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   43857   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:
    Allopurinol as a possible new therapy for acute coronary syndromes: The Next Steps

    Summary
    EudraCT number
    		 2011-004996-35
    Trial protocol
    		 GB  
    Global end of trial date
    13 Mar 2015

    Results information
    Results version number
    		 v1(current)
    This version publication date
    10 Jul 2016
    First version publication date
    10 Jul 2016
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    2010CV30
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT01457820
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    University of Dundee/NHS Tayside
    Sponsor organisation address
    Tayside Medical Science Centre, Dundee, United Kingdom, DD1 9SY
    Public contact
    Catrina Forde, University of Dundee, 44 1382 383890, c.forde@dundee.ac.uk
    Scientific contact
    Catrina Forde, University of Dundee, 44 1382 383890, c.forde@dundee.ac.uk
    Sponsor organisation name
    University of Dundee/NHS Tayside
    Sponsor organisation address
    Tayside Medical Science Centre, Dundee, United Kingdom, DD1 9SY
    Public contact
    Catrina Forde, University of Dundee, 44 1382 383890, c.forde@dundee.ac.uk
    Scientific contact
    Catrina Forde, University of Dundee, 44 1382 383890, c.forde@dundee.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
    21 Mar 2016
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    13 Mar 2015
    Global end of trial reached?
    Yes
    Global end of trial date
    13 Mar 2015
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The principal research question is: To establish how quickly giving a dose of allopurinol alters the time it takes for exercise to produce ST depression in the ECG. The overall design was to study patients with chronic stable angina (CSA) who develop ST depression on exercise, to examine time to exercise induced ST depression and in particular the change in this endpoint induced by various different loading doses of allopurinol.
    Protection of trial subjects
    No measures specific to this trial.
    Background therapy
    		 Standard approved drugs for ischaemic heart disease.
    Evidence for comparator
    		 Previous evidence shows that allopurinol prolongs time to ST depression in patients with ischaemic heart disease. This effect agrees with experimental work where allopurinol clearly redcues oxygen consumption for any given stroke volume.
    Actual start date of recruitment
    01 May 2012
    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
    United Kingdom: 26
    Worldwide total number of subjects
    26
    EEA total number of subjects
    26
    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)
    5
    From 65 to 84 years
    21
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 Recruitment was active between May 2012 to August 2014. A total of 133 participants were assessed for eligibility and consented for this study. 26 subjects were randomised from the 133 consented, 5 of this number dropped out prior to the end of the study.

    Pre-assignment
    Screening details
    		 Patients attended for ETT. Patients with ECG changes were invited back for a second ETT and if timing of ECG changes were within a given range they were recruited. If not, a 3rd ETT was performed and if changes consistent they could be recruited. patients without ECG changes or with changes not consistent in onset were not recruited.

    Pre-assignment period milestones
    Number of subjects started
    		 26
    Number of subjects completed
    		 26

    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, Monitor, Data analyst
    Blinding implementation details
    Double blind medication (allopurinol or placebo) was prepared and packaged by Tayside Pharmaceuticals. The medication was labeled as "participant 1", "participant 2", etc. and distributed to the participant by the research fellow according to their sequence number. randomization was carried out By Tayside Pharmaceuticals using block randomization in eleven groups of six ( with three active/placebo in each block ). They used a validated randomization program and this was securely backed up.

    Arms
    Are arms mutually exclusive
    No

    Arm title
    		 Arm 1
    Arm description
    		 IMP/Placebo Each treatment consisted of a single loading dose, either Placebo, 400mg Allopurinol or 800mg Allopurinol. This was followed by a reduced BD dose for a period of 5 days.
    Arm type
    		 either placebo or IMP

    Investigational medicinal product name
    Allopurinol
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Loading dose either placebo, 400mg or 800mg. If 400mg loading dose, followed by BD 300mg for 5 days If 800mg loading dose, followed by BD 400mg for 5 days Each treatment period followed by a 1 week washout period minimum.

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    The placebo and active tablet were visually identical.

    Arm title
    		 Arm 2
    Arm description
    		 IMP/Placebo Each treatment consisted of a single loading dose, either Placebo, 400mg Allopurinol or... more 800mg Allopurinol. This was followed by a reduced BD dose for a period of 5 days.
    Arm type
    		 IMP or placebo

    Investigational medicinal product name
    Allopurinol
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Loading dose either placebo, 400mg or 800mg. If 400mg loading dose, followed by BD 300mg for 5 days If 800mg loading dose, followed by BD 400mg for 5 days Each treatment period followed by a 1 week washout period minimum.

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Placebo and IMP were visually identical

    Arm title
    		 Arm 3
    Arm description
    		 IMP/Placebo Each treatment consisted of a single loading dose, either Placebo, 400mg Allopurinol or... more 800mg Allopurinol. This was followed by a reduced BD dose for a period of 5 days.
    Arm type
    		 IMP/placebo

    Investigational medicinal product name
    Allopurinol
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Loading dose either placebo, 400mg or 800mg. If 400mg loading dose, followed by BD 300mg for 5 days If 800mg loading dose, followed by BD 400mg for 5 days Each treatment period followed by a 1 week washout period minimum.

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Placebo and IMP were visually identical

    Number of subjects in period 1
    		Arm 1 Arm 2 Arm 3
    Started
    26
    21
    21
    Completed
    26
    21
    21

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Overall Trial
    Reporting group description
    		 -

    Reporting group values
    		 Overall Trial Total
    Number of subjects
    		 26 26
    Age categorical
    Units: Subjects
        In utero
    		 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0
        Newborns (0-27 days)
    		 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0
        Children (2-11 years)
    		 0 0
        Adolescents (12-17 years)
    		 0 0
        Adults (18-64 years)
    		 5 5
        From 65-84 years
    		 21 21
        85 years and over
    		 0 0
    Gender categorical
    Units: Subjects
        Female
    		 6 6
        Male
    		 20 20
    Subject analysis sets

    Subject analysis set title
    Intention -to-treat
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    If a subject is non compliant theyare encouraged to become compliant. If they persist it is intended to have them remain in the study , not on study medication, in order to do an "intention to treat" analysis.

    Subject analysis sets values
    		 Intention -to-treat
    Number of subjects
    26
    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)
    5
        From 65-84 years
    21
        85 years and over
    0
    Age continuous
    Units:
        
    ±
    Gender categorical
    Units: Subjects
        Female
    6
        Male
    20

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Arm 1
    Reporting group description
    		 IMP/Placebo Each treatment consisted of a single loading dose, either Placebo, 400mg Allopurinol or 800mg Allopurinol. This was followed by a reduced BD dose for a period of 5 days.

    Reporting group title
    Arm 2
    Reporting group description
    		 IMP/Placebo Each treatment consisted of a single loading dose, either Placebo, 400mg Allopurinol or... more 800mg Allopurinol. This was followed by a reduced BD dose for a period of 5 days.

    Reporting group title
    Arm 3
    Reporting group description
    		 IMP/Placebo Each treatment consisted of a single loading dose, either Placebo, 400mg Allopurinol or... more 800mg Allopurinol. This was followed by a reduced BD dose for a period of 5 days.

    Subject analysis set title
    Intention -to-treat
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    If a subject is non compliant theyare encouraged to become compliant. If they persist it is intended to have them remain in the study , not on study medication, in order to do an "intention to treat" analysis.

    Primary: Time to ST depression on ETT

    		 Close Top of page
    End point title
    		 Time to ST depression on ETT
    End point description
    Subject would start on the ETT using the Bruce protocol. ETT would finish either when subject asked to stop, Blood pressure became too elevated, clinician stopped the test.
    End point type
    Primary
    End point timeframe
    From beginning of ETT
    End point values
    		 Arm 1 Arm 2 Arm 3 Intention -to-treat
    Number of subjects analysed
    26
    21
    21
    26
    Units: seconds and minutes
    331
    353
    358
    331
    Statistical analysis title
    		 Multi level model
    Statistical analysis description
    A multi level model of Mills was used.
    Comparison groups
    Arm 1 v Arm 2 v Arm 3
    Number of subjects included in analysis
    68
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [1]
    Method
    Parameter type
    		 Multi level model
    Point estimate
    -4.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -22.6
         upper limit
    		 13.4
    Variability estimate
    Standard error of the mean
    Notes
    [1] - None

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    Duration of time participant spent in study.
    Adverse event reporting additional description
    Participants were instructed to contact the investigator at any time after consenting to join the study if any symptoms developed. All AEs were recorded in detail in the subject CRF and in an AE log. The investigator initiated appropriate treatment according to their medical judgment. Unresolved AEs at study end followed up.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    18
    Reporting groups
    Reporting group title
    Overall trial
    Reporting group description
    		 -

    Serious adverse events
    		 Overall trial
    Total subjects affected by serious adverse events
         subjects affected / exposed
    1 / 26 (3.85%)
         number of deaths (all causes)
    0
         number of deaths resulting from adverse events
    0
    Cardiac disorders
    Hypotension
    Additional description: Collapse (due to hypotension) post loading dose
         subjects affected / exposed
    1 / 26 (3.85%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    		 Overall trial
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    8 / 26 (30.77%)
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    1 / 26 (3.85%)
         occurrences all number
    1
    Dyspepsia
         subjects affected / exposed
    1 / 26 (3.85%)
         occurrences all number
    1
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    1 / 26 (3.85%)
         occurrences all number
    1
    Skin and subcutaneous tissue disorders
    Rash
         subjects affected / exposed
    1 / 26 (3.85%)
         occurrences all number
    2
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    1 / 26 (3.85%)
         occurrences all number
    1
    Pain in jaw
         subjects affected / exposed
    1 / 26 (3.85%)
         occurrences all number
    1
    Infections and infestations
    Influenza
         subjects affected / exposed
    1 / 26 (3.85%)
         occurrences all number
    1
    Urinary tract infection
         subjects affected / exposed
    1 / 26 (3.85%)
         occurrences all number
    1

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    10 Jul 2012
    Consent form version change to V.3 Participation information sheet version change to V.3 Protocol version change to V.2
    16 Nov 2012
    Protocol version change to V.3
    11 Dec 2012
    Protocol version change to V.4
    04 Apr 2013
    Consent form version change to V.3
    17 Oct 2013
    Additional sites added

    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.
    Study terminated early due to difficulties recruiting .
    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 Apr 25 03:37:26 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA