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    Clinical Trial Results:
    Improving understanding of Heroin Overdose Testing: diamorphine dose-escalation testing in a treated population

    Summary
    EudraCT number
    		 2016-001877-34
    Trial protocol
    		 GB  
    Global end of trial date
    11 Mar 2022

    Results information
    Results version number
    		 v1(current)
    This version publication date
    07 Aug 2025
    First version publication date
    07 Aug 2025
    Other versions
    Summary report(s)
    		 CSR Hot-Treated

    Trial information

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    Trial identification
    Sponsor protocol code
    Hot-Treated
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 -
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    South London and Maudsley NHS Foundation Trust
    Sponsor organisation address
    Denmark Hill, London, United Kingdom, SE5 8AZ
    Public contact
    Professor John Strang, South London and Maudsley NHS Foundation Trust, 44 02078480438, john.strang@kcl.ac.uk
    Scientific contact
    Professor John Strang, South London and Maudsley NHS Foundation Trust, 44 02078480438, john.strang@kcl.ac.uk
    Sponsor organisation name
    King's College London
    Sponsor organisation address
    The Strand, London, United Kingdom, WC2R 2LS
    Public contact
    Professor John Strang, King's College London, 44 02078480438, john.strang@kcl.ac.uk
    Scientific contact
    Professor John Strang, King's College London, 44 02078480438, john.strang@kcl.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
    26 Nov 2024
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    11 Mar 2022
    Global end of trial reached?
    Yes
    Global end of trial date
    11 Mar 2022
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    To investigate respiratory depression and hypoxaemic response to intravenous (IV) or intramuscular (IM) higher-than-regular doses of heroin as a marker for overdose
    Protection of trial subjects
    Participants have the right to withdraw from the study at any time for any reason. The investigator also has the right to withdraw patients from the study drug in the event of inter-current illness, AEs, SAEs, SUSARs, protocol violations, cure, administrative reasons or other reasons. It is understood by all concerned that an excessive rate of withdrawals can render the study uninterpretable; therefore, unnecessary withdrawal of patients should be avoided. Should a patient decide to withdraw from the study, all efforts will be made to report the reason for withdrawal as thoroughly as possible and an assessment will be made by the clinical team as to whether follow-up is necessary (i.e. in case of any adverse events).
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    18 Apr 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: 4
    Worldwide total number of subjects
    4
    EEA total number of subjects
    4
    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)
    4
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 -

    Pre-assignment period milestones
    Number of subjects started
    		 5 [1]
    Number of subjects completed
    		 4

    Pre-assignment subject non-completion reasons
    Reason: Number of subjects
    		 Consent withdrawn by subject: 1
    Notes
    [1] - The number of subjects reported to have started the pre-assignment period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
    Justification: We do not count screened participants as enrolled.
    Period 1
    Period 1 title
    Overall Trial (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Non-randomised - controlled
    Blinding used
    		 Single blind
    Roles blinded
    		 Subject

    Arms
    Arm title
    		 Diamorphine Hydrochloride BP
    Arm description
    		 Diamorphine is a narcotic analgesic which acts primarily on the central nervous system and smooth muscle. Diamorphine has a more rapid onset of activity than morphine as the first metabolite, monoacetylmorphine, more readily crosses the blood brain barrier.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Diamorphine Hydrochloride BP
    Investigational medicinal product code
    SUB13557MIG
    Other name
    Pharmaceutical forms
    Powder for solution for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    100-500 mg per day Intravenously

    Number of subjects in period 1
    		Diamorphine Hydrochloride BP
    Started
    4
    Completed
    4

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Overall Trial
    Reporting group description
    		 -

    Reporting group values
    		 Overall Trial Total
    Number of subjects
    		 4 4
    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)
    		 3 3
        From 65-84 years
    		 1 1
        85 years and over
    		 0 0
    Gender categorical
    Units: Subjects
        Female
    		 0 0
        Male
    		 4 4

    End points

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    End points reporting groups
    Reporting group title
    Diamorphine Hydrochloride BP
    Reporting group description
    		 Diamorphine is a narcotic analgesic which acts primarily on the central nervous system and smooth muscle. Diamorphine has a more rapid onset of activity than morphine as the first metabolite, monoacetylmorphine, more readily crosses the blood brain barrier.

    Primary: Primary Endpoint - Blood Oxygen Saturation (SpO2)

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    End point title
    		 Primary Endpoint - Blood Oxygen Saturation (SpO2) [1]
    End point description
    End point type
    Primary
    End point timeframe
    All endpoints will be obtained by measurements taken during the study visits. (Trial lasting no longer than 9 months)
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Please see uploaded report
    End point values
    		 Diamorphine Hydrochloride BP
    Number of subjects analysed
    4
    Units: SpO2 (%)
        arithmetic mean (standard deviation)
    94.7 ( 1.9 )
    No statistical analyses for this end point

    Primary: Primary Endpoint - End-Tidal Carbon Dioxide

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    End point title
    		 Primary Endpoint - End-Tidal Carbon Dioxide [2]
    End point description
    End point type
    Primary
    End point timeframe
    All endpoints will be obtained by measurements taken during the study visits. (Trial lasting no longer than 9 months)
    Notes
    [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Please see uploaded report
    End point values
    		 Diamorphine Hydrochloride BP
    Number of subjects analysed
    4
    Units: CO2 (%)
        arithmetic mean (standard deviation)
    6.4 ( 0.5 )
    No statistical analyses for this end point

    Primary: Primary Endpoint - Transcutaneous Carbon Dioxide

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    End point title
    		 Primary Endpoint - Transcutaneous Carbon Dioxide [3]
    End point description
    End point type
    Primary
    End point timeframe
    All endpoints will be obtained by measurements taken during the study visits. (Trial lasting no longer than 9 months)
    Notes
    [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Please see uploaded report
    End point values
    		 Diamorphine Hydrochloride BP
    Number of subjects analysed
    4
    Units: TcCO2 (%)
        arithmetic mean (standard deviation)
    6.2 ( 0.4 )
    No statistical analyses for this end point

    Primary: Primary Endpoint - Intercostal parasternal electromyography to measure neural respiratory drive

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    End point title
    		 Primary Endpoint - Intercostal parasternal electromyography to measure neural respiratory drive [4]
    End point description
    End point type
    Primary
    End point timeframe
    All endpoints will be obtained by measurements taken during the study visits. (Trial lasting no longer than 9 months)
    Notes
    [4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Please see uploaded report
    End point values
    		 Diamorphine Hydrochloride BP
    Number of subjects analysed
    4
    Units: min-1
        arithmetic mean (standard deviation)
    90.1 ( 27.3 )
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    14/08/2018 - 28/02/2024
    Assessment type
    		 Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    21.0
    Reporting groups
    Reporting group title
    Diamorphine
    Reporting group description
    		 -

    Serious adverse events
    		 Diamorphine
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 4 (0.00%)
         number of deaths (all causes)
    0
         number of deaths resulting from adverse events
    0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    		 Diamorphine
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    1 / 4 (25.00%)
    General disorders and administration site conditions
    Injection site irritation
         subjects affected / exposed
    1 / 4 (25.00%)
         occurrences all number
    2

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    04 Aug 2017
    Protocol v1.3
    25 May 2018
    Protocol v1.4
    13 Mar 2019
    Protocol v1.5
    20 Sep 2019
    Protocol v1.6
    26 Mar 2021
    Protocol v1.7

    Interruptions (globally)
    Were there any global interruptions to the trial? Yes
    Date
    Interruption
    Restart date
    20 Mar 2020
    COVID-19 Pandemic
    29 Oct 2021

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    The study was terminated prematurely because of the dwindling number of patients in the UK on diamorphine for their heroin addiction treatment and also because of a diamorphine shortage which affected the few patients who were on that treatment.
    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.

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