Ulipristal vs. GnRHa Prior to Laparoscopic Myomectomy

Phase 4

• Conditions: Fibroids
• Interventions: Drug: GnRHa; Drug: Ulipristal

• Registration Number: NCT02288130
• Lead Sponsor: Amsterdam UMC, location VUmc

Brief Summary

Rationale: Laparoscopic myomectomy is increasingly performed over laparotomic myomectomy, because of the many benefits for the patient in terms of pain, hospital stay and recovery. In order to increase the success rate of a laparoscopic procedure pre-treatment to decrease the volume might be beneficial. Gonadotropin-releasing hormone agonists (GnRHa) are used for this purpose with good results in terms of volume reduction, but sometimes resulting in loss of distinction of the right surgical planes. Ulipristal is a new pre-operative treatment option for symptomatic fibroids, which has demonstrated good results in terms of volume reduction. The effect on cleavage planes is unknown. This study is performed to evaluate if Ulipristal is as effective as GnRHa in terms of surgical outcome.

Objective: to investigate if Ulipristal is non-inferior to GnRH in terms of intra-operative blood-loss (primary outcome), surgical time, surgical ease, complications, quality of life and costs.

Study design: Double blind randomized controlled multi-center trial. Study population: Premenopausal women in whom a maximum of 2 symptomatic intramural fibroids between 5 and 12 cm in diameter will be removed. Fibroid types 3, 4, 5, 6 and 2-5 will be included.

Intervention: Three months of Ulipristal 5 mg once daily combined with a single saline injection at the onset of pretreatment (produced as placebo of Leuproreline) or (comparison) 11.25 mg Leuproreline injections at the onset of pretreatment with placebo tablets (once daily) .

Methods: Within 1 month after pre-treatment patients will undergo a laparoscopic myomectomy by experienced surgeons. Operative characteristics will be recorded prospectively. Follow up will be 6 months after surgery mainly for quality of life assessment. A cost utility analysis will be conducted alongside the trial.

Main study parameters/endpoints: Ulipristal is non-inferior to GnRHa in terms of blood loss during surgery when the average difference between the two groups is below 150 ml (standard deviation 250 ml).

Nature and extent of the burden and risks associated with participation, benefit and group relatedness: Both Ulipristal and GnRHa have been registered for this indication. Safety has been tested and no specific risks apply.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2014-11-06
• Study First Submitted QC: 2014-11-10
• Study First Posted: 2014-11-11
• Study Start: 2014-12
• Status Verified: 2016-11
• Last Update Submitted: 2016-11-02
• Last Update Posted: 2016-11-03
• Primary Completion: 2017-07
• Study Completion: 2017-11

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: Female
• Target Recruitment: 100

Inclusion Criteria

Women visiting the gynecological outpatient department with symptomatic fibroids will be screened for eligibility. In order to be eligible to participate in this trial, a subject must meet all of the following criteria:

• provide written consent prior to any study related procedures
• pre-menopausal
• a planned resection of a maximum of 2 FIGO (PALM-COEIN classification) type 3, 4, 5, 6 or 2-5 fibroids of >5 cm
• the(se) fibroid(s) should be between 5 and 12 cm (maximum diameter)
• other fibroids should be small (<2 cm), not clinically relevant, or not resectable (e.g. difficult position), or type 7 (any size)
• eligible for laparoscopic myomectomy

Exclusion Criteria

A potential subject who meets any of the following criteria will be excluded from participation in this trial:

• Current pregnancy
• (suspicion of) malignancy
• any type 0-2 fibroids smaller than 5 cm
• more than 2 type 3-6 fibroids > 5 cm that need to be removed (except type 7 fibroids of any size)
• use of any hormonal agents and not willing to discontinue their use
• use of anticoagulants
• coagulopathy
• Use of NSAIDs impacting bleeding before surgery
• Contraindication to laparoscopy procedure or causes of complications (multiple laparotomies, frozen pelvis, severe endometriosis)
• allergy to leuprolide acetate/comparable nonapeptides or Ulipristal

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
GnRHa and placebo tablets	GnRHa	11.25 mg Leuproreline injections at the onset of pretreatment with placebo tablets (once daily)
Ulipristal	Ulipristal	Three months of Ulipristal 5 mg once daily combined with a single saline injection at the onset of pretreatment (produced as placebo of Leuproreline)

Primary Outcome Measures

Name	Time	Method
Blood loss during surgery	Reported directly after surgery	Ulipristal is non-inferior to GnRHa in terms of blood loss during surgery when the average difference between the two groups is below 150 ml (standard deviation 250 ml)

Trial Locations

Locations (9)

Flevoziekenhuis; 🇳🇱 Almere, Netherlands

Onze Lieve Vrouwen Gasthuis; 🇳🇱 Amsterdam, Netherlands

Sint Lucas Andreas Ziekenhuis; 🇳🇱 Amsterdam, Netherlands

VU medical center; 🇳🇱 Amsterdam, Netherlands

Catharina Ziekenhuis; 🇳🇱 Eindhoven, Netherlands

Maasstad ziekenhuis; 🇳🇱 Rotterdam, Netherlands

Radboud University Medical Center; 🇳🇱 Nijmegen, Netherlands

Spaarne Gasthuis; 🇳🇱 Haarlem, Netherlands

Maxima Medisch Centrum; 🇳🇱 Veldhoven, Netherlands