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Ulipristal Acetate for the Preoperative Management of Hypoechoic Cellular Leiomyomas

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ClinicalTrials.gov Identifier: NCT02361905
Recruitment Status : Unknown
Verified November 2016 by Fulvio Zullo, University Magna Graecia.
Recruitment status was:  Recruiting
First Posted : February 12, 2015
Last Update Posted : November 18, 2016
Sponsor:
Information provided by (Responsible Party):
Fulvio Zullo, University Magna Graecia

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.


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Study Type : Interventional  (Clinical Trial)
Estimated 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 : February 2015
Estimated Primary Completion Date : September 2017
Estimated Study Completion Date : September 2017

Resource links provided by the National Library of Medicine


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 Name: 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 Name: Enantone 11.25




Primary Outcome Measures :
  1. Operative time (minutes) [ Time Frame: 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 :
  1. Difficulty of leiomyoma enucleation assessed by surgeon on a VAS scale [ Time Frame: Within 2 hours after the end of the myomectomy ]
    To compare surgical feasibility (VAS) in patients treated with Ulipristal Acetate and GnRH-a.

  2. Intraoperative blood loss (delta Hb) [ Time Frame: 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.

  3. Post-operative evaluation of leiomyomas characteristics [ Time Frame: 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.



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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02361905


Contacts
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Contact: Fulvio Zullo, MD,PhD 00390961883234 zullo@unicz.it
Contact: Roberta Venturella, MD 00390961883401 rovefa@libero.it

Locations
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Italy
Azienda Ospedaliera Pugliese-Ciaccio Recruiting
Catanzaro, Italy, 88100
Contact: Fulvio Zullo    00390961883234    zullo@unicz.it   
Principal Investigator: Roberta Venturella, MD         
Sponsors and Collaborators
University Magna Graecia
Investigators
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Study Director: Fulvio Zullo, MD,PhD Magna Graecia University of Catanzaro
Principal Investigator: Roberta Venturella Magna Graecia University of Catanzaro

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Responsible Party: Fulvio Zullo, Full professor, University Magna Graecia
ClinicalTrials.gov Identifier: NCT02361905     History of Changes
Other Study ID Numbers: UPA hypoecoic myomas
First Posted: February 12, 2015    Key Record Dates
Last Update Posted: November 18, 2016
Last Verified: November 2016

Keywords provided by Fulvio Zullo, University Magna Graecia:
fibroid
cellular leiomyomas
GnRH analogue
ulipristal acetate

Additional relevant MeSH terms:
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Leiomyoma
Myofibroma
Neoplasms, Muscle Tissue
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Connective Tissue
Connective Tissue Diseases
Leuprolide
Ulipristal acetate
Fertility Agents, Female
Fertility Agents
Reproductive Control Agents
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Contraceptive Agents, Female
Contraceptive Agents