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:
    PRE-EMPT: Preventing Recurrence of Endometriosis by Means of long acting Protestogen Therapy

    Summary
    EudraCT number
    		 2013-001984-21
    Trial protocol
    		 GB  
    Global end of trial date
    31 May 2023

    Results information
    Results version number
    		 v1(current)
    This version publication date
    14 Feb 2024
    First version publication date
    14 Feb 2024
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    3/013/13
    Additional study identifiers
    ISRCTN number
    		 ISRCTN97865475
    US NCT number
    		 -
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    University of Aberdeen and NHS Grampian
    Sponsor organisation address
    Aberdeen Royal Infirmary, Cornhill Road, Aberdeen , United Kingdom, AB25 2ZD
    Public contact
    Dr Gail Holland, University of Aberdeen & NHS Grampian, 44 01224 551123, G.Holland@abdn.ac.uk
    Scientific contact
    Dr Gail Holland, University of Aberdeen & NHS Grampian, 44 01224 551123, G.Holland@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
    31 May 2023
    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?
    No
    General information about the trial
    Main objective of the trial
    Main study principal objective: To compare, in women undergoing conservative surgery for pain due to endometriosis, the effectiveness of some or all of the following four post-surgical treatment options in controlling the recurrence of symptoms and improving quality of life: 1) no treatment 2) levonorgestrel-releasing intra-uterine System (LNG IUS) 3) three monthly depot medroxyprogesterone acetate injections (DMPA) 4) the combined oral contraceptive pill (COC), dependent on the groups carried forward from the pilot.
    Protection of trial subjects
    We ensure that all staff are GCP trained and will only grant access to allow staff at site to become involved in the trial if their GCP is in date. It is imperative that all investigators and staff at the sites have a thorough understanding of anticipated adverse events and the reporting process of these events as it is their responsibility to notify adverse events and SAE's to the Trial Office and for the Sponsor, or designated delegate, to report to the regulatory authority and ethics committee. The patient Information Sheet contained the details of the Patient Advice and Liaison Service (PALS) for the individual sites. The Data Monitoring & Ethics Committee (DMEC) are assigned to review overall safety and morbidity data to identify safety issues which may not be apparent on an individual case basis.
    Background therapy
    		 -
    Evidence for comparator
    		 Randomisation occurred either intra-operatively, or immediately post-operatively, according to the randomisation options and the intention of the investigator. The stage of endometriosis, the need for additional surgery and the extent of the surgical excision or ablation of the endometriosis are the remaining eligibility criteria and stratification variables that could only established at laparoscopy. A ‘minimisation’ procedure using a computer-based algorithm was used to avoid chance imbalances in important stratification variables. • Stage of endometriosis (using Classification of the American Society of Reproductive Medicine): I (minimal) II (mild) versus III (moderate)/ IV (severe) • Extent of excision of endometriosis: complete versus incomplete, as judged by the surgeon at the time of conservative surgery • Age in years:<35 versus >=35 • Selection of LNG-IUS or DMPA if randomised to LARC • Whether selection of LARC was due to patient preference or not • Centre, to balance for experience of the gynaecologist If the LARC needed to be randomly allocated prior to LARC v COCP allocation this was completed using a random blocked list (variable length) incorporated into the computer-based algorithm.
    Actual start date of recruitment
    01 Jan 2014
    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: 405
    Worldwide total number of subjects
    405
    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)
    5
    Adults (18-64 years)
    400
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 PRE- EMPT participants were recruited from the gynaecological, out-patient clinics of participating centres, fitting around their current service provision. Long term medical treatment i.e. repeat COCP prescriptions and DMPA injections, were delivered by the participants GP or sexual health clinics, as per current practice.

    Pre-assignment
    Screening details
    		 In women aged 16-46 years presenting with pelvic pain associated with endometriosis, anatomical location, severity of the disease and degree of involvement of neighbouring organs can all show a remarkable degree of variation.

    Period 1
    Period 1 title
    Baseline
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded
    Blinding implementation details
    N/A

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 LARC
    Arm description
    		 Long-acting reversible contraception
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Long-acting reversible contraception: LNG-IUS or DMPA
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Implant
    Routes of administration
    Vaginal use
    Dosage and administration details
    Implant

    Arm title
    		 COCP
    Arm description
    		 Combined oral contraceptive pill
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Combined oral contraceptive pill
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    30mcg ethinylestradiol and 150 mcg levonorgestrel e.g. Microgynon-30 or Rigevidon.

    Number of subjects in period 1
    		LARC COCP
    Started
    205
    200
    Completed
    205
    200
    Period 2
    Period 2 title
    3 Years
    Is this the baseline period?
    		 No
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 LARC
    Arm description
    		 -
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Long-acting reversible contraception: LNG-IUS or DMPA
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Implant
    Routes of administration
    Vaginal use
    Dosage and administration details
    Implant

    Arm title
    		 COCP
    Arm description
    		 -
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Combined oral contraceptive pill
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    30mcg ethinylestradiol and 150 mcg levonorgestrel e.g. Microgynon-30 or Rigevidon.

    Number of subjects in period 2
    		LARC COCP
    Started
    205
    200
    6 Months
    176
    173
    1 Year
    176
    171
    2 Year
    174
    165
    Completed
    173
    164
    Not completed
    32
    36
         Lost to follow-up
    32
    36

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    LARC
    Reporting group description
    		 Long-acting reversible contraception

    Reporting group title
    COCP
    Reporting group description
    		 Combined oral contraceptive pill

    Reporting group values
    		 LARC COCP Total
    Number of subjects
    		 205 200 405
    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)
    		 3 2 5
        Adults (18-64 years)
    		 202 198 400
        From 65-84 years
    		 0 0 0
        85 years and over
    		 0 0 0
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 29.6 ± 6.7 29.3 ± 6.6 -
    Gender categorical
    Units: Subjects
        Female
    		 205 200 405
        Male
    		 0 0 0

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    LARC
    Reporting group description
    		 Long-acting reversible contraception

    Reporting group title
    COCP
    Reporting group description
    		 Combined oral contraceptive pill
    Reporting group title
    LARC
    Reporting group description
    		 -

    Reporting group title
    COCP
    Reporting group description
    		 -

    Subject analysis set title
    LARC Baseline
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Analysis population who completed at Baseline

    Subject analysis set title
    LARC 6 Months
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Analysis population who completed at 6 Months

    Subject analysis set title
    LARC 1 Year
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Analysis population who completed at 1 Year

    Subject analysis set title
    LARC 2 Years
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Analysis population who completed at 2 Years

    Subject analysis set title
    LARC 3 Years
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Analysis population who completed at 3 Years

    Subject analysis set title
    COCP Baseline
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Analysis population who completed at Baseline

    Subject analysis set title
    COCP 6 Months
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Analysis population who completed at 6 Months

    Subject analysis set title
    COCP 1 Year
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Analysis population who completed at 1 Year

    Subject analysis set title
    COCP 2 Year
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Analysis population who completed at 2 Years

    Subject analysis set title
    COCP 3 Year
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Analysis population who completed at 3 Years

    Primary: Primary Outcome EHP-30 - Pain scores

    		 Close Top of page
    End point title
    		 Primary Outcome EHP-30 - Pain scores
    End point description
    End point type
    Primary
    End point timeframe
    3 Years
    End point values
    		 LARC COCP
    Number of subjects analysed
    173
    164
    Units: Pain Scores
        arithmetic mean (standard deviation)
    32.9 ± 25.0
    32.9 ± 27.6
    Statistical analysis title
    		 Adjusted Mean Difference
    Comparison groups
    LARC v COCP
    Number of subjects included in analysis
    337
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.76
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -0.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -5.7
         upper limit
    		 4.2

    Secondary: Baseline EHP-30 - Pain scores

    		 Close Top of page
    End point title
    		 Baseline EHP-30 - Pain scores
    End point description
    End point type
    Secondary
    End point timeframe
    Baseline
    End point values
    		 LARC Baseline COCP Baseline
    Number of subjects analysed
    197
    192
    Units: Pain Scores
        arithmetic mean (standard deviation)
    56.6 ± 17.3
    55.8 ± 19.9
    No statistical analyses for this end point

    Secondary: 1 Year EHP-30 - Pain scores

    		 Close Top of page
    End point title
    		 1 Year EHP-30 - Pain scores
    End point description
    End point type
    Secondary
    End point timeframe
    1 Year
    End point values
    		 LARC 1 Year COCP 1 Year
    Number of subjects analysed
    150
    153
    Units: Pain Scores
        arithmetic mean (standard deviation)
    35.1 ± 26.4
    37.5 ± 25.4
    Statistical analysis title
    		 Adjusted Mean Difference
    Comparison groups
    COCP 1 Year v LARC 1 Year
    Number of subjects included in analysis
    303
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -2.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -7.5
         upper limit
    		 2.9

    Secondary: 2 Year EHP-30 - Pain scores

    		 Close Top of page
    End point title
    		 2 Year EHP-30 - Pain scores
    End point description
    End point type
    Secondary
    End point timeframe
    2 Year
    End point values
    		 LARC 2 Years COCP 2 Year
    Number of subjects analysed
    157
    140
    Units: Pain Scores
        arithmetic mean (standard deviation)
    32.1 ± 26.2
    33.6 ± 26.5
    Statistical analysis title
    		 Adjusted Mean Difference
    Comparison groups
    LARC 2 Years v COCP 2 Year
    Number of subjects included in analysis
    297
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -0.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -5.6
         upper limit
    		 4.9

    Secondary: 6 Month EHP-30 - Pain scores

    		 Close Top of page
    End point title
    		 6 Month EHP-30 - Pain scores
    End point description
    End point type
    Secondary
    End point timeframe
    6 Months
    End point values
    		 LARC 6 Months COCP 6 Months
    Number of subjects analysed
    162
    150
    Units: Pain Scores
        arithmetic mean (standard deviation)
    35.0 ± 25.6
    38.0 ± 26.4
    Statistical analysis title
    		 Adjusted Mean Difference
    Comparison groups
    LARC 6 Months v COCP 6 Months
    Number of subjects included in analysis
    312
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -1.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -7
         upper limit
    		 3.2

    Secondary: Further therapeutic surgery or second-line treatment for endometriosis over 3 years

    		 Close Top of page
    End point title
    		 Further therapeutic surgery or second-line treatment for endometriosis over 3 years
    End point description
    Time to further therapeutic surgery or second line treatment: HR=0.67 (95% CI: 0.44, 1.00)
    End point type
    Secondary
    End point timeframe
    Over 3 years
    End point values
    		 LARC 3 Years COCP 3 Year
    Number of subjects analysed
    73
    97
    Units: No. of participants
        Hysterectomy
    6
    14
        Surgery for endometriosis
    21
    30
        Laparoscopy
    22
    28
        GnRH treatment
    24
    25
        Total no. of women experiencing treatment failure
    50
    61
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information [1]
    Timeframe for reporting adverse events
    PRE-EMPT AE reporting was conducted primarily by the participant. This was captured in the routine follow up questionnaires received during follow up.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    26.1
    Reporting groups
    Reporting group title
    LARC
    Reporting group description
    		 Long-acting reversible contraception

    Reporting group title
    COCP
    Reporting group description
    		 Combined oral contraceptive pill

    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: No non-serious adverse events were recorded
    Serious adverse events
    		 LARC COCP
    Total subjects affected by serious adverse events
         subjects affected / exposed
    14 / 205 (6.83%)
    15 / 200 (7.50%)
         number of deaths (all causes)
    0
    0
         number of deaths resulting from adverse events
    Injury, poisoning and procedural complications
    Bleeding time
    Additional description: Patient bleed more than expected during surgery. Kept in overnight for observation . Discharged home the following day.
         subjects affected / exposed
    1 / 205 (0.49%)
    0 / 200 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Surgical and medical procedures
    Bowel obstruction surgery
    Additional description: Resection of bowel tumour
         subjects affected / exposed
    0 / 205 (0.00%)
    1 / 200 (0.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Laparoscopy
         subjects affected / exposed
    2 / 205 (0.98%)
    3 / 200 (1.50%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Carpal tunnel syndrome
    Additional description: Patient reported to BCTU that she had surgery for Capral tunnel syndrome. No date on clinical records to supper this. Seen by Plastics who recommended decompression under local anaesthetic to relieve symptoms. Th
         subjects affected / exposed
    0 / 205 (0.00%)
    1 / 200 (0.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pregnancy, puerperium and perinatal conditions
    Hyperemesis gravidarum
         subjects affected / exposed
    1 / 205 (0.49%)
    0 / 200 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pregnancy
         subjects affected / exposed
    3 / 205 (1.46%)
    3 / 200 (1.50%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Abdominal pain
    Additional description: Admitted via A&E ,sever abdo pain & reflux. Admitted with intermittent back pan & right sided abdominal pain radiating to flank & right lilac fossa.
         subjects affected / exposed
    1 / 205 (0.49%)
    1 / 200 (0.50%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pelvic pain
         subjects affected / exposed
    8 / 205 (3.90%)
    4 / 200 (2.00%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Concussion
    Additional description: Had concussion which resulted in an overnight stay (don't know exact date) had an MRI or cat scan doesn't know which. Unable to access GP records. Patient had stopped trial med (Depo)
         subjects affected / exposed
    1 / 205 (0.49%)
    0 / 200 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Endometriosis
    Additional description: Extensive grade 4 pelvic endometriosis
         subjects affected / exposed
    0 / 205 (0.00%)
    1 / 200 (0.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    Pyelonephritis
         subjects affected / exposed
    0 / 205 (0.00%)
    1 / 200 (0.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Fracture
    Additional description: Stress fracture left sacral
         subjects affected / exposed
    0 / 205 (0.00%)
    1 / 200 (0.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Product issues
    Discontinued product administered
    Additional description: Patient randomised to depo injection. Only had 1 dose then discontinued treatment, affected her mood adversely.
         subjects affected / exposed
    1 / 205 (0.49%)
    0 / 200 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Overdose
         subjects affected / exposed
    2 / 205 (0.98%)
    1 / 200 (0.50%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Epstein-Barr virus infection
         subjects affected / exposed
    1 / 205 (0.49%)
    0 / 200 (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: 0%
    Non-serious adverse events
    		 LARC COCP
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    0 / 205 (0.00%)
    0 / 200 (0.00%)

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    01 Nov 2014
    Updates to protocol and trial documents.
    23 Oct 2015
    Move from pilot to substantive study • Removal of no treatment arm. • Removal of qualitative study • Update protocol with change of DMC member • PIS updated with design change • Consent updated to reflect PIS • GP letter and follow-up form update
    18 May 2017
    Extension until 31/12/17. Introduction of vouchers for follow up participants. Addition of Levosert as additional LNG-IUS.
    05 Apr 2018
    Update to protocol and trial documents.
    06 Oct 2020
    Revision of section 6 within the protocol to reject the wording previously added exempting congenital abnormalities from SAE reporting.
    02 Mar 2022
    £25 sent to final participants on completion of follow-up form.

    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-Mon May 06 08:00:30 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA