Ulipristal Acetate for the Preoperative Management of Hypoechoic Cellular Leiomyomas

NCT ID: NCT02361905

Last Updated: 2016-11-18

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 42 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-02-28
• Study Completion Date: 2017-09-30

Brief Summary

Cellular leiomyomas (CLs) are described as leiomyomas that are significantly more cellular than the surrounding myometrium, often with crowding and overlapping of nuclei. they often are soft and appear more tan or yellow and less circumscribed than the usual leiomyomas. Pre-operatively CLs can be recognized at ultrasound evaluation because they appear as hypoechoic uterine lesions. patients with hypoechoic myoma have a significantly longer surgery time after treatment with a gonadotropin-releasing hormone (GnRH) analog probably related to degenerative changes induced by this treatment. Hypoechoic CLs should be more responsive to ulipristal acetate treatment than common leiomyomas. The antiproliferative ulipristal effect, moreover, induces a condition of apoptotic necrosis that, compared to GnRH-a myxoid necrosis, probably allows an easier surgical enucleation of the tumor.

Detailed Description

Rationale why study should be conducted: Leiomyomas are the most common benign neoplasm in women; it has been estimated that these tumors occur in at least 25% of all women, which is probably an underestimation, because this figure is based on a select population. They are histologically composed by smooth muscle cells with bland, uniform, cigar-shaped nuclei that are arranged in interlacing bundles, showing little or no mitotic activity. Cellular leiomyomas (CLs) are described as leiomyomas that are significantly more cellular than the surrounding myometrium, often with crowding and overlapping of nuclei.

The presenting symptoms do not differ from those of patients with typical leiomyomas. On gross examination, CLs are more often soft and appear more tan or yellow and less circumscribed than the usual leiomyomas.

Pre-operatively, anyway, CLs can be recognized at ultrasound evaluation because they appear as hypoechoic uterine lesions. It has been demonstrated that patients with hypoechoic myoma have a significantly longer surgery time after treatment with a GnRH analog than for the rest of the pretreated fibroids or the untreated patients with hypoechoic myomas. Considering the predominant relevance of the traction maneuvers in laparoscopic myomectomy, the difficulty in adequately grasping the tumor is the key element in the longer operative time. The greater softening of the fibroid tissue is probably related to degenerative changes induced by the GnRH-analog pretreatment, particularly in those fibroids without an adequate fibrous "skeleton" and thus with the appearance as hypoechoic at the admission ultrasonography. From a pathologic point of view, these fibroids, when pretreated, showed a predominance of areas of coagulative necrosis and mixoid degeneration, causing longer operative time and showing unequivocally the negative effect of preoperative GnRH analog treatment for these kinds of uterine fibroids.

At the same time, hypoechoic CLs should be more responsive to ulipristal acetate treatment than common leiomyomas, given its antiproliferative activity in cultured leiomyoma cells.

The antiproliferative ulipristal effect, moreover, induces a condition of apoptotic necrosis that, compared to GnRH-a myxoid necrosis, probably allows an easier surgical enucleation of the tumor.

Conditions

Fibroid

Keywords

fibroid; cellular leiomyomas; GnRH analogue; ulipristal acetate

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Ulipristal acetate

women will be treated with an oral dose of ulipristal acetate 5 mg/day for 3 months

Group Type: EXPERIMENTAL

ulipristal acetate

Intervention Type: DRUG

5 mg/day will be administered starting from day 1 of the cycle and up to three months later

Leuprolile acetate

Women will be treated with an intramuscular (IM) injection of leuprolide acetate 11.25 mg in the luteal phase

Group Type: ACTIVE_COMPARATOR

Leuprolide acetate

Intervention Type: DRUG

One dose of 11.25 GnRH analogue depot will be administered in the luteal phase of the menstrual cycle (days 21-24)

Interventions

ulipristal acetate

5 mg/day will be administered starting from day 1 of the cycle and up to three months later

Intervention Type: 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)

Intervention Type: DRUG

Other Intervention Names

Esmya; Enantone 11.25

Eligibility Criteria

Inclusion Criteria

• hypoechoic uterine leiomyoma (echogenicity <3),
• intramural leiomyomas with an ultrasonographic size <20 cm but >4cm,
• indication to surgery (symptoms of menometrorrhagia,
• menstrual disorder,
• infertility,
• pelvic pain or pelvic pressure

Exclusion Criteria

• submucosal leiomyoma,
• endometrial hyperplasia with atypia,
• history of uterine surgery

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

University Magna Graecia

OTHER

Sponsor Role: lead

Responsible Party

Fulvio Zullo

Full professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Fulvio Zullo, MD,PhD

Role: STUDY_DIRECTOR

Magna Graecia University of Catanzaro

Roberta Venturella

Role: PRINCIPAL_INVESTIGATOR

Magna Graecia University of Catanzaro

Locations

Azienda Ospedaliera Pugliese-Ciaccio

Catanzaro, Catanzaro, Italy

Site Status: RECRUITING

Countries

Italy

Central Contacts

Fulvio Zullo, MD,PhD

Role: CONTACT

Phone: 00390961883234

Email: zullo@unicz.it

Roberta Venturella, MD

Role: CONTACT

Phone: 00390961883401

Email: rovefa@libero.it

Facility Contacts

Fulvio Zullo

Role: primary

Other Identifiers

UPA hypoecoic myomas

Identifier Type: -

Identifier Source: org_study_id