Ulipristal Acetate Versus GnRH Analogue and Myometrial Preservation

Ulipristal Acetate Versus GnRH Analogue for Myometrial Preservation in Patients With Submucosal Uterine Leiomyoma G2

Submucosal fibroid grow inside the uterine cavity and are associated with menorrhagia, abnormal uterine bleeding (AUB) and infertility. Type II (G2) fibroids often require more surgeries due to their particular position in the myometrium. Surgery, moreover, should always be tailored, particularly in patients wishing to conceive, to preserve the integrity of the myometrium. Preoperative use of GnRH agonist appears to be relevant and beneficial in patients with submucous fibroids, but are associated with several side effects. the eighty percent of patients treated by UPA showed a clinically meaningful reduction of more than 25% in fibroid volume, and 50% of patients a reduction of 50%. fibroid volume reduction appeared to be maintained for 6 months after the end of UPA treatment

Study Overview

• Status: Unknown
• Conditions: Fibroid
• Intervention / Treatment: Drug: ulipristal acetate; Drug: Leuprolide acetate

Detailed Description

Uterine leiomyoma is the most common benign tumor of the female genital tract. Submucosal fibroid are about 10% of all uterine myoma. They grow inside the uterine cavity and are usually associated with menorrhagia, abnormal uterine bleeding (AUB) and infertility. According to the degree of myometrial penetration, the European Society for Gynaecological Endoscopy (ESGE) classified submucosal myomas in Type 0 (G0, totally intracavitary fibroids), Type I (G1, <50% myometral penetration), or Type II (G2, >50% myometral penetration).

Hysteroscopic removal of submucosal myomas improves menorrhagia and AUB but can be challenging in women with Type II (G2) fibroids, since they often require more and more surgeries due to their particular position in the context of myometrium. Surgery, moreover, should always be tailored, particularly in patients wishing to conceive, to preserve the integrity of the myometrium. In this particular population, indeed, the possibility of avoiding any kind of uterine surgery should always be exploited. Up to now, hysteroscopic resection of submucosal fibroids is considered the gold standard for symptomatic patients, since no medication has been able to restore uterine cavity in a permanent manner. In this setting, use of a GnRH agonist before surgery is still a matter of debate, but literature reports that preoperative use of GnRH agonist appears to be relevant and beneficial in patients with submucous fibroids. Benefits include a resolution of preoperative anemia, a decrease in fibroid size, a reduction of endometrial thickness and vascularization with subsequently improved visibility and reduced fluid absorption, and the possibility of surgical scheduling.

Conversely, this preoperative treatment is associated with some side effects such as hot flushes and postinjection endometrial bleeding due to the flare-up effect.

Data on SPRM showed that eighty percent of patients treated by UPA showed a clinically meaningful reduction of more than 25% in fibroid volume, and 50% of patients a reduction of 50%. In the subpopulation of patients not undergoing surgery, fibroid volume reduction appeared to be maintained for 6 months after the end of UPA treatment.

This was in contrast to patients receiving a GnRH agonist, in whom fibroids began to regrow 1 to 3 months after the last dose, reaching their baseline size after 6 months.

No sub-analysis have been conducted on submucosal fibroids, but is of interest to underline that, when myomas regress so much that they no longer distort the uterine cavity, surgery may not be required. This could represent a safe way to avoid surgery in patients with G2 fibroids desiring pregnancy.

• Study Type: Interventional
• Enrollment (Anticipated): 110
• Phase: Phase 4

Contacts and Locations

Study Locations

• Italy
  • Catanzaro, Italy, 88100
    • Recruiting
    • Azienda Ospedaliera Pugliese-Ciaccio

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

G2 submucosal leiomyoma <3 cm, symptoms of menomethrorragia, menstrual disorder, infertility, pelvic pain

Exclusion Criteria:

submucosal leyomyoma other than G2 or greater than 3 cm, intramural or subserosal leiomyomas endometrial hyperplasia with atypia history of uterine surgery

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ulipristal acetate; Women will be treated with an oral dose of ulipristal acetate 5 mg/day for 2 courses of 3 months each	Drug: ulipristal acetate; 5 mg/day will be administered starting from day 1 of the cycle and up to three months later for two courses, with an interval between the courses of 1 month; Other Names: Esmya
Active Comparator: Leuprolile acetate; Women will be treated with an injection IM on leuprolide acetate 11,25 in the luteal phase repeated 3 months later	Drug: Leuprolide acetate; One dose of 11.25 GnRH analogue depot will be administered in the luteal phase of the menstrual cycle (days 21-24) and repeated 3 months later; Other Names: Enantone 11.25

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of restored uterine cavity 1 year after enrollment	To compare the proportion of patients, treated by UPA or by GnRh-a, with uterine cavity no longer distorted by their submucous myoma	1 year after treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to pregnancy	to compare time to pregnancy in patients treated with Ulipristal Acetate and GnRH-a	from the end of treatment to the obtainance of pregnancy
Live birth rate	to compare live birth rate in patients treated with Ulipristal Acetate and GnRH-a	A the time of delivery
Proportion of patients needing surgery after UPA or GnRH-a	to compare need for surgery in patients treated with Ulipristal Acetate and GnRH-a.	24 weeks after the first dose of drugs

Collaborators and Investigators

• Sponsor: University Magna Graecia

Study record dates

Study Major Dates

• Study Start: February 1, 2015
• Primary Completion (Anticipated): September 1, 2017
• Study Completion (Anticipated): September 1, 2017

Study Registration Dates

• First Submitted: February 2, 2015
• First Submitted That Met QC Criteria: February 2, 2015
• First Posted (Estimate): February 6, 2015

Study Record Updates

• Last Update Posted (Estimate): November 18, 2016
• Last Update Submitted That Met QC Criteria: November 17, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Keywords: GnRH analogue; ulipristal acetate; fibroid
• Additional Relevant MeSH Terms: Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Muscle Tissue; Leiomyoma; Physiological Effects of Drugs; Antineoplastic Agents; Antineoplastic Agents, Hormonal; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Contraceptive Agents, Female; Fertility Agents, Female; Fertility Agents; Leuprolide; Ulipristal acetate
• Other Study ID Numbers: UPA myometrial