Aqua Therapeutics Thermal Therapy Vapor Ablation System (ATTTVAS) Abnormal Uterine Bleeding Safety Study

Overview

Abnormal uterine bleeding (AUB) is defined as "flow outside of normal volume, duration, regularity, or frequency". Acute AUB is excessive bleeding that requires immediate intervention to prevent further blood loss. Chronic AUB refers to irregularities in menstrual bleeding for most of the previous 6 months. AUB can be frequent or infrequent, prolonged, irregular, or heavy. Heavy menstrual bleeding (HMB) is defined as "excessive menstrual blood loss which interferes with a woman's physical, social, emotional and/or material quality of life". Causes of AUB are classified as polyps, adenomyosis, leiomyomas (AUB-L), malignancy and premalignant conditions, coagulopathy, ovulatory disorders (AUB-O), endometrial disorders (AUB-E), iatrogenic, and ''not classified'' . AUB affects approximately one in four women between 30 and 50 years of age, with serious implications on woman's quality of life (QoL). Endometrial ablation (EA) is a uterus-preserving procedure that aims to destroy or remove the endometrial tissue in selected women who have no desire for future fertility. EA has become an alternative to hysterectomy in the treatment of AUB because it is less invasive and has a shorter recovery period. At present, many different techniques are available to remove the endometrial tissue. Resectoscopic endometrial ablation (REA) consists of targeted endometrial destruction under direct hysteroscopic visualization. REA techniques include endometrial laser ablation, transcervical resection of the endometrium, and rollerball endometrial ablation. Non-resectoscopic endometrial ablation (NREA) uses a variety of energy sources to non-selectively destroy the endometrial lining and include thermal balloon endometrial ablation, microwave endometrial ablation, hydrothermal ablation, bipolar radiofrequency endometrial ablation, endometrial cryotherapy, and more recently vapor endometrial ablation. NREA technologies require short surgical time and can also be performed in the outpatient setting. Vapor EA is one of the newest approaches in the field. In this context, the Aqua Therapeutics Thermal Therapy Vapor Ablation system (ATTTVAS; AQUA Therapeutics Inc.) is a novel system designed to ablate uterine tissue using vapor thermal therapy technology. The ATTTVAS is indicated to ablate the endometrial lining of the uterus in premenopausal women with abnormal uterine bleeding (AUB) due to benign causes for whom childbearing is complete. In this Pre-Market, First-In-Human, Pilot, Interventional, Clinical Investigation we aim to evaluate the Safety of the Aqua Therapeutics Thermal Therapy Vapor Ablation System (ATTTVAS) in premenopausal women with AUB.

The Aqua Therapeutics Thermal Therapy Vapor Ablation System (ATTTVAS) is a system designed to ablate uterine tissue by vapor thermal therapy technology. The ATTTVAS consists of a reusable Generator, a DISPOSABLE APPLICATOR, a DISPOSABLE CATHETER and a SYRINGE. The ATTTVAS is intended for outpatient use although it can easily be utilized in both a surgery centre and the operating room as well. This is a Pre-Market, First-In-Human, Pilot, Interventional, Clinical Investigation to Evaluate the Safety of the Aqua Therapeutics Thermal Therapy Vapor Ablation System (ATTTVAS) in premenopausal women with AUB. For each patient, a total of 6 visits (5 on-site and 1 remote) will be planned according to the flowchart. Unscheduled visit(s) will be planned on-site according to Principal Investigator judgement. Each Subject, after signing the Informed Consent Form (ICF), will enter a screening phase (V-1) during which several assessments (e.g., demographics, medical history, current menstrual condition, blood analysis) will be conducted. At the screening visit, patients will receive a menstrual calendar and a PBAC to be completed. The PBAC score must be recorded as soon as available to confirm that the patient can be enrolled at baseline (PBAC must be ≥150). The PBAC score will also be recorded at the End of Study (EOS) visit. At baseline (V0) and at EOS, on site, patients will also complete the Menorrhagia Impact Questionnaire (MIQ). If the Investigator can complete all the assessments foreseen at baseline visit (V0) and V1-EA in one day, V0 and V1 may coincide. At V1, enrolled Subjects will undergo EA with the ATTTVAS. EA must be performed within 15-20 days from the beginning of the menstrual cycle. EA cannot be performed in the presence of heavy menstrual bleeding, but it can be performed in the presence of light bleeding/spotting. Sedation will be performed before the EA by intravenous administration of propofol and fentanyl. The duration (seconds) of the ablation cycle will be recorded on the CRF. After the procedure is completed, the PI will fill a questionnaire on procedural ease of use. Device deficiencies (if any) will be recorded. At discharge, after 24 hours and 1 week from discharge, patients will be asked to rate pain intensity on a Numeric Rating Scale (NRS). At discharge patients will receive a diary to record AEs and concomitant medications through the study period. Follow-up visits will be performed after 1 week and 6 weeks from discharge. Satisfaction with the procedure will be evaluated using a 5-Likert Scale (completed by patient and PI) at discharge and at EOS. Physical examination, monitoring of vital signs and AEs will be performed at each applicable visit. Current menstrual condition will be monitored during the entire study period. To evaluate the need for surgical or medical intervention to treat AUB after EA, any surgical or medical intervention required to treat AUB after EA will be recorded during the study. An Interim Analysis was performed on the clinical data collected from V-1 to EOS (included) for the first 5 patients enrolled. The primary aim of the interim analysis was to evaluate the safety of the medical device. During the interim analysis, the enrollment of patients stopped. The results of the interim analysis were submitted to the Ethic Committee (EC) and Competent Authority (CA). Based on the interim analysis results and, after EC/CA feedback, the study activities could continue as planned.