Ulipristal Acetate for the Preoperative Management of Hypoechoic Cellular Leiomyomas

Fibroid Clinical Trial

Official title:

Advantages of Ulipristal Acetate for the Preoperative Treatment of Hypoechoic Cellular Leiomyomas

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02361905
• Other study ID #: UPA hypoecoic myomas
• Status: Recruiting
• Phase: Phase 4
• First received: February 2, 2015
• Last updated: November 17, 2016
• Start date: February 2015
• Est. completion date: September 2017

Study information

• Verified date: November 2016
• Source: University Magna Graecia
• Contact: Fulvio Zullo, MD,PhD
• Phone: 00390961883234
• Email: zullo[@]unicz.it
• Is FDA regulated: No
• Health authority: Italy: National Institute of Health
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 42
• Est. completion date: September 2017
• Est. primary completion date: September 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 55 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Fibroid
• Leiomyoma

Intervention

Drug:
• ulipristal acetate
5 mg/day will be administered starting from day 1 of the cycle and up to three months later
• Leuprolide acetate
One dose of 11.25 GnRH analogue depot will be administered in the luteal phase of the menstrual cycle (days 21-24)

Locations

Country	Name	City	State
Italy	Azienda Ospedaliera Pugliese-Ciaccio	Catanzaro

Sponsors (1)

Lead Sponsor	Collaborator
University Magna Graecia

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Operative time (minutes)	To evaluate the difference in terms of operative times in patients with hypoechoic CLs submitted to laparoscopic myomectomy and preoperatively treated by ulipristal acetate or GnRh-a .	At the time of skin closure at the end of the myomectomy	Yes
Secondary	Difficulty of leiomyoma enucleation assessed by surgeon on a VAS scale	To compare surgical feasibility (VAS) in patients treated with Ulipristal Acetate and GnRH-a.	Within 2 hours after the end of the myomectomy	Yes
Secondary	Intraoperative blood loss (delta Hb)	To compare blood loss (delta HB) in patients treated with Ulipristal Acetate and GnRH-a.	The day before surgery and 3 hours after the myomectomy	Yes
Secondary	Post-operative evaluation of leiomyomas characteristics	This is a composite outcome aimed to compare pathological myoma characteristics (cellularity, necrosis, fibrosis) in patients treated with Ulipristal Acetate and GnRH-a.	At the time of pathological assessment	Yes