Condition category
Urological and Genital Diseases
Date applied
25/03/2015
Date assigned
25/03/2015
Last edited
14/04/2015
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
Heavy menstrual bleeding (HMB) refers to when a woman loses an excessive amount of blood over a number of periods. It’s not necessarily a symptom of there being something seriously wrong, but it can have a serious effect on a woman’s quality of life. Medication is the main treatment, but surgery is also an option for women when other treatment options have failed. There is a pressing need to develop safe, simple, acceptable, fertility sparing medical treatments for HMB for women regardless of age, reproductive history and the presence of uterine fibroids (non-cancerous growths in the uterus). Limitations of current medical treatments are that they often do not work or have side effects that women find unacceptable. An exciting new class of drugs, called selective progesterone receptor modulators (SPRMs), offer the potential to revolutionise the way we treat HMB by addressing the unmet need of sustainable long term medical therapy. Here, we aim to test whether the SPRM ulipristal acetate (UPA; Esmya®), works better than the levonorgestrel-releasing intrauterine system (LNG-IUS, Mirena®) for the long term treatment of HMB.

Who can participate?
Woman (aged at least 18) with HMB.

What does the study involve?
Participants are randomly allocated intone of two groups. Those in group 1 are treated with UPA. Those in group 2 are treated with LNG-IUS. The two groups are compared to see whether UPA works better in improving HMB compared with LNG-IUS after 12 months treatment. We also look at bleeding patterns, satisfaction with treatment and safety. Women are asked to complete questionnaires before treatment, and then after 3, 6 and 12 months of treatment.

What are the possible benefits and risks of participating?
The UCON trial is led by a team of experienced researchers, who have an excellent track record of both running clinical trials and investigating menstrual bleeding problems. Women treated with UPA are monitored for side effects with scans and examining samples from the womb lining, as changes to the womb lining have been noted after 3 months. Furthermore, additional samples are taken from a smaller group of women also have a detailed MR investigation of the womb to measure uterine perfusion. This shows the effect of UPA on structure and blood supply of the uterus both in the presence and absence of fibroids. Ultimately, there could be savings to the NHS from fewer operations to remove the womb (hysterectomy) or destroy its lining (endometrial ablation).

Where is the study run from?
Royal Infirmary of Edinburgh (lead site) and 4 other hospitals in the UK.

When is the study starting and how long is it expected to run for?
February 2015 to September 2018

Who is funding the study?
National Institute for Health Research (UK)

Who is the main contact?
Professor Hilary Critchley

Trial website

Contact information

Type

Scientific

Primary contact

Prof Hilary OD Critchley

ORCID ID

Contact details

University of Edinburgh
Medical School
Teviot Place
Edinburgh
EH8 9AG
United Kingdom

Additional identifiers

EudraCT number

2014-003408-65

ClinicalTrials.gov number

Protocol/serial number

18534

Study information

Scientific title

Ulipristal acetate versus conventional management of heavy menstrual bleeding (HMB; including uterine fibroids): a randomised controlled trial and exploration of mechanism of action (UCON trial)

Acronym

UCON

Study hypothesis

The selective progesterone receptor modulator (SPRM) ulipristal acetate (UPA; Esmya®), is more effective than the levonorgestrel-releasing intrauterine system (LNGIUS, Mirena®) for the long term treatment of heavy menstrual bleeding (HMB). We also aim to acquire an understanding of the mechanism of action of UPA on the endometrium and its effects upon the vasculature and structure of the uterus.

Ethics approval

NRES Committee London - Bloomsbury, 18/11/2014, 14/LO/1602

Study design

Randomised; Interventional; Design type: Treatment

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use contact details to request a patient information sheet

Condition

Topic: Reproductive health and childbirth; Subtopic: Reproductive Health and Childb (all Subtopics); Disease: Menstrual Disorders

Intervention

1. Intervention: Ulipristal Acetate (UPA)
2. Reference/ Control group: levonorgestrel-releasing intrauterine system (LNG-IUS)
Treatment duration:12 months.
Follow-up: 12 month questionnaire. Gynaecology clinic appointment (UPA group receive 12 month ultrasound, blood sample, endometrial biopsy). LNG-IUS Group receive 12 month ultrasound and blood sample).

Intervention type

Drug

Phase

Phase III

Drug names

Ulipristal Acetate

Primary outcome measures

The primary outcome measure is the condition-specific Menorrhagia Multi-Attribute Scale (MMAS) designed and validated to capture the impact of HMB on women’s day-to-day life.

Secondary outcome measures

1. Menstrual bleeding will be captured by validated Pictorial Blood Loss Assessment Chart (PBAC). The standard PBAC is a validated and well used assessment of menstrual blood loss in women. The PBAC will be supplemented by visual analogue scales for menstruation duration, regularity and pelvic pain
2. Uterine Fibroid Symptom and Quality of Life (UFS-QoL) instrument, which contains a health related quality of life (HRQoL) domain and a symptom domain. This instrument will be only given to women diagnosed with fibroids
3. Sexual Activity Questionnaire, a measure of sexual functioning, used in other HMB trials. The sexual activity questionnaire is a valid, reliable and acceptable measure for describing the sexual functioning of women in terms of pleasure and discomfort. It is quick and easy to administer and has good face validity delineating between the sexual functioning of pre and post-menopausal women
4. Satisfaction with treatment outcome measured on a 5-point Likert scale. Specific statements about the experience and the acceptability of the treatment and the beliefs about the value of the treatment will be elicited from the participants
5. Adherence to trial treatments, as reported by the participant
6. Serious adverse events and reactions reported by participants, principally those that are serious and detailed in the respective Summary of Product Characteristics (SmPC) and those that are unexpected
7. Clinical measurements to assess safety and efficacy will include serum haemoglobin as appropriate, oestradiol, pelvic ultrasound (endometrial appearance; fibroid volume) and endometrial biopsies (reported according to pre-agreed criteria by independent pathologists blinded to treatment allocations)
8. Impact on endometrial tissue architecture including regulation of the vascular compartment
9. Impact on endometrial steroid responsiveness, proliferation, survival and inflammatory processes
10. Expression of genes implicated in pre-malignant change including tumour suppressors
11. Effects on uterine/ fibroid structure and vascularity as determined by MRI-DCE and high resolution structural MRI

Overall trial start date

24/02/2015

Overall trial end date

30/09/2018

Reason abandoned

Eligibility

Participant inclusion criteria

1. Females aged between 18 or over
2. Heavy menstrual bleeding at intervals of 25-42 days that she perceives to be heavy and troublesome
3. Willing to receive medical treatment with either UPA or LNGIUS
4. Willing to undergo two pelvic ultrasounds and at least one endometrial biopsy, but up to four if allocated to UPA
5. Willing to use barrier contraception if allocated to UPA
6. Given written informed consent
7. Willing to undergo one additional endometrial biopsy and at least three magnetic resonance imaging scan (if allocated to UPA, mechanistic substudy only)

Participant type

Patient

Age group

Adult

Gender

Female

Target number of participants

Planned Sample Size: 220; UK Sample Size: 220; Description: The Mechanistic Sub-study is carried out only at the Royal Infirmary of Edinburgh and will require a sample size of approximately 20 participants

Participant exclusion criteria

1. A >14 week fibroid uterus and/or cavity length >11 cm confirmed by ultrasound scan
2. Submucosal fibroids >2cm diameter confirmed by ultrasound scan
3. Contraindications to UPA or LNGIUS
4. Current use of Cytochrome P450 (CYP3A4) inhibitors
5. Current use of Cytochrome P450 (CYP3A4) inducers
6.Current use of Pglycoprotein substrate (e.g.digoxin)
7. A past, current or suspected diagnosis of endometrial hyperplasia or endometrial neoplasia
8. Severe hepatic impairment
9. Suffer with epilepsy managed with carbamazepine, phenytoin
10. Significant renal impairment
11. Pregnant
12. Current plans to become pregnant within 12 months
13. Currently breastfeeding
14. Severe asthma that is not sufficiently controlled by oral glucocorticoidssteroids
15.Suffer with uterine, cervical, ovarian or breast cancer
16. Receiving Pglycoprotein substrates
17. Current use of progestagen releasing intrauterine device (except if allocated within UCON)
18. Continued regular use of Mefenamic acid
19. Continued regular use of Tranexamic acid
20. Continued regular use of GnRH analogues
21. Continued regular use of Progestagen only contraceptive
22. Continued regular use of any combined oral contraceptive pills

Recruitment start date

01/04/2015

Recruitment end date

30/04/2017

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Royal Infirmary of Edinburgh (lead site)
Edinburgh
EH16 4SA
United Kingdom

Trial participating centre

Glasgow Royal Infirmary
Glasgow
G4 0SF
United Kingdom

Trial participating centre

Liverpool Women's Hospital
Liverpool
L8 7SS
United Kingdom

Trial participating centre

Aberdeen Royal Infirmary
Aberdeen
AB25 2ZN
United Kingdom

Trial participating centre

Birmingham Women’s Hospital
Birmingham
B15 2TG
United Kingdom

Sponsor information

Organisation

NHS Lothian

Sponsor details

ACCORD
The Queens Medical Research Institute
47 Little France Crescent
Edinburgh
EH16 4TJ
United Kingdom

Sponsor type

Hospital/treatment centre

Website

Funders

Funder type

Government

Funder name

National Institute for Health Research

Alternative name(s)

NIHR

Funding Body Type

government organisation

Funding Body Subtype

Federal/National Government

Location

United Kingdom

Results and Publications

Publication and dissemination plan

The final report will be written in accordance with funder (NIHR EME) guidelines and is due to be submitted 14th October 2015.

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes