (very mildly) for both assessments at day 4 (WURSS-21 was filled in twice daily by the patient or in case of children by their parents at home).
    End point type
    Primary
    End point timeframe
    Study day 4
    End point values
    IFC arm [PP analysis set] ST arm [PP analysis set] ST arm [ITT analysis set] IFC arm [ITT analysis set]
    Number of subjects analysed
    224
    221
    252 [1]
    259 [2]
    Units: Patients
        No
    191
    209
    235
    219
        Yes
    33
    12
    17
    40
    Notes
    [1] - 4 out of 256 ST arm [ITT analysis set] patients were excluded from due to invalid diary data.
    [2] - 2 out of 261 IFC arm [ITT analysis set] patients were excluded from due to invalid diary data.
    Statistical analysis title
    Test for equality of fractions between arms [PP]
    Statistical analysis description
    Explorative analysis of upper respiratory tract infection [URTI] symptom alleviation at day 4. Categorization of symptom alleviation at day 4 ('Response' [Yes/No]) was tested for treatment related differences. Presented values for risk difference are related to the difference in responsive patients between treatments taking into account the direction 'IFC - ST'.
    Comparison groups
    ST arm [PP analysis set] v IFC arm [PP analysis set]
    Number of subjects included in analysis
    445
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    = 0.0011 [3]
    Method
    Chi-squared
    Parameter type
    Risk difference (RD)
    Point estimate
    9.3
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    3.33
         upper limit
    15.27
    Notes
    [3] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly higher number of patients with URTI symptom alleviation (“Response”) at study day 4 in IFC compared to ST arm [PP analysis set].
    Statistical analysis title
    Test for equality of fractions between arms [ITT]
    Statistical analysis description
    Explorative analysis of URTI symptom alleviation at day 4. Categorization of symptom alleviation at day 4 ('Response' [Yes/No]) was tested for treatment related differences. Presented values for risk difference are related to the difference in responsive patients between treatments taking into account the direction 'IFC - ST'.
    Comparison groups
    IFC arm [ITT analysis set] v ST arm [ITT analysis set]
    Number of subjects included in analysis
    511
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    = 0.0018 [4]
    Method
    Chi-squared
    Parameter type
    Risk difference (RD)
    Point estimate
    8.7
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    2.93
         upper limit
    14.47
    Notes
    [4] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly higher number of patients with URTI symptom alleviation (“Response”) at study day 4 in IFC compared to ST arm [ITT analysis set].

    Secondary: Time to symptom alleviation

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    End point title
    Time to symptom alleviation
    End point description
    The first day a patient had rated item 1 of WURSS-21 (“How sick do you feel today”) not higher than 1 (=”very mildly sick”) for both morning and evening assessments was used for evaluating the time to symptom alleviation. Only patients with valid diary data and WURSS-21 item 1 assessed at baseline were considered. Symptom had to be present at baseline, i.e. assessment of WURSS-21 item 1 (if available) at baseline visit had to be scored with value ">1". Finally, only patients who who had a symptom alleviation until study day 14 could be taken into account for this analysis.
    End point type
    Secondary
    End point timeframe
    Study day 2 to study day 14
    End point values
    ST arm [ITT analysis set] IFC arm [ITT analysis set]
    Number of subjects analysed
    215 [5]
    236 [6]
    Units: [days]
        median (inter-quartile range (Q1-Q3))
    8 (7 to 10)
    7 (5 to 8)
    Notes
    [5] - 41 out of 256 ST arm [ITT analysis set] patients were excluded due to missing data.
    [6] - 25 out of 261 IFC arm [ITT analysis set] patients were excluded due to missing data.
    Statistical analysis title
    Time to symptom alleviation [ITT]
    Statistical analysis description
    Explorative analysis of time to symptom alleviation. Time to symptom alleviation [days] was tested for treatment related differences. Presented values for estimated location shift are related to the difference in time to symptom alleviation between treatments taking into account the direction 'IFC - ST'.
    Comparison groups
    ST arm [ITT analysis set] v IFC arm [ITT analysis set]
    Number of subjects included in analysis
    451
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    < 0.0001 [7]
    Method
    Wilcoxon (Mann-Whitney)
    Parameter type
    Hodges Lehman estimate of location shift
    Point estimate
    -2
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2
         upper limit
    -1
    Notes
    [7] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly shorter time to symptom alleviation [days] in IFC compared to ST arm [ITT analysis set].

    Secondary: Fraction of patients with symptom alleviation as defined for primary objective at study day 2, 3, 5, etc. until end of study

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    End point title
    Fraction of patients with symptom alleviation as defined for primary objective at study day 2, 3, 5, etc. until end of study
    End point description
    Presented counts refer to the number of patients per study day with observed symptom alleviation. Symptoms alleviation is defined as: - Absence of fever (axillary temperature ≤ 37.2°C) and - Absence or very mild degree of the symptoms assessed by Wisconsin Upper Respiratory Symptom Survey 21 (WURSS-21). Fever was measured 3-times daily by the patient (or in case of children by their parents) at home. Mean value covering last 24 hours was basis for this definition. Absence or very mild degree of symptoms is defined as answer to question “How sick do you feel today?” with “0” (not sick) or “1” (very mildly) for both assessments at corresponding day (WURSS-21 was filled in twice daily by the patient or in case of children by their parents at home).
    End point type
    Secondary
    End point timeframe
    study day 2 to study day 14
    End point values
    ST arm [ITT analysis set] IFC arm [ITT analysis set]
    Number of subjects analysed
    252 [8]
    259 [9]
    Units: patients
        Day 2
    1
    2
        Day 3
    7
    15
        Day 4
    17
    40
        Day 5
    31
    76
        Day 6
    53
    111
        Day 7
    73
    150
        Day 8
    109
    178
        Day 9
    141
    194
        Day 10
    169
    204
        Day 11
    181
    212
        Day 12
    198
    219
        Day 13
    207
    227
        Day 14
    217
    230
    Attachments
    Difference between treatment arms per day
    Notes
    [8] - 4 out of 256 ST arm [ITT analysis set] patients were excluded from due to invalid diary data.
    [9] - 2 out of 261 IFC arm [ITT analysis set] patients were excluded from due to invalid diary data.
    Statistical analysis title
    Day 2: Equality of fractions between arms [ITT]
    Statistical analysis description
    Explorative analysis of URTI symptom alleviation as defined for primary endpoint. Categorization of symptom alleviation ('Response' [Yes/No]) was tested for treatment related differences. Presented values for risk difference are related to the difference in responsive patients between treatments taking into account the direction 'IFC - ST'.
    Comparison groups
    ST arm [ITT analysis set] v IFC arm [ITT analysis set]
    Number of subjects included in analysis
    511
    Analysis specification
    Pre-specified
    Analysis type
    other [10]
    P-value
    = 0.5787
    Method
    Chi-squared
    Parameter type
    Risk difference (RD)
    Point estimate
    0.4
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.3
         upper limit
    2.1
    Notes
    [10] - Contributing categories are "No" and "Yes". Missing data category, resulting from invalid diary data is not taken into account (invalid diary data was observed for 4 patients of ST and 2 patients of IFC arm, respectively).
    Statistical analysis title
    Day 3: Equality of fractions between arms [ITT]
    Statistical analysis description
    Explorative analysis of URTI symptom alleviation as defined for primary endpoint. Categorization of symptom alleviation ('Response' [Yes/No]) was tested for treatment related differences. Presented values for risk difference are related to the difference in responsive patients between treatments taking into account the direction 'IFC - ST'.
    Comparison groups
    ST arm [ITT analysis set] v IFC arm [ITT analysis set]
    Number of subjects included in analysis
    511
    Analysis specification
    Pre-specified
    Analysis type
    other [11]
    P-value
    = 0.0933
    Method
    Chi-squared
    Parameter type
    Risk difference (RD)
    Point estimate
    3
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.9
         upper limit
    6.9
    Notes
    [11] - Contributing categories are "No" and "Yes". Missing data category, resulting from invalid diary data is not taken into account (invalid diary data was observed for 4 patients of ST and 2 patients of IFC arm, respectively).
    Statistical analysis title
    Day 4: Equality of fractions between arms [ITT]
    Statistical analysis description
    Explorative analysis of URTI symptom alleviation as defined for primary endpoint. Categorization of symptom alleviation ('Response' [Yes/No]) was tested for treatment related differences. Presented values for risk difference are related to the difference in responsive patients between treatments taking into account the direction 'IFC - ST'.
    Comparison groups
    ST arm [ITT analysis set] v IFC arm [ITT analysis set]
    Number of subjects included in analysis
    511
    Analysis specification
    Pre-specified
    Analysis type
    other [12]
    P-value
    = 0.0018 [13]
    Method
    Chi-squared
    Parameter type
    Risk difference (RD)
    Point estimate
    8.7
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    2.9
         upper limit
    14.5
    Notes
    [12] - Contributing categories are "No" and "Yes". Missing data category, resulting from invalid diary data is not taken into account (invalid diary data was observed for 4 patients of ST and 2 patients of IFC arm, respectively).
    [13] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly higher number of patients with URTI symptom alleviation (“Response”) at study day 4 in IFC compared to ST arm [ITT analysis set].
    Statistical analysis title
    Day 5: Equality of fractions between arms [ITT]
    Statistical analysis description
    Explorative analysis of URTI symptom alleviation as defined for primary endpoint. Categorization of symptom alleviation ('Response' [Yes/No]) was tested for treatment related differences. Presented values for risk difference are related to the difference in responsive patients between treatments taking into account the direction 'IFC - ST'.
    Comparison groups
    ST arm [ITT analysis set] v IFC arm [ITT analysis set]
    Number of subjects included in analysis
    511
    Analysis specification
    Pre-specified
    Analysis type
    other [14]
    P-value
    < 0.0001 [15]
    Method
    Chi-squared
    Parameter type
    Risk difference (RD)
    Point estimate
    17
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    9.8
         upper limit
    24.3
    Notes
    [14] - Contributing categories are "No" and "Yes". Missing data category, resulting from invalid diary data is not taken into account (invalid diary data was observed for 4 patients of ST and 2 patients of IFC arm, respectively).
    [15] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly higher number of patients with URTI symptom alleviation (“Response”) at study day 5 in IFC compared to ST arm [ITT analysis set].
    Statistical analysis title
    Day 6: Equality of fractions between arms [ITT]
    Statistical analysis description
    Explorative analysis of URTI symptom alleviation as defined for primary endpoint. Categorization of symptom alleviation ('Response' [Yes/No]) was tested for treatment related differences. Presented values for risk difference are related to the difference in responsive patients between treatments taking into account the direction 'IFC - ST'.
    Comparison groups
    ST arm [ITT analysis set] v IFC arm [ITT analysis set]
    Number of subjects included in analysis
    511
    Analysis specification
    Pre-specified
    Analysis type
    other [16]
    P-value
    < 0.0001 [17]
    Method
    Chi-squared
    Parameter type
    Risk difference (RD)
    Point estimate
    21.8
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    13.6
         upper limit
    30.1
    Notes
    [16] - Contributing categories are "No" and "Yes". Missing data category, resulting from invalid diary data is not taken into account (invalid diary data was observed for 4 patients of ST and 2 patients of IFC arm, respectively).
    [17] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly higher number of patients with URTI symptom alleviation (“Response”) at study day 6 in IFC compared to ST arm [ITT analysis set].
    Statistical analysis title
    Day 7: Equality of fractions between arms [ITT]
    Statistical analysis description
    Explorative analysis of URTI symptom alleviation as defined for primary endpoint. Categorization of symptom alleviation ('Response' [Yes/No]) was tested for treatment related differences. Presented values for risk difference are related to the difference in responsive patients between treatments taking into account the direction 'IFC - ST'.
    Comparison groups
    ST arm [ITT analysis set] v IFC arm [ITT analysis set]
    Number of subjects included in analysis
    511
    Analysis specification
    Pre-specified
    Analysis type
    other [18]
    P-value
    < 0.0001 [19]
    Method
    Chi-squared
    Parameter type
    Risk difference (RD)
    Point estimate
    28.9
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    20.3
         upper limit
    37.6
    Notes
    [18] - Contributing categories are "No" and "Yes". Missing data category, resulting from invalid diary data is not taken into account (invalid diary data was observed for 4 patients of ST and 2 patients of IFC arm, respectively).
    [19] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly higher number of patients with URTI symptom alleviation (“Response”) at study day 7 in IFC compared to ST arm [ITT analysis set].
    Statistical analysis title
    Day 8: Equality of fractions between arms [ITT]
    Statistical analysis description
    Explorative analysis of URTI symptom alleviation as defined for primary endpoint. Categorization of symptom alleviation ('Response' [Yes/No]) was tested for treatment related differences. Presented values for risk difference are related to the difference in responsive patients between treatments taking into account the direction 'IFC - ST'.
    Comparison groups
    ST arm [ITT analysis set] v IFC arm [ITT analysis set]
    Number of subjects included in analysis
    511
    Analysis specification
    Pre-specified
    Analysis type
    other [20]
    P-value
    < 0.0001 [21]
    Method
    Chi-squared
    Parameter type
    Risk difference (RD)
    Point estimate
    25.5
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    16.8
         upper limit
    34.2
    Notes
    [20] - Contributing categories are "No" and "Yes". Missing data category, resulting from invalid diary data is not taken into account (invalid diary data was observed for 4 patients of ST and 2 patients of IFC arm, respectively).
    [21] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly higher number of patients with URTI symptom alleviation (“Response”) at study day 8 in IFC compared to ST arm [ITT analysis set].
    Statistical analysis title
    Day 9: Equality of fractions between arms [ITT]
    Statistical analysis description
    Explorative analysis of URTI symptom alleviation as defined for primary endpoint. Categorization of symptom alleviation ('Response' [Yes/No]) was tested for treatment related differences. Presented values for risk difference are related to the difference in responsive patients between treatments taking into account the direction 'IFC - ST'.
    Comparison groups
    ST arm [ITT analysis set] v IFC arm [ITT analysis set]
    Number of subjects included in analysis
    511
    Analysis specification
    Pre-specified
    Analysis type
    other [22]
    P-value
    < 0.0001 [23]
    Method
    Chi-squared
    Parameter type
    Risk difference (RD)
    Point estimate
    19
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    10.5
         upper limit
    27.4
    Notes
    [22] - Contributing categories are "No" and "Yes". Missing data category, resulting from invalid diary data is not taken into account (invalid diary data was observed for 4 patients of ST and 2 patients of IFC arm, respectively).
    [23] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly higher number of patients with URTI symptom alleviation (“Response”) at study day 9 in IFC compared to ST arm [ITT analysis set].
    Statistical analysis title
    Day 10: Equality of fractions between arms [ITT]
    Statistical analysis description
    Explorative analysis of URTI symptom alleviation as defined for primary endpoint. Categorization of symptom alleviation ('Response' [Yes/No]) was tested for treatment related differences. Presented values for risk difference are related to the difference in responsive patients between treatments taking into account the direction 'IFC - ST'.
    Comparison groups
    ST arm [ITT analysis set] v IFC arm [ITT analysis set]
    Number of subjects included in analysis
    511
    Analysis specification
    Pre-specified
    Analysis type
    other [24]
    P-value
    = 0.0029 [25]
    Method
    Chi-squared
    Parameter type
    Risk difference (RD)
    Point estimate
    11.7
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    3.7
         upper limit
    19.7
    Notes
    [24] - Contributing categories are "No" and "Yes". Missing data category, resulting from invalid diary data is not taken into account (invalid diary data was observed for 4 patients of ST and 2 patients of IFC arm, respectively).
    [25] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly higher number of patients with URTI symptom alleviation (“Response”) at study day 10 in IFC compared to ST arm [ITT analysis set].
    Statistical analysis title
    Day 11: Equality of fractions between arms [ITT]
    Statistical analysis description
    Explorative analysis of URTI symptom alleviation as defined for primary endpoint. Categorization of symptom alleviation ('Response' [Yes/No]) was tested for treatment related differences. Presented values for risk difference are related to the difference in responsive patients between treatments taking into account the direction 'IFC - ST'.
    Comparison groups
    ST arm [ITT analysis set] v IFC arm [ITT analysis set]
    Number of subjects included in analysis
    511
    Analysis specification
    Pre-specified
    Analysis type
    other [26]
    P-value
    = 0.0072 [27]
    Method
    Chi-squared
    Parameter type
    Risk difference (RD)
    Point estimate
    10
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    2.4
         upper limit
    17.7
    Notes
    [26] - Contributing categories are "No" and "Yes". Missing data category, resulting from invalid diary data is not taken into account (invalid diary data was observed for 4 patients of ST and 2 patients of IFC arm, respectively).
    [27] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly higher number of patients with URTI symptom alleviation (“Response”) at study day 11 in IFC compared to ST arm [ITT analysis set].
    Statistical analysis title
    Day 12: Equality of fractions between arms [ITT]
    Statistical analysis description
    Explorative analysis of URTI symptom alleviation as defined for primary endpoint. Categorization of symptom alleviation ('Response' [Yes/No]) was tested for treatment related differences. Presented values for risk difference are related to the difference in responsive patients between treatments taking into account the direction 'IFC - ST'.
    Comparison groups
    ST arm [ITT analysis set] v IFC arm [ITT analysis set]
    Number of subjects included in analysis
    511
    Analysis specification
    Pre-specified
    Analysis type
    other [28]
    P-value
    = 0.0809
    Method
    Chi-squared
    Parameter type
    Risk difference (RD)
    Point estimate
    6
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.1
         upper limit
    13.1
    Notes
    [28] - Contributing categories are "No" and "Yes". Missing data category, resulting from invalid diary data is not taken into account (invalid diary data was observed for 4 patients of ST and 2 patients of IFC arm, respectively).
    Statistical analysis title
    Day 13: Equality of fractions between arms [ITT]
    Statistical analysis description
    Explorative analysis of URTI symptom alleviation as defined for primary endpoint. Categorization of symptom alleviation ('Response' [Yes/No]) was tested for treatment related differences. Presented values for risk difference are related to the difference in responsive patients between treatments taking into account the direction 'IFC - ST'.
    Comparison groups
    ST arm [ITT analysis set] v IFC arm [ITT analysis set]
    Number of subjects included in analysis
    511
    Analysis specification
    Pre-specified
    Analysis type
    other [29]
    P-value
    = 0.0822
    Method
    Chi-squared
    Parameter type
    Risk difference (RD)
    Point estimate
    5.5
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.1
         upper limit
    12.1
    Notes
    [29] - Contributing categories are "No" and "Yes". Missing data category, resulting from invalid diary data is not taken into account (invalid diary data was observed for 4 patients of ST and 2 patients of IFC arm, respectively).
    Statistical analysis title
    Day 14: Equality of fractions between arms [ITT]
    Statistical analysis description
    Explorative analysis of URTI symptom alleviation as defined for primary endpoint. Categorization of symptom alleviation ('Response' [Yes/No]) was tested for treatment related differences. Presented values for risk difference are related to the difference in responsive patients between treatments taking into account the direction 'IFC - ST'.
    Comparison groups
    ST arm [ITT analysis set] v IFC arm [ITT analysis set]
    Number of subjects included in analysis
    511
    Analysis specification
    Pre-specified
    Analysis type
    other [30]
    P-value
    = 0.358
    Method
    Chi-squared
    Parameter type
    Risk difference (RD)
    Point estimate
    2.7
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -3.4
         upper limit
    8.8
    Notes
    [30] - Contributing categories are "No" and "Yes". Missing data category, resulting from invalid diary data is not taken into account (invalid diary data was observed for 4 patients of ST and 2 patients of IFC arm, respectively).

    Secondary: Fraction of patients with maintenance of symptom alleviation as defined for primary objective until end of study

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    End point title
    Fraction of patients with maintenance of symptom alleviation as defined for primary objective until end of study
    End point description
    Subjects who showed URTI symptom alleviation as defined for primary endpoint within study period were evaluated for duration of (initial) response's duration. Only patients with occurrence of symptom alleviation are shown. Patients not showing URTI symptom alleviation throughout the whole study period are not considered.
    End point type
    Secondary
    End point timeframe
    study day 2 to study day 14
    End point values
    ST arm [ITT analysis set] IFC arm [ITT analysis set]
    Number of subjects analysed
    228 [31]
    242 [32]
    Units: patients
        Maintenance until end of study
    199
    213
        Reoccurrence of symptom(s)
    29
    29
    Notes
    [31] - 24 patients had no symptom at all during the whole study.
    [32] - 17 patients had no symptom at all during the whole study.
    No statistical analyses for this end point

    Secondary: Time to return to normal daily activity [investigators' assessment]

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    End point title
    Time to return to normal daily activity [investigators' assessment]
    End point description
    Patients who were rated as having an impaired ability to perform their normal daily activities at baseline visit were evaluated for their individual time to return to normal daily activity, as assessed by the physician at FU calls and visits. The table shows the cumulated number of patients resuming normal daily activity at respective call/visit or earlier (Note: categories are ordered with respect to study schedule).
    End point type
    Secondary
    End point timeframe
    1st FU call, 2nd FU call, 1st FU visit, 2nd FU visit and termination visit
    End point values
    ST arm [ITT analysis set] IFC arm [ITT analysis set]
    Number of subjects analysed
    209 [33]
    196 [34]
    Units: patients
        1st FU call (day 2)
    11
    11
        2nd FU call (day 3)
    30
    41
        1st FU visit (day 4±1)
    58
    94
        2nd FU visit (day 8±1 )
    136
    171
        Termination visit (day 15 ±2)
    196
    186
    Notes
    [33] - 47 ST arm [ITT set] patients had no impairment at baseline and are therefore not considered.
    [34] - 65 IFC arm [ITT set] patients had no impairment at baseline and are therefore not considered.
    Statistical analysis title
    FU call 1:Equality of fractions between arms [ITT]
    Statistical analysis description
    Explorative analysis of patients patients resuming normal daily activity at FU call 1. (Only patients with impairment of normal daily activities as assessed at baseline are considered in analysis.) Presented values for risk difference are related to the difference between treatments taking into account the direction 'IFC - ST'.
    Comparison groups
    ST arm [ITT analysis set] v IFC arm [ITT analysis set]
    Number of subjects included in analysis
    405
    Analysis specification
    Pre-specified
    Analysis type
    other [35]
    P-value
    = 0.8769
    Method
    Chi-squared
    Parameter type
    Risk difference (RD)
    Point estimate
    0.35
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -4.57
         upper limit
    5.26
    Notes
    [35] - Binary categorization of "Resumption normal daily activity at FU call 1" [Yes/No] based on cumulated counts is basis for presented statistical test.
    Statistical analysis title
    FU call 2:Equality of fractions between arms [ITT]
    Statistical analysis description
    Explorative analysis of patients patients resuming normal daily activity at or prior to FU call 2. (Only patients with impairment of normal daily activities as assessed at baseline are considered in analysis.) Presented values for risk difference are related to the difference between treatments taking into account the direction 'IFC - ST'.
    Comparison groups
    ST arm [ITT analysis set] v IFC arm [ITT analysis set]
    Number of subjects included in analysis
    405
    Analysis specification
    Pre-specified
    Analysis type
    other [36]
    P-value
    = 0.0825
    Method
    Chi-squared
    Parameter type
    Risk difference (RD)
    Point estimate
    6.56
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.35
         upper limit
    14.48
    Notes
    [36] - Binary categorization of "Resumption normal daily activity at or prior to FU call 2" [Yes/No] based on cumulated counts is basis for presented statistical test.
    Statistical analysis title
    FU visit1:Equality of fractions between arms [ITT]
    Statistical analysis description
    Explorative analysis of patients patients resuming normal daily activity at or prior to FU visit 1. (Only patients with impairment of normal daily activities as assessed at baseline are considered in analysis.) Presented values for risk difference are related to the difference between treatments taking into account the direction 'IFC - ST'.
    Comparison groups
    ST arm [ITT analysis set] v IFC arm [ITT analysis set]
    Number of subjects included in analysis
    405
    Analysis specification
    Pre-specified
    Analysis type
    other [37]
    P-value
    < 0.0001 [38]
    Method
    Chi-squared
    Parameter type
    Risk difference (RD)
    Point estimate
    20.21
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    10.46
         upper limit
    29.96
    Notes
    [37] - Binary categorization of "Resumption normal daily activity at or prior to FU visit 1" [Yes/No] based on cumulated counts is basis for presented statistical test.
    [38] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly higher number of patients with resumption normal daily activity at or prior to FU visit 1 in IFC compared to ST arm [ITT analysis set].
    Statistical analysis title
    FU visit2:Equality of fractions between arms [ITT]
    Statistical analysis description
    Explorative analysis of patients patients resuming normal daily activity at or prior to FU visit 2. (Only patients with impairment of normal daily activities as assessed at baseline are considered in analysis.) Presented values for risk difference are related to the difference between treatments taking into account the direction 'IFC - ST'.
    Comparison groups
    ST arm [ITT analysis set] v IFC arm [ITT analysis set]
    Number of subjects included in analysis
    405
    Analysis specification
    Pre-specified
    Analysis type
    other [39]
    P-value
    < 0.0001 [40]
    Method
    Chi-squared
    Parameter type
    Risk difference (RD)
    Point estimate
    22.17
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    13.7
         upper limit
    30.64
    Notes
    [39] - Binary categorization of "Resumption normal daily activity at or prior to FU visit 2" [Yes/No] based on cumulated counts is basis for presented statistical test.
    [40] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly higher number of patients with resumption normal daily activity at or prior to FU visit 2 in IFC compared to ST arm [ITT analysis set].
    Statistical analysis title
    T. visit :Equality of fractions between arms [ITT]
    Statistical analysis description
    Explorative analysis of patients patients resuming normal daily activity at or prior to termination visit. (Only patients with impairment of normal daily activities as assessed at baseline are considered in analysis.) Presented values for risk difference are related to the difference between treatments taking into account the direction 'IFC - ST'.
    Comparison groups
    ST arm [ITT analysis set] v IFC arm [ITT analysis set]
    Number of subjects included in analysis
    405
    Analysis specification
    Pre-specified
    Analysis type
    other [41]
    P-value
    = 0.6271
    Method
    Chi-squared
    Parameter type
    Risk difference (RD)
    Point estimate
    1.12
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -3.87
         upper limit
    6.11
    Notes
    [41] - Binary categorization of "Resumption normal daily activity at or prior to termination visit" [Yes/No] based on cumulated counts is basis for presented statistical test.

    Secondary: Resolution of individual symptoms (analysed via WURSS-21)

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    End point title
    Resolution of individual symptoms (analysed via WURSS-21)
    End point description
    WURSS-21 items 2-20 assessed in patients diary are basis for individual symptom resolution evaluation. Between each distinct item, the number of subjects initially suffering a respective symptom (assessed by baseline WURSS-21 questionnaire item ratings '>1') may differ. The table therefore presents (i) the number of patients initially suffering from symptom /item, (ii) the number of patients with symptom resolved within study period - by WURSS-21 item. Note that the number of patients with symptom remaining unresolved at the end of study is the difference between (i) and (ii). The endpoint has been evaluated for N=504 ITT analysis set patients, as for N=6 patients (ST=4; IFC=2) no diary WURSS-21 records were available and for additional N=7 patients (ST=2; IFC=5) no baseline WURSS-21 questionnaire rating was available.
    End point type
    Secondary
    End point timeframe
    study day 2 to study day 14
    End point values
    ST arm [ITT analysis set] IFC arm [ITT analysis set]
    Number of subjects analysed
    250 [42]
    254 [43]
    Units: patients
        Item 2: Present impairment at baseline
    184
    173
        Item 2: Resolution within study period
    169
    165
        Item 3: Present impairment at baseline
    194
    199
        Item 3: Resolution within study period
    177
    190
        Item 4: Present impairment at baseline
    176
    165
        Item 4: Resolution within study period
    168
    162
        Item 5: Present impairment at baseline
    182
    186
        Item 5: Resolution within study period
    171
    184
        Item 6: Present impairment at baseline
    182
    194
        Item 6: Resolution within study period
    172
    188
        Item 7: Present impairment at baseline
    194
    184
        Item 7: Resolution within study period
    173
    166
        Item 8: Present impairment at baseline
    141
    150
        Item 8: Resolution within study period
    132
    146
        Item 9: Present impairment at baseline
    208
    204
        Item 9: Resolution within study period
    199
    200
        Item10: Present impairment at baseline
    103
    97
        Item 10: Resolution within study period
    97
    95
        Item11: Present impairment at baseline
    238
    244
        Item11: Resolution within study period
    220
    237
        Item12: Present impairment at baseline
    183
    171
        Item12: Resolution within study period
    171
    163
        Item13: Present impairment at baseline
    220
    229
        Item13: Resolution within study period
    203
    216
        Item14: Present impairment at baseline
    217
    216
        Item14: Resolution within study period
    200
    200
        Item15: Present impairment at baseline
    211
    210
        Item15: Resolution within study period
    191
    202
        Item16: Present impairment at baseline
    208
    215
        Item16: Resolution within study period
    192
    207
        Item17: Present impairment at baseline
    207
    213
        Item17: Resolution within study period
    191
    205
        Item18: Present impairment at baseline
    208
    215
        Item18: Resolution within study period
    195
    207
        Item19: Present impairment at baseline
    202
    211
        Item19: Resolution within study period
    187
    203
        Item20: Present impairment at baseline
    200
    213
        Item20: Resolution within study period
    187
    205
    Notes
    [42] - 6 ST arm [ITT set] patients had either missing baseline WURSS-21 questionnaire or no diary data.
    [43] - 7 IFC arm [ITT set] patients had either missing baseline WURSS-21 questionnaire or no diary data.
    Statistical analysis title
    Item 2: Equality of fractions between arms [ITT]
    Statistical analysis description
    Explorative analysis referring to observed resolution within study period [Yes/No] within those patients initially suffering from symptom (assessed by baseline WURSS-21 questionnaire item ratings '>1'). Presented values for risk difference are related to the difference in patients with resolution of symptom between treatments taking into account the direction 'IFC - ST'.
    Comparison groups
    ST arm [ITT analysis set] v IFC arm [ITT analysis set]
    Number of subjects included in analysis
    504
    Analysis specification
    Pre-specified
    Analysis type
    other [44]
    P-value
    = 0.1748
    Method
    Chi-squared
    Parameter type
    Risk difference (RD)
    Point estimate
    3.53
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.08
         upper limit
    9.13
    Notes
    [44] - The total number of patients contributing to this analysis is the number of patients with "item's impairment present at baseline" for each comparison group.
    Statistical analysis title
    Item 3: Equality of fractions between arms [ITT]
    Statistical analysis description
    Explorative analysis referring to observed resolution within study period [Yes/No] within those patients initially suffering from symptom (assessed by baseline WURSS-21 questionnaire item ratings '>1'). Presented values for risk difference are related to the difference in patients with resolution of symptom between treatments taking into account the direction 'IFC - ST'.
    Comparison groups
    ST arm [ITT analysis set] v IFC arm [ITT analysis set]
    Number of subjects included in analysis
    504
    Analysis specification
    Pre-specified
    Analysis type
    other [45]
    P-value
    = 0.0909
    Method
    Chi-squared
    Parameter type
    Risk difference (RD)
    Point estimate
    4.24
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.18
         upper limit
    9.67
    Notes
    [45] - The total number of patients contributing to this analysis is the number of patients with "item's impairment present at baseline" for each comparison group.
    Statistical analysis title
    Item 4: Equality of fractions between arms [ITT]
    Statistical analysis description
    Explorative analysis referring to observed resolution within study period [Yes/No] within those patients initially suffering from symptom (assessed by baseline WURSS-21 questionnaire item ratings '>1'). Presented values for risk difference are related to the difference in patients with resolution of symptom between treatments taking into account the direction 'IFC - ST'.
    Comparison groups
    ST arm [ITT analysis set] v IFC arm [ITT analysis set]
    Number of subjects included in analysis
    504
    Analysis specification
    Pre-specified
    Analysis type
    other [46]
    P-value
    = 0.1543
    Method
    Chi-squared
    Parameter type
    Risk difference (RD)
    Point estimate
    2.73
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.55
         upper limit
    7.01
    Notes
    [46] - The total number of patients contributing to this analysis is the number of patients with "item's impairment present at baseline" for each comparison group.
    Statistical analysis title
    Item 5: Equality of fractions between arms [ITT]
    Statistical analysis description
    Explorative analysis referring to observed resolution within study period [Yes/No] within those patients initially suffering from symptom (assessed by baseline WURSS-21 questionnaire item ratings '>1'). Presented values for risk difference are related to the difference in patients with resolution of symptom between treatments taking into account the direction 'IFC - ST'.
    Comparison groups
    ST arm [ITT analysis set] v IFC arm [ITT analysis set]
    Number of subjects included in analysis
    504
    Analysis specification
    Pre-specified
    Analysis type
    other [47]
    P-value
    = 0.0098 [48]
    Method
    Chi-squared
    Parameter type
    Risk difference (RD)
    Point estimate
    4.97
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.66
         upper limit
    9.28
    Notes
    [47] - The total number of patients contributing to this analysis is the number of patients with "item's impairment present at baseline" for each comparison group.
    [48] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly higher number of patients with item 5 resolution in IFC compared to ST arm [ITT analysis set].
    Statistical analysis title
    Item 6: Equality of fractions between arms [ITT]
    Statistical analysis description
    Explorative analysis referring to observed resolution within study period [Yes/No] within those patients initially suffering from symptom (assessed by baseline WURSS-21 questionnaire item ratings '>1'). Presented values for risk difference are related to the difference in patients with resolution of symptom between treatments taking into account the direction 'IFC - ST'.
    Comparison groups
    ST arm [ITT analysis set] v IFC arm [ITT analysis set]
    Number of subjects included in analysis
    504
    Analysis specification
    Pre-specified
    Analysis type
    other [49]
    P-value
    = 0.2489
    Method
    Chi-squared
    Parameter type
    Risk difference (RD)
    Point estimate
    2.4
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.24
         upper limit
    7.04
    Notes
    [49] - The total number of patients contributing to this analysis is the number of patients with "item's impairment present at baseline" for each comparison group.
    Statistical analysis title
    Item 7: Equality of fractions between arms [ITT]
    Statistical analysis description
    Explorative analysis referring to observed resolution within study period [Yes/No] within those patients initially suffering from symptom (assessed by baseline WURSS-21 questionnaire item ratings '>1'). Presented values for risk difference are related to the difference in patients with resolution of symptom between treatments taking into account the direction 'IFC - ST'.
    Comparison groups
    ST arm [ITT analysis set] v IFC arm [ITT analysis set]
    Number of subjects included in analysis
    504
    Analysis specification
    Pre-specified
    Analysis type
    other [50]
    P-value
    = 0.7392
    Method
    Chi-squared
    Parameter type
    Risk difference (RD)
    Point estimate
    1.04
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -5.61
         upper limit
    7.7
    Notes
    [50] - The total number of patients contributing to this analysis is the number of patients with "item's impairment present at baseline" for each comparison group.
    Statistical analysis title
    Item 8: Equality of fractions between arms [ITT]
    Statistical analysis description
    Explorative analysis referring to observed resolution within study period [Yes/No] within those patients initially suffering from symptom (assessed by baseline WURSS-21 questionnaire item ratings '>1'). Presented values for risk difference are related to the difference in patients with resolution of symptom between treatments taking into account the direction 'IFC - ST'.
    Comparison groups
    ST arm [ITT analysis set] v IFC arm [ITT analysis set]
    Number of subjects included in analysis
    504
    Analysis specification
    Pre-specified
    Analysis type
    other [51]
    P-value
    = 0.1251
    Method
    Chi-squared
    Parameter type
    Risk difference (RD)
    Point estimate
    3.72
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.76
         upper limit
    9.19
    Notes
    [51] - The total number of patients contributing to this analysis is the number of patients with "item's impairment present at baseline" for each comparison group.
    Statistical analysis title
    Item 9: Equality of fractions between arms [ITT]
    Statistical analysis description
    Explorative analysis referring to observed resolution within study period [Yes/No] within those patients initially suffering from symptom (assessed by baseline WURSS-21 questionnaire item ratings '>1'). Presented values for risk difference are related to the difference in patients with resolution of symptom between treatments taking into account the direction 'IFC - ST'.
    Comparison groups
    ST arm [ITT analysis set] v IFC arm [ITT analysis set]
    Number of subjects included in analysis
    504
    Analysis specification
    Pre-specified
    Analysis type
    other [52]
    P-value
    = 0.1695
    Method
    Chi-squared
    Parameter type
    Risk difference (RD)
    Point estimate
    2.37
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.48
         upper limit
    6.21
    Notes
    [52] - The total number of patients contributing to this analysis is the number of patients with "item's impairment present at baseline" for each comparison group.
    Statistical analysis title
    Item 10: Equality of fractions between arms [ITT]
    Statistical analysis description
    Explorative analysis referring to observed resolution within study period [Yes/No] within those patients initially suffering from symptom (assessed by baseline WURSS-21 questionnaire item ratings '>1'). Presented values for risk difference are related to the difference in patients with resolution of symptom between treatments taking into account the direction 'IFC - ST'.
    Comparison groups
    ST arm [ITT analysis set] v IFC arm [ITT analysis set]
    Number of subjects included in analysis
    504
    Analysis specification
    Pre-specified
    Analysis type
    other [53]
    P-value
    = 0.1747
    Method
    Chi-squared
    Parameter type
    Risk difference (RD)
    Point estimate
    3.76
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.57
         upper limit
    10.1
    Notes
    [53] - The total number of patients contributing to this analysis is the number of patients with "item's impairment present at baseline" for each comparison group.
    Statistical analysis title
    Item11: Equality of fractions between arms [ITT]
    Statistical analysis description
    Explorative analysis referring to observed resolution within study period [Yes/No] within those patients initially suffering from symptom (assessed by baseline WURSS-21 questionnaire item ratings '>1'). Presented values for risk difference are related to the difference in patients with resolution of symptom between treatments taking into account the direction 'IFC - ST'.
    Comparison groups
    ST arm [ITT analysis set] v IFC arm [ITT analysis set]
    Number of subjects included in analysis
    504
    Analysis specification
    Pre-specified
    Analysis type
    other [54]
    P-value
    = 0.0202 [55]
    Method
    Chi-squared
    Parameter type
    Risk difference (RD)
    Point estimate
    4.69
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.32
         upper limit
    9.07
    Notes
    [54] - The total number of patients contributing to this analysis is the number of patients with "item's impairment present at baseline" for each comparison group.
    [55] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly higher number of patients with item 11 resolution in IFC compared to ST arm [ITT analysis set].
    Statistical analysis title
    Item12: Equality of fractions between arms [ITT]
    Statistical analysis description
    Explorative analysis referring to observed resolution within study period [Yes/No] within those patients initially suffering from symptom (assessed by baseline WURSS-21 questionnaire item ratings '>1'). Presented values for risk difference are related to the difference in patients with resolution of symptom between treatments taking into account the direction 'IFC - ST'.
    Comparison groups
    ST arm [ITT analysis set] v IFC arm [ITT analysis set]
    Number of subjects included in analysis
    504
    Analysis specification
    Pre-specified
    Analysis type
    other [56]
    P-value
    = 0.4442
    Method
    Chi-squared
    Parameter type
    Risk difference (RD)
    Point estimate
    1.88
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -3.47
         upper limit
    7.23
    Notes
    [56] - The total number of patients contributing to this analysis is the number of patients with "item's impairment present at baseline" for each comparison group.
    Statistical analysis title
    Item13: Equality of fractions between arms [ITT]
    Statistical analysis description
    Explorative analysis referring to observed resolution within study period [Yes/No] within those patients initially suffering from symptom (assessed by baseline WURSS-21 questionnaire item ratings '>1'). Presented values for risk difference are related to the difference in patients with resolution of symptom between treatments taking into account the direction 'IFC - ST'.
    Comparison groups
    ST arm [ITT analysis set] v IFC arm [ITT analysis set]
    Number of subjects included in analysis
    504
    Analysis specification
    Pre-specified
    Analysis type
    other [57]
    P-value
    = 0.3844
    Method
    Chi-squared
    Parameter type
    Risk difference (RD)
    Point estimate
    2.05
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -3.02
         upper limit
    7.13
    Notes
    [57] - The total number of patients contributing to this analysis is the number of patients with "item's impairment present at baseline" for each comparison group.
    Statistical analysis title
    Item14: Equality of fractions between arms [ITT]
    Statistical analysis description
    Explorative analysis referring to observed resolution within study period [Yes/No] within those patients initially suffering from symptom (assessed by baseline WURSS-21 questionnaire item ratings '>1'). Presented values for risk difference are related to the difference in patients with resolution of symptom between treatments taking into account the direction 'IFC - ST'.
    Comparison groups
    ST arm [ITT analysis set] v IFC arm [ITT analysis set]
    Number of subjects included in analysis
    504
    Analysis specification
    Pre-specified
    Analysis type
    other [58]
    P-value
    = 0.8671
    Method
    Chi-squared
    Parameter type
    Risk difference (RD)
    Point estimate
    0.43
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -5.03
         upper limit
    5.89
    Notes
    [58] - The total number of patients contributing to this analysis is the number of patients with "item's impairment present at baseline" for each comparison group.
    Statistical analysis title
    Item15: Equality of fractions between arms [ITT]
    Statistical analysis description
    Explorative analysis referring to observed resolution within study period [Yes/No] within those patients initially suffering from symptom (assessed by baseline WURSS-21 questionnaire item ratings '>1'). Presented values for risk difference are related to the difference in patients with resolution of symptom between treatments taking into account the direction 'IFC - ST'.
    Comparison groups
    ST arm [ITT analysis set] v IFC arm [ITT analysis set]
    Number of subjects included in analysis
    504
    Analysis specification
    Pre-specified
    Analysis type
    other [59]
    P-value
    = 0.0196 [60]
    Method
    Chi-squared
    Parameter type
    Risk difference (RD)
    Point estimate
    5.67
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.47
         upper limit
    10.87
    Notes
    [59] - The total number of patients contributing to this analysis is the number of patients with "item's impairment present at baseline" for each comparison group.
    [60] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly higher number of patients with item 15 resolution in IFC compared to ST arm [ITT analysis set].
    Statistical analysis title
    Item16: Equality of fractions between arms [ITT]
    Statistical analysis description
    Explorative analysis referring to observed resolution within study period [Yes/No] within those patients initially suffering from symptom (assessed by baseline WURSS-21 questionnaire item ratings '>1'). Presented values for risk difference are related to the difference in patients with resolution of symptom between treatments taking into account the direction 'IFC - ST'.
    Comparison groups
    ST arm [ITT analysis set] v IFC arm [ITT analysis set]
    Number of subjects included in analysis
    504
    Analysis specification
    Pre-specified
    Analysis type
    other [61]
    P-value
    = 0.0775
    Method
    Chi-squared
    Parameter type
    Risk difference (RD)
    Point estimate
    3.97
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.92
         upper limit
    8.86
    Notes
    [61] - The total number of patients contributing to this analysis is the number of patients with "item's impairment present at baseline" for each comparison group.
    Statistical analysis title
    Item17: Equality of fractions between arms [ITT]
    Statistical analysis description
    Explorative analysis referring to observed resolution within study period [Yes/No] within those patients initially suffering from symptom (assessed by baseline WURSS-21 questionnaire item ratings '>1'). Presented values for risk difference are related to the difference in patients with resolution of symptom between treatments taking into account the direction 'IFC - ST'.
    Comparison groups
    ST arm [ITT analysis set] v IFC arm [ITT analysis set]
    Number of subjects included in analysis
    504
    Analysis specification
    Pre-specified
    Analysis type
    other [62]
    P-value
    = 0.0794
    Method
    Chi-squared
    Parameter type
    Risk difference (RD)
    Point estimate
    3.97
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.95
         upper limit
    8.89
    Notes
    [62] - The total number of patients contributing to this analysis is the number of patients with "item's impairment present at baseline" for each comparison group.
    Statistical analysis title
    Item18: Equality of fractions between arms [ITT]
    Statistical analysis description
    Explorative analysis referring to observed resolution within study period [Yes/No] within those patients initially suffering from symptom (assessed by baseline WURSS-21 questionnaire item ratings '>1'). Presented values for risk difference are related to the difference in patients with resolution of symptom between treatments taking into account the direction 'IFC - ST'.
    Comparison groups
    ST arm [ITT analysis set] v IFC arm [ITT analysis set]
    Number of subjects included in analysis
    504
    Analysis specification
    Pre-specified
    Analysis type
    other [63]
    P-value
    = 0.2312
    Method
    Chi-squared
    Parameter type
    Risk difference (RD)
    Point estimate
    2.53
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.09
         upper limit
    7.15
    Notes
    [63] - The total number of patients contributing to this analysis is the number of patients with "item's impairment present at baseline" for each comparison group.
    Statistical analysis title
    Item19: Equality of fractions between arms [ITT]
    Statistical analysis description
    Explorative analysis referring to observed resolution within study period [Yes/No] within those patients initially suffering from symptom (assessed by baseline WURSS-21 questionnaire item ratings '>1'). Presented values for risk difference are related to the difference in patients with resolution of symptom between treatments taking into account the direction 'IFC - ST'.
    Comparison groups
    ST arm [ITT analysis set] v IFC arm [ITT analysis set]
    Number of subjects included in analysis
    504
    Analysis specification
    Pre-specified
    Analysis type
    other [64]
    P-value
    = 0.1074
    Method
    Chi-squared
    Parameter type
    Risk difference (RD)
    Point estimate
    3.63
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.29
         upper limit
    8.56
    Notes
    [64] - The total number of patients contributing to this analysis is the number of patients with "item's impairment present at baseline" for each comparison group.
    Statistical analysis title
    Item20: Equality of fractions between arms [ITT]
    Statistical analysis description
    Explorative analysis referring to observed resolution within study period [Yes/No] within those patients initially suffering from symptom (assessed by baseline WURSS-21 questionnaire item ratings '>1'). Presented values for risk difference are related to the difference in patients with resolution of symptom between treatments taking into account the direction 'IFC - ST'.
    Comparison groups
    ST arm [ITT analysis set] v IFC arm [ITT analysis set]
    Number of subjects included in analysis
    504
    Analysis specification
    Pre-specified
    Analysis type
    other [65]
    P-value
    = 0.2046
    Method
    Chi-squared
    Parameter type
    Risk difference (RD)
    Point estimate
    2.74
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.01
         upper limit
    7.49
    Notes
    [65] - The total number of patients contributing to this analysis is the number of patients with "item's impairment present at baseline" for each comparison group.

    Secondary: Time to resolution of individual symptoms (analysed via diary WURSS-21)

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    End point title
    Time to resolution of individual symptoms (analysed via diary WURSS-21)
    End point description
    Analysis refers to the observed time point, when an item's resolution within study period was recorded in patients diary. Only patients with corresponding "item's impairment present at baseline" who showed resolution within study period contribute to this analysis. The endpoint has been evaluated for N=504 ITT analysis set patients, as for N=6 patients (ST=4; IFC=2) no diary WURSS-21 records were available and for additional N=7 patients (ST=2; IFC=5) no baseline WURSS-21 questionnaire rating was available. As stated above, the number of analysed patients differs between items, depending on the number of patients with observed resolution. [Please also refer to endpoint 'Resolution of individual symptoms (analysed via WURSS-21)']
    End point type
    Secondary
    End point timeframe
    study day 2 to study day 14
    End point values
    ST arm [ITT analysis set] IFC arm [ITT analysis set]
    Number of subjects analysed
    250 [66]
    254 [67]
    Units: [days]
    median (inter-quartile range (Q1-Q3))
        Item 2 (Runny nose)
    8 (6 to 10)
    6 (4 to 8)
        Item 3 (Plugged nose)
    8 (5 to 9)
    6 (4 to 8)
        Item 4 (Sneezing)
    6 (4 to 8)
    4 (3 to 6)
        Item 5 (Sore throat)
    6 (5 to 8)
    5 (4 to 7)
        Item 6 (Scratchy throat)
    6 (4 to 8)
    5 (4 to 7)
        Item 7 (Cough)
    9 (7 to 11)
    7 (4 to 9)
        Item 8 (Hoarseness)
    6 (3 to 8)
    4 (3 to 7)
        Item 9 (Head congestion)
    6 (5 to 8)
    4 (3 to 6)
        Item 10 (Chest congestion)
    7 (4 to 10)
    5 (3 to 8)
        Item 11 (Feeling tired)
    8 (6 to 10)
    6 (4 to 7)
        Item 12 (Think clearly)
    7 (5 to 9)
    5 (4 to 7)
        Item 13 (Sleep well)
    7 (5 to 9)
    5 (3 to 7)
        Item 14 (Breathe easily)
    8 (5 to 9)
    6 (4 to 7)
        Item 15 (Walk / climb stairs / exercise)
    8 (6 to 10)
    6 (4 to 7)
        Item 16 (Accomplish daily activities)
    8 (6 to 9)
    6 (4 to 7)
        Item 17 (Work outside the home)
    8 (6 to 10)
    6 (4 to 7)
        Item 18 (Work inside the home)
    7 (5 to 9)
    5 (4 to 7)
        Item 19 (Interact with others)
    7 (5 to 9)
    5 (4 to 7)
        Item 20 (Live your personal life)
    7 (5 to 9)
    5 (4 to 7)
    Notes
    [66] - 6 ST arm [ITT set] patients had either missing baseline WURSS-21 questionnaire or no diary data.
    [67] - 7 IFC arm [ITT set] patients had either missing baseline WURSS-21 questionnaire or no diary data.
    Statistical analysis title
    Item 2: Time to symptom resolution [ITT]
    Statistical analysis description
    Explorative analysis of individual item’s/ symptom’s time to resolution. Time to symptom resolution [days] was tested for treatment related differences. Presented values for estimated location shift are related to the difference in time to symptom resolution between treatments taking into account the direction 'IFC - ST'. Negative values indicate a shorter duration until symptom alleviation for IFC patients compared to ST patients.
    Comparison groups
    ST arm [ITT analysis set] v IFC arm [ITT analysis set]
    Number of subjects included in analysis
    504
    Analysis specification
    Pre-specified
    Analysis type
    other [68]
    P-value
    < 0.0001 [69]
    Method
    Wilcoxon (Mann-Whitney)
    Parameter type
    Hodges Lehman estimate of location shift
    Point estimate
    -2
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2
         upper limit
    -1
    Notes
    [68] - The total number of patients contributing to this test is the number of patients with item's “Resolution within study period” as presented in secondary end point “Resolution of individual symptoms (analysed via WURSS-21)”.
    [69] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly shorter time to symptom resolution [days] in IFC compared to ST arm [ITT analysis set] for WURSS-21 item 2.
    Statistical analysis title
    Item 3: Time to symptom resolution [ITT]
    Statistical analysis description
    Explorative analysis of individual item’s/ symptom’s time to resolution. Time to symptom resolution [days] was tested for treatment related differences. Presented values for estimated location shift are related to the difference in time to symptom resolution between treatments taking into account the direction 'IFC - ST'. Negative values indicate a shorter duration until symptom alleviation for IFC patients compared to ST patients.
    Comparison groups
    ST arm [ITT analysis set] v IFC arm [ITT analysis set]
    Number of subjects included in analysis
    504
    Analysis specification
    Pre-specified
    Analysis type
    other [70]
    P-value
    < 0.0001 [71]
    Method
    Wilcoxon (Mann-Whitney)
    Parameter type
    Hodges Lehman estimate of location shift
    Point estimate
    -2
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2
         upper limit
    -1
    Notes
    [70] - The total number of patients contributing to this test is the number of patients with item's “Resolution within study period” as presented in secondary end point “Resolution of individual symptoms (analysed via WURSS-21)”.
    [71] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly shorter time to symptom resolution [days] in IFC compared to ST arm [ITT analysis set] for WURSS-21 item 3.
    Statistical analysis title
    Item 4: Time to symptom resolution [ITT]
    Statistical analysis description
    Explorative analysis of individual item’s/ symptom’s time to resolution. Time to symptom resolution [days] was tested for treatment related differences. Presented values for estimated location shift are related to the difference in time to symptom resolution between treatments taking into account the direction 'IFC - ST'. Negative values indicate a shorter duration until symptom alleviation for IFC patients compared to ST patients.
    Comparison groups
    ST arm [ITT analysis set] v IFC arm [ITT analysis set]
    Number of subjects included in analysis
    504
    Analysis specification
    Pre-specified
    Analysis type
    other [72]
    P-value
    < 0.0001 [73]
    Method
    Wilcoxon (Mann-Whitney)
    Parameter type
    Hodges Lehman estimate of location shift
    Point estimate
    -1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2
         upper limit
    -1
    Notes
    [72] - The total number of patients contributing to this test is the number of patients with item's “Resolution within study period” as presented in secondary end point “Resolution of individual symptoms (analysed via WURSS-21)”.
    [73] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly shorter time to symptom resolution [days] in IFC compared to ST arm [ITT analysis set] for WURSS-21 item 4.
    Statistical analysis title
    Item 5: Time to symptom resolution [ITT]
    Statistical analysis description
    Explorative analysis of individual item’s/ symptom’s time to resolution. Time to symptom resolution [days] was tested for treatment related differences. Presented values for estimated location shift are related to the difference in time to symptom resolution between treatments taking into account the direction 'IFC - ST'. Negative values indicate a shorter duration until symptom alleviation for IFC patients compared to ST patients.
    Comparison groups
    ST arm [ITT analysis set] v IFC arm [ITT analysis set]
    Number of subjects included in analysis
    504
    Analysis specification
    Pre-specified
    Analysis type
    other [74]
    P-value
    < 0.0001 [75]
    Method
    Wilcoxon (Mann-Whitney)
    Parameter type
    Hodges Lehman estimate of location shift
    Point estimate
    -1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2
         upper limit
    -1
    Notes
    [74] - The total number of patients contributing to this test is the number of patients with item's “Resolution within study period” as presented in secondary end point “Resolution of individual symptoms (analysed via WURSS-21)”.
    [75] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly shorter time to symptom resolution [days] in IFC compared to ST arm [ITT analysis set] for WURSS-21 item 5.
    Statistical analysis title
    Item 6: Time to symptom resolution [ITT]
    Statistical analysis description
    Explorative analysis of individual item’s/ symptom’s time to resolution. Time to symptom resolution [days] was tested for treatment related differences. Presented values for estimated location shift are related to the difference in time to symptom resolution between treatments taking into account the direction 'IFC - ST'. Negative values indicate a shorter duration until symptom alleviation for IFC patients compared to ST patients.
    Comparison groups
    ST arm [ITT analysis set] v IFC arm [ITT analysis set]
    Number of subjects included in analysis
    504
    Analysis specification
    Pre-specified
    Analysis type
    other [76]
    P-value
    = 0.0003 [77]
    Method
    Wilcoxon (Mann-Whitney)
    Parameter type
    Hodges Lehman estimate of location shift
    Point estimate
    -1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2
         upper limit
    0
    Notes
    [76] - The total number of patients contributing to this test is the number of patients with item's “Resolution within study period” as presented in secondary end point “Resolution of individual symptoms (analysed via WURSS-21)”.
    [77] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly shorter time to symptom resolution [days] in IFC compared to ST arm [ITT analysis set] for WURSS-21 item 6.
    Statistical analysis title
    Item 7: Time to symptom resolution [ITT]
    Statistical analysis description
    Explorative analysis of individual item’s/ symptom’s time to resolution. Time to symptom resolution [days] was tested for treatment related differences. Presented values for estimated location shift are related to the difference in time to symptom resolution between treatments taking into account the direction 'IFC - ST'. Negative values indicate a shorter duration until symptom alleviation for IFC patients compared to ST patients.
    Comparison groups
    ST arm [ITT analysis set] v IFC arm [ITT analysis set]
    Number of subjects included in analysis
    504
    Analysis specification
    Pre-specified
    Analysis type
    other [78]
    P-value
    < 0.0001 [79]
    Method
    Wilcoxon (Mann-Whitney)
    Parameter type
    Hodges Lehman estimate of location shift
    Point estimate
    -2
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -3
         upper limit
    -1
    Notes
    [78] - The total number of patients contributing to this test is the number of patients with item's “Resolution within study period” as presented in secondary end point “Resolution of individual symptoms (analysed via WURSS-21)”.
    [79] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly shorter time to symptom resolution [days] in IFC compared to ST arm [ITT analysis set] for WURSS-21 item 7.
    Statistical analysis title
    Item 8: Time to symptom resolution [ITT]
    Statistical analysis description
    Explorative analysis of individual item’s/ symptom’s time to resolution. Time to symptom resolution [days] was tested for treatment related differences. Presented values for estimated location shift are related to the difference in time to symptom resolution between treatments taking into account the direction 'IFC - ST'. Negative values indicate a shorter duration until symptom alleviation for IFC patients compared to ST patients.
    Comparison groups
    ST arm [ITT analysis set] v IFC arm [ITT analysis set]
    Number of subjects included in analysis
    504
    Analysis specification
    Pre-specified
    Analysis type
    other [80]
    P-value
    = 0.0015 [81]
    Method
    Wilcoxon (Mann-Whitney)
    Parameter type
    Hodges Lehman estimate of location shift
    Point estimate
    -1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2
         upper limit
    0
    Notes
    [80] - The total number of patients contributing to this test is the number of patients with item's “Resolution within study period” as presented in secondary end point “Resolution of individual symptoms (analysed via WURSS-21)”.
    [81] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly shorter time to symptom resolution [days] in IFC compared to ST arm [ITT analysis set] for WURSS-21 item 8.
    Statistical analysis title
    Item 9: Time to symptom resolution [ITT]
    Statistical analysis description
    Explorative analysis of individual item’s/ symptom’s time to resolution. Time to symptom resolution [days] was tested for treatment related differences. Presented values for estimated location shift are related to the difference in time to symptom resolution between treatments taking into account the direction 'IFC - ST'. Negative values indicate a shorter duration until symptom alleviation for IFC patients compared to ST patients.
    Comparison groups
    ST arm [ITT analysis set] v IFC arm [ITT analysis set]
    Number of subjects included in analysis
    504
    Analysis specification
    Pre-specified
    Analysis type
    other [82]
    P-value
    < 0.0001 [83]
    Method
    Wilcoxon (Mann-Whitney)
    Parameter type
    Hodges Lehman estimate of location shift
    Point estimate
    -1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2
         upper limit
    -1
    Notes
    [82] - The total number of patients contributing to this test is the number of patients with item's “Resolution within study period” as presented in secondary end point “Resolution of individual symptoms (analysed via WURSS-21)”.
    [83] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly shorter time to symptom resolution [days] in IFC compared to ST arm [ITT analysis set] for WURSS-21 item 9.
    Statistical analysis title
    Item10: Time to symptom resolution [ITT]
    Statistical analysis description
    Explorative analysis of individual item’s/ symptom’s time to resolution. Time to symptom resolution [days] was tested for treatment related differences. Presented values for estimated location shift are related to the difference in time to symptom resolution between treatments taking into account the direction 'IFC - ST'. Negative values indicate a shorter duration until symptom alleviation for IFC patients compared to ST patients.
    Comparison groups
    ST arm [ITT analysis set] v IFC arm [ITT analysis set]
    Number of subjects included in analysis
    504
    Analysis specification
    Pre-specified
    Analysis type
    other [84]
    P-value
    = 0.0012 [85]
    Method
    Wilcoxon (Mann-Whitney)
    Parameter type
    Hodges Lehman estimate of location shift
    Point estimate
    -2
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -3
         upper limit
    -1
    Notes
    [84] - The total number of patients contributing to this test is the number of patients with item's “Resolution within study period” as presented in secondary end point “Resolution of individual symptoms (analysed via WURSS-21)”.
    [85] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly shorter time to symptom resolution [days] in IFC compared to ST arm [ITT analysis set] for WURSS-21 item 10.
    Statistical analysis title
    Item11: Time to symptom resolution [ITT]
    Statistical analysis description
    Explorative analysis of individual item’s/ symptom’s time to resolution. Time to symptom resolution [days] was tested for treatment related differences. Presented values for estimated location shift are related to the difference in time to symptom resolution between treatments taking into account the direction 'IFC - ST'. Negative values indicate a shorter duration until symptom alleviation for IFC patients compared to ST patients.
    Comparison groups
    ST arm [ITT analysis set] v IFC arm [ITT analysis set]
    Number of subjects included in analysis
    504
    Analysis specification
    Pre-specified
    Analysis type
    other [86]
    P-value
    < 0.0001 [87]
    Method
    Wilcoxon (Mann-Whitney)
    Parameter type
    Hodges Lehman estimate of location shift
    Point estimate
    -2
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2
         upper limit
    -1
    Notes
    [86] - The total number of patients contributing to this test is the number of patients with item's “Resolution within study period” as presented in secondary end point “Resolution of individual symptoms (analysed via WURSS-21)”.
    [87] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly shorter time to symptom resolution [days] in IFC compared to ST arm [ITT analysis set] for WURSS-21 item 11.
    Statistical analysis title
    Item12: Time to symptom resolution [ITT]
    Statistical analysis description
    Explorative analysis of individual item’s/ symptom’s time to resolution. Time to symptom resolution [days] was tested for treatment related differences. Presented values for estimated location shift are related to the difference in time to symptom resolution between treatments taking into account the direction 'IFC - ST'. Negative values indicate a shorter duration until symptom alleviation for IFC patients compared to ST patients.
    Comparison groups
    ST arm [ITT analysis set] v IFC arm [ITT analysis set]
    Number of subjects included in analysis
    504
    Analysis specification
    Pre-specified
    Analysis type
    other [88]
    P-value
    < 0.0001 [89]
    Method
    Wilcoxon (Mann-Whitney)
    Parameter type
    Hodges Lehman estimate of location shift
    Point estimate
    -1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2
         upper limit
    -1
    Notes
    [88] - The total number of patients contributing to this test is the number of patients with item's “Resolution within study period” as presented in secondary end point “Resolution of individual symptoms (analysed via WURSS-21)”.
    [89] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly shorter time to symptom resolution [days] in IFC compared to ST arm [ITT analysis set] for WURSS-21 item 12.
    Statistical analysis title
    Item13: Time to symptom resolution [ITT]
    Statistical analysis description
    Explorative analysis of individual item’s/ symptom’s time to resolution. Time to symptom resolution [days] was tested for treatment related differences. Presented values for estimated location shift are related to the difference in time to symptom resolution between treatments taking into account the direction 'IFC - ST'. Negative values indicate a shorter duration until symptom alleviation for IFC patients compared to ST patients.
    Comparison groups
    ST arm [ITT analysis set] v IFC arm [ITT analysis set]
    Number of subjects included in analysis
    504
    Analysis specification
    Pre-specified
    Analysis type
    other [90]
    P-value
    < 0.0001 [91]
    Method
    Wilcoxon (Mann-Whitney)
    Parameter type
    Hodges Lehman estimate of location shift
    Point estimate
    -1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2
         upper limit
    -1
    Notes
    [90] - The total number of patients contributing to this test is the number of patients with item's “Resolution within study period” as presented in secondary end point “Resolution of individual symptoms (analysed via WURSS-21)”.
    [91] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly shorter time to symptom resolution [days] in IFC compared to ST arm [ITT analysis set] for WURSS-21 item 13.
    Statistical analysis title
    Item14: Time to symptom resolution [ITT]
    Statistical analysis description
    Explorative analysis of individual item’s/ symptom’s time to resolution. Time to symptom resolution [days] was tested for treatment related differences. Presented values for estimated location shift are related to the difference in time to symptom resolution between treatments taking into account the direction 'IFC - ST'. Negative values indicate a shorter duration until symptom alleviation for IFC patients compared to ST patients.
    Comparison groups
    ST arm [ITT analysis set] v IFC arm [ITT analysis set]
    Number of subjects included in analysis
    504
    Analysis specification
    Pre-specified
    Analysis type
    other [92]
    P-value
    < 0.0001 [93]
    Method
    Wilcoxon (Mann-Whitney)
    Parameter type
    Hodges Lehman estimate of location shift
    Point estimate
    -2
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2
         upper limit
    -1
    Notes
    [92] - The total number of patients contributing to this test is the number of patients with item's “Resolution within study period” as presented in secondary end point “Resolution of individual symptoms (analysed via WURSS-21)”.
    [93] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly shorter time to symptom resolution [days] in IFC compared to ST arm [ITT analysis set] for WURSS-21 item 14.
    Statistical analysis title
    Item15: Time to symptom resolution [ITT]
    Statistical analysis description
    Explorative analysis of individual item’s/ symptom’s time to resolution. Time to symptom resolution [days] was tested for treatment related differences. Presented values for estimated location shift are related to the difference in time to symptom resolution between treatments taking into account the direction 'IFC - ST'. Negative values indicate a shorter duration until symptom alleviation for IFC patients compared to ST patients.
    Comparison groups
    ST arm [ITT analysis set] v IFC arm [ITT analysis set]
    Number of subjects included in analysis
    504
    Analysis specification
    Pre-specified
    Analysis type
    other [94]
    P-value
    < 0.0001 [95]
    Method
    Wilcoxon (Mann-Whitney)
    Parameter type
    Hodges Lehman estimate of location shift
    Point estimate
    -2
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2
         upper limit
    -1
    Notes
    [94] - The total number of patients contributing to this test is the number of patients with item's “Resolution within study period” as presented in secondary end point “Resolution of individual symptoms (analysed via WURSS-21)”.
    [95] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly shorter time to symptom resolution [days] in IFC compared to ST arm [ITT analysis set] for WURSS-21 item 15.
    Statistical analysis title
    Item16: Time to symptom resolution [ITT]
    Statistical analysis description
    Explorative analysis of individual item’s/ symptom’s time to resolution. Time to symptom resolution [days] was tested for treatment related differences. Presented values for estimated location shift are related to the difference in time to symptom resolution between treatments taking into account the direction 'IFC - ST'. Negative values indicate a shorter duration until symptom alleviation for IFC patients compared to ST patients.
    Comparison groups
    ST arm [ITT analysis set] v IFC arm [ITT analysis set]
    Number of subjects included in analysis
    504
    Analysis specification
    Pre-specified
    Analysis type
    other [96]
    P-value
    < 0.0001 [97]
    Method
    Wilcoxon (Mann-Whitney)
    Parameter type
    Hodges Lehman estimate of location shift
    Point estimate
    -2
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2
         upper limit
    -1
    Notes
    [96] - The total number of patients contributing to this test is the number of patients with item's “Resolution within study period” as presented in secondary end point “Resolution of individual symptoms (analysed via WURSS-21)”.
    [97] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly shorter time to symptom resolution [days] in IFC compared to ST arm [ITT analysis set] for WURSS-21 item 16.
    Statistical analysis title
    Item17: Time to symptom resolution [ITT]
    Statistical analysis description
    Explorative analysis of individual item’s/ symptom’s time to resolution. Time to symptom resolution [days] was tested for treatment related differences. Presented values for estimated location shift are related to the difference in time to symptom resolution between treatments taking into account the direction 'IFC - ST'. Negative values indicate a shorter duration until symptom alleviation for IFC patients compared to ST patients.
    Comparison groups
    ST arm [ITT analysis set] v IFC arm [ITT analysis set]
    Number of subjects included in analysis
    504
    Analysis specification
    Pre-specified
    Analysis type
    other [98]
    P-value
    < 0.0001 [99]
    Method
    Wilcoxon (Mann-Whitney)
    Parameter type
    Hodges Lehman estimate of location shift
    Point estimate
    -2
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2
         upper limit
    -1
    Notes
    [98] - The total number of patients contributing to this test is the number of patients with item's “Resolution within study period” as presented in secondary end point “Resolution of individual symptoms (analysed via WURSS-21)”.
    [99] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly shorter time to symptom resolution [days] in IFC compared to ST arm [ITT analysis set] for WURSS-21 item 17.
    Statistical analysis title
    Item18: Time to symptom resolution [ITT]
    Statistical analysis description
    Explorative analysis of individual item’s/ symptom’s time to resolution. Time to symptom resolution [days] was tested for treatment related differences. Presented values for estimated location shift are related to the difference in time to symptom resolution between treatments taking into account the direction 'IFC - ST'. Negative values indicate a shorter duration until symptom alleviation for IFC patients compared to ST patients.
    Comparison groups
    ST arm [ITT analysis set] v IFC arm [ITT analysis set]
    Number of subjects included in analysis
    504
    Analysis specification
    Pre-specified
    Analysis type
    other [100]
    P-value
    < 0.0001 [101]
    Method
    Wilcoxon (Mann-Whitney)
    Parameter type
    Hodges Lehman estimate of location shift
    Point estimate
    -2
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2
         upper limit
    -1
    Notes
    [100] - The total number of patients contributing to this test is the number of patients with item's “Resolution within study period” as presented in secondary end point “Resolution of individual symptoms (analysed via WURSS-21)”.
    [101] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly shorter time to symptom resolution [days] in IFC compared to ST arm [ITT analysis set] for WURSS-21 item 18.
    Statistical analysis title
    Item19: Time to symptom resolution [ITT]
    Statistical analysis description
    Explorative analysis of individual item’s/ symptom’s time to resolution. Time to symptom resolution [days] was tested for treatment related differences. Presented values for estimated location shift are related to the difference in time to symptom resolution between treatments taking into account the direction 'IFC - ST'. Negative values indicate a shorter duration until symptom alleviation for IFC patients compared to ST patients.
    Comparison groups
    ST arm [ITT analysis set] v IFC arm [ITT analysis set]
    Number of subjects included in analysis
    504
    Analysis specification
    Pre-specified
    Analysis type
    other [102]
    P-value
    < 0.0001 [103]
    Method
    Wilcoxon (Mann-Whitney)
    Parameter type
    Hodges Lehman estimate of location shift
    Point estimate
    -2
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2
         upper limit
    -1
    Notes
    [102] - The total number of patients contributing to this test is the number of patients with item's “Resolution within study period” as presented in secondary end point “Resolution of individual symptoms (analysed via WURSS-21)”.
    [103] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly shorter time to symptom resolution [days] in IFC compared to ST arm [ITT analysis set] for WURSS-21 item 19.
    Statistical analysis title
    Item20: Time to symptom resolution [ITT]
    Statistical analysis description
    Explorative analysis of individual item’s/ symptom’s time to resolution. Time to symptom resolution [days] was tested for treatment related differences. Presented values for estimated location shift are related to the difference in time to symptom resolution between treatments taking into account the direction 'IFC - ST'. Negative values indicate a shorter duration until symptom alleviation for IFC patients compared to ST patients.
    Comparison groups
    ST arm [ITT analysis set] v IFC arm [ITT analysis set]
    Number of subjects included in analysis
    504
    Analysis specification
    Pre-specified
    Analysis type
    other [104]
    P-value
    < 0.0001 [105]
    Method
    Wilcoxon (Mann-Whitney)
    Parameter type
    Hodges Lehman estimate of location shift
    Point estimate
    -2
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2
         upper limit
    -1
    Notes
    [104] - The total number of patients contributing to this test is the number of patients with item's “Resolution within study period” as presented in secondary end point “Resolution of individual symptoms (analysed via WURSS-21)”.
    [105] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly shorter time to symptom resolution [days] in IFC compared to ST arm [ITT analysis set] for WURSS-21 item 20.

    Secondary: Area under the curve (AUC) describing severity and course of the infection

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    End point title
    Area under the curve (AUC) describing severity and course of the infection
    End point description
    WURSS-21 questionnaire was answered by patients/parents twice a day. The cumulated (until study day 14) scorings for symptom (items2-11), quality of life (items12-20) and total (items 2-20) sum scores are shown here. In order to be able to compare between time-related randomization groups (i.e. patients randomized "till noon" or "after noon"), analysis was based on distance to baseline [DTB] (Evaluation “per day” would skew the calculation results as “till noon patients” would have answered one additional questionnaire compared to “after noon patients”). Presented AUC values refer to DTB=13.5. The endpoint has been evaluated for N=504 ITT analysis set patients, as for N=6 patients (ST=4; IFC=2) no diary WURSS-21 records were available and for additional N=7 patients (ST=2; IFC=5) no baseline WURSS-21 questionnaire rating was available. Please note that due to missing single items in baseline WURSS-21 questionnaire, AUC for sum scores could not be derived for all 504 analyzed patients.
    End point type
    Secondary
    End point timeframe
    study day 2 to study day 14
    End point values
    ST arm [ITT analysis set] IFC arm [ITT analysis set]
    Number of subjects analysed
    250 [106]
    254 [107]
    Units: SCORE
    median (inter-quartile range (Q1-Q3))
        Symptom sum score (WURSS items 2-11)
    425 (289.5 to 610.5)
    304 (197 to 453)
        QoL sum score (WURSS items 12-20)
    484 (285 to 710)
    342 (192 to 524)
        Total sum score (WURSS items 2-20)
    928 (597 to 1312)
    643.5 (395 to 952)
    Notes
    [106] - Thereof subjects with evaluable data per sum score: Symptom: N=240 | QoL: N= 234 | Total: N= 230
    [107] - Thereof subjects with evaluable data per sum score: Symptom: N=242 | QoL: N= 247 | Total: N= 238
    Statistical analysis title
    AUC: Symptom sum score [ITT]
    Statistical analysis description
    Explorative analysis of symptom sum score as calculated from WURSS-21 questionnaire items 2 to 11. Sum score AUC values were tested for treatment related differences. Presented values for estimated location shift are related to the difference in AUC between treatments taking into account the direction 'IFC - ST'. Negative values indicate lower scores (lower severity) for IFC group patients compared to ST group patients.
    Comparison groups
    ST arm [ITT analysis set] v IFC arm [ITT analysis set]
    Number of subjects included in analysis
    504
    Analysis specification
    Pre-specified
    Analysis type
    other [108]
    P-value
    < 0.0001 [109]
    Method
    Wilcoxon (Mann-Whitney)
    Parameter type
    Hodges Lehman estimate of location shift
    Point estimate
    -111
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -149
         upper limit
    -74
    Notes
    [108] - The total number of patients contributing to this test is the number of patients with valid baseline assessment for contributing to score calculation WURSS-21 items (2-11).
    [109] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly lower severity (WURSS-21 symptom sum score) within study period in IFC compared to ST arm [ITT analysis set].
    Statistical analysis title
    AUC: QoL sum score [ITT]
    Statistical analysis description
    Explorative analysis of QoL sum score as calculated from WURSS-21 questionnaire items 12 to 20. Sum score AUC values were tested for treatment related differences. Presented values for estimated location shift are related to the difference in AUC between treatments taking into account the direction 'IFC - ST'. Negative values indicate lower scores (lower severity) for IFC group patients compared to ST group patients.
    Comparison groups
    ST arm [ITT analysis set] v IFC arm [ITT analysis set]
    Number of subjects included in analysis
    504
    Analysis specification
    Pre-specified
    Analysis type
    other [110]
    P-value
    < 0.0001 [111]
    Method
    Wilcoxon (Mann-Whitney)
    Parameter type
    Hodges Lehman estimate of location shift
    Point estimate
    -127
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -175
         upper limit
    -76
    Notes
    [110] - The total number of patients contributing to this test is the number of patients with valid baseline assessment for contributing to score calculation WURSS-21 items (12-20).
    [111] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly lower severity (WURSS-21 QoL sum score) within study period in IFC compared to ST arm [ITT analysis set].
    Statistical analysis title
    AUC: Total sum score [ITT]
    Statistical analysis description
    Explorative analysis of total sum score as calculated from WURSS-21 questionnaire items 2 to 20. Sum score AUC values were tested for treatment related differences. Presented values for estimated location shift are related to the difference in AUC between treatments taking into account the direction 'IFC - ST'. Negative values indicate lower scores (lower severity) for IFC group patients compared to ST group patients.
    Comparison groups
    ST arm [ITT analysis set] v IFC arm [ITT analysis set]
    Number of subjects included in analysis
    504
    Analysis specification
    Pre-specified
    Analysis type
    other [112]
    P-value
    < 0.0001 [113]
    Method
    Wilcoxon (Mann-Whitney)
    Parameter type
    Hodges Lehman estimate of location shift
    Point estimate
    -246
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -331
         upper limit
    -162
    Notes
    [112] - The total number of patients contributing to this test is the number of patients with valid baseline assessment for contributing to score calculation WURSS-21 items (2-20).
    [113] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly lower severity (WURSS-21 total sum score) within study period in IFC compared to ST arm [ITT analysis set].

    Secondary: Total amount and amount per day of paracetamol consumption

    Close Top of page
    End point title
    Total amount and amount per day of paracetamol consumption
    End point description
    Paracetamol has been dispensed at discretion of the treating physician. Intake has been recorded in patient diary. The total amount [mg] of medication taken as well as the amount [mg] per day (average dosage) were calculated by considering (i) all patients with valid diary data [N=511; ITT both arms] and (ii) only those patients with valid diary data, to whom paracetamol has been actually dispensed. [Note: Presented values refer to the amount of active substance.]
    End point type
    Secondary
    End point timeframe
    study day 1 to study day 14
    End point values
    ST arm [ITT analysis set] IFC arm [ITT analysis set]
    Number of subjects analysed
    252 [114]
    259 [115]
    Units: mg
    median (inter-quartile range (Q1-Q3))
        Total amount [mg] (all patients)
    1750 (400 to 5450)
    600 (0 to 2200)
        Total amount [mg] (dispensed medication)
    2200 (800 to 6000)
    1000 (400 to 2600)
        Average dosage [mg] (all patients)
    533.3 (200 to 1020.5)
    300 (0 to 750)
        Average dosage [mg] (dispensed medication)
    600 (400 to 1100)
    466.7 (200 to 800)
    Notes
    [114] - 4 ST [ITT] patients had no valid diary data. Paracetamol dispense was recorded for N=228 patients.
    [115] - 2 IFC [ITT] patients had no valid diary data. Paracetamol dispense was recorded for N=205 patients.
    Statistical analysis title
    Paracetamol: Total amount (all patients) [ITT]
    Statistical analysis description
    Explorative analysis of the total (cumulated) amount of paracetamol taken. Analysis accounts for all patients with valid diary data. The total amount was tested for treatment related differences. Presented values for estimated location shift are related to the difference in consumed paracetamol between treatments taking into account the direction 'IFC - ST'
    Comparison groups
    ST arm [ITT analysis set] v IFC arm [ITT analysis set]
    Number of subjects included in analysis
    511
    Analysis specification
    Pre-specified
    Analysis type
    other [116]
    P-value
    < 0.0001 [117]
    Method
    Wilcoxon (Mann-Whitney)
    Parameter type
    Hodges Lehman estimate of location shift
    Point estimate
    -900
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1400
         upper limit
    -500
    Notes
    [116] - Analysis is based on diary data entries from all patients with valid diary data.
    [117] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly lower amount of paracetamol consumed in IFC compared to ST arm [ITT analysis set].
    Statistical analysis title
    Paracetamol: Total amount (dispensed medication)
    Statistical analysis description
    Explorative analysis of the total (cumulated) amount of paracetamol taken. Analysis accounts for all patients with valid diary data to whom paracetamol has been dispensed. The total amount was tested for treatment related differences. Presented values for estimated location shift are related to the difference in consumed paracetamol between treatments taking into account the direction 'IFC - ST'
    Comparison groups
    ST arm [ITT analysis set] v IFC arm [ITT analysis set]
    Number of subjects included in analysis
    511
    Analysis specification
    Pre-specified
    Analysis type
    other [118]
    P-value
    < 0.0001 [119]
    Method
    Wilcoxon (Mann-Whitney)
    Parameter type
    Hodges Lehman estimate of location shift
    Point estimate
    -1000
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1500
         upper limit
    -600
    Notes
    [118] - Analysis is based on valid diary data entries from patients with recorded dispense of paracetamol (as prescribed by treating physician on his/her discretion).
    [119] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly lower amount of paracetamol consumed in IFC compared to ST arm [ITT analysis set].
    Statistical analysis title
    Paracetamol: Average dosage (all patients) [ITT]
    Statistical analysis description
    Explorative analysis of the average amount of paracetamol taken by all patients with valid diary data is defined as the cumulated amount of paracetamol taken by these patients divided by the number of days of intake. The average dosage was tested for treatment related differences. Presented values for estimated location shift are related to the difference in paracetamol dosis between treatments taking into account the direction 'IFC - ST'.
    Comparison groups
    ST arm [ITT analysis set] v IFC arm [ITT analysis set]
    Number of subjects included in analysis
    511
    Analysis specification
    Pre-specified
    Analysis type
    other [120]
    P-value
    < 0.0001 [121]
    Method
    Wilcoxon (Mann-Whitney)
    Parameter type
    Hodges Lehman estimate of location shift
    Point estimate
    -200
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -300
         upper limit
    -100
    Notes
    [120] - Analysis is based on diary data entries from all patients with valid diary data.
    [121] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly lower average amount of paracetamol consumed in IFC compared to ST arm [ITT analysis set].
    Statistical analysis title
    Paracetamol: Average dosage (dispensed medication)
    Statistical analysis description
    Explorative analysis of the average amount of paracetamol taken by all patients with valid diary data to whom paracetamol has been dispensed, which is defined as the cumulated amount of paracetamol taken by these patients divided by the number of days of intake. The average dosage was tested for treatment related differences. Presented values for estimated location shift are related to the difference in paracetamol dosis between treatments taking into account the direction 'IFC - ST'.
    Comparison groups
    ST arm [ITT analysis set] v IFC arm [ITT analysis set]
    Number of subjects included in analysis
    511
    Analysis specification
    Pre-specified
    Analysis type
    other [122]
    P-value
    = 0.0005 [123]
    Method
    Wilcoxon (Mann-Whitney)
    Parameter type
    Hodges Lehman estimate of location shift
    Point estimate
    -175
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -250
         upper limit
    -65
    Notes
    [122] - Analysis is based on valid diary data entries from patients with recorded dispense of paracetamol.
    [123] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly lower average amount of paracetamol consumed in IFC compared to ST arm [ITT analysis set].

    Secondary: Total amount and amount per day of ambroxol consumption

    Close Top of page
    End point title
    Total amount and amount per day of ambroxol consumption
    End point description
    Ambroxol has been dispensed at discretion of the treating physician. Intake has been recorded in patient diary. The total amount [mg] of medication taken as well as the amount [mg] per day were calculated by considering (i) all patients with valid diary data [N=511; ITT both arms] and (ii) only those patients with valid diary data, to whom ambroxol has been actually dispensed. [Note: Presented values refer to the amount of active substance.]
    End point type
    Secondary
    End point timeframe
    study day 1 to study day 14
    End point values
    ST arm [ITT analysis set] IFC arm [ITT analysis set]
    Number of subjects analysed
    252 [124]
    259 [125]
    Units: [mg]
    median (inter-quartile range (Q1-Q3))
        Total amount [mg] (all patients)
    315 (112.5 to 630)
    112.5 (0 to 390)
        Total amount [mg] (dispensed medication)
    375 (157.5 to 660)
    240 (75 to 501)
        Average dosage [mg] (all patients)
    38 (17.7 to 69.5)
    22 (0 to 55.7)
        Average dosage [mg] (dispensed medication)
    42.5 (22.5 to 72.9)
    37.5 (20 to 70)
    Notes
    [124] - 4 ST [ITT] patients had no valid diary data. Ambroxol dispense was recorded for N=227 patients.
    [125] - 2 IFC [ITT] patients had no valid diary data. Ambroxol dispense was recorded for N=187 patients.
    Statistical analysis title
    Ambroxol: Total amount (all patients) [ITT]
    Statistical analysis description
    Explorative analysis of the total (cumulated) amount of ambroxol taken. Analysis accounts for all patients with valid diary data. The total amount was tested for treatment related differences. Presented values for estimated location shift are related to the difference in consumed ambroxol between treatments taking into account the direction 'IFC - ST'.
    Comparison groups
    ST arm [ITT analysis set] v IFC arm [ITT analysis set]
    Number of subjects included in analysis
    511
    Analysis specification
    Pre-specified
    Analysis type
    other [126]
    P-value
    < 0.0001 [127]
    Method
    Wilcoxon (Mann-Whitney)
    Parameter type
    Hodges Lehman estimate of location shift
    Point estimate
    -135
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -180
         upper limit
    -90
    Notes
    [126] - Analysis is based on diary data entries from all patients with valid diary data.
    [127] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly lower amount of ambroxol consumed in IFC compared to ST arm [ITT analysis set].
    Statistical analysis title
    Ambroxol: Total amount (dispensed medication)
    Statistical analysis description
    Explorative analysis of the total (cumulated) amount of ambroxol taken. Analysis accounts for all patients with valid diary data to whom ambroxol has been dispensed. The total amount was tested for treatment related differences. Presented values for estimated location shift are related to the difference in consumed ambroxol between treatments taking into account the direction 'IFC - ST'.
    Comparison groups
    ST arm [ITT analysis set] v IFC arm [ITT analysis set]
    Number of subjects included in analysis
    511
    Analysis specification
    Pre-specified
    Analysis type
    other [128]
    P-value
    = 0.0004 [129]
    Method
    Wilcoxon (Mann-Whitney)
    Parameter type
    Hodges Lehman estimate of location shift
    Point estimate
    -97.5
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -150
         upper limit
    -45
    Notes
    [128] - Analysis is based on valid diary data entries from patients with recorded dispense of ambroxol.
    [129] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly lower amount of ambroxol consumed in IFC compared to ST arm [ITT analysis set].
    Statistical analysis title
    Ambroxol: Average dosage (all patients) [ITT]
    Statistical analysis description
    Explorative analysis of the average amount of ambroxol taken by all patients with valid diary data is defined as the cumulated amount of ambroxol taken by these patients divided by the number of days of intake. The average dosage was tested for treatment related differences. Presented values for estimated location shift are related to the difference in ambroxol dosis between treatments taking into account the direction 'IFC - ST'.
    Comparison groups
    ST arm [ITT analysis set] v IFC arm [ITT analysis set]
    Number of subjects included in analysis
    511
    Analysis specification
    Pre-specified
    Analysis type
    other [130]
    P-value
    < 0.0001 [131]
    Method
    Wilcoxon (Mann-Whitney)
    Parameter type
    Hodges Lehman estimate of location shift
    Point estimate
    -11.25
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -17.8
         upper limit
    -4
    Notes
    [130] - Analysis is based on diary data entries from all patients with valid diary data.
    [131] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly lower average amount of ambroxol consumed in IFC compared to ST arm [ITT analysis set].
    Statistical analysis title
    Ambroxol: Average dosage (dispensed medication)
    Statistical analysis description
    Explorative analysis of the average amount of ambroxol taken by all patients with valid diary data to whom ambroxol has been dispensed, which is defined as the cumulated amount of ambroxol taken by these patients divided by the number of days of intake. The average dosage was tested for treatment related differences. Presented values for estimated location shift are related to the difference in ambroxol dosis between treatments taking into account the direction 'IFC - ST'.
    Comparison groups
    ST arm [ITT analysis set] v IFC arm [ITT analysis set]
    Number of subjects included in analysis
    511
    Analysis specification
    Pre-specified
    Analysis type
    other [132]
    P-value
    = 0.1971
    Method
    Wilcoxon (Mann-Whitney)
    Parameter type
    Hodges Lehman estimate of location shift
    Point estimate
    -2.8
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -9
         upper limit
    1.3
    Notes
    [132] - Analysis is based on valid diary data entries from patients with recorded dispense of ambroxol.

    Secondary: Total amount and amount per day of oxymetazoline consumption

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    End point title
    Total amount and amount per day of oxymetazoline consumption
    End point description
    Oxymetazoline has been dispensed at discretion of the treating physician. Intake has been recorded in patient diary. The total amount [μg] of medication taken as well as the amount [μg] per day were calculated by considering (i) all patients with valid diary data [N=511; ITT both arms] and (ii) only those patients with valid diary data, to whom oxymetazoline has been actually dispensed. [Note: Presented values refer to the amount of active substance.]
    End point type
    Secondary
    End point timeframe
    study day 1 to study day 14
    End point values
    ST arm [ITT analysis set] IFC arm [ITT analysis set]
    Number of subjects analysed
    252 [133]
    259 [134]
    Units: [µg]
    median (inter-quartile range (Q1-Q3))
        Total amount [µg] (all patients)
    720 (253.1 to 1080)
    292.5 (0 to 675)
        Total amount [µg] (dispensed medication)
    810 (472.5 to 1147.5)
    472.5 (202.5 to 810)
        Average dosage [µg] (all patients)
    96.3 (48.9 to 135)
    60.8 (0 to 112.5)
        Average dosage [µg] (dispensed medication)
    108.4 (61.9 to 135)
    80.3 (45 to 127)
    Notes
    [133] - 4 ST [ITT] patients had no valid diary data. Oxymetazoline dispense was listed for N=222 patients.
    [134] - 2 IFC [ITT] patients had no valid diary data. Oxymetazoline dispense was listed for N=196 patients.
    Statistical analysis title
    Oxymetazoline: Total amount (all patients) [ITT]
    Statistical analysis description
    Explorative analysis of the total (cumulated) amount of oxymetazoline taken. Analysis accounts for all patients with valid diary data. The total amount was tested for treatment related differences. Presented values for estimated location shift are related to the difference in consumed oxymetazoline between treatments taking into account the direction 'IFC - ST'.
    Comparison groups
    ST arm [ITT analysis set] v IFC arm [ITT analysis set]
    Number of subjects included in analysis
    511
    Analysis specification
    Pre-specified
    Analysis type
    other [135]
    P-value
    < 0.0001 [136]
    Method
    Wilcoxon (Mann-Whitney)
    Parameter type
    Hodges Lehman estimate of location shift
    Point estimate
    -315
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -405
         upper limit
    -202.5
    Notes
    [135] - Analysis is based on diary data entries from all patients with valid diary data.
    [136] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly lower amount of oxymetazoline consumed in IFC compared to ST arm [ITT analysis set].
    Statistical analysis title
    Oxymetazoline: Total amount (dispensed medication)
    Statistical analysis description
    Explorative analysis of the total (cumulated) amount of oxymetazoline taken. Analysis accounts for all patients with valid diary data to whom oxymetazoline has been dispensed. The total amount was tested for treatment related differences. Presented values for estimated location shift are related to the difference in consumed oxymetazoline between treatments taking into account the direction 'IFC - ST'.
    Comparison groups
    ST arm [ITT analysis set] v IFC arm [ITT analysis set]
    Number of subjects included in analysis
    511
    Analysis specification
    Pre-specified
    Analysis type
    other [137]
    P-value
    < 0.0001 [138]
    Method
    Wilcoxon (Mann-Whitney)
    Parameter type
    Hodges Lehman estimate of location shift
    Point estimate
    -270
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -360
         upper limit
    -157.5
    Notes
    [137] - Analysis is based on valid diary data entries from patients with recorded dispense of oxymetazoline.
    [138] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly lower amount of oxymetazoline consumed in IFC compared to ST arm [ITT analysis set].
    Statistical analysis title
    Oxymetazoline: Average dosage (all patients) [ITT]
    Statistical analysis description
    Explorative analysis of the average amount of oxymetazoline taken by all patients with valid diary data is defined as the cumulated amount of oxymetazoline taken by these patients divided by the number of days of intake. The average dosage was tested for treatment related differences. Presented values for estimated location shift are related to the difference in oxymetazoline dosis between treatments taking into account the direction 'IFC - ST'.
    Comparison groups
    ST arm [ITT analysis set] v IFC arm [ITT analysis set]
    Number of subjects included in analysis
    511
    Analysis specification
    Pre-specified
    Analysis type
    other [139]
    P-value
    < 0.0001 [140]
    Method
    Wilcoxon (Mann-Whitney)
    Parameter type
    Hodges Lehman estimate of location shift
    Point estimate
    -28.1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -43.4
         upper limit
    -13.5
    Notes
    [139] - Analysis is based on diary data entries from all patients with valid diary data.
    [140] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly lower average amount of oxymetazoline consumed in IFC compared to ST arm [ITT analysis set].
    Statistical analysis title
    Oxymetazoline:Average dosage(dispensed medication)
    Statistical analysis description
    Explorative analysis of the average amount of oxymetazoline taken by all patients with valid diary data to whom oxymetazoline has been dispensed, which is defined as the cumulated amount of oxymetazoline taken by these patients divided by the number of days of intake. The average dosage was tested for treatment related differences. Presented values for estimated location shift are related to the difference in oxymetazoline dosis between treatments taking into account the direction 'IFC - ST'.
    Comparison groups
    ST arm [ITT analysis set] v IFC arm [ITT analysis set]
    Number of subjects included in analysis
    511
    Analysis specification
    Pre-specified
    Analysis type
    other [141]
    P-value
    = 0.0026 [142]
    Method
    Wilcoxon (Mann-Whitney)
    Parameter type
    Hodges Lehman estimate of location shift
    Point estimate
    -16.9
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -29.25
         upper limit
    -4.5
    Notes
    [141] - Analysis is based on valid diary data entries from patients with recorded dispense of oxymetazoline.
    [142] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly lower average amount of oxymetazoline consumed in IFC compared to ST arm [ITT analysis set].

    Secondary: Duration of symptomatic medication consumption

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    End point title
    Duration of symptomatic medication consumption
    End point description
    Symptomatic medication (paracetamol, ambroxol, oxymetazoline 0.05% and 0.025%) have been dispensed at discretion of the treating physician. Intake has been recorded in patient diary. The number of days with recorded symptomatic medication intake is presented by considering (i) all patients with valid diary data [N=511; ITT both arms] and (ii) only those patients with valid diary data, to whom symptomatic medication has been actually dispensed. Number of days with individual substances (paracetamol, ambroxol and oxymetazoline) as well as with "any symptomatic medication" is presented. [Note: The number of patients with distinct symptomatic medication actually dispensed may be obtained from respective 'Total amount and amount per day' endpoint data presentations.]
    End point type
    Secondary
    End point timeframe
    study day 1 to study day 14
    End point values
    ST arm [ITT analysis set] IFC arm [ITT analysis set]
    Number of subjects analysed
    252 [143]
    259 [144]
    Units: [days]
    median (inter-quartile range (Q1-Q3))
        Days with: Any sympt.med. (all patients)
    9 (7 to 12)
    6 (4 to 9)
        Days with: Any sympt.med. (dispensed medication)
    9 (7 to 12)
    7 (5 to 9)
        Days with: paracetamol (all patients)
    3 (1 to 5)
    2 (0 to 3)
        Days with: paracetamol (dispensed medication)
    4 (2 to 5)
    2 (1 to 3)
        Days with: ambroxol (all patients)
    8 (5 to 11)
    4 (0 to 8)
        Days with: ambroxol (dispensed medication)
    8 (6 to 12)
    6 (4 to 9)
        Days with: oxymetazoline (all patients)
    7 (4 to 9)
    4 (0 to 7)
        Days with: oxymetazoline (dispensed medication)
    7 (6 to 10)
    5 (3 to 8)
    Notes
    [143] - 4 ST [ITT] patients had no valid diary. Any sympt. med. dispense was recorded for N=252 patients.
    [144] - 2 IFC [ITT] patients had no valid diary. Any sympt. med. dispense was lrecorded for N=234 patients.
    Statistical analysis title
    Duration: Any sympt.med. (all patients) [ITT]
    Statistical analysis description
    Explorative analysis of any symptomatic medication intake duration for all patients with valid diary data is defined as the number of days with any symptomatic medication intake as recorded in patient diary. The duration [days] was tested for treatment related differences. Presented values for estimated location shift are related to the difference in duration of any symptomatic medication intake between treatments taking into account the direction 'IFC - ST'.
    Comparison groups
    ST arm [ITT analysis set] v IFC arm [ITT analysis set]
    Number of subjects included in analysis
    511
    Analysis specification
    Pre-specified
    Analysis type
    other [145]
    P-value
    < 0.0001 [146]
    Method
    Wilcoxon (Mann-Whitney)
    Parameter type
    Hodges Lehman estimate of location shift
    Point estimate
    -3
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -3
         upper limit
    -2
    Notes
    [145] - Analysis is based on diary data entries from all patients with valid diary data.
    [146] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly shorter duration of any symptomatic medication consumed in IFC compared to ST arm [ITT analysis set].
    Statistical analysis title
    Duration: Any sympt.med. (dispensed medication)
    Statistical analysis description
    Explorative analysis of any symptomatic medication intake duration for all patients with valid diary data to whom any symptomatic medication was dispensed is defined as the number of days of any symptomatic medication intake as recorded in patient diary for those patients. Duration was tested for treatment related differences. Presented values for estimated location shift are related to the difference in duration of intake between treatments taking into account the direction 'IFC - ST'.
    Comparison groups
    ST arm [ITT analysis set] v IFC arm [ITT analysis set]
    Number of subjects included in analysis
    511
    Analysis specification
    Pre-specified
    Analysis type
    other [147]
    P-value
    < 0.0001 [148]
    Method
    Wilcoxon (Mann-Whitney)
    Parameter type
    Hodges Lehman estimate of location shift
    Point estimate
    -2
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -3
         upper limit
    -1
    Notes
    [147] - Analysis is based on valid diary data entries from patients with recorded dispense of either paracetamol, ambroxol or oxymetazoline.
    [148] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly shorter duration of any symptomatic medication consumed in IFC compared to ST arm [ITT analysis set].
    Statistical analysis title
    Duration: Paracetamol (all patients) [ITT]
    Statistical analysis description
    Explorative analysis of paracetamol intake duration for all patients with valid diary data is defined as the number of days with paracetamol intake as recorded in patient diary. The duration [days] was tested for treatment related differences. Presented values for estimated location shift are related to the difference in duration of paracetamol intake between treatments taking into account the direction 'IFC - ST'.
    Comparison groups
    ST arm [ITT analysis set] v IFC arm [ITT analysis set]
    Number of subjects included in analysis
    511
    Analysis specification
    Pre-specified
    Analysis type
    other [149]
    P-value
    < 0.0001 [150]
    Method
    Wilcoxon (Mann-Whitney)
    Parameter type
    Hodges Lehman estimate of location shift
    Point estimate
    -1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2
         upper limit
    -1
    Notes
    [149] - Analysis is based on diary data entries from all patients with valid diary data.
    [150] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly shorter duration of paracetamol consumed in IFC compared to ST arm [ITT analysis set].
    Statistical analysis title
    Duration: Ambroxol (all patients) [ITT]
    Statistical analysis description
    Explorative analysis of ambroxol intake duration for all patients with valid diary data is defined as the number of days with ambroxol intake as recorded in patient diary. The duration [days] was tested for treatment related differences. Presented values for estimated location shift are related to the difference in duration of ambroxol intake between treatments taking into account the direction 'IFC - ST'.
    Comparison groups
    ST arm [ITT analysis set] v IFC arm [ITT analysis set]
    Number of subjects included in analysis
    511
    Analysis specification
    Pre-specified
    Analysis type
    other [151]
    P-value
    < 0.0001 [152]
    Method
    Wilcoxon (Mann-Whitney)
    Parameter type
    Hodges Lehman estimate of location shift
    Point estimate
    -3
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -4
         upper limit
    -2
    Notes
    [151] - Analysis is based on diary data entries from all patients with valid diary data.
    [152] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly shorter duration of ambroxol consumed in IFC compared to ST arm [ITT analysis set].
    Statistical analysis title
    Duration: Paracetamol (dispensed medication) [ITT]
    Statistical analysis description
    Explorative analysis of paracetamol intake duration for all patients with valid diary data to whom paracetamol was dispensed is defined as the number of days of paracetamol intake as recorded in patient diary for those patients. The duration [days] was tested for treatment related differences. Presented values for estimated location shift are related to the difference in duration of paracetamol intake between treatments taking into account the direction 'IFC - ST'.
    Comparison groups
    ST arm [ITT analysis set] v IFC arm [ITT analysis set]
    Number of subjects included in analysis
    511
    Analysis specification
    Pre-specified
    Analysis type
    other [153]
    P-value
    < 0.0001 [154]
    Method
    Wilcoxon (Mann-Whitney)
    Parameter type
    Hodges Lehman estimate of location shift
    Point estimate
    -1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2
         upper limit
    -1
    Notes
    [153] - Analysis is based on valid diary data entries from patients with recorded dispense of paracetamol.
    [154] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly shorter duration of paracetamol consumed in IFC compared to ST arm [ITT analysis set].
    Statistical analysis title
    Duration: Ambroxol (dispensed medication) [ITT]
    Statistical analysis description
    Explorative analysis of ambroxol intake duration for all patients with valid diary data to whom ambroxol was dispensed is defined as the number of days of ambroxol intake as recorded in patient diary for those patients. The duration [days] was tested for treatment related differences. Presented values for estimated location shift are related to the difference in duration of ambroxol intake between treatments taking into account the direction 'IFC - ST'.
    Comparison groups
    ST arm [ITT analysis set] v IFC arm [ITT analysis set]
    Number of subjects included in analysis
    511
    Analysis specification
    Pre-specified
    Analysis type
    other [155]
    P-value
    < 0.0001 [156]
    Method
    Wilcoxon (Mann-Whitney)
    Parameter type
    Hodges Lehman estimate of location shift
    Point estimate
    -2
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -3
         upper limit
    -1
    Notes
    [155] - Analysis is based on valid diary data entries from patients with recorded dispense of ambroxol.
    [156] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly shorter duration of ambroxol consumed in IFC compared to ST arm [ITT analysis set].
    Statistical analysis title
    Duration: Oxymetazoline (all patients) [ITT]
    Statistical analysis description
    Explorative analysis of oxymetazoline intake duration for all patients with valid diary data is defined as the number of days with oxymetazoline intake as recorded in patient diary. The duration [days] was tested for treatment related differences. Presented values for estimated location shift are related to the difference in duration of oxymetazoline intake between treatments taking into account the direction 'IFC - ST'.
    Comparison groups
    ST arm [ITT analysis set] v IFC arm [ITT analysis set]
    Number of subjects included in analysis
    511
    Analysis specification
    Pre-specified
    Analysis type
    other [157]
    P-value
    < 0.0001 [158]
    Method
    Wilcoxon (Mann-Whitney)
    Parameter type
    Hodges Lehman estimate of location shift
    Point estimate
    -2
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -3
         upper limit
    -1
    Notes
    [157] - Analysis is based on diary data entries from all patients with valid diary data.
    [158] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly shorter duration of oxymetazoline consumed in IFC compared to ST arm [ITT analysis set].
    Statistical analysis title
    Duration: Oxymetazoline(dispensed medication)[ITT]
    Statistical analysis description
    Explorative analysis of oxymetazoline intake duration for all patients with valid diary data to whom oxymetazoline was dispensed is defined as the number of days of oxymetazoline intake as recorded in patient diary for those patients. The duration [days] was tested for treatment related differences. Presented values for estimated location shift are related to the difference in duration of oxymetazoline intake between treatments taking into account the direction 'IFC - ST'.
    Comparison groups
    ST arm [ITT analysis set] v IFC arm [ITT analysis set]
    Number of subjects included in analysis
    511
    Analysis specification
    Pre-specified
    Analysis type
    other [159]
    P-value
    < 0.0001 [160]
    Method
    Wilcoxon (Mann-Whitney)
    Parameter type
    Hodges Lehman estimate of location shift
    Point estimate
    -2
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2
         upper limit
    -1
    Notes
    [159] - Analysis is based on valid diary data entries from patients with recorded dispense of oxymetazoline.
    [160] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly shorter duration of oxymetazoline consumed in IFC compared to ST arm [ITT analysis set].

    Secondary: Fraction of patients who must be withdrawn from the study due to prohibited medication

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    End point title
    Fraction of patients who must be withdrawn from the study due to prohibited medication
    End point description
    The analysis of withdrawals due to prohibited medication was based on the consumption of concomitant medication recorded in the diary and CRF.
    End point type
    Secondary
    End point timeframe
    study day 2 to study day 14
    End point values
    ST arm [ITT analysis set] IFC arm [ITT analysis set]
    Number of subjects analysed
    256
    261
    Units: patients
        Withdrawal due to prohibited medication
    9
    5
        No withdrawal OR not due to prohibited medication
    247
    256
    Statistical analysis title
    Test for equality of fractions between arms [ITT]
    Statistical analysis description
    Explorative analysis of fraction of patients who must be withdrawn from the study due to prohibited medication. Presented values for risk difference are related to the difference in prohibited medication related withdrawals between treatments taking into account the direction 'IFC - ST'
    Comparison groups
    ST arm [ITT analysis set] v IFC arm [ITT analysis set]
    Number of subjects included in analysis
    517
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    = 0.2625
    Method
    Chi-squared
    Parameter type
    Risk difference (RD)
    Point estimate
    -1.6
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -4.8
         upper limit
    1.6

    Secondary: Treatment outcome according to integrative medicine outcomes scale (IMOS)

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    End point title
    Treatment outcome according to integrative medicine outcomes scale (IMOS)
    End point description
    Treatment outcome was assessed by both the investigator and the patient at each study visit using IMOS (5-point rating scale). Distinct values are presented for physicians and patients answers. The total number of patients assessments varies between presented visits as discontinuations occured between visits.
    End point type
    Secondary
    End point timeframe
    1st FU visit, 2nd FU visit and termination visit
    End point values
    ST arm [ITT analysis set] IFC arm [ITT analysis set]
    Number of subjects analysed
    256 [161]
    261 [162]
    Units: patients
        1st FU V.: Complete recovery (physician)
    5
    13
        1st FU V.: Major improvement (physician)
    62
    143
        1st FU V.: Slight to moderate improvement (phys.)
    121
    82
        1st FU V.: No change (physician)
    54
    17
        1st FU V.: Deterioration (physician)
    14
    6
        2nd FU V.: Complete recovery (physician)
    28
    118
        2nd FU V.: Major improvement (physician)
    164
    121
        2nd FU V.: Slight to moderate improvement (phys.)
    48
    16
        2nd FU V.: No change (physician)
    5
    0
        2nd FU V.: Deterioration (physician)
    6
    4
        Term. V.: Complete recovery (physician)
    186
    225
        Term. V.: Major improvement (physician)
    47
    22
        Term. V.: Slight to moderate improvement (phys.)
    10
    2
        Term. V.: No change (physician)
    0
    3
        Term. V.: Deterioration (physician)
    3
    4
        1st FU V.: Complete recovery (patient)
    7
    18
        1st FU V.: Major improvement (patient)
    58
    129
        1st FU V.: Slight to moderate improvement (pat.)
    121
    89
        1st FU V.: No change (patient)
    52
    17
        1st FU V.: Deterioration (patient)
    18
    8
        2nd FU V.: Complete recovery (patient)
    29
    115
        2nd FU V.: Major improvement (patient)
    164
    126
        2nd FU V.: Slight to moderate improvement (pat.)
    47
    14
        2nd FU V.: No change (patient)
    5
    0
        2nd FU V.: Deterioration (patient)
    6
    4
        Term. V.: Complete recovery (patient)
    191
    225
        Term. V.: Major improvement (patient)
    42
    22
        Term. V.: Slight to moderate improvement (pat.)
    9
    2
        Term. V.: No change (patient)
    1
    3
        Term. V.: Deterioration (patient)
    3
    4
    Notes
    [161] - Total assessments per visit: 1st FU: N=256 2ndFU: N=252 Termination: N=246
    [162] - Total assessments per visit: 1st FU: N=261 2ndFU: N=259 Termination: N=256
    Statistical analysis title
    IMOS 1st FU: At least 'major impr.' (patient)[ITT]
    Statistical analysis description
    Explorative analysis of combined IMOS categories. Binary categorization of IMOS is done by considering groups "complete recovery or major improvement" and "slight to moderate improvement or no change or deterioration" resulting from combination of IMOS assessment categories. Presented values for risk difference are related to the difference between treatments taking into account the direction 'IFC - ST'.
    Comparison groups
    ST arm [ITT analysis set] v IFC arm [ITT analysis set]
    Number of subjects included in analysis
    517
    Analysis specification
    Pre-specified
    Analysis type
    other [163]
    P-value
    < 0.001 [164]
    Method
    Chi-squared
    Parameter type
    Risk difference (RD)
    Point estimate
    30.93
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    22.5
         upper limit
    39.36
    Notes
    [163] - Analysis refers to patients' assessments.
    [164] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly higher fraction of patients with IMOS assessed as 'complete recovery or major improvement’ in IFC compared to ST arm [ITT analysis set].
    Statistical analysis title
    IMOS 1st FU: At least 'major impr.' (physician)
    Statistical analysis description
    Explorative analysis of combined IMOS categories. Binary categorization of IMOS is done by considering groups "complete recovery or major improvement" and "slight to moderate improvement or no change or deterioration" resulting from combination of IMOS assessment categories. Presented values for risk difference are related to the difference between treatments taking into account the direction 'IFC - ST'.
    Comparison groups
    ST arm [ITT analysis set] v IFC arm [ITT analysis set]
    Number of subjects included in analysis
    517
    Analysis specification
    Pre-specified
    Analysis type
    other [165]
    P-value
    < 0.001 [166]
    Method
    Chi-squared
    Parameter type
    Risk difference (RD)
    Point estimate
    33.6
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    25.19
         upper limit
    42.01
    Notes
    [165] - Analysis refers to physicians' assessments.
    [166] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly higher fraction of patients with IMOS assessed as 'complete recovery or major improvement’ in IFC compared to ST arm [ITT analysis set].
    Statistical analysis title
    IMOS 2nd FU: At least 'major impr.' (patient)
    Statistical analysis description
    Explorative analysis of combined IMOS categories. Binary categorization of IMOS is done by considering groups "complete recovery or major improvement" and "slight to moderate improvement or no change or deterioration" resulting from combination of IMOS assessment categories. Presented values for risk difference are related to the difference between treatments taking into account the direction 'IFC - ST'.
    Comparison groups
    ST arm [ITT analysis set] v IFC arm [ITT analysis set]
    Number of subjects included in analysis
    517
    Analysis specification
    Pre-specified
    Analysis type
    other [167]
    P-value
    < 0.001 [168]
    Method
    Chi-squared
    Parameter type
    Risk difference (RD)
    Point estimate
    16.46
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    9.99
         upper limit
    22.93
    Notes
    [167] - Analysis refers to patients' assessments. [Note: 1 missing assessment in ST arm.]
    [168] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly higher fraction of patients with IMOS assessed as 'complete recovery or major improvement’ in IFC compared to ST arm [ITT analysis set].
    Statistical analysis title
    IMOS 2nd FU: At least 'major impr.' (physician)
    Statistical analysis description
    Explorative analysis of combined IMOS categories. Binary categorization of IMOS is done by considering groups "complete recovery or major improvement" and "slight to moderate improvement or no change or deterioration" resulting from combination of IMOS assessment categories. Presented values for risk difference are related to the difference between treatments taking into account the direction 'IFC - ST'.
    Comparison groups
    ST arm [ITT analysis set] v IFC arm [ITT analysis set]
    Number of subjects included in analysis
    517
    Analysis specification
    Pre-specified
    Analysis type
    other [169]
    P-value
    < 0.001 [170]
    Method
    Chi-squared
    Parameter type
    Risk difference (RD)
    Point estimate
    16.09
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    9.51
         upper limit
    22.66
    Notes
    [169] - Analysis refers to physicians' assessments. [Note: 1 missing assessment in ST arm.]
    [170] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly higher fraction of patients with IMOS assessed as 'complete recovery or major improvement’ in IFC compared to ST arm [ITT analysis set].
    Statistical analysis title
    IMOS Term. V.: At least 'major impr.' (patient)
    Statistical analysis description
    Explorative analysis of combined IMOS categories. Binary categorization of IMOS is done by considering groups "complete recovery or major improvement" and "slight to moderate improvement or no change or deterioration" resulting from combination of IMOS assessment categories. Presented values for risk difference are related to the difference between treatments taking into account the direction 'IFC - ST'.
    Comparison groups
    ST arm [ITT analysis set] v IFC arm [ITT analysis set]
    Number of subjects included in analysis
    517
    Analysis specification
    Pre-specified
    Analysis type
    other [171]
    P-value
    = 0.333
    Method
    Chi-squared
    Parameter type
    Risk difference (RD)
    Point estimate
    1.77
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.22
         upper limit
    5.76
    Notes
    [171] - Analysis refers to patients' assessments.
    Statistical analysis title
    IMOS Term. V.: At least 'major impr.' (physician)
    Statistical analysis description
    Explorative analysis of combined IMOS categories. Binary categorization of IMOS is done by considering groups "complete recovery or major improvement" and "slight to moderate improvement or no change or deterioration" resulting from combination of IMOS assessment categories. Presented values for risk difference are related to the difference between treatments taking into account the direction 'IFC - ST'.
    Comparison groups
    ST arm [ITT analysis set] v IFC arm [ITT analysis set]
    Number of subjects included in analysis
    517
    Analysis specification
    Pre-specified
    Analysis type
    other [172]
    P-value
    = 0.333
    Method
    Chi-squared
    Parameter type
    Risk difference (RD)
    Point estimate
    1.77
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.22
         upper limit
    5.76
    Notes
    [172] - Analysis refers to physicians' assessments.
    Statistical analysis title
    IMOS 1st FU: 'Complete recovery' (patient)
    Statistical analysis description
    Explorative analysis of combined IMOS categories. Binary categorization of IMOS is done by considering groups "complete recovery" and "major improvement or slight to moderate improvement or no change or deterioration" as resulting from combination of IMOS assessment categories. I.e. binary categorization in terms of complete recovery [Yes/No] is evaluated. Presented values for risk difference are related to the difference between treatments taking into account the direction 'IFC - ST'.
    Comparison groups
    ST arm [ITT analysis set] v IFC arm [ITT analysis set]
    Number of subjects included in analysis
    517
    Analysis specification
    Pre-specified
    Analysis type
    other [173]
    P-value
    = 0.027 [174]
    Method
    Chi-squared
    Parameter type
    Risk difference (RD)
    Point estimate
    4.16
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.11
         upper limit
    8.22
    Notes
    [173] - Analysis refers to patients' assessments.
    [174] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly higher fraction of completely recovered patients (IMOS assessment) in IFC compared to ST arm [ITT analysis set].
    Statistical analysis title
    IMOS 1st FU: 'Complete recovery' (physician)
    Statistical analysis description
    Explorative analysis of combined IMOS categories. Binary categorization of IMOS is done by considering groups "complete recovery" and "major improvement or slight to moderate improvement or no change or deterioration" as resulting from combination of IMOS assessment categories. I.e. binary categorization in terms of complete recovery [Yes/No] is evaluated. Presented values for risk difference are related to the difference between treatments taking into account the direction 'IFC - ST'.
    Comparison groups
    ST arm [ITT analysis set] v IFC arm [ITT analysis set]
    Number of subjects included in analysis
    517
    Analysis specification
    Pre-specified
    Analysis type
    other [175]
    P-value
    = 0.06
    Method
    Chi-squared
    Parameter type
    Risk difference (RD)
    Point estimate
    3.03
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.5
         upper limit
    6.55
    Notes
    [175] - Analysis refers to physicians' assessments.
    Statistical analysis title
    IMOS 2nd FU: 'Complete recovery' (patient)
    Statistical analysis description
    Explorative analysis of combined IMOS categories. Binary categorization of IMOS is done by considering groups "complete recovery" and "major improvement or slight to moderate improvement or no change or deterioration" as resulting from combination of IMOS assessment categories. I.e. binary categorization in terms of complete recovery [Yes/No] is evaluated. Presented values for risk difference are related to the difference between treatments taking into account the direction 'IFC - ST'.
    Comparison groups
    ST arm [ITT analysis set] v IFC arm [ITT analysis set]
    Number of subjects included in analysis
    517
    Analysis specification
    Pre-specified
    Analysis type
    other [176]
    P-value
    < 0.001 [177]
    Method
    Chi-squared
    Parameter type
    Risk difference (RD)
    Point estimate
    32.89
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    25.28
         upper limit
    40.51
    Notes
    [176] - Analysis refers to patients' assessments. [Note: 1 missing assessment in ST arm.]
    [177] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly higher fraction of completely recovered patients (IMOS assessment) in IFC compared to ST arm [ITT analysis set].
    Statistical analysis title
    IMOS 2nd FU: 'Complete recovery' (physician)
    Statistical analysis description
    Explorative analysis of combined IMOS categories. Binary categorization of IMOS is done by considering groups "complete recovery" and "major improvement or slight to moderate improvement or no change or deterioration" as resulting from combination of IMOS assessment categories. I.e. binary categorization in terms of complete recovery [Yes/No] is evaluated. Presented values for risk difference are related to the difference between treatments taking into account the direction 'IFC - ST'.
    Comparison groups
    ST arm [ITT analysis set] v IFC arm [ITT analysis set]
    Number of subjects included in analysis
    517
    Analysis specification
    Pre-specified
    Analysis type
    other [178]
    P-value
    < 0.001 [179]
    Method
    Chi-squared
    Parameter type
    Risk difference (RD)
    Point estimate
    34.45
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    26.86
         upper limit
    42.04
    Notes
    [178] - Analysis refers to physicians' assessments. [Note: 1 missing assessment in ST arm.]
    [179] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly higher fraction of completely recovered patients (IMOS assessment) in IFC compared to ST arm [ITT analysis set].
    Statistical analysis title
    IMOS Term. V.: 'Complete recovery' (patient)
    Statistical analysis description
    Explorative analysis of combined IMOS categories. Binary categorization of IMOS is done by considering groups "complete recovery" and "major improvement or slight to moderate improvement or no change or deterioration" as resulting from combination of IMOS assessment categories. I.e. binary categorization in terms of complete recovery [Yes/No] is evaluated. Presented values for risk difference are related to the difference between treatments taking into account the direction 'IFC - ST'.
    Comparison groups
    ST arm [ITT analysis set] v IFC arm [ITT analysis set]
    Number of subjects included in analysis
    517
    Analysis specification
    Pre-specified
    Analysis type
    other [180]
    P-value
    = 0.002 [181]
    Method
    Chi-squared
    Parameter type
    Risk difference (RD)
    Point estimate
    10.25
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    3.29
         upper limit
    17.21
    Notes
    [180] - Analysis refers to patients' assessments.
    [181] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly higher fraction of completely recovered patients (IMOS assessment) in IFC compared to ST arm [ITT analysis set].
    Statistical analysis title
    IMOS Term. V.: 'Complete recovery' (physician)
    Statistical analysis description
    Explorative analysis of combined IMOS categories. Binary categorization of IMOS is done by considering groups "complete recovery" and "major improvement or slight to moderate improvement or no change or deterioration" as resulting from combination of IMOS assessment categories. I.e. binary categorization in terms of complete recovery [Yes/No] is evaluated. Presented values for risk difference are related to the difference between treatments taking into account the direction 'IFC - ST'.
    Comparison groups
    ST arm [ITT analysis set] v IFC arm [ITT analysis set]
    Number of subjects included in analysis
    517
    Analysis specification
    Pre-specified
    Analysis type
    other [182]
    P-value
    < 0.001 [183]
    Method
    Chi-squared
    Parameter type
    Risk difference (RD)
    Point estimate
    12.28
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    5.19
         upper limit
    19.37
    Notes
    [182] - Analysis refers to physicians' assessments.
    [183] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly higher fraction of completely recovered patients (IMOS assessment) in IFC compared to ST arm [ITT analysis set].

    Secondary: Satisfaction with treatment according to integrative medicine patient satisfaction scale [IMPSS]

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    End point title
    Satisfaction with treatment according to integrative medicine patient satisfaction scale [IMPSS]
    End point description
    IMPSS has been assessed by patients / parents at study termination visit.
    End point type
    Secondary
    End point timeframe
    Study termination visit.
    End point values
    ST arm [ITT analysis set] IFC arm [ITT analysis set]
    Number of subjects analysed
    246 [184]
    256 [185]
    Units: patients
        not applicable
    1
    0
        Very satisfied
    84
    196
        Satisfied
    120
    53
        Neutral
    37
    4
        Dissatisfied
    4
    3
        Very dissatisfied
    0
    0
    Notes
    [184] - Total assessments: Termination: N=246
    [185] - Total assessments: Termination: N=256
    Statistical analysis title
    IMPSS: Very satisfied patients [ITT]
    Statistical analysis description
    Explorative analysis of combined IMPSS categories. Binary categorization of IMPSS is done by considering the "very satisfied" group against all other categories. Presented values for risk difference are related to the difference between treatments taking into account the direction 'IFC - ST'.
    Comparison groups
    ST arm [ITT analysis set] v IFC arm [ITT analysis set]
    Number of subjects included in analysis
    502
    Analysis specification
    Pre-specified
    Analysis type
    other [186]
    P-value
    < 0.0001 [187]
    Method
    Chi-squared
    Parameter type
    Risk difference (RD)
    Point estimate
    42.82
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    34.56
         upper limit
    51.08
    Notes
    [186] - Analysis refers to patients' assessments at termination visit.
    [187] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly higher fraction of patients beeing "very satisfied" (IMPSS) in IFC compared to ST arm [ITT analysis set].
    Statistical analysis title
    IMPSS: Neutral and dissatisfied patients [ITT]
    Statistical analysis description
    Explorative analysis of combined IMPSS categories. Binary categorization of IMPSS is done by considering the combined "neutral or dissatisfied or very dissatisfied" group against combination of remaining categories. Presented values for risk difference are related to the difference between treatments taking into account the direction 'IFC - ST'.
    Comparison groups
    ST arm [ITT analysis set] v IFC arm [ITT analysis set]
    Number of subjects included in analysis
    502
    Analysis specification
    Pre-specified
    Analysis type
    other [188]
    P-value
    < 0.0001 [189]
    Method
    Chi-squared
    Parameter type
    Risk difference (RD)
    Point estimate
    -14.75
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -20.29
         upper limit
    -9.2
    Notes
    [188] - Analysis refers to patients' assessments at termination visit.
    [189] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly lower fraction of patients beeing "neutral or dissatisfied or very dissatisfied" (IMPSS) in IFC compared to ST arm [ITT analysis set].

    Secondary: Patients’ / parents’ assessment of tolerability of treatment

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    End point title
    Patients’ / parents’ assessment of tolerability of treatment
    End point description
    Tolerability of treatment has been assessed by patients / parents and investigators at each of FU calls and visits on a verbal rating scale. Distinct values are presented for physicians and patients answers. The total number of patients assessments varies between presented calls and visits as (i) some calls were not done and (ii) discontinuations have occurred between visits.
    End point type
    Secondary
    End point timeframe
    FU calls and visits
    End point values
    ST arm [ITT analysis set] IFC arm [ITT analysis set]
    Number of subjects analysed
    256 [190]
    261 [191]
    Units: patients
        1st FU call: Excellent (patient)
    43
    79
        1st FU call: Good (patient)
    202
    179
        1st FU call: Moderate (patient)
    7
    3
        1st FU call: Poor (patient)
    3
    0
        1st FU call: not assessed (patient)
    1
    0
        2nd FU call: Excellent (patient)
    38
    83
        2nd FU call: Good (patient)
    184
    161
        2nd FU call: Moderate (patient)
    13
    3
        2nd FU call: Poor (patient)
    2
    0
        2nd FU call: not assessed (patient)
    1
    0
        1st FU visit: Excellent (patient)
    55
    118
        1st FU visit: Good (patient)
    183
    140
        1st FU visit: Moderate (patient)
    11
    3
        1st FU visit: Poor (patient)
    4
    0
        1st FU visit: not assessed (patient)
    3
    0
        2nd FU visit: Excellent (patient)
    63
    145
        2nd FU visit: Good (patient)
    174
    112
        2nd FU visit: Moderate (patient)
    9
    2
        2nd FU visit: Poor (patient)
    2
    0
        2nd FU visit: not assessed (patient)
    4
    0
        Term. visit: Excellent (patient)
    70
    175
        Term. visit: Good (patient)
    163
    79
        Term. visit: Moderate (patient)
    7
    2
        Term. visit: Poor (patient)
    2
    0
        Term. visit: not assessed (patient)
    4
    0
        1st FU call: Excellent (physician)
    45
    80
        1st FU call: Good (physician)
    203
    178
        1st FU call: Moderate (physician)
    5
    3
        1st FU call: Poor (physician)
    2
    0
        1st FU call: not assessed (physician)
    1
    0
        2nd FU call: Excellent (physician)
    39
    81
        2nd FU call: Good (physician)
    187
    164
        2nd FU call: Moderate (physician)
    9
    2
        2nd FU call: Poor (physician)
    2
    0
        2nd FU call: not assessed (physician)
    1
    0
        1st FU visit: Excellent (physician)
    55
    118
        1st FU visit: Good (physician)
    185
    141
        1st FU visit: Moderate (physician)
    11
    2
        1st FU visit: Poor (physician)
    2
    0
        1st FU visit: not assessed (physician)
    3
    0
        2nd FU visit: Excellent (physician)
    63
    139
        2nd FU visit: Good (physician)
    175
    118
        2nd FU visit: Moderate (physician)
    9
    2
        2nd FU visit: Poor (physician)
    1
    0
        2nd FU visit: not assessed (physician)
    4
    0
        Term. visit: Excellent (physician)
    71
    172
        Term. visit: Good (physician)
    165
    82
        Term. visit: Moderate (physician)
    5
    2
        Term. visit: Poor (physician)
    1
    0
        Term. visit: not assessed (physician)
    4
    0
    Notes
    [190] - Totals: 1st call: N=256 2nd call: N=238 1st FU V.: N=256 2nd FU V.: N=252 Term. V.: N=246
    [191] - Totals: 1st call: N=261 2nd call: N=247 1st FU V.: N=261 2nd FU V.: N=259 Term. V.: N=256
    Statistical analysis title
    1st FU call: 'Excellent' tolerability (patient)
    Statistical analysis description
    Explorative analysis of combined tolerability assessment related categories. Binary categorization of tolerability is done by considering the "excellent" category against all other categories. [Note: Missing assessments are not considered.]
    Comparison groups
    ST arm [ITT analysis set] v IFC arm [ITT analysis set]
    Number of subjects included in analysis
    517
    Analysis specification
    Pre-specified
    Analysis type
    other [192]
    P-value
    = 0.0003 [193]
    Method
    Chi-squared
    Parameter type
    Risk difference (RD)
    Point estimate
    13.4
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    5.8
         upper limit
    21
    Notes
    [192] - Analysis refers to patients' assessments.
    [193] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly higher fraction of patients with 'excellent' tolerability of treatment in IFC compared to ST arm [ITT analysis set].
    Statistical analysis title
    1st FU call: 'Excellent' tolerability (physician)
    Statistical analysis description
    Explorative analysis of combined tolerability assessment related categories. Binary categorization of tolerability is done by considering the "excellent" category against all other categories. [Note: Missing assessments are not considered.]
    Comparison groups
    ST arm [ITT analysis set] v IFC arm [ITT analysis set]
    Number of subjects included in analysis
    517
    Analysis specification
    Pre-specified
    Analysis type
    other [194]
    P-value
    = 0.0006 [195]
    Method
    Chi-squared
    Parameter type
    Risk difference (RD)
    Point estimate
    13
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    5.3
         upper limit
    20.7
    Notes
    [194] - Analysis refers to physicians' assessments.
    [195] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly higher fraction of patients with 'excellent' tolerability of treatment in IFC compared to ST arm [ITT analysis set].
    Statistical analysis title
    2nd FU call: 'Excellent' tolerability (patient)
    Statistical analysis description
    Explorative analysis of combined tolerability assessment related categories. Binary categorization of tolerability is done by considering the "excellent" category against all other categories. [Note: Missing assessments are not considered.]
    Comparison groups
    ST arm [ITT analysis set] v IFC arm [ITT analysis set]
    Number of subjects included in analysis
    517
    Analysis specification
    Pre-specified
    Analysis type
    other [196]
    P-value
    < 0.0001 [197]
    Method
    Chi-squared
    Parameter type
    Risk difference (RD)
    Point estimate
    17.6
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    9.6
         upper limit
    25.5
    Notes
    [196] - Analysis refers to patients' assessments.
    [197] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly higher fraction of patients with 'excellent' tolerability of treatment in IFC compared to ST arm [ITT analysis set].
    Statistical analysis title
    2nd FU call: 'Excellent' tolerability (physician)
    Statistical analysis description
    Explorative analysis of combined tolerability assessment related categories. Binary categorization of tolerability is done by considering the "excellent" category against all other categories. [Note: Missing assessments are not considered.]
    Comparison groups
    ST arm [ITT analysis set] v IFC arm [ITT analysis set]
    Number of subjects included in analysis
    517
    Analysis specification
    Pre-specified
    Analysis type
    other [198]
    P-value
    < 0.0001 [199]
    Method
    Chi-squared
    Parameter type
    Risk difference (RD)
    Point estimate
    16.3
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    8.4
         upper limit
    24.3
    Notes
    [198] - Analysis refers to physicians' assessments.
    [199] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly higher fraction of patients with 'excellent' tolerability of treatment in IFC compared to ST arm [ITT analysis set].
    Statistical analysis title
    1st FU visit: 'Excellent' tolerability (patient)
    Statistical analysis description
    Explorative analysis of combined tolerability assessment related categories. Binary categorization of tolerability is done by considering the "excellent" category against all other categories. [Note: Missing assessments are not considered.]
    Comparison groups
    ST arm [ITT analysis set] v IFC arm [ITT analysis set]
    Number of subjects included in analysis
    517
    Analysis specification
    Pre-specified
    Analysis type
    other [200]
    P-value
    < 0.0001 [201]
    Method
    Chi-squared
    Parameter type
    Risk difference (RD)
    Point estimate
    23.5
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    15.2
         upper limit
    31.8
    Notes
    [200] - Analysis refers to patients' assessments.
    [201] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly higher fraction of patients with 'excellent' tolerability of treatment in IFC compared to ST arm [ITT analysis set].
    Statistical analysis title
    1st FU visit: 'Excellent' tolerability (physician)
    Statistical analysis description
    Explorative analysis of combined tolerability assessment related categories. Binary categorization of tolerability is done by considering the "excellent" category against all other categories. [Note: Missing assessments are not considered.]
    Comparison groups
    ST arm [ITT analysis set] v IFC arm [ITT analysis set]
    Number of subjects included in analysis
    517
    Analysis specification
    Pre-specified
    Analysis type
    other [202]
    P-value
    < 0.0001 [203]
    Method
    Chi-squared
    Parameter type
    Risk difference (RD)
    Point estimate
    23.5
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    15.2
         upper limit
    31.8
    Notes
    [202] - Analysis refers to physicians' assessments.
    [203] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly higher fraction of patients with 'excellent' tolerability of treatment in IFC compared to ST arm [ITT analysis set].
    Statistical analysis title
    2nd FU visit: 'Excellent' tolerability (patient)
    Statistical analysis description
    Explorative analysis of combined tolerability assessment related categories. Binary categorization of tolerability is done by considering the "excellent" category against all other categories. [Note: Missing assessments are not considered.]
    Comparison groups
    ST arm [ITT analysis set] v IFC arm [ITT analysis set]
    Number of subjects included in analysis
    517
    Analysis specification
    Pre-specified
    Analysis type
    other [204]
    P-value
    < 0.0001 [205]
    Method
    Chi-squared
    Parameter type
    Risk difference (RD)
    Point estimate
    30.6
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    22.1
         upper limit
    39.1
    Notes
    [204] - Analysis refers to patients' assessments.
    [205] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly higher fraction of patients with 'excellent' tolerability of treatment in IFC compared to ST arm [ITT analysis set].
    Statistical analysis title
    2nd FU visit: 'Excellent' tolerability (physician)
    Statistical analysis description
    Explorative analysis of combined tolerability assessment related categories. Binary categorization of tolerability is done by considering the "excellent" category against all other categories. [Note: Missing assessments are not considered.]
    Comparison groups
    ST arm [ITT analysis set] v IFC arm [ITT analysis set]
    Number of subjects included in analysis
    517
    Analysis specification
    Pre-specified
    Analysis type
    other [206]
    P-value
    < 0.0001 [207]
    Method
    Chi-squared
    Parameter type
    Risk difference (RD)
    Point estimate
    28.3
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    19.7
         upper limit
    36.8
    Notes
    [206] - Analysis refers to physicians' assessments.
    [207] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly higher fraction of patients with 'excellent' tolerability of treatment in IFC compared to ST arm [ITT analysis set].
    Statistical analysis title
    Term. visit: 'Excellent' tolerability (patient)
    Statistical analysis description
    Explorative analysis of combined tolerability assessment related categories. Binary categorization of tolerability is done by considering the "excellent" category against all other categories. [Note: Missing assessments are not considered.]
    Comparison groups
    ST arm [ITT analysis set] v IFC arm [ITT analysis set]
    Number of subjects included in analysis
    517
    Analysis specification
    Pre-specified
    Analysis type
    other [208]
    P-value
    < 0.0001 [209]
    Method
    Chi-squared
    Parameter type
    Risk difference (RD)
    Point estimate
    39.4
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    31
         upper limit
    47.9
    Notes
    [208] - Analysis refers to patients' assessments.
    [209] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly higher fraction of patients with 'excellent' tolerability of treatment in IFC compared to ST arm [ITT analysis set].
    Statistical analysis title
    Term. visit: 'Excellent' tolerability (physician)
    Statistical analysis description
    Explorative analysis of combined tolerability assessment related categories. Binary categorization of tolerability is done by considering the "excellent" category against all other categories. [Note: Missing assessments are not considered.]
    Comparison groups
    ST arm [ITT analysis set] v IFC arm [ITT analysis set]
    Number of subjects included in analysis
    517
    Analysis specification
    Pre-specified
    Analysis type
    other [210]
    P-value
    < 0.0001 [211]
    Method
    Chi-squared
    Parameter type
    Risk difference (RD)
    Point estimate
    37.8
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    29.3
         upper limit
    46.4
    Notes
    [210] - Analysis refers to physicians' assessments.
    [211] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly higher fraction of patients with 'excellent' tolerability of treatment in IFC compared to ST arm [ITT analysis set].

    Other pre-specified: Present complaints of upper respiratory tract infection: Fever, mucosal hyperaemia, nasal breathing impairment

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    End point title
    Present complaints of upper respiratory tract infection: Fever, mucosal hyperaemia, nasal breathing impairment
    End point description
    Presence of individual URTI symptoms fever, mucosal hyperaemia [MucHyp] and nasal breathing impairment [NBImp] has been assessed by physician at each visit.
    End point type
    Other pre-specified
    End point timeframe
    1st FU visit, 2nd FU visit and termination visit
    End point values
    IFC arm [PP analysis set] ST arm [ITT analysis set]
    Number of subjects analysed
    261 [212]
    256 [213]
    Units: patients
        1st FU V.: Presence of fever
    46
    80
        1st FU V.: Absence of fever
    215
    176
        1st FU V.: missing data: fever
    0
    0
        2nd FU V.: Presence of fever
    8
    16
        2nd FU V.: Absence of fever
    251
    235
        2nd FU V.: missing data: fever
    0
    1
        Term. V.: Presence of fever
    5
    8
        Term. V.: Absence of fever
    251
    238
        Term. V.: missing data: fever
    0
    0
        1st FU V.: Presence of MucHyp
    188
    208
        1st FU V.: Absence of MucHyp
    73
    48
        1st FU V.: missing data: MucHyp
    0
    0
        2nd FU V.: Presence of MucHyp
    55
    96
        2nd FU V.: Absence of MucHyp
    204
    155
        2nd FU V.: missing data: MucHyp
    0
    1
        Term. V.: Presence of MucHyp
    12
    16
        Term. V.: Absence of MucHyp
    244
    230
        Term. V.: missing data: MucHyp
    0
    0
        1st FU V.: Presence of NBImp
    169
    208
        1st FU V.: Absence of NBImp
    92
    48
        1st FU V.: missing data: NBImp
    0
    0
        2nd FU V.: Presence of NBImp
    68
    111
        2nd FU V.: Absence of NBImp
    191
    140
        2nd FU V.: missing data: NBImp
    0
    1
        Term. V.: Presence of NBImp
    23
    26
        Term. V.: Absence of NBImp
    233
    220
        Term. V.: missing data: NBImp
    0
    0
    Notes
    [212] - Total assessments per visit: 1st FU: N=261 2ndFU: N=259 Termination: N=256
    [213] - Total assessments per visit: 1st FU: N=256 2ndFU: N=252 Termination: N=246
    Statistical analysis title
    1st FU: Presence of fever
    Statistical analysis description
    Explorative analysis of URTI complaint's presence as assessed by physical examination at each visit [ITT analysis set]. Binary categorization "absence" vs. "presence" with respect to symptom is considered. Presented values for risk difference are related to the difference in symptom's presence between treatments taking into account the direction 'IFC - ST'.
    Comparison groups
    ST arm [ITT analysis set] v IFC arm [PP analysis set]
    Number of subjects included in analysis
    517
    Analysis specification
    Pre-specified
    Analysis type
    other [214]
    P-value
    = 0.0003 [215]
    Method
    Chi-squared
    Parameter type
    Risk difference (RD)
    Point estimate
    -13.6
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -21.3
         upper limit
    -5.9
    Notes
    [214] - Analysis refers to physicians' physical examination assessments not taking missing values into account.
    [215] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly lower fraction of patients with presence of fever (assessed by physical examination) in IFC compared to ST arm [ITT analysis set].
    Statistical analysis title
    2nd FU: Presence of fever
    Statistical analysis description
    Explorative analysis of URTI complaint's presence as assessed by physical examination at each visit [ITT analysis set]. Binary categorization "absence" vs. "presence" with respect to symptom is considered. Presented values for risk difference are related to the difference in symptom's presence between treatments taking into account the direction 'IFC - ST'.
    Comparison groups
    ST arm [ITT analysis set] v IFC arm [PP analysis set]
    Number of subjects included in analysis
    517
    Analysis specification
    Pre-specified
    Analysis type
    other [216]
    P-value
    = 0.0798
    Method
    Chi-squared
    Parameter type
    Risk difference (RD)
    Point estimate
    -3.3
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -7.4
         upper limit
    0.8
    Notes
    [216] - Analysis refers to physicians' physical examination assessments not taking missing values into account.
    Statistical analysis title
    Term.visit: Presence of fever
    Statistical analysis description
    Explorative analysis of URTI complaint's presence as assessed by physical examination at each visit [ITT analysis set]. Binary categorization "absence" vs. "presence" with respect to symptom is considered. Presented values for risk difference are related to the difference in symptom's presence between treatments taking into account the direction 'IFC - ST'.
    Comparison groups
    ST arm [ITT analysis set] v IFC arm [PP analysis set]
    Number of subjects included in analysis
    517
    Analysis specification
    Pre-specified
    Analysis type
    other [217]
    P-value
    = 0.3597
    Method
    Chi-squared
    Parameter type
    Risk difference (RD)
    Point estimate
    -1.3
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -4.5
         upper limit
    1.9
    Notes
    [217] - Analysis refers to physicians' physical examination assessments not taking missing values into account.
    Statistical analysis title
    1st FU: Presence of mucosal hyperaemia
    Statistical analysis description
    Explorative analysis of URTI complaint's presence as assessed by physical examination at each visit [ITT analysis set]. Binary categorization "absence" vs. "presence" with respect to symptom is considered. Presented values for risk difference are related to the difference in symptom's presence between treatments taking into account the direction 'IFC - ST'.
    Comparison groups
    ST arm [ITT analysis set] v IFC arm [PP analysis set]
    Number of subjects included in analysis
    517
    Analysis specification
    Pre-specified
    Analysis type
    other [218]
    P-value
    = 0.0133 [219]
    Method
    Chi-squared
    Parameter type
    Risk difference (RD)
    Point estimate
    -9.2
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -16.9
         upper limit
    -1.6
    Notes
    [218] - Analysis refers to physicians' physical examination assessments not taking missing values into account.
    [219] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly lower fraction of patients with present mucosal hyperaemia (assessed by physical examination) in IFC compared to ST arm [ITT analysis set].
    Statistical analysis title
    2nd FU: Presence of mucosal hyperaemia
    Statistical analysis description
    Explorative analysis of URTI complaint's presence as assessed by physical examination at each visit [ITT analysis set]. Binary categorization "absence" vs. "presence" with respect to symptom is considered. Presented values for risk difference are related to the difference in symptom's presence between treatments taking into account the direction 'IFC - ST'.
    Comparison groups
    ST arm [ITT analysis set] v IFC arm [PP analysis set]
    Number of subjects included in analysis
    517
    Analysis specification
    Pre-specified
    Analysis type
    other [220]
    P-value
    < 0.0001 [221]
    Method
    Chi-squared
    Parameter type
    Risk difference (RD)
    Point estimate
    -17
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -25.2
         upper limit
    -8.8
    Notes
    [220] - Analysis refers to physicians' physical examination assessments not taking missing values into account.
    [221] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly lower fraction of patients with present mucosal hyperaemia (assessed by physical examination) in IFC compared to ST arm [ITT analysis set].
    Statistical analysis title
    Term.visit: Presence of mucosal hyperaemia
    Statistical analysis description
    Explorative analysis of URTI complaint's presence as assessed by physical examination at each visit [ITT analysis set]. Binary categorization "absence" vs. "presence" with respect to symptom is considered. Presented values for risk difference are related to the difference in symptom's presence between treatments taking into account the direction 'IFC - ST'.
    Comparison groups
    ST arm [ITT analysis set] v IFC arm [PP analysis set]
    Number of subjects included in analysis
    517
    Analysis specification
    Pre-specified
    Analysis type
    other [222]
    P-value
    = 0.3753
    Method
    Chi-squared
    Parameter type
    Risk difference (RD)
    Point estimate
    -1.8
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -6.2
         upper limit
    2.6
    Notes
    [222] - Analysis refers to physicians' physical examination assessments not taking missing values into account.
    Statistical analysis title
    1st FU: Presence of nasal breathing impairment
    Statistical analysis description
    Explorative analysis of URTI complaint's presence as assessed by physical examination at each visit [ITT analysis set]. Binary categorization "absence" vs. "presence" with respect to symptom is considered. Presented values for risk difference are related to the difference in symptom's presence between treatments taking into account the direction 'IFC - ST'.
    Comparison groups
    ST arm [ITT analysis set] v IFC arm [PP analysis set]
    Number of subjects included in analysis
    517
    Analysis specification
    Pre-specified
    Analysis type
    other [223]
    P-value
    < 0.0001 [224]
    Method
    Chi-squared
    Parameter type
    Risk difference (RD)
    Point estimate
    -16.5
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -24.4
         upper limit
    -8.6
    Notes
    [223] - Analysis refers to physicians' physical examination assessments not taking missing values into account.
    [224] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly lower fraction of patients with present nasal breathing impairment(assessed by physical examination) in IFC compared to ST arm [ITT analysis set].
    Statistical analysis title
    2nd FU: Presence of nasal breathing impairment
    Statistical analysis description
    Explorative analysis of URTI complaint's presence as assessed by physical examination at each visit [ITT analysis set]. Binary categorization "absence" vs. "presence" with respect to symptom is considered. Presented values for risk difference are related to the difference in symptom's presence between treatments taking into account the direction 'IFC - ST'.
    Comparison groups
    ST arm [ITT analysis set] v IFC arm [PP analysis set]
    Number of subjects included in analysis
    517
    Analysis specification
    Pre-specified
    Analysis type
    other [225]
    P-value
    < 0.0001 [226]
    Method
    Chi-squared
    Parameter type
    Risk difference (RD)
    Point estimate
    -18
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -26.5
         upper limit
    -9.4
    Notes
    [225] - Analysis refers to physicians' physical examination assessments not taking missing values into account.
    [226] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly lower fraction of patients with present nasal breathing impairment (assessed by physical examination) in IFC compared to ST arm [ITT analysis set].
    Statistical analysis title
    Term.visit: Presence of nasal breathing impairment
    Statistical analysis description
    Explorative analysis of URTI complaint's presence as assessed by physical examination at each visit [ITT analysis set]. Binary categorization "absence" vs. "presence" with respect to symptom is considered. Presented values for risk difference are related to the difference in symptom's presence between treatments taking into account the direction 'IFC - ST'.
    Comparison groups
    ST arm [ITT analysis set] v IFC arm [PP analysis set]
    Number of subjects included in analysis
    517
    Analysis specification
    Pre-specified
    Analysis type
    other [227]
    P-value
    = 0.5498
    Method
    Chi-squared
    Parameter type
    Risk difference (RD)
    Point estimate
    -1.6
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -7.2
         upper limit
    4
    Notes
    [227] - Analysis refers to physicians' physical examination assessments not taking missing values into account.

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Whole study period.
    Adverse event reporting additional description
    Adverse event [AE] monitoring has been done at all post-baseline visits and during both FU calls. All AEs, irrespective of severity, seriousness and relationship to study drug, had to be monitored by the investigator until they had satisfactorily subsided or stabilised to such an extent that further marked improvement was not longer to be expected.
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    12
    Reporting groups
    Reporting group title
    ST [SAF]
    Reporting group description
    The control group "ST" was treated only with symptomatic medication on-demand.

    Reporting group title
    IFC [SAF]
    Reporting group description
    The test group “IFC” received 7 days of treatment with Influcid tablets (day 1 - day 7) additionally to on-demand symptomatic treatment

    Serious adverse events
    ST [SAF] IFC [SAF]
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 258 (0.00%)
    0 / 265 (0.00%)
         number of deaths (all causes)
    0
    0
         number of deaths resulting from adverse events
    0
    0
    Frequency threshold for reporting non-serious adverse events: 1%
    Non-serious adverse events
    ST [SAF] IFC [SAF]
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    15 / 258 (5.81%)
    13 / 265 (4.91%)
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    1 / 258 (0.39%)
    3 / 265 (1.13%)
         occurrences all number
    1
    3
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    3 / 258 (1.16%)
    4 / 265 (1.51%)
         occurrences all number
    3
    5
    Vomiting
         subjects affected / exposed
    0 / 258 (0.00%)
    3 / 265 (1.13%)
         occurrences all number
    0
    3
    Nausea
         subjects affected / exposed
    3 / 258 (1.16%)
    1 / 265 (0.38%)
         occurrences all number
    3
    1
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    1 / 258 (0.39%)
    3 / 265 (1.13%)
         occurrences all number
    1
    3
    Infections and infestations
    Bronchitis
         subjects affected / exposed
    7 / 258 (2.71%)
    1 / 265 (0.38%)
         occurrences all number
    7
    1

    More information

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    14 Oct 2010
    Amendment 1 corresponds to the implementation of protocol final V2.0 from 14OCT2010 which included the changes to the original protocol (final V1.0 from 28JUN2010) required by the ethics committee of the Bavarian State Medical Association (Germany). In addition the patient informed consents for adults, legal representatives and children were updated and a patient informed consent for adolescents was implemented in Germany.

    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
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