Ulipristal vs. GnRHa Prior to Laparoscopic Myomectomy (MYOMEX)

Ulipristal Versus Gonadotropin-releasing Hormone Agonists Prior to Laparoscopic Myomectomy: a Double Blind Randomized Controlled Trial

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.

Study Overview

• Status: Unknown
• Conditions: Fibroids
• Intervention / Treatment: Drug: GnRHa; Drug: Ulipristal

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Phase 4

Contacts and Locations

Study Locations

• Netherlands
  • Almere, Netherlands
    • Recruiting
    • Flevoziekenhuis
    • Contact: Marchien van Baal
  • Amsterdam, Netherlands
    • Recruiting
    • Onze Lieve Vrouwen Gasthuis
    • Contact: P Van Kesteren
  • Amsterdam, Netherlands
    • Recruiting
    • VU Medical Center
    • Contact: Wouter Hehenkamp, PhD; Phone Number: +31204444444; Email: w.hehenkamp@vumc.nl
  • Amsterdam, Netherlands
    • Recruiting
    • Sint Lucas Andreas Ziekenhuis
    • Contact: Andreas Thurkow
  • Eindhoven, Netherlands
    • Recruiting
    • Catharina Ziekenhuis
    • Contact: D Schoot
  • Haarlem, Netherlands
    • Recruiting
    • Spaarne Gasthuis
    • Contact: Jonas van de Lande
  • Nijmegen, Netherlands
    • Recruiting
    • Radboud University Medical Center
    • Contact: Sjors Coppus
  • Rotterdam, Netherlands
    • Recruiting
    • Maasstad Ziekenhuis
    • Contact: M Aktas
  • Veldhoven, Netherlands
    • Recruiting
    • Maxima Medisch Centrum
    • Contact: M Bongers

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: GnRHa and placebo tablets; 11.25 mg Leuproreline injections at the onset of pretreatment with placebo tablets (once daily)	Drug: GnRHa; Other Names: Lucrin
Active Comparator: 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)	Drug: Ulipristal; Other Names: Esmya
No Intervention: Control; No pre-treatment prior to laparoscopic myomectomy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood loss during 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)	Reported directly after surgery

Collaborators and Investigators

• Sponsor: Amsterdam UMC, location VUmc
• Investigators: Study Chair: Wouter Hehenkamp, PhD, Amsterdam UMC, location VUmc

Study record dates

Study Major Dates

• Study Start: December 1, 2014
• Primary Completion (Anticipated): July 1, 2017
• Study Completion (Anticipated): November 1, 2017

Study Registration Dates

• First Submitted: November 6, 2014
• First Submitted That Met QC Criteria: November 10, 2014
• First Posted (Estimate): November 11, 2014

Study Record Updates

• Last Update Posted (Estimate): November 3, 2016
• Last Update Submitted That Met QC Criteria: November 2, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Muscle Tissue; Leiomyoma; Physiological Effects of Drugs; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Contraceptive Agents, Female; Ulipristal acetate
• Other Study ID Numbers: 2014.421