Flag of the European Union EU Clinical Trials Register Help

Clinical trials

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

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

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

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

    < Back to search results

    Download PDF

    Clinical Trial Results:
    Efficacy and safety of Sinusitis Hevert SL tablets compared to placebo in adult patients with acute, uncomplicated rhinosinusitis. A multicenter, randomized, double-blind, placebo-controlled, parallel group phase IV study.

    Summary
    EudraCT number
    		 2014-000907-29
    Trial protocol
    		 DE   BG  
    Global end of trial date
    24 Apr 2015

    Results information
    Results version number
    		 v1(current)
    This version publication date
    13 Aug 2022
    First version publication date
    13 Aug 2022
    Other versions
    Summary report(s)
    		 SHDE-1 Synopsis

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    SHDE-1
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 -
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Hevert-Arzneimittel GmbH & Co. KG
    Sponsor organisation address
    In der Weiherwiese 1, Nussbaum, Germany,
    Public contact
    Clinical Research, AtoZ-CRO, +49 220695990,
    Scientific contact
    Clinical Research, AtoZ-CRO, +49 220695990,
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    13 Sep 2016
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    24 Apr 2015
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The objective of the present clinical trial is to assess the efficacy, safety and tolerability of Sinusitis Hevert SL, compared to placebo, in adult patients with uncomplicated, acute rhinosinusitis
    Protection of trial subjects
    As rescue treatment, water steam inhalation without any additives, maximally three times per day, was permitted. If medically indicated for symptomatic treatment, paracetamol, at a maximal dose of 4 gram per day (e.g. 1 – 2 tablets containing 500 or 1000 mg paracetamol up to 4 times daily), was also permitted as rescue medication.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    24 Nov 2014
    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
    Germany: 308
    Worldwide total number of subjects
    308
    EEA total number of subjects
    308
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    288
    From 65 to 84 years
    20
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 Patients with acute uncomplicated or acute recurrent rhinosinusitis were recruited by primary care practitioners, commercial trial sites and specialists for otorhinolaryngology in Germany. Recruitment started on 24 NOV 2014. The last patient completed the study on 24 APR 2015.

    Pre-assignment
    Screening details
    		 After signing the informed consent form patients were screened for elegibility.

    Period 1
    Period 1 title
    Treatment period (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor
    Blinding implementation details
    Sinusitis Hevert SL and placebo were identical in appearance so that neither the CRO nor the investigators or the patients were aware of the identity of the treatment assigned to the patient. Study medication and fitting emergency envelopes were provided to the investigators and were stored in the Investigator Site Files (ISF). All emergency envelopes were collected during close-out from the investigational sites at the end of the trial.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Test
    Arm description
    		 -
    Arm type
    		 Experimental

    Investigational medicinal product name
    Sinusitis Hevert SL
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Dosing on day 0 varied depending on the time when the patient was included into the study. During the first week (days 1 – 7), 2 tablets of Sinusitis Hevert SL were taken 6 times daily. During the second week (days 8 – 14), 2 tablets had to be taken 4 times daily.

    Arm title
    		 Placebo
    Arm description
    		 -
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Dosing on day 0 varied depending on the time when the patient was included into the study. During the first week (days 1 – 7), 2 tablets of Sinusitis Hevert SL were taken 6 times daily. During the second week (days 8 – 14), 2 tablets had to be taken 4 times daily.

    Number of subjects in period 1
    		Test Placebo
    Started
    153
    155
    Completed
    128
    140
    Not completed
    25
    15
         Consent withdrawn by subject
    2
    3
         Adverse event, non-fatal
    3
    3
         Cure
    8
    4
         Problems with intake
    1
    -
         Lost to follow-up
    2
    2
         Protocol deviation
    8
    3
         Lack of efficacy
    1
    -

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Treatment period
    Reporting group description
    		 -

    Reporting group values
    		 Treatment period Total
    Number of subjects
    		 308 308
    Age categorical
    Units: Subjects
        In utero
    		 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0
        Newborns (0-27 days)
    		 0
        Infants and toddlers (28 days-23 months)
    		 0
        Children (2-11 years)
    		 0
        Adolescents (12-17 years)
    		 0
        Adults (18-64 years)
    		 0
        From 65-84 years
    		 0
        85 years and over
    		 0
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 39.7 ± 14.7 -
    Gender categorical
    Units: Subjects
        Female
    		 197 197
        Male
    		 111 111

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Test
    Reporting group description
    		 -

    Reporting group title
    Placebo
    Reporting group description
    		 -

    Subject analysis set title
    Full analysis set Test
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    The FAS consists of patients who have been enrolled in the study according to the inclusion / exclusion criteria and were treated

    Subject analysis set title
    Valid case analysis set Test
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    The VCAS Test consists of patients who have been enrolled in the study according to the inclusion / exclusion criteria, were treated with Test and had completed the study without major protocol violations

    Subject analysis set title
    Full analysis set Placebo
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    The FAS placbeo consists of patients who have been enrolled in the study according to the inclusion / exclusion criteria and were treated with placebo

    Subject analysis set title
    Valid case analysis set Placebo
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    The VCAS placebo consists of patients who have been enrolled in the study according to the inclusion / exclusion criteria, were treated with lacebo and had completed the study without major protocol violations

    Subject analysis set title
    Full analysis set
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    The FAS consists of patients who have been enrolled in the study according to the inclusion / exclusion criteria and were treated

    Subject analysis set title
    Valid case analysis set
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    The VCAS consists of patients who have been enrolled in the study according to the inclusion / exclusion criteria, were treated and had completed the study without major protocol violations.

    Primary: Responder rate

    		 Close Top of page
    End point title
    		 Responder rate
    End point description
    The first primary endpoint is the rate of responders which occur between baseline and treatment end after maximum 14 days. A response is defined as stable reduction of MRSSpat (sum of 5 main rhinosinusitis symptoms daily assessed by the patient) by at least 50%, i.e. reduction by at least 50% and no subsequent change from baseline > –50% up to treatment termination.
    End point type
    Primary
    End point timeframe
    After maximum 14 days of treatment
    End point values
    		 Full analysis set Test Valid case analysis set Test Full analysis set Placebo Valid case analysis set Placebo
    Number of subjects analysed
    153
    142
    155
    146
    Units: patients
    131
    124
    125
    120
    Statistical analysis title
    		 Comparison responder rate FAS
    Comparison groups
    Full analysis set Test v Full analysis set Placebo
    Number of subjects included in analysis
    308
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [1]
    P-value
    		 = 0.2438 [2]
    Method
    		 Chi-squared
    Parameter type
    		 Comparison of responder rate
    Confidence interval
    Notes
    [1] - The test of superiority of Sinusitis Hevert SL in comparison with placebo with respect to the responder rate was performed one-sided on the overall significance level of alpha=0.025 in a two-step adaptive design according to Bauer and Köhne.
    [2] - In the FAS, the responder rates amounted to - Sinusitis Hevert SL : 131/153 (85.6%) - Placebo : 125/155 (80.6%) (Chi-sqaure^2 test: p=0.2438 in favor of Sinusitis Hevert SL).
    Statistical analysis title
    		 Comparison responder rate VCAS
    Comparison groups
    Valid case analysis set Test v Valid case analysis set Placebo
    Number of subjects included in analysis
    288
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [3]
    P-value
    		 = 0.2262 [4]
    Method
    		 Chi-squared
    Confidence interval
    Notes
    [3] - The test of superiority of Sinusitis Hevert SL in comparison with placebo with respect to the responder rate was performed one-sided on the overall significance level of alpha=0.025 in a two-step adaptive design according to Bauer and Köhn
    [4] - In the VCAS, the responder rates amounted to - Sinusitis Hevert SL : 124/142 (87.3%) - Placebo : 120/146 (82.2%) (Chi-square^2 test: p=0.2262 in favor of Sinusitis Hevert SL).

    Primary: Remission rate

    		 Close Top of page
    End point title
    		 Remission rate
    End point description
    End point type
    Primary
    End point timeframe
    Up to day 14
    End point values
    		 Full analysis set Test Valid case analysis set Test Full analysis set Placebo Valid case analysis set Placebo
    Number of subjects analysed
    153
    142
    155
    146
    Units: Number
        number (not applicable)
    48
    47
    58
    58
    Statistical analysis title
    		 Remission rate FAS
    Statistical analysis description
    The second primary endpoint is the rate of remitters which occur between baseline and treatment end after maximum 14 days. A remission is defined as complete disappearance of all 5 main rhinosinusitis symptoms with no subsequent reoccurrence of any symptom up to treatment termination.
    Comparison groups
    Full analysis set Test v Full analysis set Placebo
    Number of subjects included in analysis
    308
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.2641 [5]
    Method
    		 Chi-squared
    Parameter type
    		 Comparison of remission rate
    Confidence interval
    Notes
    [5] - In the FAS, the remission rates amounted to - Sinusitis Hevert SL : 48/153 (31.4%) - Placebo : 58/155 (37.4%) (Chi-square^2 test: p=0.2641 in favor of placebo).
    Statistical analysis title
    		 Remission rate VCAS
    Comparison groups
    Valid case analysis set Test v Valid case analysis set Placebo
    Number of subjects included in analysis
    288
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [6]
    P-value
    		 = 0.2427 [7]
    Method
    		 Chi-squared
    Parameter type
    		 Comparison of remission rate
    Confidence interval
    Notes
    [6] - In the VCAS, the remission rates amounted to - Sinusitis Hevert SL : 47/142 (33.1%) - Placebo : 58/146 (39.7%) (Chi-sqquare^2 test: p=0.2427 in favor of placebo).
    [7] - In the VCAS, the remission rates amounted to - Sinusitis Hevert SL : 47/142 (33.1%) - Placebo : 58/146 (39.7%) (Chi-sqquare^2 test: p=0.2427 in favor of placebo).

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    From treatment to Day 14
    Assessment type
    		 Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    17.1
    Reporting groups
    Reporting group title
    Test
    Reporting group description
    		 -

    Reporting group title
    Placebo
    Reporting group description
    		 -

    Serious adverse events
    		 Test Placebo
    Total subjects affected by serious adverse events
         subjects affected / exposed
    1 / 153 (0.65%)
    0 / 155 (0.00%)
         number of deaths (all causes)
    0
    0
         number of deaths resulting from adverse events
    0
    0
    Nervous system disorders
    Migraine
    Additional description: Due to headache with vomiting the patient was admitted to hospital. The patient has left the hospital the following day.
         subjects affected / exposed
    1 / 153 (0.65%)
    0 / 155 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 1%
    Non-serious adverse events
    		 Test Placebo
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    24 / 153 (15.69%)
    22 / 155 (14.19%)
    Vascular disorders
    Vascular disorder
         subjects affected / exposed
    2 / 153 (1.31%)
    0 / 155 (0.00%)
         occurrences all number
    2
    0
    Nervous system disorders
    Nervous system disorder
         subjects affected / exposed
    4 / 153 (2.61%)
    3 / 155 (1.94%)
         occurrences all number
    4
    3
    Ear and labyrinth disorders
    Ear disorder
         subjects affected / exposed
    1 / 153 (0.65%)
    2 / 155 (1.29%)
         occurrences all number
    1
    2
    Gastrointestinal disorders
    Gastrointestinal disorder
         subjects affected / exposed
    5 / 153 (3.27%)
    5 / 155 (3.23%)
         occurrences all number
    5
    5
    Respiratory, thoracic and mediastinal disorders
    Respiratory disorder
         subjects affected / exposed
    2 / 153 (1.31%)
    4 / 155 (2.58%)
         occurrences all number
    2
    4
    Skin and subcutaneous tissue disorders
    Skin disorder
         subjects affected / exposed
    1 / 153 (0.65%)
    3 / 155 (1.94%)
         occurrences all number
    1
    3
    Infections and infestations
    Infections
         subjects affected / exposed
    9 / 153 (5.88%)
    5 / 155 (3.23%)
         occurrences all number
    9
    5

    More information

    		 Close Top of page

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

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

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Sun May 05 21:16:30 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA