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:
    A prospective controlled proof-of-concept trial to demonstrate anti-viral effects of oral bromelaine in COVID-19 positive patients

    Summary
    EudraCT number
    		 2020-005523-37
    Trial protocol
    		 DE  
    Global end of trial date
    14 Feb 2022

    Results information
    Results version number
    		 v1(current)
    This version publication date
    09 Feb 2023
    First version publication date
    09 Feb 2023
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    BromCO
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 -
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Ursapharm Arzneimittel GmbH
    Sponsor organisation address
    Industriestr. 35, Saarbrücken, Germany, 66129
    Public contact
    Medical Scientific Department , Ursapharm Arzneimittel GmbH, +49 68059292105, peter.meiser@ursapharm.de
    Scientific contact
    Medical Scientific Department , Ursapharm Arzneimittel GmbH, +49 68059292105, peter.meiser@ursapharm.de
    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
    03 Nov 2022
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    14 Feb 2022
    Global end of trial reached?
    Yes
    Global end of trial date
    14 Feb 2022
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    The primary objective of the trial was to assess the clinical impact of the treatment with bromelaine tablets with regard to COVID-19 symptoms via a patient diary.
    Protection of trial subjects
    Due to the COVID-19 pandemic, participating patients had to undergo quarantine. Therefore, patients were visited by a member of the study team at their homes on visits V1 (Day 1), V2 (Day 4 ±1 day), V3 (Day 7 ±1 day), V4 (Day 11 ±2 days) and V5 (D16 ±1 day). Patients were called on Day 60±4 days (V6) for a safety follow up.
    Background therapy
    		 no background therapy given
    Evidence for comparator
    		 n.a.
    Actual start date of recruitment
    15 May 2021
    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: 77
    Worldwide total number of subjects
    77
    EEA total number of subjects
    77
    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)
    77
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 COVID-19 postively tested subjects interested in study participation were asked to contact the study hotline for receiving information regarding the trial and for pre-screening of eligibility. If a subject agreed to participate, he/she was visited at home by a study investigator for the baseline visit (V1).

    Pre-assignment
    Screening details
    		 main inclusion/non-inclusion criteria: - aged 18-60 years - PCR documented SARS-CoV-2 infection and at least on typical symptom present - no enrolment permitted if COVID-19 testing performed >48 hours ago - no enrolment permitted if presence of coagulation disorders or being on risk for serious course of the disease

    Pre-assignment period milestones
    Number of subjects started
    		 77
    Number of subjects completed
    		 77

    Period 1
    Period 1 title
    overall period
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor
    Blinding implementation details
    Placebo and verum tablets were indistinguishable regarding their appearance. The list with the assignment of treatment number was kept at the production facility until the end of the trial. No person involved in the conduct or evaluation of the study did know the treatment assignment of the individual patients.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Bromelaine tablets hysan (1-0-1)
    Arm description
    		 Bromelaine low dose group
    Arm type
    		 Experimental

    Investigational medicinal product name
    Bromelaine tablets hysan (1-0-1)
    Investigational medicinal product code
    Bromelaine low dose
    Other name
    Pharmaceutical forms
    Gastro-resistant tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Application: two tablets per day (1-0-1: one tablet in the morning and the evening), to be swallowed with sufficient amount of liquid approximately ½ hour before meals.

    Arm title
    		 Bromelaine tablets hysan (2-1-1)
    Arm description
    		 Bromelaine high dose
    Arm type
    		 Experimental

    Investigational medicinal product name
    Bromelaine tablets hysan (2-1-1)
    Investigational medicinal product code
    Bromelaine high dose
    Other name
    Pharmaceutical forms
    Gastro-resistant tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Application: four tablets per day (2-1-1: two tablets in the morning, one tablet at midday, and one tablet in the evening), to be swallowed with sufficient amount of liquid approximately ½ hour before meals.

    Arm title
    		 Placebo (1-0-1)
    Arm description
    		 Placebo low dose
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo tablets (1-0-1)
    Investigational medicinal product code
    Placebo low dose
    Other name
    Pharmaceutical forms
    Gastro-resistant tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Application: two tablets per day (1-0-1: one tablet in the morning and the evening), to be swallowed with sufficient amount of liquid approximately ½ hour before meals.

    Arm title
    		 Placebo (2-1-1)
    Arm description
    		 Placebo high dose
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo tablets (2-1-1)
    Investigational medicinal product code
    Placebo high dose
    Other name
    Pharmaceutical forms
    Gastro-resistant tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Application: four tablets per day (2-1-1: two tablets in the morning, one tablet at midday and one tablet in the evening), to be swallowed with sufficient amount of liquid approximately ½ hour before meals.

    Number of subjects in period 1
    		Bromelaine tablets hysan (1-0-1) Bromelaine tablets hysan (2-1-1) Placebo (1-0-1) Placebo (2-1-1)
    Started
    27
    26
    12
    12
    Completed
    27
    26
    12
    12

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Bromelaine tablets hysan (1-0-1)
    Reporting group description
    		 Bromelaine low dose group

    Reporting group title
    Bromelaine tablets hysan (2-1-1)
    Reporting group description
    		 Bromelaine high dose

    Reporting group title
    Placebo (1-0-1)
    Reporting group description
    		 Placebo low dose

    Reporting group title
    Placebo (2-1-1)
    Reporting group description
    		 Placebo high dose

    Reporting group values
    		 Bromelaine tablets hysan (1-0-1) Bromelaine tablets hysan (2-1-1) Placebo (1-0-1) Placebo (2-1-1) Total
    Number of subjects
    		 27 26 12 12 77
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0 0 0
        Newborns (0-27 days)
    		 0 0 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0 0 0
        Children (2-11 years)
    		 0 0 0 0 0
        Adolescents (12-17 years)
    		 0 0 0 0 0
        Adults (18-64 years)
    		 27 26 12 12 77
        From 65-84 years
    		 0 0 0 0 0
        85 years and over
    		 0 0 0 0 0
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 34.74 ± 9.925 33.92 ± 12.309 33.42 ± 12.161 33.67 ± 10.360 -
    Gender categorical
    Units: Subjects
        Female
    		 11 13 8 5 37
        Male
    		 16 13 4 7 40
    Subject analysis sets

    Subject analysis set title
    Safety population
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    The safety population refers to all randomized patients who have been exposed to the investigational medicinal product at least once

    Subject analysis set title
    ITT population
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    The ITT population refers to all randomized patients who meet key eligibility and evaluability criteria and have diary data of at least day 1.

    Subject analysis set title
    PP population
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    The PP population refers to all evaluable patients who comply with the protocol in all points relevant to the analysis and deliver a complete data set of measurements for the evaluation of the primary efficacy variable.

    Subject analysis set title
    futility population
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    A planned interim analysis for futility was performed based on patient diary data, blood tests and adverse event reporting data of 41 enrolled and randomized patients

    Subject analysis sets values
    		 Safety population ITT population PP population futility population
    Number of subjects
    77
    75
    72
    41
    Age categorical
    Units: Subjects
        In utero
    0
    0
    0
    0
        Preterm newborn infants (gestational age < 37 wks)
    0
    0
    0
    0
        Newborns (0-27 days)
    0
    0
    0
    0
        Infants and toddlers (28 days-23 months)
    0
    0
    0
    0
        Children (2-11 years)
    0
    0
    0
    0
        Adolescents (12-17 years)
    0
    0
    0
    0
        Adults (18-64 years)
    77
    75
    72
    41
        From 65-84 years
    0
    0
    0
    0
        85 years and over
    0
    0
    0
    0
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    34.09 ± 10.99
    33.55 ± 10.60
    34.01 ± 10.94
    32.24 ± 10.30
    Gender categorical
    Units: Subjects
        Female
    37
    36
    34
    17
        Male
    40
    39
    38
    24

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Bromelaine tablets hysan (1-0-1)
    Reporting group description
    		 Bromelaine low dose group

    Reporting group title
    Bromelaine tablets hysan (2-1-1)
    Reporting group description
    		 Bromelaine high dose

    Reporting group title
    Placebo (1-0-1)
    Reporting group description
    		 Placebo low dose

    Reporting group title
    Placebo (2-1-1)
    Reporting group description
    		 Placebo high dose

    Subject analysis set title
    Safety population
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    The safety population refers to all randomized patients who have been exposed to the investigational medicinal product at least once

    Subject analysis set title
    ITT population
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    The ITT population refers to all randomized patients who meet key eligibility and evaluability criteria and have diary data of at least day 1.

    Subject analysis set title
    PP population
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    The PP population refers to all evaluable patients who comply with the protocol in all points relevant to the analysis and deliver a complete data set of measurements for the evaluation of the primary efficacy variable.

    Subject analysis set title
    futility population
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    A planned interim analysis for futility was performed based on patient diary data, blood tests and adverse event reporting data of 41 enrolled and randomized patients

    Primary: change in COVID-19 symptom severity score

    		 Close Top of page
    End point title
    		 change in COVID-19 symptom severity score
    End point description
    The primary objective of this study was to assess the change in COVID-19 symptom severity reported by the patients daily via a patient diary. The following symptoms assessed from day 1 (baseline) to day 11 (V4): anosmia, ageusia, fever, cough, sore throat, shortness of breath, coryza, general weakness, headache, aching limbs, loss of appetite, nausea, abdominal pain, vomiting, diarrhoea, conjunctivitis, rash, lymph node swelling, apathy and somnolence.
    End point type
    Primary
    End point timeframe
    day 1 (baseline / V1) to day 11 (V4)
    End point values
    		 Bromelaine tablets hysan (1-0-1) Bromelaine tablets hysan (2-1-1) Placebo (1-0-1) Placebo (2-1-1)
    Number of subjects analysed
    25
    25
    11
    11
    Units: symptom score
        arithmetic mean (standard deviation)
    -11.39 ± 8.29
    -11.02 ± 10.33
    -11.23 ± 7.01
    -12.64 ± 7.42
    Statistical analysis title
    		 Statistical analysis BromCO
    Statistical analysis description
    The analysis of the data was performed by using descriptive and exploratory statistics. Subgroups were analysed exploratorily (e.g., subgroups regarding the sex, age, severity, etc.). Continuous data was be described by statistical estimates (number all cases and valid cases, mean, standard deviation, median, Q1, Q3, minimum, and maximum values), whereby categorical data was described by absolute frequencies and percentage of valid cases.
    Comparison groups
    Bromelaine tablets hysan (1-0-1) v Bromelaine tablets hysan (2-1-1) v Placebo (1-0-1) v Placebo (2-1-1)
    Number of subjects included in analysis
    72
    Analysis specification
    Pre-specified
    Analysis type
    		 other [1]
    P-value
    		 < 0.05 [2]
    Method
    		 ANOVA
    Parameter type
    		 Mean difference (final values)
    Confidence interval
    Variability estimate
    Standard deviation
    Notes
    [1] - Primary and secondary study endpoints were not analysed by confirmatory statistics. As there was no formal testing of a given hypothesis, data was analysed descriptively and exploratively. Normally distributed data were compared with the One-Way ANOVA and t-tests to perform pairwise comparisons. In case of non-normally distributed data, the Kruskal-Wallis and the Mann-Whitney tests were used to compare the groups. The comparison of categorial variables between groups were performed by chi-square
    [2] - A two-sided p value of less than 0.05 was considered to indicate statistical significance.

    Secondary: clinical improvement of the patient state (WHO score)

    		 Close Top of page
    End point title
    		 clinical improvement of the patient state (WHO score)
    End point description
    assessment of the clinical improvement of the patient state via an 11-category ordinal score as proposed by the WHO
    End point type
    Secondary
    End point timeframe
    day 1 (v1)
    End point values
    		 Bromelaine tablets hysan (1-0-1) Bromelaine tablets hysan (2-1-1) Placebo (1-0-1) Placebo (2-1-1)
    Number of subjects analysed
    27
    25
    12
    11
    Units: WHO score
        number (not applicable)
    2
    2
    2
    2
    No statistical analyses for this end point

    Secondary: clinical improvement of the patient state (WHO score)

    		 Close Top of page
    End point title
    		 clinical improvement of the patient state (WHO score)
    End point description
    To assess the clinical improvement of the patient state via a World Health Organisation (WHO) ordinal scale
    End point type
    Secondary
    End point timeframe
    d60 (V6)
    End point values
    		 Bromelaine tablets hysan (1-0-1) Bromelaine tablets hysan (2-1-1) Placebo (1-0-1) Placebo (2-1-1)
    Number of subjects analysed
    27
    24
    12
    11
    Units: WHO score
        number (not applicable)
    0
    0
    0
    0
    No statistical analyses for this end point

    Secondary: body temperature V1

    		 Close Top of page
    End point title
    		 body temperature V1
    End point description
    clinical improvement of the patient state via measurement of body temperature (fever)
    End point type
    Secondary
    End point timeframe
    day 1 (V1) to day 11 (V4)
    End point values
    		 Bromelaine tablets hysan (1-0-1) Bromelaine tablets hysan (2-1-1) Placebo (1-0-1) Placebo (2-1-1)
    Number of subjects analysed
    27
    25
    11
    11
    Units: degree celsius
        arithmetic mean (standard deviation)
    36.59 ± 0.58
    36.77 ± 0.56
    36.71 ± 0.45
    36.77 ± 0.32
    No statistical analyses for this end point

    Secondary: baseline-adjusted mean oxygen saturation of blood

    		 Close Top of page
    End point title
    		 baseline-adjusted mean oxygen saturation of blood
    End point description
    clinical improvement of the patient state via measurement of blood oxygen saturation
    End point type
    Secondary
    End point timeframe
    day 1 (V1) to day 11 (V4)
    End point values
    		 Bromelaine tablets hysan (1-0-1) Bromelaine tablets hysan (2-1-1) Placebo (1-0-1) Placebo (2-1-1)
    Number of subjects analysed
    27
    25
    11
    11
    Units: percentage
        arithmetic mean (standard deviation)
    0.15 ± 1.37
    0.43 ± 1.01
    -0.48 ± 1.25
    0.45 ± 0.73
    No statistical analyses for this end point

    Secondary: baseline-adjusted Ct values

    		 Close Top of page
    End point title
    		 baseline-adjusted Ct values
    End point description
    The assessment of the clinical improvement of the patient state via measurement of SARS-CoV-2 virus load in nasopharyngeal swabs (Cycle threshold [Ct] value at V1, V2, V3 and V4).
    End point type
    Secondary
    End point timeframe
    day 1 (V1) to day 11 (V4)
    End point values
    		 Bromelaine tablets hysan (1-0-1) Bromelaine tablets hysan (2-1-1) Placebo (1-0-1) Placebo (2-1-1)
    Number of subjects analysed
    27
    25
    11
    11
    Units: Ct value
        arithmetic mean (standard deviation)
    18.97 ± 6.63
    20.34 ± 5.58
    20.54 ± 4.11
    22.34 ± 3.68
    No statistical analyses for this end point

    Secondary: change in quality of life (SF-36)

    		 Close Top of page
    End point title
    		 change in quality of life (SF-36)
    End point description
    The change in quality of life as assessed by the SF-36 generic quality of life questionnaire
    End point type
    Secondary
    End point timeframe
    day 1 (V1) to day 11 (V4)
    End point values
    		 Bromelaine tablets hysan (1-0-1) Bromelaine tablets hysan (2-1-1) Placebo (1-0-1) Placebo (2-1-1)
    Number of subjects analysed
    27
    25
    12
    11
    Units: SF-36 score
        arithmetic mean (standard deviation)
    4.05 ± 9.34
    4.40 ± 9.62
    4.63 ± 7.95
    2.32 ± 8.11
    No statistical analyses for this end point

    Secondary: adverse events

    		 Close Top of page
    End point title
    		 adverse events
    End point description
    Safety assessment (occurrence of adverse events), including a safety follow-up call 60 days after the start of the treatment
    End point type
    Secondary
    End point timeframe
    day 1 (V1) to day 60 (V6)
    End point values
    		 Bromelaine tablets hysan (1-0-1) Bromelaine tablets hysan (2-1-1) Placebo (1-0-1) Placebo (2-1-1)
    Number of subjects analysed
    27
    26
    12
    12
    Units: total number
        number (not applicable)
    71
    88
    28
    28
    No statistical analyses for this end point

    Secondary: body temperature V4

    		 Close Top of page
    End point title
    		 body temperature V4
    End point description
    The assessment of the clinical improvement of the patient state via measurement of body temperature (fever)
    End point type
    Secondary
    End point timeframe
    day 1 (V1) to day 11 (V4)
    End point values
    		 Bromelaine tablets hysan (1-0-1) Bromelaine tablets hysan (2-1-1) Placebo (1-0-1) Placebo (2-1-1)
    Number of subjects analysed
    27
    25
    11
    11
    Units: degree celsius
        arithmetic mean (standard deviation)
    36.31 ± 0.41
    36.13 ± 0.44
    36.38 ± 0.43
    36.47 ± 0.43
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    day 1 (V1) to day 60 (V6)
    Adverse event reporting additional description
    Safety assessment (occurrence of adverse events), including a safety follow-up call 60 days after the start of the treatment
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    25.0
    Reporting groups
    Reporting group title
    Bromelaine tablets hysan (1-0-1)
    Reporting group description
    		 Bromelaine low dose group

    Reporting group title
    Bromelaine tablets hysan (2-1-1)
    Reporting group description
    		 Bromelaine high dose

    Reporting group title
    Placebo (1-0-1)
    Reporting group description
    		 Placebo low dose

    Reporting group title
    Placebo (2-1-1)
    Reporting group description
    		 Placebo high dose

    Serious adverse events
    		 Bromelaine tablets hysan (1-0-1) Bromelaine tablets hysan (2-1-1) Placebo (1-0-1) Placebo (2-1-1)
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 27 (0.00%)
    0 / 26 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
         number of deaths (all causes)
    0
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    		 Bromelaine tablets hysan (1-0-1) Bromelaine tablets hysan (2-1-1) Placebo (1-0-1) Placebo (2-1-1)
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    24 / 27 (88.89%)
    21 / 26 (80.77%)
    9 / 12 (75.00%)
    12 / 12 (100.00%)
    Vascular disorders
    Blood pressure increased
         subjects affected / exposed
    0 / 27 (0.00%)
    1 / 26 (3.85%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Hypertension
         subjects affected / exposed
    4 / 27 (14.81%)
    2 / 26 (7.69%)
    1 / 12 (8.33%)
    1 / 12 (8.33%)
         occurrences all number
    4
    2
    1
    1
    General disorders and administration site conditions
    Chest pressure
         subjects affected / exposed
    0 / 27 (0.00%)
    1 / 26 (3.85%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Exhaustion
         subjects affected / exposed
    3 / 27 (11.11%)
    3 / 26 (11.54%)
    0 / 12 (0.00%)
    3 / 12 (25.00%)
         occurrences all number
    3
    4
    0
    3
    Fever
         subjects affected / exposed
    1 / 27 (3.70%)
    3 / 26 (11.54%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    3
    0
    0
    Flu like symptoms
         subjects affected / exposed
    0 / 27 (0.00%)
    0 / 26 (0.00%)
    1 / 12 (8.33%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Mucosal dryness
         subjects affected / exposed
    0 / 27 (0.00%)
    1 / 26 (3.85%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Weakness
         subjects affected / exposed
    3 / 27 (11.11%)
    2 / 26 (7.69%)
    1 / 12 (8.33%)
    1 / 12 (8.33%)
         occurrences all number
    3
    2
    1
    1
    Weakness worsened
         subjects affected / exposed
    1 / 27 (3.70%)
    2 / 26 (7.69%)
    1 / 12 (8.33%)
    0 / 12 (0.00%)
         occurrences all number
    1
    2
    1
    0
    Respiratory, thoracic and mediastinal disorders
    Breath shortness
         subjects affected / exposed
    2 / 27 (7.41%)
    3 / 26 (11.54%)
    0 / 12 (0.00%)
    2 / 12 (16.67%)
         occurrences all number
    2
    3
    0
    2
    Cough
         subjects affected / exposed
    1 / 27 (3.70%)
    2 / 26 (7.69%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    2
    0
    0
    Cough aggravated
         subjects affected / exposed
    0 / 27 (0.00%)
    1 / 26 (3.85%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    2
    0
    0
    Increased shortness of breath
         subjects affected / exposed
    0 / 27 (0.00%)
    1 / 26 (3.85%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Pain throat
         subjects affected / exposed
    2 / 27 (7.41%)
    1 / 26 (3.85%)
    1 / 12 (8.33%)
    1 / 12 (8.33%)
         occurrences all number
    6
    1
    1
    1
    Tonsillar inflammation
         subjects affected / exposed
    0 / 27 (0.00%)
    1 / 26 (3.85%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Tonsillitis
         subjects affected / exposed
    1 / 27 (3.70%)
    0 / 26 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Psychiatric disorders
    Depression
         subjects affected / exposed
    0 / 27 (0.00%)
    1 / 26 (3.85%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Disorder sleep
         subjects affected / exposed
    1 / 27 (3.70%)
    0 / 26 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Restlessness
         subjects affected / exposed
    1 / 27 (3.70%)
    0 / 26 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Investigations
    Blood pressure systolic increased
         subjects affected / exposed
    2 / 27 (7.41%)
    2 / 26 (7.69%)
    3 / 12 (25.00%)
    0 / 12 (0.00%)
         occurrences all number
    2
    2
    3
    0
    Diastolic blodd pressure increased
         subjects affected / exposed
    0 / 27 (0.00%)
    1 / 26 (3.85%)
    0 / 12 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    0
    1
    Fibrin D dimer increased
         subjects affected / exposed
    0 / 27 (0.00%)
    2 / 26 (7.69%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    2
    0
    0
    NT-proBNP increased
         subjects affected / exposed
    1 / 27 (3.70%)
    0 / 26 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Cardiac disorders
    Heart pressure
         subjects affected / exposed
    0 / 27 (0.00%)
    1 / 26 (3.85%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Nervous system disorders
    Nervousness
         subjects affected / exposed
    1 / 27 (3.70%)
    0 / 26 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Concentration impaired
         subjects affected / exposed
    0 / 27 (0.00%)
    1 / 26 (3.85%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Forgetfulness
         subjects affected / exposed
    0 / 27 (0.00%)
    0 / 26 (0.00%)
    0 / 12 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    0
    0
    1
    Headache
         subjects affected / exposed
    6 / 27 (22.22%)
    5 / 26 (19.23%)
    2 / 12 (16.67%)
    4 / 12 (33.33%)
         occurrences all number
    5
    5
    2
    4
    Headache aggravated
         subjects affected / exposed
    1 / 27 (3.70%)
    1 / 26 (3.85%)
    1 / 12 (8.33%)
    0 / 12 (0.00%)
         occurrences all number
    1
    1
    1
    0
    Light headedness
         subjects affected / exposed
    0 / 27 (0.00%)
    2 / 26 (7.69%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    2
    0
    0
    Loss of smell
         subjects affected / exposed
    2 / 27 (7.41%)
    0 / 26 (0.00%)
    1 / 12 (8.33%)
    0 / 12 (0.00%)
         occurrences all number
    3
    0
    1
    0
    Loss of taste
         subjects affected / exposed
    5 / 27 (18.52%)
    4 / 26 (15.38%)
    0 / 12 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    5
    4
    0
    1
    Sleepiness
         subjects affected / exposed
    2 / 27 (7.41%)
    4 / 26 (15.38%)
    1 / 12 (8.33%)
    1 / 12 (8.33%)
         occurrences all number
    2
    4
    1
    1
    Smell loss
         subjects affected / exposed
    4 / 27 (14.81%)
    6 / 26 (23.08%)
    1 / 12 (8.33%)
    2 / 12 (16.67%)
         occurrences all number
    4
    6
    1
    2
    Gastrointestinal disorders
    Belly ache
         subjects affected / exposed
    2 / 27 (7.41%)
    5 / 26 (19.23%)
    2 / 12 (16.67%)
    1 / 12 (8.33%)
         occurrences all number
    2
    5
    2
    1
    Diarrhoea
         subjects affected / exposed
    3 / 27 (11.11%)
    3 / 26 (11.54%)
    4 / 12 (33.33%)
    1 / 12 (8.33%)
         occurrences all number
    3
    3
    4
    1
    Esophageal reflux
         subjects affected / exposed
    0 / 27 (0.00%)
    1 / 26 (3.85%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Nausea
         subjects affected / exposed
    2 / 27 (7.41%)
    3 / 26 (11.54%)
    2 / 12 (16.67%)
    2 / 12 (16.67%)
         occurrences all number
    2
    3
    2
    2
    Vomiting
         subjects affected / exposed
    0 / 27 (0.00%)
    2 / 26 (7.69%)
    1 / 12 (8.33%)
    0 / 12 (0.00%)
         occurrences all number
    0
    2
    1
    0
    Skin and subcutaneous tissue disorders
    Hair loss
         subjects affected / exposed
    1 / 27 (3.70%)
    1 / 26 (3.85%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    1
    0
    0
    Localised itching
         subjects affected / exposed
    0 / 27 (0.00%)
    1 / 26 (3.85%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Localised skin reaction
         subjects affected / exposed
    1 / 27 (3.70%)
    0 / 26 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Skin rash
         subjects affected / exposed
    1 / 27 (3.70%)
    1 / 26 (3.85%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    1
    0
    0
    Endocrine disorders
    Hypothyroidism
         subjects affected / exposed
    0 / 27 (0.00%)
    0 / 26 (0.00%)
    1 / 12 (8.33%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Musculoskeletal and connective tissue disorders
    Limb discomfort
         subjects affected / exposed
    2 / 27 (7.41%)
    4 / 26 (15.38%)
    1 / 12 (8.33%)
    0 / 12 (0.00%)
         occurrences all number
    2
    4
    1
    0
    Muscle ache
         subjects affected / exposed
    0 / 27 (0.00%)
    1 / 26 (3.85%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Infections and infestations
    Acute bacterial bronchitis
         subjects affected / exposed
    0 / 27 (0.00%)
    1 / 26 (3.85%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Bronchitis bacterial
         subjects affected / exposed
    0 / 27 (0.00%)
    0 / 26 (0.00%)
    1 / 12 (8.33%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Cold
         subjects affected / exposed
    1 / 27 (3.70%)
    0 / 26 (0.00%)
    1 / 12 (8.33%)
    1 / 12 (8.33%)
         occurrences all number
    2
    0
    1
    1
    Common cold
         subjects affected / exposed
    2 / 27 (7.41%)
    3 / 26 (11.54%)
    1 / 12 (8.33%)
    2 / 12 (16.67%)
         occurrences all number
    2
    3
    1
    2
    Conjunctivitis
         subjects affected / exposed
    1 / 27 (3.70%)
    0 / 26 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Herpes NOS
         subjects affected / exposed
    0 / 27 (0.00%)
    1 / 26 (3.85%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Sinusitis
         subjects affected / exposed
    1 / 27 (3.70%)
    1 / 26 (3.85%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    1
    0
    0
    Metabolism and nutrition disorders
    Appetite lost
         subjects affected / exposed
    4 / 27 (14.81%)
    4 / 26 (15.38%)
    0 / 12 (0.00%)
    2 / 12 (16.67%)
         occurrences all number
    4
    4
    0
    3

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    29 Jul 2021
    Implementation of CAPAs from the findings of an inspection of another COVID-19 study in a similar setting, resulting in protocol version V2.0 dated 21.07.2021
    03 Nov 2021
    The measurement of immunologic blood parameters will only be analysed in the subgroup of patients who will be included in the futility analysis (at least 36 patients). This amendment resulted in protocol version V3.0 dated 14.10.2021

    Interruptions (globally)
    Were there any global interruptions to the trial? Yes
    Date
    Interruption
    Restart date
    03 Nov 2021
    Upon approval of the study protocol Version V3.9 dated 14.10.2021 (date of approval: 03.11.2021), the immunologic blood parameters were only analysed in a subgroup of patients who were included in the futility analyisis. After at least 36 patients had completed the study up to day 16, an interim futiliy analysis based on patient diary data, patient status (via measurement of blood parameters) and adverse event reporting was performed.
    03 Nov 2021

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    Recruitment of patients was stopped after the inclusion of 77 patients (instead of planned 120 patients) based on results of the futility analysis results.
    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 07:25:49 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA