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   43861   clinical trials with a EudraCT protocol, of which   7284   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:
    Prevention and Treatment of Steroid-Induced Osteopenia in children and adolescents with rheumatic diseases

    Summary
    EudraCT number
    		 2005-003129-23
    Trial protocol
    		 GB  
    Global end of trial date
    27 Feb 2015

    Results information
    Results version number
    		 v1(current)
    This version publication date
    17 Jun 2022
    First version publication date
    17 Jun 2022
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    04/MR/111
    Additional study identifiers
    ISRCTN number
    		 ISRCTN66814619
    US NCT number
    		 -
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Belfast Health and Social Care Trust
    Sponsor organisation address
    Research Office, 2nd Floor King Edward Building, Royal Hospital Site, Belfast, United Kingdom, BT12 6BA
    Public contact
    Alison Murphy, Research Office, Belfast Health and Social Care Trust, ResearchSponsor@belfasttrust.hscni.net
    Scientific contact
    Research Office, Research Office, Belfast Health and Social Care Trust, ResearchSponsor@belfasttrust.hscni.net
    Sponsor organisation name
    Queen's University Belfast (QUB)
    Sponsor organisation address
    Research Governance, Ethics and Integrity, QUB, 63 University Road, Belfast, United Kingdom, BT7 1NN
    Public contact
    Research Governance, Research Governance, Ethics and Integrity, QUB, +44 90972572, researchgovernance@qub.ac.uk
    Scientific contact
    Research Governance, Research Governance, Ethics and Integrity, QUB, +44 90972572, researchgovernance@qub.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
    16 Mar 2017
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    27 Feb 2015
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    Primary objective of this study is to demonstrate whether 1-hydroxycholecalciferol or the Bisphosphonate Risedronate is superior to placebo in preventing osteopaenia in children with rheumatic diseases commencing or established on steroids.
    Protection of trial subjects
    All patients and parents / guardians provided written informed consent. All female participants of child bearing age undertook a pregnancy test at each visit. Renal function was undertaken prior to and during the trial. Blood testing was kept to the minimum required to address efficacy and safety issues. All patients, parents/guardians were informed of their freedom to withdraw at any time from the trial. Treatment of their underlying rheumatological conditions continued during the trial according to clinical need as perceived by the local PI
    Background therapy
    		 All patients received Calcium and vitamin D supplements. All medications including steroids continued according to clinical need
    Evidence for comparator
    		 There was limited evidence of the benefit of either interventions to improve bone mineral density in children. There is a large body of evidence for the use of bisphosphonates for improving bone density and reducing fracture risk in adults treated with steroids. Paediatric rheumatologists used active vitamin D metabolites in an attempt to prevent bone loss in children treated with steroids. Thus the comparators were placebo and the active Vitamin D metabolite One Alpha
    Actual start date of recruitment
    22 Aug 2007
    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: 217
    Worldwide total number of subjects
    217
    EEA total number of subjects
    217
    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)
    88
    Adolescents (12-17 years)
    129
    Adults (18-64 years)
    0
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 Patients were recruited from 11 centres throughout the UK. Centres commenced recruitment in a sequential fashion. Recruitment began on 22nd Aug 2007.

    Pre-assignment
    Screening details
    		 PI were advised to identify all children and young people commencing or already treated with steroids for a rheumatic disease. Screening logs were introduced during the trial in order to improve patient identification and recruitment. 516 patient were screened in 11 centres

    Period 1
    Period 1 title
    Overall trial (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator
    Blinding implementation details
    This was a multicentre double-blind randomised placebo-controlled trial. Patients were randomised to take one of two active treatments or one of two placebos. To reduce the amount of placebos the children would have to take, and improve recruitment and compliance the two placebo arms were then combined for the analysis, so that there were 3 groups. Patients were randomised centrally into one of three treatment arms.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Placebo
    Arm description
    		 1 alpha hydroxycholecalciferol and risedronate placebos
    Arm type
    		 Placebo

    Investigational medicinal product name
    Identical Placebo
    Investigational medicinal product code
    Other name
    Placebo
    Pharmaceutical forms
    Coated tablet, Oral liquid
    Routes of administration
    Oral use
    Dosage and administration details
    Matching placebo for Hydroxycholecalciferol or Risedronate

    Arm title
    		 1-Alphahydroxycholecalciferol
    Arm description
    		 1-Alphahydroxycholecalciferol 15ng/kg/day
    Arm type
    		 Experimental

    Investigational medicinal product name
    1-Alphahydroxycholecalciferol
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Oral liquid
    Routes of administration
    Oral use
    Dosage and administration details
    15ng/kg per day (max 1mg)

    Arm title
    		 Risedronate
    Arm description
    		 risedronate 1mg/kg for 15-30kg weekly risedronate >30kg, 35mg weekly
    Arm type
    		 Experimental

    Investigational medicinal product name
    Risedronate
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Chewable tablet
    Routes of administration
    Oral use
    Dosage and administration details
    15-30mg if <30kgs 35mg weekly if >30kgs

    Number of subjects in period 1
    		Placebo 1-Alphahydroxycholecalciferol Risedronate
    Started
    77
    71
    69
    Completed
    72
    67
    59
    Not completed
    5
    4
    10
         Patient receives other vitamin D supplements
    -
    -
    1
         Consent withdrawn by subject
    3
    2
    5
         Adverse event, non-fatal
    -
    -
    2
         Cannot get time off
    -
    -
    1
         Migrated to another country
    1
    -
    -
         Protocol deviation
    1
    2
    1

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 1 alpha hydroxycholecalciferol and risedronate placebos

    Reporting group title
    1-Alphahydroxycholecalciferol
    Reporting group description
    		 1-Alphahydroxycholecalciferol 15ng/kg/day

    Reporting group title
    Risedronate
    Reporting group description
    		 risedronate 1mg/kg for 15-30kg weekly risedronate >30kg, 35mg weekly

    Reporting group values
    		 Placebo 1-Alphahydroxycholecalciferol Risedronate Total
    Number of subjects
    		 77 71 69 217
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0 0
        Newborns (0-27 days)
    		 0 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0 0
        Children (2-11 years)
    		 34 26 28 88
        Adolescents (12-17 years)
    		 43 45 41 129
        Adults (18-64 years)
    		 0 0 0 0
        From 65-84 years
    		 0 0 0 0
        85 years and over
    		 0 0 0 0
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 12.1 ± 3.5 12.1 ± 3.7 12.0 ± 3.4 -
    Gender categorical
    Units: Subjects
        Female
    		 55 48 53 156
        Male
    		 22 23 16 61
    Steroid dose
    Units: Subjects
        <= 0.2 mg/kg
    		 37 30 32 99
        > 0.2 mg/kg
    		 40 41 37 118
    Ethnic origin
    Units: Subjects
        Caucasian
    		 59 54 55 168
        Black
    		 4 4 6 14
        Oriental
    		 0 1 0 1
        Asian
    		 11 10 6 27
        Other
    		 3 2 2 7
    Relevant medical conditions
    Units: Subjects
        Yes
    		 42 39 43 124
        No
    		 35 32 26 93
    Prior fracture history
    Units: Subjects
        Yes
    		 13 9 8 30
        No
    		 64 62 61 187
    Medication at baseline - DMARDS
    Units: Subjects
        Yes
    		 71 64 62 197
        No
    		 6 7 7 20
    Medication at baseline - Biologics
    Units: Subjects
        Yes
    		 8 17 7 32
        No
    		 69 54 62 185
    Disease group - JIA
    Units: Subjects
        Yes
    		 21 30 20 71
        No
    		 56 41 49 146
    Disease group - JSLE
    Units: Subjects
        Yes
    		 31 21 24 76
        No
    		 46 50 45 141
    Disease group - JDM
    Units: Subjects
        Yes
    		 17 13 16 46
        No
    		 60 58 53 171
    Disease group - Vasculitis
    Units: Subjects
        Yes
    		 11 12 13 36
        No
    		 66 59 56 181
    Tanner score
    Units: score
        median (inter-quartile range (Q1-Q3))
    		 2 (1 to 4) 2 (1 to 4) 2 (1 to 3) -
    Cumulative Steroid dose
    Units: mg/kg
        arithmetic mean (standard deviation)
    		 8403.7 ± 9206.9 9108.7 ± 7528.0 8090.4 ± 9390.1 -

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 1 alpha hydroxycholecalciferol and risedronate placebos

    Reporting group title
    1-Alphahydroxycholecalciferol
    Reporting group description
    		 1-Alphahydroxycholecalciferol 15ng/kg/day

    Reporting group title
    Risedronate
    Reporting group description
    		 risedronate 1mg/kg for 15-30kg weekly risedronate >30kg, 35mg weekly

    Primary: Lumbar Spine Bone Mineral Density

    		 Close Top of page
    End point title
    		 Lumbar Spine Bone Mineral Density
    End point description
    The change from baseline to year 1 was calculated and the difference between the three groups were compared using analysis of variance.
    End point type
    Primary
    End point timeframe
    Baseline to Year 1
    End point values
    		 Placebo 1-Alphahydroxycholecalciferol Risedronate
    Number of subjects analysed
    72
    67
    58
    Units: gram(s)/square centimeter
        arithmetic mean (standard deviation)
    0.034 ± 0.047
    0.031 ± 0.052
    0.069 ± 0.057
    Statistical analysis title
    		 Lumbar Spine BMD - ANOVA
    Comparison groups
    Risedronate v 1-Alphahydroxycholecalciferol v Placebo
    Number of subjects included in analysis
    197
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0001
    Method
    		 ANOVA
    Confidence interval

    Primary: Lumbar Spine Bone Mineral Density (Z Score)

    		 Close Top of page
    End point title
    		 Lumbar Spine Bone Mineral Density (Z Score)
    End point description
    The change from baseline to year 1 was calculated and the difference between the three groups were compared using analysis of variance technique.
    End point type
    Primary
    End point timeframe
    Change from Baseline to year 1
    End point values
    		 Placebo 1-Alphahydroxycholecalciferol Risedronate
    Number of subjects analysed
    72
    64
    56
    Units: gram(s)/square meter
        arithmetic mean (standard deviation)
    -0.036 ± 0.435
    -0.109 ± 0.516
    0.229 ± 0.556
    Statistical analysis title
    		 Lumbar Spine BMD (Z Score) - ANOVA
    Statistical analysis description
    Analysis of variance (ANOVA)
    Comparison groups
    Risedronate v 1-Alphahydroxycholecalciferol v Placebo
    Number of subjects included in analysis
    192
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0008
    Method
    		 ANOVA
    Confidence interval

    Primary: Total Body Bone Mineral Density

    		 Close Top of page
    End point title
    		 Total Body Bone Mineral Density
    End point description
    The change from baseline and year 1 was calculated and the difference between groups were compared using analysis of variance.
    End point type
    Primary
    End point timeframe
    The change from baseline to year 1
    End point values
    		 Placebo 1-Alphahydroxycholecalciferol Risedronate
    Number of subjects analysed
    70
    65
    59
    Units: gram(s)/square centimeter
        arithmetic mean (standard deviation)
    0.016 ± 0.032
    0.029 ± 0.034
    0.040 ± 0.030
    Statistical analysis title
    		 Total Body BMD - ANOVA
    Comparison groups
    Risedronate v 1-Alphahydroxycholecalciferol v Placebo
    Number of subjects included in analysis
    194
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0001
    Method
    		 ANOVA
    Confidence interval

    Primary: Total Body Bone Mineral Density (Z Score)

    		 Close Top of page
    End point title
    		 Total Body Bone Mineral Density (Z Score)
    End point description
    The change from baseline and year 1 was calculated and the difference between groups were compared using analysis of variance.
    End point type
    Primary
    End point timeframe
    The change from baseline to year 1
    End point values
    		 Placebo 1-Alphahydroxycholecalciferol Risedronate
    Number of subjects analysed
    70
    62
    57
    Units: gram(s)/square centimeter
        arithmetic mean (standard deviation)
    -0.129 ± 0.458
    -0.052 ± 0.403
    0.151 ± 0.409
    Statistical analysis title
    		 Total Body BMD (Z Score) - ANOVA
    Comparison groups
    Risedronate v 1-Alphahydroxycholecalciferol v Placebo
    Number of subjects included in analysis
    189
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0011
    Method
    		 ANOVA
    Confidence interval

    Secondary: Fracture rate

    		 Close Top of page
    End point title
    		 Fracture rate
    End point description
    End point type
    Secondary
    End point timeframe
    Year 1
    End point values
    		 Placebo 1-Alphahydroxycholecalciferol Risedronate
    Number of subjects analysed
    76
    71
    68
    Units: Percentage
    4
    2
    5
    Statistical analysis title
    		 Secondary outcome analysis
    Comparison groups
    Placebo v 1-Alphahydroxycholecalciferol v Risedronate
    Number of subjects included in analysis
    215
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.51
    Method
    		 Fisher's exact test
    Confidence interval

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    Adverse event data was captured at each patient visit and serious adverse events was to be reported within 24 hours.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 NA
    Dictionary version
    NA
    Reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 -

    Reporting group title
    One-alpha
    Reporting group description
    		 -

    Reporting group title
    Risedronate
    Reporting group description
    		 -

    Serious adverse events
    		 Placebo One-alpha Risedronate
    Total subjects affected by serious adverse events
         subjects affected / exposed
    18 / 77 (23.38%)
    14 / 71 (19.72%)
    21 / 69 (30.43%)
         number of deaths (all causes)
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    Injury, poisoning and procedural complications
    Trauma
         subjects affected / exposed
    0 / 77 (0.00%)
    2 / 71 (2.82%)
    1 / 69 (1.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Headache
         subjects affected / exposed
    2 / 77 (2.60%)
    0 / 71 (0.00%)
    0 / 69 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Biochemistry
         subjects affected / exposed
    1 / 77 (1.30%)
    0 / 71 (0.00%)
    1 / 69 (1.45%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Haematology test
         subjects affected / exposed
    1 / 77 (1.30%)
    0 / 71 (0.00%)
    2 / 69 (2.90%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    MAS
         subjects affected / exposed
    0 / 77 (0.00%)
    0 / 71 (0.00%)
    1 / 69 (1.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    0 / 77 (0.00%)
    0 / 71 (0.00%)
    1 / 69 (1.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Weakness
         subjects affected / exposed
    2 / 77 (2.60%)
    1 / 71 (1.41%)
    0 / 69 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Eye disorders
    Raised IoP
         subjects affected / exposed
    1 / 77 (1.30%)
    0 / 71 (0.00%)
    0 / 69 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 71 (1.41%)
    0 / 69 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    2 / 77 (2.60%)
    0 / 71 (0.00%)
    0 / 69 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatosplenomegaly
         subjects affected / exposed
    0 / 77 (0.00%)
    0 / 71 (0.00%)
    1 / 69 (1.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nausea and Vomiting
         subjects affected / exposed
    2 / 77 (2.60%)
    0 / 71 (0.00%)
    2 / 69 (2.90%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Pleural effusion
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 71 (1.41%)
    0 / 69 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Ingrowing nail
         subjects affected / exposed
    0 / 77 (0.00%)
    0 / 71 (0.00%)
    1 / 69 (1.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Rash
         subjects affected / exposed
    0 / 77 (0.00%)
    0 / 71 (0.00%)
    3 / 69 (4.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    GUT
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 71 (1.41%)
    0 / 69 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hematuria
         subjects affected / exposed
    0 / 77 (0.00%)
    0 / 71 (0.00%)
    1 / 69 (1.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Fracture
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 71 (1.41%)
    0 / 69 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Arthralgia
         subjects affected / exposed
    1 / 77 (1.30%)
    0 / 71 (0.00%)
    3 / 69 (4.35%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Arthritis
         subjects affected / exposed
    2 / 77 (2.60%)
    0 / 71 (0.00%)
    0 / 69 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Disease flare
         subjects affected / exposed
    4 / 77 (5.19%)
    8 / 71 (11.27%)
    5 / 69 (7.25%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 9
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Disease progression
         subjects affected / exposed
    0 / 77 (0.00%)
    0 / 71 (0.00%)
    1 / 69 (1.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Enthesitis
         subjects affected / exposed
    0 / 77 (0.00%)
    0 / 71 (0.00%)
    1 / 69 (1.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Reflex Sympathetic Dystrophy
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 71 (1.41%)
    0 / 69 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Fever
         subjects affected / exposed
    0 / 77 (0.00%)
    0 / 71 (0.00%)
    1 / 69 (1.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infection
         subjects affected / exposed
    1 / 77 (1.30%)
    5 / 71 (7.04%)
    0 / 69 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 5
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Fungal infection
         subjects affected / exposed
    0 / 77 (0.00%)
    0 / 71 (0.00%)
    1 / 69 (1.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bacterial Infection
         subjects affected / exposed
    2 / 77 (2.60%)
    1 / 71 (1.41%)
    2 / 69 (2.90%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Viral Infection
         subjects affected / exposed
    3 / 77 (3.90%)
    0 / 71 (0.00%)
    3 / 69 (4.35%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Upper Respiratory Tract Infection
         subjects affected / exposed
    1 / 77 (1.30%)
    1 / 71 (1.41%)
    0 / 69 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    		 Placebo One-alpha Risedronate
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    60 / 77 (77.92%)
    55 / 71 (77.46%)
    57 / 69 (82.61%)
    Vascular disorders
    Depression
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 71 (1.41%)
    1 / 69 (1.45%)
         occurrences all number
    0
    1
    1
    General disorders and administration site conditions
    Allergic reaction
         subjects affected / exposed
    1 / 77 (1.30%)
    1 / 71 (1.41%)
    0 / 69 (0.00%)
         occurrences all number
    1
    1
    0
    Allergy
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 71 (1.41%)
    0 / 69 (0.00%)
         occurrences all number
    0
    1
    0
    Fatigue
         subjects affected / exposed
    5 / 77 (6.49%)
    1 / 71 (1.41%)
    1 / 69 (1.45%)
         occurrences all number
    5
    1
    3
    Fever
         subjects affected / exposed
    3 / 77 (3.90%)
    1 / 71 (1.41%)
    0 / 69 (0.00%)
         occurrences all number
    3
    1
    0
    Lethargy
         subjects affected / exposed
    2 / 77 (2.60%)
    4 / 71 (5.63%)
    2 / 69 (2.90%)
         occurrences all number
    2
    4
    2
    Pyrexia
         subjects affected / exposed
    2 / 77 (2.60%)
    0 / 71 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    2
    0
    0
    Weakness
         subjects affected / exposed
    2 / 77 (2.60%)
    0 / 71 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    2
    0
    1
    Respiratory, thoracic and mediastinal disorders
    Respiratory sob
         subjects affected / exposed
    1 / 77 (1.30%)
    0 / 71 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    1
    0
    0
    Psychiatric disorders
    Hyperventilation
         subjects affected / exposed
    0 / 77 (0.00%)
    0 / 71 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    1
    Injury, poisoning and procedural complications
    Fracture
         subjects affected / exposed
    5 / 77 (6.49%)
    2 / 71 (2.82%)
    4 / 69 (5.80%)
         occurrences all number
    6
    2
    5
    Overdose
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 71 (1.41%)
    0 / 69 (0.00%)
         occurrences all number
    0
    1
    0
    Cardiac disorders
    Hypertension
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 71 (1.41%)
    0 / 69 (0.00%)
         occurrences all number
    0
    1
    0
    Oedema
         subjects affected / exposed
    1 / 77 (1.30%)
    0 / 71 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    1
    0
    0
    Raynaud's phenomenon
         subjects affected / exposed
    0 / 77 (0.00%)
    0 / 71 (0.00%)
    2 / 69 (2.90%)
         occurrences all number
    0
    0
    2
    Vasculitis
         subjects affected / exposed
    1 / 77 (1.30%)
    0 / 71 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    1
    0
    0
    Epislaxis
         subjects affected / exposed
    4 / 77 (5.19%)
    0 / 71 (0.00%)
    3 / 69 (4.35%)
         occurrences all number
    4
    0
    3
    Nervous system disorders
    Central nervous system
         subjects affected / exposed
    3 / 77 (3.90%)
    2 / 71 (2.82%)
    2 / 69 (2.90%)
         occurrences all number
    7
    2
    2
    Headache
         subjects affected / exposed
    21 / 77 (27.27%)
    12 / 71 (16.90%)
    15 / 69 (21.74%)
         occurrences all number
    28
    16
    23
    Seizure
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 71 (1.41%)
    0 / 69 (0.00%)
         occurrences all number
    0
    1
    0
    Syncope
         subjects affected / exposed
    0 / 77 (0.00%)
    0 / 71 (0.00%)
    2 / 69 (2.90%)
         occurrences all number
    0
    0
    3
    Tremor
         subjects affected / exposed
    2 / 77 (2.60%)
    0 / 71 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    2
    0
    0
    Insomnia
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 71 (1.41%)
    0 / 69 (0.00%)
         occurrences all number
    0
    1
    0
    Blood and lymphatic system disorders
    Biochemistry
         subjects affected / exposed
    4 / 77 (5.19%)
    2 / 71 (2.82%)
    6 / 69 (8.70%)
         occurrences all number
    5
    3
    6
    Haematology test abnormal
         subjects affected / exposed
    1 / 77 (1.30%)
    1 / 71 (1.41%)
    2 / 69 (2.90%)
         occurrences all number
    1
    1
    2
    Enlarged thymus
         subjects affected / exposed
    1 / 77 (1.30%)
    0 / 71 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    1
    0
    0
    Lymphadenopathy
         subjects affected / exposed
    0 / 77 (0.00%)
    0 / 71 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    1
    Eye disorders
    Eye damage
         subjects affected / exposed
    1 / 77 (1.30%)
    0 / 71 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    2
    0
    0
    Eye damage/Pathology
         subjects affected / exposed
    1 / 77 (1.30%)
    0 / 71 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    1
    0
    0
    Eyes
         subjects affected / exposed
    1 / 77 (1.30%)
    0 / 71 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    1
    0
    0
    Raised lop
         subjects affected / exposed
    1 / 77 (1.30%)
    0 / 71 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    1
    0
    0
    Uveitis
         subjects affected / exposed
    0 / 77 (0.00%)
    2 / 71 (2.82%)
    0 / 69 (0.00%)
         occurrences all number
    0
    2
    0
    Gastrointestinal disorders
    Abdominal Pain
         subjects affected / exposed
    13 / 77 (16.88%)
    9 / 71 (12.68%)
    12 / 69 (17.39%)
         occurrences all number
    15
    9
    13
    Anorexia
         subjects affected / exposed
    1 / 77 (1.30%)
    0 / 71 (0.00%)
    2 / 69 (2.90%)
         occurrences all number
    1
    0
    2
    Constipation
         subjects affected / exposed
    3 / 77 (3.90%)
    2 / 71 (2.82%)
    2 / 69 (2.90%)
         occurrences all number
    3
    2
    2
    Diarrhoea
         subjects affected / exposed
    5 / 77 (6.49%)
    5 / 71 (7.04%)
    2 / 69 (2.90%)
         occurrences all number
    6
    8
    3
    Gastritis
         subjects affected / exposed
    2 / 77 (2.60%)
    2 / 71 (2.82%)
    1 / 69 (1.45%)
         occurrences all number
    2
    2
    1
    GI upset
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 71 (1.41%)
    2 / 69 (2.90%)
         occurrences all number
    0
    1
    3
    GIT
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 71 (1.41%)
    0 / 69 (0.00%)
         occurrences all number
    0
    1
    0
    Mouth
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 71 (1.41%)
    1 / 69 (1.45%)
         occurrences all number
    0
    1
    1
    Mouth ulceration
         subjects affected / exposed
    1 / 77 (1.30%)
    2 / 71 (2.82%)
    2 / 69 (2.90%)
         occurrences all number
    1
    2
    2
    Nausea
         subjects affected / exposed
    5 / 77 (6.49%)
    1 / 71 (1.41%)
    4 / 69 (5.80%)
         occurrences all number
    5
    1
    4
    Nausea and Vomiting
         subjects affected / exposed
    9 / 77 (11.69%)
    4 / 71 (5.63%)
    6 / 69 (8.70%)
         occurrences all number
    10
    4
    7
    Mouth pain
         subjects affected / exposed
    0 / 77 (0.00%)
    0 / 71 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    1
    Vomiting
         subjects affected / exposed
    0 / 77 (0.00%)
    0 / 71 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    1
    Weight Gain
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 71 (1.41%)
    0 / 69 (0.00%)
         occurrences all number
    0
    1
    0
    Skin and subcutaneous tissue disorders
    Alopecia
         subjects affected / exposed
    0 / 77 (0.00%)
    2 / 71 (2.82%)
    1 / 69 (1.45%)
         occurrences all number
    0
    2
    1
    Bruising
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 71 (1.41%)
    2 / 69 (2.90%)
         occurrences all number
    0
    1
    2
    Calcinosis
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 71 (1.41%)
    0 / 69 (0.00%)
         occurrences all number
    0
    3
    0
    Itching
         subjects affected / exposed
    2 / 77 (2.60%)
    1 / 71 (1.41%)
    1 / 69 (1.45%)
         occurrences all number
    2
    1
    1
    Pigmentation
         subjects affected / exposed
    0 / 77 (0.00%)
    0 / 71 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    1
    Rash
         subjects affected / exposed
    6 / 77 (7.79%)
    13 / 71 (18.31%)
    5 / 69 (7.25%)
         occurrences all number
    8
    16
    6
    Skin abnormality
         subjects affected / exposed
    1 / 77 (1.30%)
    0 / 71 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    1
    0
    2
    Skin lesion
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 71 (1.41%)
    1 / 69 (1.45%)
         occurrences all number
    0
    1
    2
    Renal and urinary disorders
    Dysuria
         subjects affected / exposed
    1 / 77 (1.30%)
    0 / 71 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    1
    0
    0
    Haematuria
         subjects affected / exposed
    2 / 77 (2.60%)
    0 / 71 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    3
    0
    1
    Nephritis
         subjects affected / exposed
    0 / 77 (0.00%)
    0 / 71 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    1
    Proteinuria
         subjects affected / exposed
    1 / 77 (1.30%)
    1 / 71 (1.41%)
    1 / 69 (1.45%)
         occurrences all number
    1
    1
    1
    Testicular torsion
         subjects affected / exposed
    1 / 77 (1.30%)
    0 / 71 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    1
    0
    0
    Urinary
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 71 (1.41%)
    0 / 69 (0.00%)
         occurrences all number
    0
    1
    0
    BXO
         subjects affected / exposed
    0 / 77 (0.00%)
    0 / 71 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    1
    Pain
         subjects affected / exposed
    0 / 77 (0.00%)
    0 / 71 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    1
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    16 / 77 (20.78%)
    16 / 71 (22.54%)
    18 / 69 (26.09%)
         occurrences all number
    27
    32
    23
    Arthritis
         subjects affected / exposed
    6 / 77 (7.79%)
    10 / 71 (14.08%)
    6 / 69 (8.70%)
         occurrences all number
    8
    13
    10
    Bone pain
         subjects affected / exposed
    0 / 77 (0.00%)
    0 / 71 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    1
    Decreased movement
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 71 (1.41%)
    1 / 69 (1.45%)
         occurrences all number
    0
    2
    1
    Inflammation
         subjects affected / exposed
    0 / 77 (0.00%)
    0 / 71 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    1
    Muscle spasm
         subjects affected / exposed
    1 / 77 (1.30%)
    1 / 71 (1.41%)
    0 / 69 (0.00%)
         occurrences all number
    1
    1
    0
    Myalgia
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 71 (1.41%)
    0 / 69 (0.00%)
         occurrences all number
    0
    1
    0
    Tendinitis
         subjects affected / exposed
    0 / 77 (0.00%)
    0 / 71 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    1
    Infections and infestations
    Conjuctivitis
         subjects affected / exposed
    1 / 77 (1.30%)
    0 / 71 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    1
    0
    0
    Infection
         subjects affected / exposed
    24 / 77 (31.17%)
    19 / 71 (26.76%)
    21 / 69 (30.43%)
         occurrences all number
    37
    27
    35
    Fungal infection
         subjects affected / exposed
    3 / 77 (3.90%)
    1 / 71 (1.41%)
    1 / 69 (1.45%)
         occurrences all number
    3
    1
    1
    Bacterial infection
         subjects affected / exposed
    3 / 77 (3.90%)
    5 / 71 (7.04%)
    6 / 69 (8.70%)
         occurrences all number
    3
    5
    6
    Skin infection
         subjects affected / exposed
    0 / 77 (0.00%)
    0 / 71 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    1
    Viral infection
         subjects affected / exposed
    17 / 77 (22.08%)
    18 / 71 (25.35%)
    19 / 69 (27.54%)
         occurrences all number
    25
    26
    24
    Upper respiratory tract infection
         subjects affected / exposed
    17 / 77 (22.08%)
    10 / 71 (14.08%)
    14 / 69 (20.29%)
         occurrences all number
    21
    11
    16

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    05 Feb 2007
    Protocol amendment V4.0: Ethics reference corrected. Contact page updated to include new trial statistician and specification of PI at a site. Trial interventions paragraph update for dose for sub groups <30kgs and inclusion of patient support networks as a recruitment source. Administrative amends to table of contents, abbreviations, revision to allow for clearer instructions and addition of appendices. Schedule of events includes exact requirement and time points for conduct events. Treatment schedule update for clarification. Concomitant treatment allowed – inclusion of immunosuppressant’s point. Revision of section to include changes to clinical measures. X-rays will be read chronologically. Adverse reporting will end 3 months after stopping study medication. Assessment of causality has been added. 15 years has been added as the recommended time to retain records. Updates to Patient Information Sheets, Parent and Patient Information Sheets and consent form.
    27 Feb 2007
    Protocol amendment V5.0. Addition of 2 PIs. Updates to Patient Information Sheets, Parent and Patient Information Sheets and consent form.
    19 Jul 2007
    Protocol amendment V5.1: Contact page updated to include new trial statistician and 2 PIs. Additional point giving permission for any sample remaining after genetic studies carried out to be stored and sued for future research purposes only, into rheumatic diseases in children and adolescents. Updates to Patient Information Sheets, Parent and Patient Information Sheets.
    15 Dec 2008
    Protocol amendment V5.2: Addition of new PI and site and removal of PI. PI working on 2 sites and another PI seeking approval to recruit from her second hospital. Change of Trial Coordinator surname. Inclusion of ‘2.5 years’ for methodology and study duration ‘at each centre’.
    20 Jan 2010
    Change of sponsor to the Belfast Health and Social Care Trust.
    01 Jun 2010
    Protocol amendment V6.0: The required sample size initially was 270 children. In order to detect an improvement between the treatment groups of 6.25 and between the treatment groups and the control groups of 6.25, using a SD of 12.5 (observed in our 1 year growth hormone study), recruitment of 75 children in each of the three study arms offers 80% power to detect a significant difference at the 5% level of significance, allowing for a 15% dropout rate. It was further expected that approximately 20% of this population will not receive steroids for one year. Thus to ensure that an adequate number of children do complete the study on steroids will require 90 children per treatment group; a total of 270. However following interim analysis the dropout rate was ~ 8% and there were no reports of patients being taken off steroids very early in the study. Taking a conservative position it was estimated that the dropout rate would be 10%. This would imply an overall recruitment target of 216 patients. A protocol amendment was therefore requested and obtained.

    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

    Online references
    http://www.ncbi.nlm.nih.gov/pubmed/31388666
    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 Apr 26 06:35:52 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA