Flag of the European Union EU Clinical Trials Register Help

Clinical trials

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

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

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

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

    < Back to search results

    Download PDF

    Clinical Trial Results:
    The PRedictive value of bOne turnover markerS during discontinuation of Alendronate: The PROSA study

    Summary
    EudraCT number
    		 2016-003110-27
    Trial protocol
    		 DK  
    Global end of trial date
    15 Sep 2020

    Results information
    Results version number
    		 v1(current)
    This version publication date
    10 Dec 2020
    First version publication date
    10 Dec 2020
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    21.07.2016
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT03051620
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Dept. of Endocrinology and Internal Medicine, Aarhus University Hospital
    Sponsor organisation address
    Palle Juul-Jensens Boulevard 99, Aarhus, Denmark, 8200
    Public contact
    Bente Lomholt Langdahl, Dept. of Endocrinology and Internal Medicine, Aarhus University Hospital , benlan@rm.dk
    Scientific contact
    Bente Lomholt Langdahl, Dept. of Endocrinology and Internal Medicine, Aarhus University Hospital , benlan@rm.dk
    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
    15 Sep 2020
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    15 Sep 2020
    Global end of trial reached?
    Yes
    Global end of trial date
    15 Sep 2020
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary endpoint was if p-CTX measured three and six months after stopping alendronate (ALN) predicts changes in total hip BMD (THBMD) after one year. The secondary endpoints were if baseline p-CTX, p-PINP, the ratio p-CTX/p-PINP, or changes thereof measured three and six months after stopping ALN treatment predict changes in BMD at any site after one and two years. Additional endpoints were the proportion of the study population in which bone turnover increased above premenopausal/young adult reference levels after 3, 6, 12 and 24 months, and the proportion of the study population who lost BMD beyond the least significant change at the lumbar spine and total hip.
    Protection of trial subjects
    We re-initiated alendronate if there was a rapid decrease in BMD >8% (any site), if a patient suffered a low energy fracture or if a patient with BMD T-score < -2.5 initiated daily treatment with systemic glucocorticoids.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    17 Feb 2017
    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
    Denmark: 142
    Worldwide total number of subjects
    142
    EEA total number of subjects
    142
    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)
    41
    From 65 to 84 years
    101
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 The Department of Endocrinology and Internal Medicine, Aarhus University Hospital The Department of Internal Medicine, Horsens Regional Hospital Advertisements in daily newspapers and online Data extraction from The Danish Health Data Authority

    Pre-assignment
    Screening details
    		 DXA Blood samples Inclusions and exclusions criteria

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

    Arms
    Arm title
    		 study population
    Arm description
    		 Treatment pause with alendronate
    Arm type
    		 Experimental

    Investigational medicinal product name
    No treatment
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Other use
    Dosage and administration details
    Treatment pause with alendronate after min 5 years of treatment

    Number of subjects in period 1
    		study population
    Started
    142
    Completed
    124
    Not completed
    18
         Withdraw on medical grounds
    8
         Lost to follow-up
    10

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Overall period
    Reporting group description
    		 Study population: n=142

    Reporting group values
    		 Overall period Total
    Number of subjects
    		 142 142
    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)
    		 68 ( 6 ) -
    Gender categorical
    Units: Subjects
        Female
    		 122 122
        Male
    		 20 20
    Subject analysis sets

    Subject analysis set title
    Analysis plan: BMD, BTM, TBS
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Paired sample-t-test Mixed model analysis of variance Stratified analyses

    Subject analysis set title
    Analysis plan: correlations
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Stratified analyses multiple linear regression

    Subject analysis sets values
    		 Analysis plan: BMD, BTM, TBS Analysis plan: correlations
    Number of subjects
    142
    142
    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)
    68 ( 6 )
    ( )
    Gender categorical
    Units: Subjects
        Female
    122
        Male
    20

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    study population
    Reporting group description
    		 Treatment pause with alendronate

    Subject analysis set title
    Analysis plan: BMD, BTM, TBS
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Paired sample-t-test Mixed model analysis of variance Stratified analyses

    Subject analysis set title
    Analysis plan: correlations
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Stratified analyses multiple linear regression

    Primary: Primary endpoint

    		 Close Top of page
    End point title
    		 Primary endpoint
    End point description
    The primary endpoint was if p-CTX measured three and six months after stopping alendronate predicts changes in THBMD after one year.
    End point type
    Primary
    End point timeframe
    1 year
    End point values
    		 Analysis plan: BMD, BTM, TBS Analysis plan: correlations
    Number of subjects analysed
    142
    142
    Units: p value
        number (not applicable)
    142
    142
    Statistical analysis title
    		 Analysis plan
    Statistical analysis description
    Paired sample-t-test Mixed model analysis of variance Stratified analyses multiple linear regression
    Comparison groups
    Analysis plan: BMD, BTM, TBS v Analysis plan: correlations
    Number of subjects included in analysis
    284
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 ≤ 0 [1]
    Method
    		 Regression, Linear
    Confidence interval
    Notes
    [1] - Hypothesis tested p <= 0.05

    Secondary: Secondary endpoint

    		 Close Top of page
    End point title
    		 Secondary endpoint
    End point description
    The secondary endpoints were if baseline p-CTX, p-PINP, the ratio p-CTX/p-PINP, or changes thereof measured three and six months after stopping alendronate treatment predict changes in BMD at any site after one and two years. Additional endpoints were the proportion of the study population in which bone turnover increased above premenopausal/young adult reference levels after 3, 6, 12 and 24 months, and the proportion of the study population who lost BMD beyond the least significant change at the lumbar spine and total hip.
    End point type
    Secondary
    End point timeframe
    one and two years
    End point values
    		 Analysis plan: BMD, BTM, TBS Analysis plan: correlations
    Number of subjects analysed
    142
    142
    Units: p value
        number (not applicable)
    142
    142
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    February the 17th 2017 to February the 1st 2020
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 non specified
    Dictionary version
    x
    Reporting groups
    Reporting group title
    Study population
    Reporting group description
    		 Study population (n=142): baseline to month 24

    Serious adverse events
    		 Study population
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 142 (0.00%)
         number of deaths (all causes)
    0
         number of deaths resulting from adverse events
    0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Study population
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    68 / 142 (47.89%)
    Cardiac disorders
    Arrhythmia, acute myocardial infarction, hypertension
    Additional description: Arrhythmia, acute myocardial infarction, hypertension
         subjects affected / exposed
    10 / 142 (7.04%)
         occurrences all number
    10
    Eye disorders
    Cataract, glaucoma
    Additional description: Cataract, glaucoma
         subjects affected / exposed
    9 / 142 (6.34%)
         occurrences all number
    9
    Respiratory, thoracic and mediastinal disorders
    Upper and lower respiratory tract infection, pneumonia, bronchitis
    Additional description: Upper and lower respiratory tract infection, pneumonia, bronchitis
         subjects affected / exposed
    10 / 142 (7.04%)
         occurrences all number
    10
    Renal and urinary disorders
    Lower urinary symptoms, infection and kidney stones
    Additional description: Lower urinary symptoms, infection and kidney stones
         subjects affected / exposed
    9 / 142 (6.34%)
         occurrences all number
    9
    Musculoskeletal and connective tissue disorders
    Fracture
    Additional description: Fracture
         subjects affected / exposed
    15 / 142 (10.56%)
         occurrences all number
    15
    Arthralgia, osteoarthritis, back pain
    Additional description: Arthralgia, osteoarthritis, back pain
         subjects affected / exposed
    15 / 142 (10.56%)
         occurrences all number
    15

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    03 Dec 2018
    We extended the trial with an additional year

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

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

    European Medicines Agency © 1995-Thu May 02 01:13:43 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA