Comparison of drug ulipristal acetate with existing treatment of levonorgestrel-releasing intra-uterine system.

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) - UCON

Status

Not yet recruiting

Phases

Phase 3

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2014-003408-65-GB

Enrollment

220

Registered

2014-12-02

Start date

2016-08-26

Completion date

Unknown

Last updated

2018-10-15

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Heavy menstrual bleeding MedDRA version: 18.0 Level: LLT Classification code 10046784 Term: Uterine fibroids System Organ Class: 100000004864 MedDRA version: 18.0 Level: PT Classification code 10027313 Term: Menorrhagia System Organ Class: 10038604 - Reproductive system and breast disorders

Interventions

Trade Name: Esmya Product Name: Ulipristal acetate Pharmaceutical Form: Tablet Trade Name: Mirena Product Name: Levonorgestrel-releasing intra-uterine system Pharmaceutical Form:

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: • Aged 18 years or over • Menstrual bleeding at intervals of 21-42 days that she perceives to be heavy and troublesome • Willing to receive medical treatment with either UPA or LNG-IUS • Willing to undergo two pelvic ultrasounds • If allocated to UPA, willing and eligible to undergo two endometrial biopsies with the possibility of a third and fourth (i.e. up to four biopsies) • If allocated to UPA mechanistic sub-study, willing and eligible to undergo three biopsies with the possibility of a fourth and fifth (i.e. up to five biopsies). If ‘No’ may be randomised to RCT if UPA endometrial biopsy consent given • Willing to use barrier contraception if allocated to UPA • Given written informed consent • Willing and eligible to undergo up to three magnetic resonance imaging scans? If allocated to UPA, mechanistic sub-study only. If ‘No’ may still be randomised to RCT Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 219 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 1

Exclusion criteria

Exclusion criteria: • Post-menopausal • A >14 week fibroid uterus and/or cavity length >11 cm confirmed by ultrasound scan • Submucosal fibroids >2cm diameter confirmed by ultrasound scan • Contraindications to UPA or LNG-IUS • Intention to continue current use of current use of Cytochrome P450 (CYP3A4) inhibitors • Intention to continue current use of current use of Cytochrome P450 (CYP3A4) inducers (e.g. Phenytoin, carbamazepine, rifampicin, St John’s Wort) • Intention to continue current use of P-glycoprotein substrates (e.g. digoxin) • A past, current or suspected diagnosis of endometrial hyperplasia or neoplasia • Severe hepatic impairment • Epilepsy managed with carbamazepine, phenytoin • Significant renal impairment • Pregnant • Current plans to become pregnant within 12 months • Currently breastfeeding • Severe asthma that is not sufficiently controlled by oral glucocorticoids • Past or current known history of with uterine, cervical, ovarian or breast cancer. • Current use of progestagen-releasing intrauterine device (except if allocated within UCON) • Intention to continue regular use of Mefenamic acid • Intention to continue regular use of Tranexamic acid • Intention to continue regular use of GnRH analogues • Intention to continue regular use of Progestagen-only contraceptive • Intention to continue regular use of any combined oral contraceptive pills • Intention to continue regular use of hormonal replacement therapy

Design outcomes

Primary

Measure	Time frame
Main Objective: Is UPA more effective at reducing the burden of HMB symptoms than LNG-IUS after 12 months of treatment? ;Secondary Objective: SECONDARY CLINICAL TRIAL OBJECTIVES: • Ascertain whether UPA use beyond 3 months and up to 12 months duration is associated with histological changes to the endometrium, and if so, whether this compromises safety. • Ascertain whether UPA is more effective than LNG-IUS in relation to menstrual blood loss, sexual activity, generic quality of life, satisfaction with treatment, patient reported adverse events, and compliance at 3, 6 and 12 months. • Determine the response to UPA and LNG-IUS treatment difference in the presence of uterine fibroids in terms of (i) alleviation of HMB and (ii) change in uterine/fibroid volume. MECHANISTIC SUB-STUDY OBJECTIVES: • To understand how UPA causes a reduction in menstrual bleeding and uterine/ fibroid volume in women with HMB, we will determine whether: • Administration of UPA alters endometrial cell function (proliferation, apoptosis, expression of steroid receptors, tumour suppressors or inflammatory mediators). • UPA reduces blood flo;Timepoint(s) of evaluation of this end point: Validated Menorrhagia Multi-attribute Assessment Scale (MMAS) to assess impact of HMB on women’s life, measured at 12 months. This is now an accepted primary outcome for randomised trials of interventions to improve HMB.;Primary end point(s): The primary outcome measure is the conditon-specific Menorrhagia Multi-Attribute Scale (MMAS) designed and validated to capture the impact of HMB on women’s day-to-day life.Summary scores range from 0 (not affected) to 100 (worst affected). The primary time point for analysis will be at 12 months.	—

Measure

Time frame

Main Objective: Is UPA more effective at reducing the burden of HMB symptoms than LNG-IUS after 12 months of treatment? ;Secondary Objective: SECONDARY CLINICAL TRIAL OBJECTIVES: • Ascertain whether UPA use beyond 3 months and up to 12 months duration is associated with histological changes to the endometrium, and if so, whether this compromises safety. • Ascertain whether UPA is more effective than LNG-IUS in relation to menstrual blood loss, sexual activity, generic quality of life, satisfaction with treatment, patient reported adverse events, and compliance at 3, 6 and 12 months. • Determine the response to UPA and LNG-IUS treatment difference in the presence of uterine fibroids in terms of (i) alleviation of HMB and (ii) change in uterine/fibroid volume. MECHANISTIC SUB-STUDY OBJECTIVES: • To understand how UPA causes a reduction in menstrual bleeding and uterine/ fibroid volume in women with HMB, we will determine whether: • Administration of UPA alters endometrial cell function (proliferation, apoptosis, expression of steroid receptors, tumour suppressors or inflammatory mediators). • UPA reduces blood flo;Timepoint(s) of evaluation of this end point: Validated Menorrhagia Multi-attribute Assessment Scale (MMAS) to assess impact of HMB on women’s life, measured at 12 months. This is now an accepted primary outcome for randomised trials of interventions to improve HMB.;Primary end point(s): The primary outcome measure is the conditon-specific Menorrhagia Multi-Attribute Scale (MMAS) designed and validated to capture the impact of HMB on women’s day-to-day life.Summary scores range from 0 (not affected) to 100 (worst affected). The primary time point for analysis will be at 12 months.

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Secondary

Measure	Time frame
Secondary end point(s): SECONDARY CLINICAL OUTCOMES INCLUDE: Satisfaction, Surgical intervention (hysterectomy or endometrial ablation), menstrual blood loss, menstrual regularity, pain, fibroid symptom and quality of life, sexual activity and compliance will be assessed at 3, 6 and 12 months. Endometrial biopsy at 12 months for exclusion of pre-malignant or other pathology. MECHANISTIC OUTCOMES (subset of UPA group only): Study of impact of UPA on cell fate including markers of steroid responsiveness, inflammation, survival and proliferation and complemented with imaging of the uterus using high resolution Magnetic Resonance Imaging (MRI) of the uterine matrix and fibroids and Dynamic Contrast Enhanced (DCE-MRI) to measure uterine perfusion.;Timepoint(s) of evaluation of this end point: Satisfaction, menstrual blood loss, menstrual regularity, pain, fibroid symptom and quality of life, sexual activity and compliance will be assessed at 3, 6 and 12 months. Endometrial biopsy at 12 months for exclusion of pre-malignant or other pathology. MECHANISTIC OUTCOMES (subset of UPA group only): Study of impact of UPA on cell fate including markers of steroid responsiveness, inflammation, survival and proliferation and complemented with imaging of the uterus using high resolution Magnetic Resonance Imaging (MRI) of the uterine matrix and fibroids and Dynamic Contrast Enhanced (DCE-MRI) to measure uterine perfusion. Measured up to 18 months.	—

Measure

Time frame

Secondary end point(s): SECONDARY CLINICAL OUTCOMES INCLUDE: Satisfaction, Surgical intervention (hysterectomy or endometrial ablation), menstrual blood loss, menstrual regularity, pain, fibroid symptom and quality of life, sexual activity and compliance will be assessed at 3, 6 and 12 months. Endometrial biopsy at 12 months for exclusion of pre-malignant or other pathology. MECHANISTIC OUTCOMES (subset of UPA group only): Study of impact of UPA on cell fate including markers of steroid responsiveness, inflammation, survival and proliferation and complemented with imaging of the uterus using high resolution Magnetic Resonance Imaging (MRI) of the uterine matrix and fibroids and Dynamic Contrast Enhanced (DCE-MRI) to measure uterine perfusion.;Timepoint(s) of evaluation of this end point: Satisfaction, menstrual blood loss, menstrual regularity, pain, fibroid symptom and quality of life, sexual activity and compliance will be assessed at 3, 6 and 12 months. Endometrial biopsy at 12 months for exclusion of pre-malignant or other pathology. MECHANISTIC OUTCOMES (subset of UPA group only): Study of impact of UPA on cell fate including markers of steroid responsiveness, inflammation, survival and proliferation and complemented with imaging of the uterus using high resolution Magnetic Resonance Imaging (MRI) of the uterine matrix and fibroids and Dynamic Contrast Enhanced (DCE-MRI) to measure uterine perfusion. Measured up to 18 months.

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Countries

United Kingdom

Contacts

Public ContactProfessor Hilary Critchley

University of Edinburgh

hilary.critchley@ed.ac.uk01312426858

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 15, 2026