Clinical trial NCT02361905: Ulipristal Acetate for the Preoperative Management of Hypoechoic Cellular Leiomyomas
Official title: Advantages of Ulipristal Acetate for the Preoperative Treatment of Hypoechoic Cellular Leiomyomas
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Fibroid
Keywords: fibroid
cellular leiomyomas
GnRH analogue
ulipristal acetate
Lead sponsor: University Magna Graecia
Sponsor class: OTHER
First posted: 2015-02-12
Enrollment: 42
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Operative time (minutes)
timeFrame: At the time of skin closure at the end of the myomectomy
Secondary outcomes:
measure: Difficulty of leiomyoma enucleation assessed by surgeon on a VAS scale
timeFrame: Within 2 hours after the end of the myomectomy
measure: Intraoperative blood loss (delta Hb)
timeFrame: The day before surgery and 3 hours after the myomectomy
measure: Post-operative evaluation of leiomyomas characteristics
timeFrame: At the time of pathological assessment
Other outcomes:
Locations:
city: Catanzaro
country: Italy
facility: Azienda Ospedaliera Pugliese-Ciaccio
Study officials:
affiliation: Magna Graecia University of Catanzaro
name: Fulvio Zullo, MD,PhD
role: STUDY_DIRECTOR
affiliation: Magna Graecia University of Catanzaro
name: Roberta Venturella
role: PRINCIPAL_INVESTIGATOR
References: