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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Fibroid

Intervention / Treatment
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* Drug: ulipristal acetate
* Drug: Leuprolide acetate


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ulipristal acetate<br>Womens will be treated with 5 mg/day of oral ulipristal acetate for 3 months | Drug: ulipristal acetate<br>* 5 mg/day will be administered starting from day 1 of the cycle and up to three months later<br>* Other names: Esmya;|
| Active Comparator: Leuprolile acetate<br>women will be treated with 1 IM injection of leuprolide acetate 11,25 mg in in the luteal phase | Drug: Leuprolide acetate<br>* One dose of 11.25 GnRH analogue depot will be administered in the luteal phase of the menstrual cycle (days 21-24)<br>* Other names: Enantone 11.25;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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fibroids, gnrh analogue, ulipristal acetate, hysteroscopy