Ulipristal Acetate Versus GnRH Analogue Treatment Before Hysteroscopic Resection of Uterine Leiomyoma

The uterine leiomyoma is the most common female benign disease. Submucosal fibroid are about 10%, they distort the endometrial cavity causing heavy and/or irregular bleeding (AUB) and infertility. Hysteroscopic removal of submucosal myomas improves this conditions. GnRH analogues are commonly used before hysteroscopic myomectomy to make surgery easier and safer, but they are expensive, have potential side effects and lack a robust evidence base to support this practice. Ulipristal acetate treatment was able and faster to control in 90% of cases uterine bleeding associated with fibroids than GnRH agonists. UPA significantly improved quality of life and pain reduction.

Study Overview

• Status: Unknown
• Conditions: Fibroid
• Intervention / Treatment: Drug: ulipristal acetate; Drug: Leuprolide acetate

Detailed Description

The uterine leiomyoma is the most common benign tumor of the female genital tract. The myomas are usually clinically apparent in 25% of patients. Submucosal fibroid are about 10% of all uterine myoma; they distort the endometrial cavity causing heavy and/or irregular bleeding (AUB) and infertility. According to the degree of myometrial penetration, the European Society for Gynaecological Endoscopy (ESGE) classified submucosal myomas in Type 0 (totally intracavitary fibroids), Type I (<50% myometral penetration), or Type II (>50% myometral penetration).

Hysteroscopic removal of submucosal myomas improves menorrhagia and AUB. GnRH analogues are commonly used before hysteroscopic myomectomy to make surgery easier and safer, but they are expensive, have potential side effects and lack a robust evidence base to support this practice. A recent meta-analysis of data demonstrated that symptomatic relief in patients undergoing surgery was similar either following pre-operative GnRH-a administration or without GnRH-a administration, mainly due to the persistence of abnormal bleeding due to the protrusion of the myoma into the uterine cavity.

In recent studies, Ulipristal acetate treatment was able to control uterine bleeding associated with fibroids in more than 90% of cases. Moreover, it controlled bleeding faster than GnRH agonists, with median times to amenorrhea of 5-7 days in patients receiving UPA compared to 21 days in patients receiving a GnRH agonist. It was demonstrated that UPA significantly improved also quality of life. Pain, as measured by the visual analogue scale, showed a degree of relief similar to that achieved for postoperative pain with narcotic and non-narcotic analgesics. This pain reduction is related to the high amenorrhea rate during treatment (severe bleeding being responsible for uterine contractions and prostaglandin secretion). No sub-analysis have been conducted on submucosal fibroids but, according to our experience, this subgroup of myomas may be the one who most benefits from the administration of UPA.

• Study Type: Interventional
• Enrollment (Anticipated): 146
• Phase: Phase 4

Contacts and Locations

Study Locations

• Italy
  • Catanzaro, Italy, 88100
    • Recruiting
    • Azienda Ospedaliera Pugliese-Ciaccio

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria: submucosal leiomyoma, symptoms of menomethrorragia, menstrual disorder, infertility, pelvic pain.

Exclusion Criteria: intramural or subserosal leiomyomas, endometrial hyperplasia with atypia, history of uterine surgery

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ulipristal acetate; Womens will be treated with 5 mg/day of oral ulipristal acetate 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 1 IM injection of leuprolide acetate 11,25 mg in 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Uterine bleeding assessed by pictorial blood-loss assessment chart (PBAC)	To compare the proportion of controlled uterine bleeding in patients with submucous myoma preoperatively treated by ulipristal acetate or by GnRh-a	90 days after the beginning of the treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility of myoma hysteroscopic resection (VAS score)	Surgeon experience about the hysteroscopy	Within 2 hours after the end of the hysteroscopy
Operative time	It will be expressed in minutes	Within 2 hours after the end of the hysteroscopy
Haemoglobin concentration	It will be expressed in mg/dL	The day before and 3 hours after the hysteroscopy
Fluid absorption	It will be expressed in mL	Within 2 hours after the end of the hysteroscopy

Collaborators and Investigators

• Sponsor: University Magna Graecia

Study record dates

Study Major Dates

• Study Start: February 1, 2015
• Primary Completion (Anticipated): September 1, 2017
• Study Completion (Anticipated): September 1, 2017

Study Registration Dates

• First Submitted: February 2, 2015
• First Submitted That Met QC Criteria: February 8, 2015
• First Posted (Estimate): February 12, 2015

Study Record Updates

• Last Update Posted (Estimate): November 18, 2016
• Last Update Submitted That Met QC Criteria: November 17, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Keywords: hysteroscopy; fibroids; gnrh analogue; ulipristal acetate
• Additional Relevant MeSH Terms: Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Connective Tissue Diseases; Neoplasms, Connective Tissue; Neoplasms, Muscle Tissue; Leiomyoma; Myofibroma; Physiological Effects of Drugs; Antineoplastic Agents; Antineoplastic Agents, Hormonal; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Contraceptive Agents, Female; Fertility Agents, Female; Fertility Agents; Leuprolide; Ulipristal acetate
• Other Study ID Numbers: UPA and hysteroscopy

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No