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    Clinical Trial Results:
    A multicentre, open-label clinical trial to evaluate the effectiveness and safety of intravenous tocilizumab for treating patients with COVID-19 pneumonia: the BREATH-19 Study

    Summary
    EudraCT number
    		 2020-001995-13
    Trial protocol
    		 ES  
    Global end of trial date
    17 Jun 2022

    Results information
    Results version number
    		 v1(current)
    This version publication date
    12 Apr 2026
    First version publication date
    12 Apr 2026
    Other versions
    Summary report(s)
    		 BREATH-19_SUMMARY

    Trial information

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    Trial identification
    Sponsor protocol code
    BREATH-19
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 -
    WHO universal trial number (UTN)
    		 -
    Other trial identifiers
    		 FSG011-20: FSG011-20
    Sponsors
    Sponsor organisation name
    Fundación SEIMC-GeSIDA
    Sponsor organisation address
    Agustín de Betancourt, 13, Madrid, Spain, 29003
    Public contact
    Raúl Montalbán Casado, Dynamic Science S.L., 0034 91 456 11 05, raul.m@dynasolutions.com
    Scientific contact
    Raúl Montalbán Casado, Dynamic Science S.L., 0034 91 456 11 05, raul.m@dynasolutions.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?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    17 Jun 2022
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    17 Jun 2022
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The objectives of this study are evaluated in both the overall and retrospective cohorts. The main objective is to evaluate the effectiveness of IV tocilizumab in treating patients with COVID-19 pneumonia by describing the: - Improvement of respiratory function based on: - Time to intubation (if not previously intubated) and duration of intubation. - Time of non-invasive mechanical ventilation. - Time of oxygen therapy. - Mortality rate
    Protection of trial subjects
    In this study, patients were closely monitored for the development of signs and symptoms of infection during and after treatment with tocilizumab. The risk to subjects in this trial was minimized by compliance with the inclusion/exclusion criteria, close clinical monitoring, and minimal study duration.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    01 May 2020
    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
    Spain: 444
    Worldwide total number of subjects
    444
    EEA total number of subjects
    444
    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)
    235
    From 65 to 84 years
    209
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 Patients were included in the study between May 14th, 2020, and November 23rd, 2020.

    Pre-assignment
    Screening details
    		 According to the inclusion criteria, patients could be included prospectively and retrospectively. A total of 462 patients were initially included in the database; however, 18 were screening failures. Therefore, the evaluable population included 444 patients, with 247 enrolled retrospectively and 197 enrolled prospectively.

    Period 1
    Period 1 title
    Overall trial
    Is this the baseline period?
    		 Yes
    Allocation method
    Not applicable
    Blinding used
    		 Not blinded

    Arms
    Arm title
    		 Tocilizumab
    Arm description
    		 -
    Arm type
    		 Experimental

    Investigational medicinal product name
    Tocilizumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Infusion
    Dosage and administration details
    Patients will receive IV tocilizumab as per clinical practice and at the discretion of the treating investigator, following the posology indicated in the SmPC or the recommendations proposed by the Spanish Ministry of Health: o The SmPC: The recommended posology for treatment of Cytokine storm syndrome (CSS) given as a 60-minute IV infusion is 8 mg/kg in patients weighing greater than or equal to 30 kg or 12 mg/kg in patients weighing less than 30 kg. If no clinical improvement in the signs and symptoms of CSS occurs after the first dose, up to 3 additional doses of tocilizumab may be administered. The interval between consecutive doses should be at least 8 hours. Doses exceeding 800 mg per infusion are not recommended in CSS patients. o The recommendations of the Spanish Ministry of Health: Patients ≥ 80 kg: first dose 600 mg; second dose 600 mg. Patients < 80 kg: first dose 600 mg; second dose 400 mg.

    Number of subjects in period 1
    		Tocilizumab
    Started
    444
    Completed
    444
    Period 2
    Period 2 title
    Visit 1 / Screening
    Is this the baseline period?
    		 No
    Allocation method
    Not applicable
    Blinding used
    		 Not blinded

    Arms
    Arm title
    		 Tocilizumab
    Arm description
    		 -
    Arm type
    		 Experimental

    Investigational medicinal product name
    Tocilizumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Infusion
    Dosage and administration details
    Patients will receive IV tocilizumab as per clinical practice and at the discretion of the treating investigator, following the posology indicated in the SmPC or the recommendations proposed by the Spanish Ministry of Health: o The SmPC: The recommended posology for treatment of Cytokine storm syndrome (CSS) given as a 60-minute IV infusion is 8 mg/kg in patients weighing greater than or equal to 30 kg or 12 mg/kg in patients weighing less than 30 kg. If no clinical improvement in the signs and symptoms of CSS occurs after the first dose, up to 3 additional doses of tocilizumab may be administered. The interval between consecutive doses should be at least 8 hours. Doses exceeding 800 mg per infusion are not recommended in CSS patients. o The recommendations of the Spanish Ministry of Health: Patients ≥ 80 kg: first dose 600 mg; second dose 600 mg. Patients < 80 kg: first dose 600 mg; second dose 400 mg.

    Number of subjects in period 2
    		Tocilizumab
    Started
    444
    Completed
    444
    Period 3
    Period 3 title
    Last available visit
    Is this the baseline period?
    		 No
    Allocation method
    Not applicable
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    No

    Arm title
    		 Tocilizumab
    Arm description
    		 -
    Arm type
    		 Experimental

    Investigational medicinal product name
    Tocilizumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Infusion
    Dosage and administration details
    Patients will receive IV tocilizumab as per clinical practice and at the discretion of the treating investigator, following the posology indicated in the SmPC or the recommendations proposed by the Spanish Ministry of Health: o The SmPC: The recommended posology for treatment of Cytokine storm syndrome (CSS) given as a 60-minute IV infusion is 8 mg/kg in patients weighing greater than or equal to 30 kg or 12 mg/kg in patients weighing less than 30 kg. If no clinical improvement in the signs and symptoms of CSS occurs after the first dose, up to 3 additional doses of tocilizumab may be administered. The interval between consecutive doses should be at least 8 hours. Doses exceeding 800 mg per infusion are not recommended in CSS patients. o The recommendations of the Spanish Ministry of Health: Patients ≥ 80 kg: first dose 600 mg; second dose 600 mg. Patients < 80 kg: first dose 600 mg; second dose 400 mg.

    Arm title
    		 Single-dose
    Arm description
    		 -
    Arm type
    		 Experimental

    Investigational medicinal product name
    Tocilizumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Infusion
    Dosage and administration details
    Patients will receive IV tocilizumab as per clinical practice and at the discretion of the treating investigator, following the posology indicated in the SmPC or the recommendations proposed by the Spanish Ministry of Health: o The SmPC: The recommended posology for treatment of Cytokine storm syndrome (CSS) given as a 60-minute IV infusion is 8 mg/kg in patients weighing greater than or equal to 30 kg or 12 mg/kg in patients weighing less than 30 kg. If no clinical improvement in the signs and symptoms of CSS occurs after the first dose, up to 3 additional doses of tocilizumab may be administered. The interval between consecutive doses should be at least 8 hours. Doses exceeding 800 mg per infusion are not recommended in CSS patients. o The recommendations of the Spanish Ministry of Health: Patients ≥ 80 kg: first dose 600 mg; second dose 600 mg. Patients < 80 kg: first dose 600 mg; second dose 400 mg.

    Arm title
    		 Multiple-dose
    Arm description
    		 -
    Arm type
    		 Experimental

    Investigational medicinal product name
    Tocilizumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Infusion
    Dosage and administration details
    Patients will receive IV tocilizumab as per clinical practice and at the discretion of the treating investigator, following the posology indicated in the SmPC or the recommendations proposed by the Spanish Ministry of Health: o The SmPC: The recommended posology for treatment of Cytokine storm syndrome (CSS) given as a 60-minute IV infusion is 8 mg/kg in patients weighing greater than or equal to 30 kg or 12 mg/kg in patients weighing less than 30 kg. If no clinical improvement in the signs and symptoms of CSS occurs after the first dose, up to 3 additional doses of tocilizumab may be administered. The interval between consecutive doses should be at least 8 hours. Doses exceeding 800 mg per infusion are not recommended in CSS patients. o The recommendations of the Spanish Ministry of Health: Patients ≥ 80 kg: first dose 600 mg; second dose 600 mg. Patients < 80 kg: first dose 600 mg; second dose 400 mg.

    Number of subjects in period 3
    		Tocilizumab Single-dose Multiple-dose
    Started
    444
    337
    107
    Completed
    444
    337
    107
    Period 4
    Period 4 title
    End of study visit
    Is this the baseline period?
    		 No
    Allocation method
    Not applicable
    Blinding used
    		 Not blinded

    Arms
    Arm title
    		 Tocilizumab
    Arm description
    		 -
    Arm type
    		 Experimental

    Investigational medicinal product name
    Tocilizumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Infusion
    Dosage and administration details
    Patients will receive IV tocilizumab as per clinical practice and at the discretion of the treating investigator, following the posology indicated in the SmPC or the recommendations proposed by the Spanish Ministry of Health: o The SmPC: The recommended posology for treatment of Cytokine storm syndrome (CSS) given as a 60-minute IV infusion is 8 mg/kg in patients weighing greater than or equal to 30 kg or 12 mg/kg in patients weighing less than 30 kg. If no clinical improvement in the signs and symptoms of CSS occurs after the first dose, up to 3 additional doses of tocilizumab may be administered. The interval between consecutive doses should be at least 8 hours. Doses exceeding 800 mg per infusion are not recommended in CSS patients. o The recommendations of the Spanish Ministry of Health: Patients ≥ 80 kg: first dose 600 mg; second dose 600 mg. Patients < 80 kg: first dose 600 mg; second dose 400 mg.

    Number of subjects in period 4
    		Tocilizumab
    Started
    444
    Completed
    444

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Tocilizumab
    Reporting group description
    		 -

    Reporting group values
    		 Tocilizumab Total
    Number of subjects
    		 444 444
    Age categorical
    Units: Subjects
        In utero
    		 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0
        Newborns (0-27 days)
    		 0
        Infants and toddlers (28 days-23 months)
    		 0
        Children (2-11 years)
    		 0
        Adolescents (12-17 years)
    		 0
        Adults (18-64 years)
    		 0
        From 65-84 years
    		 0
        85 years and over
    		 0
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 63.6 ( 14.8 ) -
    Gender categorical
    Units: Subjects
        Female
    		 137 137
        Male
    		 307 307
    RT-PCR
    Units: Subjects
        Positive
    		 444 444
    Severity
    Units: Subjects
        Mild (early infection)
    		 13 13
        Moderate (pulmonary involvement without hypoxia)
    		 157 157
        Severe (systematic hyper-inflammation)
    		 251 251
        Critical (multiple organ dysfunction syndrome)
    		 22 22
        Unknown
    		 1 1
    Chest X-ray / CT-scan performed
    Units: Subjects
        Yes
    		 438 438
        No
    		 6 6
    Type of test
    Units: Subjects
        X-ray
    		 405 405
        CT-scan
    		 33 33
        Missing
    		 6 6
    Test result
    Units: Subjects
        Normal
    		 3 3
        Abnormal
    		 435 435
        Unknown
    		 6 6
    Hospitalization / ICU
    Units: Subjects
        Hospitalization
    		 404 404
        ICU
    		 40 40
    Cytokine storm syndrome (CSS) development
    Units: Subjects
        Yes
    		 364 364
        No
    		 80 80
    Number of combined therapies
    Units: Subjects
        One
    		 10 10
        Two
    		 19 19
        Three
    		 37 37
        Four
    		 40 40
        Five
    		 41 41
        Six
    		 54 54
        Seven
    		 33 33
        Eight
    		 37 37
        Nine
    		 25 25
        Ten or more
    		 147 147
        Zero
    		 1 1
    Respiratory rate
    Units: bpm
        arithmetic mean (standard deviation)
    		 23.6 ( 6.0 ) -
    PaO2
    Units: mmHg
        arithmetic mean (standard deviation)
    		 64.0 ( 15.1 ) -
    Time from onset of symptoms to the first dose of tocilizumab
    Units: days
        arithmetic mean (standard deviation)
    		 10.3 ( 6.5 ) -
    Time from CSS to the first dose of tocilizumab
    Units: days
        arithmetic mean (standard deviation)
    		 1.3 ( 3.0 ) -
    Systolic blood pressure
    Units: mmHg
        arithmetic mean (standard deviation)
    		 125.9 ( 18.1 ) -
    Diastolic blood pressure
    Units: mmHg
        arithmetic mean (standard deviation)
    		 73.3 ( 11.1 ) -
    Heart rate
    Units: bpm
        arithmetic mean (standard deviation)
    		 82.6 ( 17.0 ) -
    Body temperature
    Units: ºC
        arithmetic mean (standard deviation)
    		 36.8 ( 1.0 ) -
    Subject analysis sets

    Subject analysis set title
    Retrospective cohort (baseline characteristics)
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    This subject analysis set has been created solely for posting results related to the baseline characteristics of the retrospective subcohort.

    Subject analysis set title
    Retrospective cohort at screening/visit 1
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    This subject analysis set was created to report results related to the retrospective subcohort at Screening/Visit 1, when applicable.

    Subject analysis set title
    Retrospective cohort at last visit available
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    This subject analysis set was created to report results related to the retrospective subcohort at last visit available, when applicable.

    Subject analysis set title
    Retrospective cohort (single dose)
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    This subject analysis set was created to report results related to the retrospective subcohort with single dose of tocilizumab, when applicable.

    Subject analysis set title
    Retrospective cohort (multiple doses)
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    This subject analysis set was created to report results related to the retrospective subcohort with multiple doses of tocilizumab, when applicable.

    Subject analysis sets values
    		 Retrospective cohort (baseline characteristics) Retrospective cohort at screening/visit 1 Retrospective cohort at last visit available Retrospective cohort (single dose) Retrospective cohort (multiple doses)
    Number of subjects
    247
    247
    247
    194
    53
    Age categorical
    Units: Subjects
        In utero
        Preterm newborn infants (gestational age < 37 wks)
        Newborns (0-27 days)
        Infants and toddlers (28 days-23 months)
        Children (2-11 years)
        Adolescents (12-17 years)
        Adults (18-64 years)
        From 65-84 years
        85 years and over
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    63.5 ( 14.2 )
    ( )
    ( )
    ( )
    ( )
    Gender categorical
    Units: Subjects
        Female
    77
        Male
    170
    RT-PCR
    Units: Subjects
        Positive
    247
    Severity
    Units: Subjects
        Mild (early infection)
    9
        Moderate (pulmonary involvement without hypoxia)
    93
        Severe (systematic hyper-inflammation)
    125
        Critical (multiple organ dysfunction syndrome)
    19
        Unknown
    1
    Chest X-ray / CT-scan performed
    Units: Subjects
        Yes
    241
        No
    6
    Type of test
    Units: Subjects
        X-ray
    224
        CT-scan
    17
        Missing
    6
    Test result
    Units: Subjects
        Normal
    1
        Abnormal
    240
        Unknown
    6
    Hospitalization / ICU
    Units: Subjects
        Hospitalization
    212
        ICU
    35
    Cytokine storm syndrome (CSS) development
    Units: Subjects
        Yes
    194
        No
    53
    Number of combined therapies
    Units: Subjects
        One
    6
        Two
    8
        Three
    19
        Four
    26
        Five
    21
        Six
    31
        Seven
    22
        Eight
    17
        Nine
    15
        Ten or more
    81
        Zero
    1
    Respiratory rate
    Units: bpm
        arithmetic mean (standard deviation)
    22.7 ( 5.8 )
    ( )
    ( )
    ( )
    ( )
    PaO2
    Units: mmHg
        arithmetic mean (standard deviation)
    63.4 ( 15.5 )
    ( )
    ( )
    ( )
    ( )
    Time from onset of symptoms to the first dose of tocilizumab
    Units: days
        arithmetic mean (standard deviation)
    11.3 ( 7.5 )
    ( )
    ( )
    ( )
    ( )
    Time from CSS to the first dose of tocilizumab
    Units: days
        arithmetic mean (standard deviation)
    1.8 ( 3.8 )
    ( )
    ( )
    ( )
    ( )
    Systolic blood pressure
    Units: mmHg
        arithmetic mean (standard deviation)
    124.9 ( 18.9 )
    ( )
    ( )
    ( )
    ( )
    Diastolic blood pressure
    Units: mmHg
        arithmetic mean (standard deviation)
    72.7 ( 11.5 )
    ( )
    ( )
    ( )
    ( )
    Heart rate
    Units: bpm
        arithmetic mean (standard deviation)
    85.1 ( 18.0 )
    ( )
    ( )
    ( )
    ( )
    Body temperature
    Units: ºC
        arithmetic mean (standard deviation)
    36.8 ( 1.0 )
    ( )
    ( )
    ( )
    ( )

    End points

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    End points reporting groups
    Reporting group title
    Tocilizumab
    Reporting group description
    		 -
    Reporting group title
    Tocilizumab
    Reporting group description
    		 -
    Reporting group title
    Tocilizumab
    Reporting group description
    		 -

    Reporting group title
    Single-dose
    Reporting group description
    		 -

    Reporting group title
    Multiple-dose
    Reporting group description
    		 -
    Reporting group title
    Tocilizumab
    Reporting group description
    		 -

    Subject analysis set title
    Retrospective cohort (baseline characteristics)
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    This subject analysis set has been created solely for posting results related to the baseline characteristics of the retrospective subcohort.

    Subject analysis set title
    Retrospective cohort at screening/visit 1
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    This subject analysis set was created to report results related to the retrospective subcohort at Screening/Visit 1, when applicable.

    Subject analysis set title
    Retrospective cohort at last visit available
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    This subject analysis set was created to report results related to the retrospective subcohort at last visit available, when applicable.

    Subject analysis set title
    Retrospective cohort (single dose)
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    This subject analysis set was created to report results related to the retrospective subcohort with single dose of tocilizumab, when applicable.

    Subject analysis set title
    Retrospective cohort (multiple doses)
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    This subject analysis set was created to report results related to the retrospective subcohort with multiple doses of tocilizumab, when applicable.

    Primary: Respiratory function

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    End point title
    		 Respiratory function
    End point description
    End point type
    Primary
    End point timeframe
    At day 1 after dosing and then every 3 days during the hospitalization
    End point values
    		 Tocilizumab Tocilizumab Retrospective cohort at last visit available
    Number of subjects analysed
    444
    444
    247
    Units: days
    arithmetic mean (standard deviation)
        Time to intubation
    2.8 ( 4.6 )
    2.8 ( 4.6 )
    3.1 ( 5.6 )
        Duration of intubation
    17.4 ( 15.2 )
    17.4 ( 15.2 )
    16.6 ( 15.1 )
        Duration of intubation in tocilizumab
    18.7 ( 15.7 )
    18.7 ( 15.7 )
    17.6 ( 15.6 )
        Time to NIMV
    2.2 ( 5.0 )
    2.2 ( 5.0 )
    2.8 ( 5.0 )
        Duration of NIMV
    8.8 ( 8.2 )
    8.8 ( 8.2 )
    10.8 ( 10.4 )
        Duration of NIMV in tocilizumab
    9.4 ( 9.4 )
    9.4 ( 9.4 )
    10.9 ( 12.2 )
        Time to oxygen therapy
    3.8 ( 8.4 )
    3.8 ( 8.4 )
    3.8 ( 8.4 )
        Duration of oxygen therapy
    9.2 ( 10.1 )
    9.2 ( 10.1 )
    11.6 ( 12.3 )
        Duration of oxygen therapy in tocilizumab
    8.6 ( 10.9 )
    8.6 ( 10.9 )
    10.9 ( 12.9 )
    Statistical analysis title
    		 Primary endpoint: improvement respiratory function
    Comparison groups
    Tocilizumab v Tocilizumab
    Number of subjects included in analysis
    888
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.05
    Method
    		 Descriptive analysis
    Parameter type
    		 NA
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0
         upper limit
    		 0
    Variability estimate
    Standard deviation
    Dispersion value
    0

    Primary: Mortality

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    End point title
    		 Mortality
    End point description
    End point type
    Primary
    End point timeframe
    At day 1 after dosing and then every 3 days during the hospitalization
    End point values
    		 Tocilizumab Tocilizumab Retrospective cohort at last visit available
    Number of subjects analysed
    444
    444
    247
    Units: Percentage
        number (not applicable)
    19.6
    19.6
    22.7
    Attachments
    		 Untitled (Filename: KM Overall survival (Primary endpoint for overall population).jpg)
    Untitled (Filename: KM Overall survival (Primary endpoint for retrospective population).jpg)
    Statistical analysis title
    		 Primary endpoint: mortality rate
    Statistical analysis description
    A descriptive statistical analysis was performed. Quantitative variables were described using measures of central tendency and dispersion. Qualitative variables were described using absolute frequencies and percentages. The 95% confidence intervals for these estimations were calculated.
    Comparison groups
    Tocilizumab v Tocilizumab
    Number of subjects included in analysis
    888
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.05
    Method
    		 Descriptive analysis
    Parameter type
    		 Mean difference (final values)
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0
         upper limit
    		 0
    Variability estimate
    Standard deviation
    Dispersion value
    0

    Secondary: Oxygenation parameters: SaO2

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    End point title
    		 Oxygenation parameters: SaO2
    End point description
    End point type
    Secondary
    End point timeframe
    At 1 day after the first dose and every 3 days during the hospitalization
    End point values
    		 Tocilizumab Retrospective cohort at last visit available
    Number of subjects analysed
    438
    242
    Units: Percentage
    arithmetic mean (standard deviation)
        SaO2
    93.1 ( 4.8 )
    92.7 ( 5.3 )
    No statistical analyses for this end point

    Secondary: Oxygenation parameters: PaFi (SaFi)

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    End point title
    		 Oxygenation parameters: PaFi (SaFi)
    End point description
    End point type
    Secondary
    End point timeframe
    At 1 day after the first dose and every 3 days during the hospitalization
    End point values
    		 Tocilizumab Retrospective cohort at last visit available
    Number of subjects analysed
    353
    181
    Units: Subjects
    number (not applicable)
        >=300
    99
    61
        <300
    254
    120
    No statistical analyses for this end point

    Secondary: Duration of hospitalization

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    End point title
    		 Duration of hospitalization
    End point description
    End point type
    Secondary
    End point timeframe
    At 1 day after the first dose and every 3 days during the hospitalization
    End point values
    		 Tocilizumab Retrospective cohort at last visit available
    Number of subjects analysed
    444
    247
    Units: days
    arithmetic mean (standard deviation)
        Time of hospitalization
    20.9 ( 24.8 )
    23.3 ( 30.2 )
        Time of hospitalization from the start of tocilizu
    15.6 ( 15.2 )
    16.5 ( 15.6 )
    No statistical analyses for this end point

    Secondary: Duration of intensive care unit stay

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    End point title
    		 Duration of intensive care unit stay
    End point description
    End point type
    Secondary
    End point timeframe
    At day 1 after dosing and then every 3 days during the hospitalization
    End point values
    		 Tocilizumab Retrospective cohort at last visit available
    Number of subjects analysed
    74
    46
    Units: days
    arithmetic mean (standard deviation)
        Time of ICU stay
    17.5 ( 16.2 )
    17.0 ( 16.5 )
        Time of ICU stay from the start of tocilizumab
    17.8 ( 17.0 )
    17.0 ( 17.7 )
    No statistical analyses for this end point

    Secondary: Organ support therapies

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    End point title
    		 Organ support therapies
    End point description
    End point type
    Secondary
    End point timeframe
    At day 1 after dosing and then every 3 days during the hospitalization
    End point values
    		 Tocilizumab Retrospective cohort at last visit available
    Number of subjects analysed
    20
    15
    Units: Subjects
        Dialysis
    5
    3
        Extracorporeal membrane oxygenation
    3
    2
        Other
    12
    10
    No statistical analyses for this end point

    Secondary: Radiological evolution

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    End point title
    		 Radiological evolution
    End point description
    End point type
    Secondary
    End point timeframe
    At day 1 after dosing and then every 3 days during the hospitalization
    End point values
    		 Tocilizumab Tocilizumab Retrospective cohort at screening/visit 1 Retrospective cohort at last visit available
    Number of subjects analysed
    438
    204
    241
    124
    Units: Subjects
    number (not applicable)
        Normal
    3
    4
    1
    3
        Abnormal
    435
    200
    240
    121
    No statistical analyses for this end point

    Secondary: Serum levels of inflammatory markers: IL-6

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    End point title
    		 Serum levels of inflammatory markers: IL-6
    End point description
    End point type
    Secondary
    End point timeframe
    At day 1 after dosing and then every 3 days during the hospitalization
    End point values
    		 Tocilizumab Tocilizumab Retrospective cohort at screening/visit 1 Retrospective cohort at last visit available
    Number of subjects analysed
    62
    62
    20
    20
    Units: pg/mL
        arithmetic mean (standard deviation)
    142.2 ( 353.6 )
    523.5 ( 1342.6 )
    149.4 ( 219.0 )
    1359.0 ( 2156.3 )
    No statistical analyses for this end point

    Secondary: Serum levels of inflammatory markers: CRP

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    End point title
    		 Serum levels of inflammatory markers: CRP
    End point description
    End point type
    Secondary
    End point timeframe
    At day 1 after dosing and then every 3 days during the hospitalization
    End point values
    		 Tocilizumab Tocilizumab Retrospective cohort at screening/visit 1 Retrospective cohort at last visit available
    Number of subjects analysed
    307
    307
    173
    173
    Units: mg/L
        arithmetic mean (standard deviation)
    106.6 ( 92.0 )
    13.8 ( 44.4 )
    114.0 ( 101.0 )
    18.1 ( 52.2 )
    No statistical analyses for this end point

    Secondary: Serum levels of inflammatory markers: D-dimer and Ferritin

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    End point title
    		 Serum levels of inflammatory markers: D-dimer and Ferritin
    End point description
    End point type
    Secondary
    End point timeframe
    At day 1 after dosing and then every 3 days during the hospitalization
    End point values
    		 Tocilizumab Tocilizumab Retrospective cohort at screening/visit 1 Retrospective cohort at last visit available
    Number of subjects analysed
    231 [1]
    231 [2]
    130 [3]
    130 [4]
    Units: ng/mL
    arithmetic mean (standard deviation)
        D-dimer
    1236.0 ( 2141.0 )
    2072.0 ( 10971.0 )
    1263.0 ( 2148.0 )
    2776.0 ( 14532.0 )
        Ferritin
    1401.0 ( 1714.0 )
    1300.0 ( 4292.0 )
    1559.0 ( 2159.0 )
    1073.0 ( 1247.0 )
    Notes
    [1] - N=231 for D-dimer N=199 for Ferritin
    [2] - N=231 for D-dimer N=199 for Ferritin
    [3] - N=130 for D-dimer N=108 for Ferritin
    [4] - N=130 for D-dimer N=108 for Ferritin
    No statistical analyses for this end point

    Secondary: Intubation

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    End point title
    		 Intubation
    End point description
    End point type
    Secondary
    End point timeframe
    At day 1 after dosing and then every 3 days during the hospitalization
    End point values
    		 Single-dose Multiple-dose Retrospective cohort (single dose) Retrospective cohort (multiple doses)
    Number of subjects analysed
    337
    107
    194
    53
    Units: days
    arithmetic mean (standard deviation)
        Time to intubation
    2.2 ( 3.0 )
    4.3 ( 6.9 )
    2.1 ( 3.4 )
    5.6 ( 8.7 )
        Duration of intubation
    16.2 ( 14.5 )
    20.4 ( 17.1 )
    15.6 ( 14.4 )
    19.8 ( 17.0 )
        Duration of intubation in tocilizumab
    16.6 ( 14.5 )
    24.4 ( 17.4 )
    15.3 ( 14.3 )
    24.9 ( 17.7 )
        Time to NIMV
    2.0 ( 4.8 )
    2.8 ( 5.6 )
    1.9 ( 6.1 )
    5.6 ( 7.6 )
        Duration of NIMV
    7.9 ( 8.1 )
    11.7 ( 8.1 )
    9.9 ( 10.7 )
    12.9 ( 9.5 )
        Duration of NIMV in tocilizumab
    8.5 ( 9.3 )
    12.1 ( 9.4 )
    9.9 ( 12.3 )
    13.6 ( 11.7 )
    No statistical analyses for this end point

    Secondary: Mortality

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    End point title
    		 Mortality
    End point description
    End point type
    Secondary
    End point timeframe
    At day 1 after dosing and then every 3 days during the hospitalization
    End point values
    		 Single-dose Multiple-dose Retrospective cohort (single dose) Retrospective cohort (multiple doses)
    Number of subjects analysed
    337
    107
    194
    53
    Units: Subjects
    number (not applicable)
        Yes
    65
    22
    42
    14
        No
    272
    85
    152
    39
    No statistical analyses for this end point

    Secondary: Time to RT-PCR virus negativity

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    End point title
    		 Time to RT-PCR virus negativity
    End point description
    End point type
    Secondary
    End point timeframe
    At day 1 after dosing and then every 3 days during the hospitalization
    End point values
    		 Tocilizumab Retrospective cohort at screening/visit 1
    Number of subjects analysed
    205
    127
    Units: days
        median (confidence interval 95%)
    27.0 (21.0 to 36.0)
    21.0 (16.0 to 30.0)
    Attachments
    		 Untitled (Filename: KM Time to PCR-negativity (overall population).jpg)
    Untitled (Filename: KM Time to PCR-negativity (retrospective population).jpg)
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    On 1 day after the first dose and every 3 days during the hospitalization
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    24.1
    Reporting groups
    Reporting group title
    Overall study
    Reporting group description
    		 -

    Serious adverse events
    		 Overall study
    Total subjects affected by serious adverse events
         subjects affected / exposed
    145 / 444 (32.66%)
         number of deaths (all causes)
    87
         number of deaths resulting from adverse events
    85
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Chronic lymphocytic leukaemia
         subjects affected / exposed
    1 / 444 (0.23%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Vascular disorders
    Circulatory collapse
         subjects affected / exposed
    1 / 444 (0.23%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Hypotension
         subjects affected / exposed
    1 / 444 (0.23%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Shock
         subjects affected / exposed
    1 / 444 (0.23%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Haemorrhage
         subjects affected / exposed
    1 / 444 (0.23%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    General disorders and administration site conditions
    Condition aggravated
         subjects affected / exposed
    1 / 444 (0.23%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Multiple organ dysfunction syndrome
         subjects affected / exposed
    4 / 444 (0.90%)
         occurrences causally related to treatment / all
    0 / 4
         deaths causally related to treatment / all
    0 / 5
    Respiratory, thoracic and mediastinal disorders
    Acute respiratory distress syndrome
         subjects affected / exposed
    75 / 444 (16.89%)
         occurrences causally related to treatment / all
    1 / 75
         deaths causally related to treatment / all
    1 / 46
    Acute respiratory failure
         subjects affected / exposed
    6 / 444 (1.35%)
         occurrences causally related to treatment / all
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    Bronchospasm
         subjects affected / exposed
    1 / 444 (0.23%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    1 / 444 (0.23%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Increased bronchial secretion
         subjects affected / exposed
    1 / 444 (0.23%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Lung infiltration
         subjects affected / exposed
    1 / 444 (0.23%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    4 / 444 (0.90%)
         occurrences causally related to treatment / all
    0 / 4
         deaths causally related to treatment / all
    0 / 1
    Pulmonary fibrosis
         subjects affected / exposed
    2 / 444 (0.45%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    Respiratory distress
         subjects affected / exposed
    1 / 444 (0.23%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Respiratory failure
         subjects affected / exposed
    22 / 444 (4.95%)
         occurrences causally related to treatment / all
    0 / 22
         deaths causally related to treatment / all
    0 / 16
    Psychiatric disorders
    Confusional state
         subjects affected / exposed
    1 / 444 (0.23%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    2 / 444 (0.45%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Red blood cell count decreased
         subjects affected / exposed
    1 / 444 (0.23%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Injury, poisoning and procedural complications
    Toxicity to various agents
         subjects affected / exposed
    1 / 444 (0.23%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Cardiac disorders
    Acute coronary syndrome
         subjects affected / exposed
    1 / 444 (0.23%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Atrial fibrillation
         subjects affected / exposed
    1 / 444 (0.23%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Cardiac failure
         subjects affected / exposed
    2 / 444 (0.45%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Cardio-respiratory arrest
         subjects affected / exposed
    4 / 444 (0.90%)
         occurrences causally related to treatment / all
    0 / 4
         deaths causally related to treatment / all
    0 / 3
    Myocardial infarction
         subjects affected / exposed
    1 / 444 (0.23%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Ventricular tachycardia
         subjects affected / exposed
    1 / 444 (0.23%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Nervous system disorders
    Cerebrovascular accident
         subjects affected / exposed
    1 / 444 (0.23%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Polyneuropathy
         subjects affected / exposed
    1 / 444 (0.23%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    3 / 444 (0.68%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Leukocytosis
         subjects affected / exposed
    2 / 444 (0.45%)
         occurrences causally related to treatment / all
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    Neutropenia
         subjects affected / exposed
    1 / 444 (0.23%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Thrombocytopenia
         subjects affected / exposed
    3 / 444 (0.68%)
         occurrences causally related to treatment / all
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    Gastrointestinal disorders
    Abdominal wall haemorrhage
         subjects affected / exposed
    1 / 444 (0.23%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Diarrhoea
         subjects affected / exposed
    1 / 444 (0.23%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Gastrointestinal haemorrhage
         subjects affected / exposed
    1 / 444 (0.23%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Ileus
         subjects affected / exposed
    1 / 444 (0.23%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Large intestine perforation
         subjects affected / exposed
    1 / 444 (0.23%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Oedematous pancreatitis
         subjects affected / exposed
    1 / 444 (0.23%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Thrombosis mesenteric vessel
         subjects affected / exposed
    1 / 444 (0.23%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Hepatobiliary disorders
    Cholecystitis acute
         subjects affected / exposed
    1 / 444 (0.23%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Hepatic cytolysis
         subjects affected / exposed
    1 / 444 (0.23%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Hepatic ischaemia
         subjects affected / exposed
    1 / 444 (0.23%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Hypertransaminasaemia
         subjects affected / exposed
    2 / 444 (0.45%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Hyperbilirubinaemia
         subjects affected / exposed
    1 / 444 (0.23%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Renal and urinary disorders
    Renal failure
         subjects affected / exposed
    1 / 444 (0.23%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Renal impairment
         subjects affected / exposed
    1 / 444 (0.23%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Infections and infestations
    Abdominal sepsis
         subjects affected / exposed
    1 / 444 (0.23%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Bacteraemia
         subjects affected / exposed
    3 / 444 (0.68%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Bacterial infection
         subjects affected / exposed
    2 / 444 (0.45%)
         occurrences causally related to treatment / all
    2 / 3
         deaths causally related to treatment / all
    1 / 1
    Bronchopulmonary aspergillosis
         subjects affected / exposed
    1 / 444 (0.23%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Cytomegalovirus infection
         subjects affected / exposed
    1 / 444 (0.23%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Enterobacter bacteraemia
         subjects affected / exposed
    2 / 444 (0.45%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Enterococcal bacteraemia
         subjects affected / exposed
    1 / 444 (0.23%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Escherichia infection
         subjects affected / exposed
    2 / 444 (0.45%)
         occurrences causally related to treatment / all
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    Herpes virus infection
         subjects affected / exposed
    1 / 444 (0.23%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Klebsiella infection
         subjects affected / exposed
    1 / 444 (0.23%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Peritonitis
         subjects affected / exposed
    1 / 444 (0.23%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Pneumonia
         subjects affected / exposed
    2 / 444 (0.45%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    Pneumonia bacterial
         subjects affected / exposed
    1 / 444 (0.23%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Pneumonia escherichia
         subjects affected / exposed
    1 / 444 (0.23%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Pneumonia fungal
         subjects affected / exposed
    2 / 444 (0.45%)
         occurrences causally related to treatment / all
    2 / 2
         deaths causally related to treatment / all
    1 / 1
    Pneumonia pseudomonal
         subjects affected / exposed
    1 / 444 (0.23%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Pseudomonas infection
         subjects affected / exposed
    1 / 444 (0.23%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Respiratory tract infection
         subjects affected / exposed
    1 / 444 (0.23%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Septic shock
         subjects affected / exposed
    1 / 444 (0.23%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Superinfection bacterial
         subjects affected / exposed
    1 / 444 (0.23%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Systemic candida
         subjects affected / exposed
    1 / 444 (0.23%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Tracheobronchitis bacterial
         subjects affected / exposed
    1 / 444 (0.23%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    1 / 444 (0.23%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 1%
    Non-serious adverse events
    		 Overall study
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    240 / 444 (54.05%)
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    5 / 444 (1.13%)
         occurrences all number
    5
    Cardiac disorders
    Atrial fibrillation
         subjects affected / exposed
    7 / 444 (1.58%)
         occurrences all number
    7
    Cardiac failure
         subjects affected / exposed
    5 / 444 (1.13%)
         occurrences all number
    5
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    14 / 444 (3.15%)
         occurrences all number
    14
    Leukocytosis
         subjects affected / exposed
    6 / 444 (1.35%)
         occurrences all number
    6
    Thrombocytopenia
         subjects affected / exposed
    11 / 444 (2.48%)
         occurrences all number
    11
    Gastrointestinal disorders
    Constipation
         subjects affected / exposed
    16 / 444 (3.60%)
         occurrences all number
    16
    Diarrhoea
         subjects affected / exposed
    8 / 444 (1.80%)
         occurrences all number
    8
    Nausea
         subjects affected / exposed
    6 / 444 (1.35%)
         occurrences all number
    6
    Hepatobiliary disorders
    Hypertransaminasaemia
         subjects affected / exposed
    13 / 444 (2.93%)
         occurrences all number
    13
    Respiratory, thoracic and mediastinal disorders
    Acute respiratory failure
         subjects affected / exposed
    7 / 444 (1.58%)
         occurrences all number
    7
    Pulmonary embolism
         subjects affected / exposed
    9 / 444 (2.03%)
         occurrences all number
    9
    Respiratory failure
         subjects affected / exposed
    24 / 444 (5.41%)
         occurrences all number
    24
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    6 / 444 (1.35%)
         occurrences all number
    6
    Confusional state
         subjects affected / exposed
    6 / 444 (1.35%)
         occurrences all number
    6
    Insomnia
         subjects affected / exposed
    20 / 444 (4.50%)
         occurrences all number
    20
    Renal and urinary disorders
    Acute respiratory distress syndrome
         subjects affected / exposed
    75 / 444 (16.89%)
         occurrences all number
    75
    Acute kidney injury
         subjects affected / exposed
    7 / 444 (1.58%)
         occurrences all number
    7
    Infections and infestations
    Bacteraemia
         subjects affected / exposed
    5 / 444 (1.13%)
         occurrences all number
    5
    Pneumonia
         subjects affected / exposed
    5 / 444 (1.13%)
         occurrences all number
    5
    Respiratory tract infection
         subjects affected / exposed
    6 / 444 (1.35%)
         occurrences all number
    6
    Superinfection bacterial
         subjects affected / exposed
    5 / 444 (1.13%)
         occurrences all number
    6
    Urinary tract infection
         subjects affected / exposed
    8 / 444 (1.80%)
         occurrences all number
    8
    Metabolism and nutrition disorders
    Hyperglycaemia
         subjects affected / exposed
    14 / 444 (3.15%)
         occurrences all number
    14
    Hypokalaemia
         subjects affected / exposed
    6 / 444 (1.35%)
         occurrences all number
    6

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    10 Jun 2020
    Version generated due to clarifications requested by the ethics committee during the initial evaluation of the study
    10 Feb 2021
    Change of principal investigator in the following sites: Hospital de la Santa Creu i Sant Pau and Hospital Público General de Tomelloso. HA does not evaluate amendments due to changes in principal investigators.

    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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