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

• ClinicalTrials.gov Identifier: NCT03948789
• Recruitment Status: Recruiting
• First Posted: May 14, 2019
• Last Update Posted: March 6, 2024
• Sponsor: Krankenhaus Nordwest
• Information provided by (Responsible Party): Krankenhaus Nordwest

Tracking Information

• First Submitted Date: May 10, 2019
• First Posted Date: May 14, 2019
• Last Update Posted Date: March 6, 2024
• Actual Study Start Date: July 15, 2020
• Estimated Primary Completion Date: March 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 20, 2019)

• WAI question 4 [ Time Frame: Until at least three consecutive days questionnaire was answered as indicated, up to 12 months ]
  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).
• Symptom Severity Score of the UFS-QoL [ Time Frame: 12 months after treatment ]
  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).

Original Primary Outcome Measures (submitted: May 10, 2019)

• WAI question 4 [ Time Frame: Until at least three consecutive days questionnaire was answered as indicated, up to 12 months ]
  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 "Do you currently hinder a medical condition or injury at work?" Is answered for at least three consecutive days with "No Disability" or "I can do my job, but have complaints" has been.
• Symptom Severity Score of the UFS-QoL [ Time Frame: 12 months after treatment ]
  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. 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.

Current Secondary Outcome Measures (submitted: September 20, 2019)

• Hospital stay in days [ Time Frame: 12 months after treatment ]
• Pain according to visual analog scale [ Time Frame: 12 months after treatment ]
  Visual analog scale ranges from 0-100, 0 indicating no pain, 100 severe pain
• Number of Adverse Events (AEs) [ Time Frame: 12 months after treatment ]
• Number of postinterventional/postsurgery treatment complications [ Time Frame: 12 months after treatment ]
• Number of re-interventions [ Time Frame: 12 months after treatment ]
• Alleviation of symptoms (irregular period, unfulfilled wish for child, pain, quality of life according to UFS-QoL [ Time Frame: 12 months after treatment ]
  QoL: Quality of Life score regarding symptoms, ranges from 0-100, 0 indicating very low QoL, 100 indicating very high QoL
• Health related quality of life according to UFS-QoL [ Time Frame: 12 months after treatment ]
  QoL: Quality of Life score regarding health, ranges from 0-100, 0 indicating very low QoL, 100 indicating very high QoL
• Sexuality related parameters according to UFS-QoL [ Time Frame: 12 months after treatment ]
  QoL: Quality of Life score regarding sexuality, ranges from 0-100, 0 indicating very low QoL, 100 indicating very high QoL
• Number of pregnancies and live births [ Time Frame: 12 months after treatment ]
• Number of late complications like venous thromboembolisms within Follow up time frame [ Time Frame: 12 months after treatment ]
• Number of fibroid recurrences (de novo fibroids) within Follow up time frame [ 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 [ Time Frame: 12 months after treatment ]
  at timepoints: months 1, 3 and 6 compared to baseline.

Original Secondary Outcome Measures (submitted: May 10, 2019)

• Hospital stay in days [ Time Frame: 12 months after treatment ]
• Pain according to visual analog scale [ Time Frame: 12 months after treatment ]
• Number of AEs [ Time Frame: 12 months after treatment ]
• Number of postinterventional/postsurgery treatment complications [ Time Frame: 12 months after treatment ]
• Number of re-interventions [ Time Frame: 12 months after treatment ]
• Alleviation of symptoms (irregular period, unfulfilled wish for child, pain, quality of life according to UFS-QoL [ Time Frame: 12 months after treatment ]
• Health related quality of life according to UFS-QoL [ Time Frame: 12 months after treatment ]
• Sexuality related parameters according to UFS-QoL [ Time Frame: 12 months after treatment ]
• Number of pregnancies and live births [ Time Frame: 12 months after treatment ]
• Number of late complications like venous thromboembolies (e.g. venous thromboemboly (VTE) related to persisting fibroid after MRgFUS- TUF) [ Time Frame: 12 months after treatment ]
• Number of fibroid recurrences (de novo fibroids) within Follow up time frame [ 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 [ Time Frame: 12 months after treatment ]
  at timepoints: months 1, 3 and 6 compared to baseline.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Phase III Study of MR-Guided Focused Ultrasound Surgery for the Treatment of Uterine Fibroids Compared to Myomectomy
• Official Title: 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
• Brief Summary: 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Uterine Fibroids

Intervention

• Procedure: Magnetic Resonance Imaging-controlled high-focussed ultrasound therapy
  Magnetic Resonance Imaging-controlled high-focussed ultrasound
• Procedure: Myomectomy (laparoscopic or open surgical)
  Myomectomy (laparoscopic or open surgical)

Study Arms

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

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: May 10, 2019): 127
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: June 2025
• Estimated Primary Completion Date: March 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Thorsten O Götze, PD Dr. med.; 06976014187; goetze.thorsten@khnw.de

• Listed Location Countries: Germany

Administrative Information

• NCT Number: NCT03948789
• Other Study ID Numbers: MARGI-T
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• 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

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Krankenhaus Nordwest
• Original Responsible Party: Same as current
• Current Study Sponsor: Krankenhaus Nordwest
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

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

• PRS Account: Krankenhaus Nordwest
• Verification Date: March 2024