Ulipristal Acetate for the Preoperative Management of Hypoechoic Cellular Leiomyomas

Sponsor

University Magna Graecia (Other)

Overall Status

Unknown status

CT.gov ID

NCT02361905

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

1.4

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Fibroid	Drug: ulipristal acetate Drug: Leuprolide acetate	Phase 4

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

42 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Feb 1, 2015

Anticipated Primary Completion Date :

Sep 1, 2017

Anticipated Study Completion Date :

Sep 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Ulipristal acetate women will be treated with an oral dose of ulipristal acetate 5 mg/day for 3 months	Drug: ulipristal acetate 5 mg/day will be administered starting from day 1 of the cycle and up to three months later Other Names: Esmya
Active Comparator: Leuprolile acetate Women will be treated with an intramuscular (IM) injection of leuprolide acetate 11.25 mg in the luteal phase	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) Other Names: Enantone 11.25

Arm

Intervention/Treatment

Experimental: Ulipristal acetate

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

Drug: ulipristal acetate

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

Other Names:

Esmya

Active Comparator: Leuprolile acetate

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

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)

Other Names:

Enantone 11.25

Outcome Measures

Primary Outcome Measures

Operative time (minutes) [At the time of skin closure at the end of the myomectomy]
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 .

Secondary Outcome Measures

Difficulty of leiomyoma enucleation assessed by surgeon on a VAS scale [Within 2 hours after the end of the myomectomy]
To compare surgical feasibility (VAS) in patients treated with Ulipristal Acetate and GnRH-a.
Intraoperative blood loss (delta Hb) [The day before surgery and 3 hours after the myomectomy]
To compare blood loss (delta HB) in patients treated with Ulipristal Acetate and GnRH-a.
Post-operative evaluation of leiomyomas characteristics [At the time of pathological assessment]
This is a composite outcome aimed to compare pathological myoma characteristics (cellularity, necrosis, fibrosis) in patients treated with Ulipristal Acetate and GnRH-a.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 55 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Yes

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Azienda Ospedaliera Pugliese-Ciaccio	Catanzaro		Italy	88100

Sponsors and Collaborators

University Magna Graecia

Investigators

Study Director: Fulvio Zullo, MD,PhD, Magna Graecia University of Catanzaro
Principal Investigator: Roberta Venturella, Magna Graecia University of Catanzaro