Safety & Efficacy of Non-Invasive Procedures Using Ultrasound-Guided HIFU 'Sonotrip V20' in Symptomatic Uterine Fibroids

A Prospective, Single Center, Single Group, Pivotal Clinical Trial to Evaluate the Safety and Efficacy of Non-Invasive Procedures Using Ultrasound-Guided High-Intensity Focused Ultrasound 'Sonotrip V20'

This is a single-arm clinical trial evaluating the safety and efficacy of ultrasound-guided HIFU (Sonotrip V20) for symptomatic uterine fibroids. 57 cases will be enrolled at a Korean institution. Participants will undergo the HIFU procedure based on a pre-established plan using MRI images. Assessments will be conducted immediately post-procedure and at 4 and 24 weeks. Primary endpoint is fibroid volume reduction at 24 weeks, with secondary endpoints including Non-Perfused Volume Ratio, quality of life, hemoglobin change, pain assessment, and additional medication use. Adverse events will be monitored.

This study is designed as a prospective, single-center, single-arm, confirmatory clinical trial to evaluate the safety and efficacy of the ultrasound-guided High-Intensity Focused Ultrasound (HIFU) device 'Sonotrip V20' in patients with symptomatic uterine fibroids, and includes a total of 57 cases (considering a dropout rate of 20%) at one institution in Korea.

After receiving a full explanation of the study, volunteers who voluntarily agree in writing to participate in this study and are found to meet the inclusion/exclusion criteria will be enrolled in the study, assigned a subject registration number, and scheduled for hospitalization and procedure. The investigator will develop a procedure plan from the MRI images prior to the procedure date and perform the HIFU procedure according to the pre-established procedure plan on the day of the procedure.

Subjects will undergo observations and tests (such as pregnancy tests and laboratory tests) to evaluate efficacy and safety immediately after the procedure and at 4 and 24 weeks after the procedure.

The primary efficacy endpoint to evaluate the safety and efficacy of the investigational medical device is "reduction in uterine fibroid volume (%) at 24 weeks post-procedure," and the secondary efficacy endpoints are "Non-Perfused Volume Ratio (NPVR) immediately after the procedure," "quality of life (score)," "post-procedure hemoglobin change (%)," "pain assessment during the procedure (score)," and "percentage of subjects receiving additional sedation or pain medication (N%). Safety is assessed by the number of adverse events that occurred in subjects during the study.

Inclusion Criteria:

1. adult women 19 years of age or older

2. with symptomatic uterine fibroids* (e.g., heavy periods, dysmenorrhea, abnormal bleeding, pressure symptoms including pelvic pain, and urinary and bowel dysfunction)12

   *Symptomatic fibroids: a Symptom Severity Score (SSS) score of 41 or higher on the UFS-QOL questionnaire for fibroid symptoms.

3. premenopausal (FSH<40 mIU/ml)

4. For women of childbearing potential, agree to use at least one clinically adequate method of contraception* for the duration of the study.

   * Clinically adequate contraception is defined as "[intrauterine device (e.g., Loop, Mirena), chemical barrier method (spermicide), or subdermal implant (e.g., Implanon)] + physical barrier method (male or female)", tubal surgery, or laparoscopic contraception (a type of tubal ligation).

5. have been diagnosed with fibroids by imaging studies.

6. have four or fewer fibroids to be treated

7. the size of the fibroids to be treated is 12 cm or less with no necrotic or calcified areas13

8. have voluntarily decided to participate in this study and have given written consent to the informed consent form and the study protocol

9. willing to comply with the protocol

Exclusion Criteria:

1. suspected intrauterine malignancy on contrast MR scan (however, if endometrial biopsy confirms that the lesion is not malignant, the patient may be eligible to participate in the study)14, 15, 16

2. the lesion to be treated is adenomyosis or highly perfused fibroid*17

   *highly perfused fibroid is defined as having an image intensity equal to or greater than the myometrium on T2-weighted images.

3. Planning to become pregnant in the future, or currently pregnant (women of childbearing potential who are β-hCG positive are not eligible to participate in the study).

4. Have a contraindication to MRI examination (e.g., claustrophobia) or a history of hypersensitivity to gadolinium-based contrast agents (MR contrast agents) or ultrasound contrast agents However, if any of the above can be controlled with medication, patients may be eligible to participate in the study.

5. currently being treated with or having been treated with gonadotropin-releasing hormone agonists (GnRHa) (however, if 12 weeks have elapsed since the end of GnRHa treatment, patients may participate in the study)

6. the fibroids to be treated are not measurable on MRI

7. the location of the fibroids to be treated falls into type 7 and/or type 8 according to the following classification