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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Uterine Fibroids

Intervention / Treatment
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* Procedure: Magnetic Resonance Imaging-controlled high-focussed ultrasound therapy
* Procedure: Myomectomy (laparoscopic or open surgical)


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

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: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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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 |