Sonalleve Fibroid Ablation Pivotal Clinical Trial for MR-HIFU of Uterine Fibroids

Study Overview
=================
Brief Summary
-----------------
The purpose of this clinical study is to determine whether treatment with the Philips Sonalleve Magnetic Resonance-guided High Intensity Focused Ultrasound (MR-HIFU) system is effective in the treatment symptomatic uterine leiomyomas (uterine fibroids).

Detailed Description
-----------------
Uterine Fibroids are the most common benign tumors in pre- and peri-menopausal women. Fibroids occur in 20-50% of women over 30 years of age, and with increasing size can produce pain, menorrhagia, pressure, bloating and urinary and bowel compression symptoms. Fibroids may also cause infertility. Symptomatic fibroids impact health and well-being of the female including lost work hours and reduced quality of life. Current medical treatments include invasive removal of the fibroid (hysterectomy, myomectomy), drug therapy, or treatments causing necrosis of the fibroid tissue such as ablation (freezing or heating) or embolization. It has been estimated that 600,000 hysterectomies are performed per year in the United States and more than half of the conducted hysterectomies are due to fibroids. For the relief of symptoms, women wishing to preserve the uterus may choose between invasive procedures of myomectomy, Uterine Artery Embolization (UAE), ablation or cryotherapy. The surgically invasive procedures require anesthesia, hospital stays, and long recovery periods. However, High Intensity Focused Ultrasound (HIFU) shows promising results in relieving fibroid symptoms. This study will confirm the safety and clinical effectiveness of Philips Sonalleve MR-HIFU Fibroid Therapy system for ablating symptomatic fibroids.

Official Title
-----------------
Philips Pivotal Clinical Trial for MRI-guided High Intensity Focused Ultrasound Ablation of Uterine Fibroids

Conditions
-----------------
Uterine Fibroids

Intervention / Treatment
-----------------
* Device: MR-HIFU treatment
* Device: Sham treatment


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Women, age between 18 and 50 years Ethnicity has a match with the intended profile for the site Weight < 140kg or 310lbs Pre- or peri-menopausal as indicated by clinical evaluation or Follicle Stimulating Hormone (FSH) level < 40 IU/L Willing and able to attend all study visits Willing and able to complete Menstrual Blood Loss (MBL) assessment with Alkaline Hematin (AH) method Willing and able to use reliable contraception methods Uterine size < 24 weeks Cervical cell assessment by Pap smear: Normal, Low Grade Squamous Intraepithelial Lesion (SIL), Low risk Human Papillomavirus (HPV) or Atypical Squamous Cells of Uncertain Significance (ASCUS) subtypes of cervical tissue MR-HIFU device accessibility to fibroids such that at least 50% of the total fibroid volume can be treated. Fibroids selected for treatment meeting the following criteria (further extrapolated in the protocol): Total planned ablation volume of all fibroids should not exceed 250 ml and No more than 5 fibroids should be planned for ablation and Dominant fibroid (diameter) is greater than or equal to 3 cm and Completely non-enhancing fibroids should not be treated as the identification of treated volume becomes ambiguous Patient's self-assessment indicates that she has had episodes of heavy menstrual bleeding in the past 6 months. Menstrual Blood Loss (MBL) ≥150 ml and ≤ 500 ml Exclusion Criteria: Other Pelvic Disease (Other mass, endometriosis, ovarian tumor, acute pelvic disease, significant adenomyosis) Desire for future pregnancy Significant systemic disease even if controlled Positive pregnancy test Hematocrit < 25% Extensive scarring along anterior lower abdominal wall (>50% of area) Surgical clips in the potential path of the HIFU beam MRI contraindicated MRI contrast agent contraindicated (including renal insufficiency) Calcifications around or throughout uterine tissues that may affect treatment Communication barrier Highly perfused or brighter than myometrium in T2-weighted MRI (according to the T2 contrast obtained using the Philips MR-HIFU MR protocol) fibroids Fibroids not quantifiable on MRI (e.g. multi-fibroid cases where volume measurements are not feasible) Menses lasting > 7 days or intermenstrual bleeding (patient can be included if there is endometrial biopsy within 6 months to exclude malignancy) Patient is currently on hormonal medication for fibroids or has a hormonal medication history as described below: 1-month Lupron dose or equivalent: less than 1 month prior to MBL measurement or 3-month Lupron dose or equivalent: less than 3 months prior to MBL measurement or Depo Provera or equivalent: less than 6 months prior to MBL measurement

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MR-HIFU treatment<br>Patients receiving MR-HIFU treatment | Device: MR-HIFU treatment<br>* A treatment session with the Philips Sonalleve MR-HIFU device for thermal ablation of uterine fibroids with high-intensity focused ultrasound.<br>* Other names: Philips Sonalleve MR-HIFU Uterine Fibroid Therapy;|
| Sham Comparator: Sham Treatment<br>Patients receiving sham treatment | Device: Sham treatment<br>* A pretend treatment session with the Philips Sonalleve MR-HIFU system in which no therapeutic ultrasound doses are delivered.<br>* Other names: pretend treatment with Philips Sonalleve MR-HIFU;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Alternative Interventional Treatment (AIT) | AIT is scored dichotomously as follows: 0 = Failure. Failure occurs if an AIT for fibroid related symptoms is administered within 12 months of study treatment. 1 = Success. Success occurs if no AIT is administered for fibroid related symptoms within 12 months of study treatment. An AIT is defined as being one of the following: hysterectomy, myomectomy, uterine artery embolization, endometrial ablation and resection, or another MR-HIFU treatment (with the exception of a 're-treatment' as defined in the protocol, e.g. because of temporarily inaccessible fibroids). | 12 months after HIFU treatment | 
| Menstrual Blood Loss (MBL) | Menstrual Blood Loss (MBL) scored dichotomously as follows: 0 = Failure. Failure occurs if the change from baseline in MBL measurement is < 50 % as measured with alkaline hematin test (AHT) method. 1 = Success. Success occurs if the change from baseline in MBL measurement is >= 50 %, or if the MBL is < 80 ml as measured with the AHT method. | at baseline and at 12 months following treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Return to Activity | Length for Return to Activity after HIFU treatment measured dichotomously: 0 = Failure. If subject takes longer than 72 hours to return to work or normal activity. 1 = Success. If subject returns to work or normal activity within 72 hours inclusive. | 72 hours | 
| Symptom Severity Score (SSS) | Symptom Severity Score (SSS) of Uterine Fibroid Symptom and Quality of Life questionnaire (UFS-QoL), assessed dichotomously at 12 months: 0 = Failure. Reduction of less than 10 points on SSS. 1 = Success. Reduction of at least 10 points on SSS. | at baseline and at 12 months following treatment | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
uterine fibroids, uterine leiomyomas, magnetic resonance imaging, focused ultrasound