Phase III Study of MR-Guided Focused Ultrasound Surgery for the Treatment of Uterine Fibroids Compared to Myomectomy

Multicenter, Randomized Phase III Study of MR-Guided Focused Ultrasound Surgery for the Treatment of Uterine Fibroids (MRgFUS TUF) Compared to Myomectomy in Symptomatic Medication and Not Sufficiently Treatable Uterine Fibroids

The aim of the study is to answer the question, whether in patients with symptomatic and medically not sufficiently treatable uterine fibroids (population) the "Magnetic-Resonance-Guided Focused Ultrasound Surgery" short, MRgFUS-TUF (intervention) offers less burdensome therapy and patient-relevant advantages (symptom relief) compared to the operative myomectomy (comparison). The study will hence investigate the therapeutic benefit of this method.

Study Overview

• Status: Recruiting
• Conditions: Uterine Fibroids
• Intervention / Treatment: Procedure: Myomectomy (laparoscopic or open surgical); Procedure: Magnetic Resonance Imaging-controlled high-focussed ultrasound therapy

• Study Type: Interventional
• Enrollment (Estimated): 127
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Thorsten O Götze, PD Dr. med.; Phone Number: 06976014187; Email: goetze.thorsten@khnw.de

Study Locations

• Germany
  • Göttingen, Germany
    • Recruiting
    • FOKUS Radiologische Gemeinschaftspraxis
    • Contact: Peter Hunold, PD Dr.
  • Leipzig, Germany
    • Recruiting
    • Leipzig University
    • Contact: Bahriye Aktas, Prof. Dr.
    • Contact: Nikolaos Bailis
  • Stuttgart, Germany
    • Recruiting
    • Marienhospital
    • Contact: Markus Zähringer, Prof. Dr.
    • Contact: Manfred Hofmann, PD Dr.
  • Hessen
    • Frankfurt, Hessen, Germany, 60488
      • Recruiting
      • Krankenhaus Nordwest
      • Contact: Markus Düx, Prof. Dr.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Women with symptomatic and medically untreatable uterine fibroids who score at least 40 points on the Symptom Severity Score (SSS) of the Uterine Fibroid Symptom and Quality of Life Questionnaire (UFS- QoL )
• Safe access for the MRgFUS possible (anatomical position of the fibroids): Pelvic magnetic resonance imaging to document the number, location and size of fibroids and to exclude malignancy and other pelvic pathologies; necessary to determine whether MRgFUS can be performed technically (presence of a stable ultrasound window and exclusion of scars in the access path)
• ≤ 5 fibroids requiring treatment
• Fibroids with a diameter ≤ 10 cm
• Total myoma volume ≤ 400 ml
• Patient is suitable for treatment with MRgFUS-TUF as well as for myomectomy
• Desire for least invasive treatment
• Indication for hysteroscopy and fractionated abrasion depending on the bleeding pattern and endometrial thickness and structure have been critically tested in advance.
• inconspicuous cytological smear of the cervix uteri not older than 12 months
• No previous uterine surgery / intervention
• Female patients aged> 18 years. Patients of reproductive age must adhere to appropriate contraception until 6 months after the procedure. (Methods of contraception that meet the criteria of highly effective contraception in the sense of the Note for guidance on non- clinical safety studies for the conduct of human clinical trials for meet pharmaceuticals [CPMP / ICH / 286/95 mod ]). Patients of childbearing potential must have a negative pregnancy test within 7 days prior to enrollment.
• Karnofsky index ≥ 70
• Given medical operability
• Written consent of the patient

Exclusion Criteria:

• Pretreatment with ulipristal acetate ( Esmya ) ≤ 2 months
• Suspected Malignancy (absolute)
• Pregnancy (absolute)
• acute inflammatory process (absolute)
• Uterus myomatosis with more than 5 fibroids (relative, case-by-case decision)
• Uterine fibroids with a diameter over 10 cm (absolute)
• insufficient sound window can be reached for treatment (eg intestinal overlays, large scars in the acoustic window, very dorsal position of the fibroid)
• subserous stalked fibroids
• Inaccessible location of fibroids
• Scarring in the treatment area
• Recurring abortions
• general contraindications to MR contrast agents
• MRI contraindications
• Presence of pacemaker or metal implants
• Karnofsky Index <70
• Severe hepatic dysfunction (Aspartat-Aminotransferase (AST) / Transaminasen Alanin-Amino-transferase (ALT)> 3.5x ULN (upper limit of normal), Alkalische Phosphatase (AP)> 6xULN)
• Active CHD (congenital heart disease), (symptoms present), cardiomyopathy or heart failure in NYHA (New York Heart Association) and EF (ejection fraction) stage III-IV <45%
• Serious internistic side-diseases or an acute infection
• Chronic inflammatory bowel disease
• Pregnancy or lactation
• Participation in another interventional study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: A Myomectomy; Removement of uterine fibroids by myomectomy	Procedure: Myomectomy (laparoscopic or open surgical); Myomectomy (laparoscopic or open surgical)
Experimental: B MRgFUS-TUF; Removement of uterine fibroids by Magnetic Resonance Imaging-controlled high-focussed ultrasound therapy (MRgFUS-TUF)	Procedure: Magnetic Resonance Imaging-controlled high-focussed ultrasound therapy; Magnetic Resonance Imaging-controlled high-focussed ultrasound

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
WAI question 4	Time to sustainably return to normal activities, based on the daily Work Activity Index (WAI) dimension, "Estimated Impairment of Disease Performance". The return to normal activities is considered to be given if the question "Hindrance of medical condition or injury at work?" (min max: 1: 'in my opinion, I am completely unable to work', 6: 'No Disability') is answered for at least three consecutive days with "No Disability" (6) or "I can do my job, but have complaints" (5).	Until at least three consecutive days questionnaire was answered as indicated, up to 12 months
Symptom Severity Score of the UFS-QoL	The symptom severity is determined to be the co- primary endpoint for assessing therapeutic efficacy, based on the SSS (Symptom Severity Score) of the UFS-QoL (Uterine fibroid symptom and quality of life questionnaire). The co-primary assessment is performed 12 months after the primary treatment and for the evaluation the proportion of patients with at least 25 points improvement in the SSS is determined (0-100 scale, 100 indicating very strong symptoms, 0 no or low symptoms).	12 months after treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hospital stay in days		12 months after treatment
Pain according to visual analog scale	Visual analog scale ranges from 0-100, 0 indicating no pain, 100 severe pain	12 months after treatment
Number of Adverse Events (AEs)		12 months after treatment
Number of postinterventional/postsurgery treatment complications		12 months after treatment
Number of re-interventions		12 months after treatment
Alleviation of symptoms (irregular period, unfulfilled wish for child, pain, quality of life according to UFS-QoL	QoL: Quality of Life score regarding symptoms, ranges from 0-100, 0 indicating very low QoL, 100 indicating very high QoL	12 months after treatment
Health related quality of life according to UFS-QoL	QoL: Quality of Life score regarding health, ranges from 0-100, 0 indicating very low QoL, 100 indicating very high QoL	12 months after treatment
Sexuality related parameters according to UFS-QoL	QoL: Quality of Life score regarding sexuality, ranges from 0-100, 0 indicating very low QoL, 100 indicating very high QoL	12 months after treatment
Number of pregnancies and live births		12 months after treatment
Number of late complications like venous thromboembolisms within Follow up time frame		12 months after treatment
Number of fibroid recurrences (de novo fibroids) within Follow up time frame		12 months after treatment
Time period until return to normal physical activities, measured by the rate of patients, who achieved an a priori clinically relevant reduction of SSS of UFS-QoL	at timepoints: months 1, 3 and 6 compared to baseline.	12 months after treatment

Collaborators and Investigators

• Sponsor: Krankenhaus Nordwest
• Investigators: Principal Investigator: Thorsten O Götze, PD Dr. med., Krankenhaus Nordwest

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): July 15, 2020
• Primary Completion (Estimated): March 1, 2025
• Study Completion (Estimated): June 1, 2025

Study Registration Dates

• First Submitted: May 10, 2019
• First Submitted That Met QC Criteria: May 10, 2019
• First Posted (Actual): May 14, 2019

Study Record Updates

• Last Update Posted (Estimated): March 6, 2024
• Last Update Submitted That Met QC Criteria: March 5, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• 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
• Other Study ID Numbers: MARGI-T

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

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