Ulipristal Acetate Versus GnRH Analogue and Myometrial Preservation

Phase 4

• Conditions: Fibroid
• Interventions: Drug: Leuprolide acetate; Drug: ulipristal acetate

• Registration Number: NCT02357563
• Lead Sponsor: University Magna Graecia

Brief Summary

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

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 Timeline

• Study Start: 2015-02
• Study First Submitted: 2015-02-02
• Study First Submitted QC: 2015-02-02
• Study First Posted: 2015-02-06
• Status Verified: 2016-11
• Last Update Submitted: 2016-11-17
• Last Update Posted: 2016-11-18
• Primary Completion: 2017-09
• Study Completion: 2017-09

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: Female
• Target Recruitment: 110

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Leuprolile acetate	Leuprolide acetate	Women will be treated with an injection IM on leuprolide acetate 11,25 in the luteal phase repeated 3 months later
Ulipristal acetate	ulipristal acetate	Women will be treated with an oral dose of ulipristal acetate 5 mg/day for 2 courses of 3 months each

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Azienda Ospedaliera Pugliese-Ciaccio; 🇮🇹 Catanzaro, Italy