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   44356   clinical trials with a EudraCT protocol, of which   7382   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 randomised, double-blind placebo controlled trial of the effectiveness of the beta-blocker bisoprolol in preventing exacerbations of chronic obstructive pulmonary disease.

    Summary
    EudraCT number
    		 2017-002779-24
    Trial protocol
    		 GB  
    Global end of trial date
    31 May 2023

    Results information
    Results version number
    		 v1(current)
    This version publication date
    17 Aug 2025
    First version publication date
    17 Aug 2025
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    3.089.17
    Additional study identifiers
    ISRCTN number
    		 ISRCTN10497306
    US NCT number
    		 -
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    University of Aberdeen
    Sponsor organisation address
    Research Governance, Health Sciences Building, Foresterhill, Aberdeen, United Kingdom, AB25 2ZD
    Public contact
    Research Governance, University of Aberdeen, +44 1224437221, researchgovernance@abdn.ac.uk
    Scientific contact
    Research Governance, University of Aberdeen, +44 1224437221, researchgovernance@abdn.ac.uk
    Sponsor organisation name
    NHS Grampian
    Sponsor organisation address
    Foresterhill House Annex, Foresterhill, Aberdeen, United Kingdom, AB25 2ZD
    Public contact
    Research Governance, NHS Grampian, researchgovernance@abdn.ac.uk
    Scientific contact
    Research Governance, NHS Grampian, researchgovernance@abdn.ac.uk
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    01 Mar 2024
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    31 May 2023
    Global end of trial reached?
    Yes
    Global end of trial date
    31 May 2023
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    The primary objective is to determine whether adding bisoprolol (maximum dose 5mg a day) to existing COPD treatment in patients who have chronic obstructive pulmonary disease will reduce the number of exacerbations (or flare ups) of the condition. If the treatment is effective, we will also assess whether it is cost effective
    Protection of trial subjects
    Bisoprolol is licensed for the treatment of angina, hypertension and heart failure. In BICS used ‘off label’. As per heart failure guidelines initiating dose is low and with gradual dose titration. Main concern is that bisoprolol induced bronchospasm (worsening of lung function) - risk minimised by excluding persons with a sole diagnosis of asthma or a diagnosis of asthma before the age of 40, titrating dose of bisoprolol slowly, with maximum study dose (5mg od) less than that recommended for heart failure. Previous systematic reviews demonstrate that cardiac specific beta blockers such as bisoprolol have no significant effect on lung function, symptoms or response to beta2 agonists when administered to people with COPD. The Chief Investigator, Clinical Trial pharmacist and Sponsor oversight committee have undertaken a review of the licensed vaccines and have confirmed that they would not expect any interaction between the COVID vaccines and the study IMP. Adverse reactions captured, in addition to SAEs and SARs. An independent DMC reviewed accumulating unblinded safety data.
    Background therapy
    		 Participants remained on all existing background COPD therapy
    Evidence for comparator
    		 Clinical equipoise allowed for placebo comparator
    Actual start date of recruitment
    17 Oct 2018
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    United Kingdom: 515
    Worldwide total number of subjects
    515
    EEA total number of subjects
    0
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    163
    From 65 to 84 years
    344
    85 years and over
    8

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 Eligible participants were identified and recruited from primary and secondary care settings across the UK. All participants provided fully informed consent.

    Pre-assignment
    Screening details
    		 Participants were screened against inclusion/exclusion criteria and eligibility was confirmed by a medically qualified doctor.

    Period 1
    Period 1 title
    Overall trial (entire period) (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor, Data analyst, Carer, Assessor
    Blinding implementation details
    Bisoprolol and placebo were manufactured and packaged to be identical. Randomisation was via a computerised web-based randomisation service created and administered by the Centre for Healthcare Randomised Trials. At randomisation, participants were allocated a drug pack (and it was not possible to identify trial arm from the pack number). An emergency unblinding facility was available.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Bisoprolol
    Arm description
    		 Bisoprolol was prepared as 1.25mg tablets and packaged in bottles of 168 tablets. Participants started on one tablet per day and were titrated over a period of approximately 4-7 weeks to a maximum of four tablets per day (equivalent to 5mg bisoprolol) based on tolerance to study medication, heart rate, systolic blood pressure, lung function and participant wishes.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Bisoprolol
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Bisoprolol was prepared as 1.25mg tablets and packaged in bottles of 168 tablets. Dose titrated over approximately 4-7 weeks to 1.25mg (1 tablet once daily), 2.5mg (2 tablets once daily), 3.75mg (3 tablets once daily) or 5mg (4 tablets once daily) based on tolerance to study medication, heart rate, systolic blood pressure, lung function and participant wishes.

    Arm title
    		 Placebo
    Arm description
    		 Placebo tablets were manufactured to be identical in appearance to 1.25mg bisoprolol tablets. Participants started on one placebo tablet per day and were titrated over a period of approximately 4-7 weeks to a maximum of four tablets per day (equivalent to 5mg bisoprolol) based on tolerance to study medication, heart rate, systolic blood pressure, lung function and participant wishes.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Placebo manufactured to look identical to 1.25mg bisoprolol.

    Number of subjects in period 1
    		Bisoprolol Placebo
    Started
    259
    256
    Completed
    259
    255
    Not completed
    0
    1
         Lost to follow-up
    -
    1

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Bisoprolol
    Reporting group description
    		 Bisoprolol was prepared as 1.25mg tablets and packaged in bottles of 168 tablets. Participants started on one tablet per day and were titrated over a period of approximately 4-7 weeks to a maximum of four tablets per day (equivalent to 5mg bisoprolol) based on tolerance to study medication, heart rate, systolic blood pressure, lung function and participant wishes.

    Reporting group title
    Placebo
    Reporting group description
    		 Placebo tablets were manufactured to be identical in appearance to 1.25mg bisoprolol tablets. Participants started on one placebo tablet per day and were titrated over a period of approximately 4-7 weeks to a maximum of four tablets per day (equivalent to 5mg bisoprolol) based on tolerance to study medication, heart rate, systolic blood pressure, lung function and participant wishes.

    Reporting group values
    		 Bisoprolol Placebo Total
    Number of subjects
    		 259 256 515
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0
        Newborns (0-27 days)
    		 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0
        Children (2-11 years)
    		 0 0 0
        Adolescents (12-17 years)
    		 0 0 0
        Adults (18-64 years)
    		 78 85 163
        From 65-84 years
    		 177 167 344
        85 years and over
    		 4 4 8
    Age continuous
    Age at recruitment
    Units: years
        arithmetic mean (standard deviation)
    		 67.7 ( 8.0 ) 67.7 ( 7.7 ) -
    Gender categorical
    Units: Subjects
        Female
    		 125 116 241
        Male
    		 134 140 274

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Bisoprolol
    Reporting group description
    		 Bisoprolol was prepared as 1.25mg tablets and packaged in bottles of 168 tablets. Participants started on one tablet per day and were titrated over a period of approximately 4-7 weeks to a maximum of four tablets per day (equivalent to 5mg bisoprolol) based on tolerance to study medication, heart rate, systolic blood pressure, lung function and participant wishes.

    Reporting group title
    Placebo
    Reporting group description
    		 Placebo tablets were manufactured to be identical in appearance to 1.25mg bisoprolol tablets. Participants started on one placebo tablet per day and were titrated over a period of approximately 4-7 weeks to a maximum of four tablets per day (equivalent to 5mg bisoprolol) based on tolerance to study medication, heart rate, systolic blood pressure, lung function and participant wishes.

    Primary: COPD exacerbations

    		 Close Top of page
    End point title
    		 COPD exacerbations
    End point description
    Participant reported COPD exacerbations treated with antibiotics and/or oral steroids, supplemented with data from medical records.
    End point type
    Primary
    End point timeframe
    12 months
    End point values
    		 Bisoprolol Placebo
    Number of subjects analysed
    259
    255
    Units: number
        arithmetic mean (standard deviation)
    2.03 ( 1.91 )
    2.01 ( 1.75 )
    Statistical analysis title
    		 Intention to treat - primary outcome
    Statistical analysis description
    Intention to treat analysis of primary outcome (adjusted incidence rate ratio)
    Comparison groups
    Bisoprolol v Placebo
    Number of subjects included in analysis
    514
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.72
    Method
    		 Mixed models analysis
    Parameter type
    		 incidence rate ratio
    Point estimate
    0.973
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.84
         upper limit
    		 1.13

    Secondary: time to first exacerbation

    		 Close Top of page
    End point title
    		 time to first exacerbation
    End point description
    time to first exacerbation
    End point type
    Secondary
    End point timeframe
    12 months
    End point values
    		 Bisoprolol Placebo
    Number of subjects analysed
    259
    255
    Units: days
        median (inter-quartile range (Q1-Q3))
    96 (27 to 103)
    70 (27 to 160)
    Statistical analysis title
    		 Intention to treat - time to first exacerbation
    Comparison groups
    Bisoprolol v Placebo
    Number of subjects included in analysis
    514
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.6
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.95
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.78
         upper limit
    		 1.16

    Secondary: Hospital admissions for COPD exacerbation

    		 Close Top of page
    End point title
    		 Hospital admissions for COPD exacerbation
    End point description
    End point type
    Secondary
    End point timeframe
    12 months
    End point values
    		 Bisoprolol Placebo
    Number of subjects analysed
    259
    255
    Units: number
        arithmetic mean (standard deviation)
    0.27 ( 0.63 )
    0.27 ( 0.65 )
    Statistical analysis title
    		 intention to treat - hospital admissions for COPD
    Comparison groups
    Bisoprolol v Placebo
    Number of subjects included in analysis
    514
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.99
    Method
    		 Mixed models analysis
    Parameter type
    		 incidence rate ratio
    Point estimate
    1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.67
         upper limit
    		 1.5

    Secondary: Non COPD hospital admissions

    		 Close Top of page
    End point title
    		 Non COPD hospital admissions
    End point description
    End point type
    Secondary
    End point timeframe
    12 months
    End point values
    		 Bisoprolol Placebo
    Number of subjects analysed
    259
    255
    Units: number
        arithmetic mean (standard deviation)
    0.18 ( 0.51 )
    0.12 ( 0.44 )
    Statistical analysis title
    		 ITT - non-COPD hospital admissions
    Comparison groups
    Bisoprolol v Placebo
    Number of subjects included in analysis
    514
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.14
    Method
    		 Mixed models analysis
    Parameter type
    		 incidence rate ratio
    Point estimate
    1.47
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.88
         upper limit
    		 2.45

    Secondary: All cause mortality

    		 Close Top of page
    End point title
    		 All cause mortality
    End point description
    End point type
    Secondary
    End point timeframe
    12 months
    End point values
    		 Bisoprolol Placebo
    Number of subjects analysed
    259
    255
    Units: number
    11
    13
    Statistical analysis title
    		 ITT - all cause mortality
    Comparison groups
    Bisoprolol v Placebo
    Number of subjects included in analysis
    514
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.53
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.77
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.34
         upper limit
    		 1.73

    Secondary: ITT - COPD mortality

    		 Close Top of page
    End point title
    		 ITT - COPD mortality
    End point description
    End point type
    Secondary
    End point timeframe
    12 months
    End point values
    		 Bisoprolol Placebo
    Number of subjects analysed
    259
    255
    Units: number
    2
    9
    Statistical analysis title
    		 ITT - COPD mortality
    Comparison groups
    Bisoprolol v Placebo
    Number of subjects included in analysis
    514
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.03
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.19
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.04
         upper limit
    		 0.88

    Secondary: ITT - dyspnoea (Transitional Dyspnoea Index)

    		 Close Top of page
    End point title
    		 ITT - dyspnoea (Transitional Dyspnoea Index)
    End point description
    End point type
    Secondary
    End point timeframe
    12 months
    End point values
    		 Bisoprolol Placebo
    Number of subjects analysed
    183
    188
    Units: score
        arithmetic mean (standard deviation)
    -1.73 ( 3.66 )
    -1.01 ( 3.58 )
    Statistical analysis title
    		 ITT - dyspnoea
    Comparison groups
    Bisoprolol v Placebo
    Number of subjects included in analysis
    371
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.05
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -0.73
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.44
         upper limit
    		 -0.01

    Secondary: ITT - COPD Assessment Test score (CAT)

    		 Close Top of page
    End point title
    		 ITT - COPD Assessment Test score (CAT)
    End point description
    End point type
    Secondary
    End point timeframe
    12 months
    End point values
    		 Bisoprolol Placebo
    Number of subjects analysed
    207
    202
    Units: score
        arithmetic mean (standard deviation)
    19.43 ( 8.86 )
    19.77 ( 9.4 )
    Statistical analysis title
    		 ITT - CAT
    Comparison groups
    Bisoprolol v Placebo
    Number of subjects included in analysis
    409
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.49
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -0.59
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.26
         upper limit
    		 1.07

    Adverse events

    		 Close Top of page
    Adverse events information [1]
    Timeframe for reporting adverse events
    -12 months
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    26
    Reporting groups
    Reporting group title
    Bisoprolol
    Reporting group description
    		 Participants randomised to bisoprolol

    Reporting group title
    Placebo
    Reporting group description
    		 Participants randomised to placebo

    Notes
    [1] - There are no non-serious adverse events recorded for these results. It is expected that there will be at least one non-serious adverse event reported.
    Justification: AEs reported by system organ class only, not possible to enter on this system. Fully reported in table 19 of Devereux et al. Bisoprolol for patients with chronic obstructive pulmonary disease at high risk of exacerbation: The BICS RCT. Health Technol Assess 2025;29(17). https://doi.org/10.3310/TNDG8641
    Serious adverse events
    		 Bisoprolol Placebo
    Total subjects affected by serious adverse events
         subjects affected / exposed
    37 / 259 (14.29%)
    36 / 256 (14.06%)
         number of deaths (all causes)
    11
    13
         number of deaths resulting from adverse events
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Brain neoplasm
         subjects affected / exposed
    0 / 259 (0.00%)
    1 / 256 (0.39%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Triple negative breast cancer
         subjects affected / exposed
    1 / 259 (0.39%)
    0 / 256 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Lung neoplasm malignant
         subjects affected / exposed
    1 / 259 (0.39%)
    4 / 256 (1.56%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 4
         deaths causally related to treatment / all
    0 / 1
    0 / 3
    Breast cancer
         subjects affected / exposed
    1 / 259 (0.39%)
    0 / 256 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Small cell lung cancer
         subjects affected / exposed
    0 / 259 (0.00%)
    1 / 256 (0.39%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Endometrial cancer
         subjects affected / exposed
    0 / 259 (0.00%)
    1 / 256 (0.39%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastric cancer
         subjects affected / exposed
    1 / 259 (0.39%)
    0 / 256 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Vascular disorders
    Cor pulmonale
         subjects affected / exposed
    0 / 259 (0.00%)
    1 / 256 (0.39%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Orthostatic hypotension
         subjects affected / exposed
    1 / 259 (0.39%)
    1 / 256 (0.39%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Non-cardiac chest pain
         subjects affected / exposed
    1 / 259 (0.39%)
    0 / 256 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Pneumothorax
         subjects affected / exposed
    0 / 259 (0.00%)
    1 / 256 (0.39%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    3 / 259 (1.16%)
    8 / 256 (3.13%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 8
         deaths causally related to treatment / all
    0 / 2
    0 / 8
    Haemoptysis
         subjects affected / exposed
    0 / 259 (0.00%)
    1 / 256 (0.39%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pleurisy
         subjects affected / exposed
    0 / 259 (0.00%)
    1 / 256 (0.39%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    1 / 259 (0.39%)
    0 / 256 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory failure
         subjects affected / exposed
    0 / 259 (0.00%)
    1 / 256 (0.39%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Psychiatric disorders
    Mental disorder
         subjects affected / exposed
    1 / 259 (0.39%)
    0 / 256 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Completed suicide
         subjects affected / exposed
    0 / 259 (0.00%)
    1 / 256 (0.39%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Injury, poisoning and procedural complications
    Overdose
         subjects affected / exposed
    1 / 259 (0.39%)
    0 / 256 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hip fracture
         subjects affected / exposed
    1 / 259 (0.39%)
    0 / 256 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rib fracture
         subjects affected / exposed
    1 / 259 (0.39%)
    0 / 256 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin laceration
         subjects affected / exposed
    1 / 259 (0.39%)
    0 / 256 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fall
         subjects affected / exposed
    1 / 259 (0.39%)
    1 / 256 (0.39%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Femoral neck fracture
         subjects affected / exposed
    1 / 259 (0.39%)
    0 / 256 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Angina pectoris
         subjects affected / exposed
    1 / 259 (0.39%)
    0 / 256 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    1 / 259 (0.39%)
    0 / 256 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrial flutter
         subjects affected / exposed
    1 / 259 (0.39%)
    0 / 256 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Atrial fibrillation
         subjects affected / exposed
    2 / 259 (0.77%)
    0 / 256 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypertension
         subjects affected / exposed
    0 / 259 (0.00%)
    1 / 256 (0.39%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Right ventricular failure
         subjects affected / exposed
    1 / 259 (0.39%)
    0 / 256 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac failure
         subjects affected / exposed
    0 / 259 (0.00%)
    1 / 256 (0.39%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Cerebrovascular accident
         subjects affected / exposed
    1 / 259 (0.39%)
    0 / 256 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Transient ischaemic attack
         subjects affected / exposed
    2 / 259 (0.77%)
    1 / 256 (0.39%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Paraesthesia
         subjects affected / exposed
    1 / 259 (0.39%)
    0 / 256 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vertigo
         subjects affected / exposed
    0 / 259 (0.00%)
    1 / 256 (0.39%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    0 / 259 (0.00%)
    1 / 256 (0.39%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Intestinal obstruction
         subjects affected / exposed
    1 / 259 (0.39%)
    0 / 256 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colitis
         subjects affected / exposed
    0 / 259 (0.00%)
    1 / 256 (0.39%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatitis
         subjects affected / exposed
    2 / 259 (0.77%)
    0 / 256 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatitis necrotising
         subjects affected / exposed
    1 / 259 (0.39%)
    0 / 256 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Enterocolitis
         subjects affected / exposed
    0 / 259 (0.00%)
    1 / 256 (0.39%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Constipation
         subjects affected / exposed
    1 / 259 (0.39%)
    0 / 256 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholecystitis
         subjects affected / exposed
    1 / 259 (0.39%)
    0 / 256 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intestinal perforation
         subjects affected / exposed
    1 / 259 (0.39%)
    0 / 256 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Renal and urinary disorders
    Urinary retention
         subjects affected / exposed
    1 / 259 (0.39%)
    0 / 256 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Myalgia
         subjects affected / exposed
    0 / 259 (0.00%)
    1 / 256 (0.39%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Pneumonia
         subjects affected / exposed
    7 / 259 (2.70%)
    1 / 256 (0.39%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    0 / 259 (0.00%)
    1 / 256 (0.39%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Influenza
         subjects affected / exposed
    1 / 259 (0.39%)
    1 / 256 (0.39%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Coronavirus infection
         subjects affected / exposed
    0 / 259 (0.00%)
    2 / 256 (0.78%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    0 / 259 (0.00%)
    1 / 256 (0.39%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Herpes simplex
         subjects affected / exposed
    1 / 259 (0.39%)
    0 / 256 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Clostridium difficile infection
         subjects affected / exposed
    1 / 259 (0.39%)
    0 / 256 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Hyponatraemia
         subjects affected / exposed
    1 / 259 (0.39%)
    0 / 256 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Bisoprolol Placebo
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    0 / 259 (0.00%)
    0 / 256 (0.00%)

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    23 Mar 2020
    Addition of continency arrangements in response to COVID-19 pandemic; ceasing face-to-face contact by moving study visits to telephone calls.
    01 Dec 2020
    Summary of the three main protocol changes to allow recruitment to restart after the COVID-19 pandemic and the justification for this: Revisions to inclusion criteria; Revisions to the titration process; Reduction in number of face-to-face study visits and associated processes.

    Interruptions (globally)
    Were there any global interruptions to the trial? Yes
    Date
    Interruption
    Restart date
    16 Mar 2020
    COVID-19; suspension to recruitment to the study. Participants already recruited in the study continued to take bisoprolol/placebo and were followed up remotely (rather than in-person)
    31 Jul 2021

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    Did not meet recruitment target (loss of funding). 27% in the bisoprolol group titrated to maximum 5mg dose. 31% of ppts took <70% of expected doses; the majority of these ceased (similar proportions in both bisoprolol and placebo)

    Online references
    http://www.ncbi.nlm.nih.gov/pubmed/38762800
    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-Fri Aug 22 00:57:56 CEST 2025 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA