HIFU Treatment of Benign Thyroid Nodules

Study Overview
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Brief Summary
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This clinical trial is to evaluate the effectiveness and the safety of high intensity focused ultrasound (HIFU) in the treatment of benign thyroid nodules.

Detailed Description
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This clinical trial is a prospective, multicentre, randomized, controlled study of high intensity focused ultrasound (HIFU) treatment of benign thyroid nodules. this study will include 240 patients with benign thyroid nodules that meet all ths the inclusion / exclusion criteria and will be randomly divided into two groups at 1: 1 ratio. Patients in the test group will be treated with high intensity focused ultrasound (HIFU), while patients in the control group will be actively observed and followed up by ultrasound examination. The primary objective of this clinical trial is to evaluate the efficacy of the test device in the treatment of benign thyroid nodules, and the secondary objective is to evaluate the safety of the test device in the treatment of benign thyroid nodules and the improvement of symptoms assessed by VAS score.

Official Title
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A Multi-center, Randomized, Controlled Trial of High Intensity Focused Ultrasound (HIFU) Treatment of Benign Thyroid Nodules

Conditions
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Thyroid Nodule (Benign)

Intervention / Treatment
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* Device: Device: Echopulse (HIFU ablation)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female patients older than 18 years and younger than 70 years No history of neck irradiation Normal thyroid function, serum calcitonin level, PTH and serum calcium at screening visit examination. No abnormal cervical lymph nodes during screening visit examination. The target thyroid nodule must meet all of the following conditions: Single nodule, 2cm≤max diameter≤4cm Causing appearance , pressure or swallowing symptoms Composition of target nodule: solid or predominantly solid (solid area≥80%) Ultrasound imaging of target nodule assessed by 2017 ACR TI-RADS(≤Grade 3), and proved benign by once FNA (bethesda categoryⅡ); Ultrasound imaging of target nodule assessed by 2017 ACR TI-RADS( Grade 4), and proved benign by twice FNA (bethesda categoryⅡ). The distance from the posterior edge of the target nodule to the skin is not less than 12.3mm, and the depth from the anterior edge of the target nodule to the skin is not more than 19.4mm. No macro-calcifications in target nodule, macro-calcifications induce a significant shadow in the ultrsound imaging. the skin is free from any significant thick scars. If there are more than one nodule on the treatment side, all of the following conditions shall be met: No more than 2 nodules except the target nodule. Maximum diameter of the nodules is smaller than 1 cm and ultrasound imaging ≤ Grade 3 assessed by 2017 ACR TI-RADS. If there are nodules on the opposite side of HIFU treatment side, one of the following conditions shall be met: Maximum diameter of these nodules is smaller than 1 cm and ultrasound imaging ≤ Grade 3 assessed by 2017 ACR TI-RADS. Only one nodule with 1cm≤ max diameter < 2cm, or/and no more than three nodule with max diameter <1cm. Ultrasonic images of all nodules≤Grade 3 assessed by 2017 ACR TI-RADS. Absence of abnormal vocal cord mobility at laryngoscopy. Patients reject or cannot tolerate invasive surgical treatment. Patient has signed a written informed consent. Exclusion Criteria: The ultrasound report indicated that follicular tumors were not excluded. Known history of thyroid cancer or other neoplasias in the neck region. Head and/or neck disease that prevents hyper-extension of neck. Patients currently in the acute phase of any disease. History of head and neck, pulmonary and systemic infections in the last 2 weeks. The white blood cell test result exceeded the upper limit of the normal range. Tenderness of the thyroid and/or thyroid nodules. History of arrhythmia, coronary heart disease or valvular heart disease, heart failure. The blood pressure is not controlled after the combination of three antihypertensive drugs (SBP ≥ 140 mmHg, DBP ≥ 90 mmHg) COPD history or acute phase of asthma attach Patients with liver dysfunction ( ALT or AST level 2.5 times higher than the upper limit of the normal reference range) Patients with renal insufficiency( eGFR< 45ml/min/1.73m2). Fasting blood glucose >8mmol/L after hypoglycemic drug treatment Patients currently sufferrign from hematological diseases or bleeding tendency, or patients currently requiring continuous administration of antiplatelet and anticoagulant drugs Pregnant or lactating woman Woman who Plan to be pregnant during the study period. Any contraindication to the assigned analgesia/ anaesthesia. Patients who participated in other clinical trials in the past 3 months. Alzhemier's patients or patient with cognitive impairment. Other patients judged by the investigators to be unsuitable for the clinical trial.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

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
Interventional Model Description: Patients in the test group will be treated with high intensity focused ultrasound (HIFU), while patients in the control group will be actively observed and followed up by ultrasound examination. during the follow-up period, the follow-up visits time and follow-up examination items (clinical examination, ultrasonic examination and laboratory examination etc.) were the same in the both groups
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Test group HIFU treatment<br>Patients in the test group (120) will be treated with high intensity focused ultrasound (HIFU). The primary objective of this clinical trial is to evaluate the efficacy of the test device in the treatment of benign thyroid nodules, and the secondary objective is to evaluate the safety of the test device in the treatment of benign thyroid nodules and the improvement of symptoms (VAS score). | Device: Device: Echopulse (HIFU ablation)<br>* High-intensity focused ultrasound (HIFU) is a non-invasive, non-invasive treatment method. The principle is to focus high-intensity ultrasound on the target area. Energy is absorbed by the target tissue and converted into thermal energy. The local temperature quickly reaches a maximum of 85 ° C. It induces coagulative necrosis of focus tissue cells, but does not damage the tissues surrounding the treatment targ<br>|
| No Intervention: Control group<br>Patients in the control group (120) will be actively observed and followed up. The primary objective of this clinical trial is to evaluate the efficacy of the test device in the treatment of benign thyroid nodules, and the secondary objective is to evaluate the safety of the test device in the treatment of benign thyroid nodules and the improvement of symptoms (VAS score). | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effectiveness evaluation using treatment effective rate | percentage of patients who achieve treatment success (volume reduction ratio > 50%) at 12 months after HIFU treatment assessed by ultrasound examination | 12 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Symptoms score improvement | Using Visual Analogic Scale between (0-100 mm) to evaluate the improvement of appearance symptoms, compression symptoms and swallowing symptoms and pain. With 0 being no pain and 100 being the worst pain imaginable | 12 Months | 
| Incidence of Treatment-Emergent Adverse Events | Incidence of local and/or general adverse reactions and other related symptoms at 1, 7 days and 1, 3, 6 and 12 months follow-up after treatment | 12 Months |