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Ulipristal Acetate for the Preoperative Management of Hypoechoic Cellular Leiomyomas

U

University Magna Graecia

Status and phase

Unknown
Phase 4

Conditions

Fibroid

Treatments

Drug: Leuprolide acetate
Drug: ulipristal acetate

Study type

Interventional

Funder types

Other

Identifiers

NCT02361905
UPA hypoecoic myomas

Details and patient eligibility

About

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.

Full 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.

Enrollment

42 estimated patients

Sex

Female

Ages

18 to 55 years old

Volunteers

Accepts Healthy Volunteers

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

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

Double Blind

42 participants in 2 patient groups

Ulipristal acetate
Experimental group
Description:
women will be treated with an oral dose of ulipristal acetate 5 mg/day for 3 months
Treatment:
Drug: ulipristal acetate
Leuprolile acetate
Active Comparator group
Description:
Women will be treated with an intramuscular (IM) injection of leuprolide acetate 11.25 mg in the luteal phase
Treatment:
Drug: Leuprolide acetate

Trial contacts and locations

1

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Central trial contact

Fulvio Zullo, MD,PhD; Roberta Venturella, MD

Data sourced from clinicaltrials.gov

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