Primary ObjectiveTo evaluate the safety of the Aqua Therapeutics Thermal Therapy Vapor Ablation System (ATTTVAS).Secondary Objectives1. To evaluate the change of menstrual blood loss (MBL).2. To evaluate the effect of MBL on the quality of life (QoL…
ID
Source
Brief title
Condition
- Menstrual cycle and uterine bleeding disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary Endpoint
To evaluate the safety of the Aqua Therapeutics Thermal Therapy Vapor Ablation
System (ATTTVAS), the incidence of device-related complications will be
assessed up to the end of study.
Secondary outcome
Secondary Endpoints
1. To evaluate the change of menstrual blood loss (MBL), the pictorial blood
loss assessment chart (PBAC) score will be assessed at baseline and at End of
Study (EOS) visit.
2. To evaluate the effect of MBL on the quality of life (QoL), the Menorrhagia
Impact Questionnaire (MIQ) will be completed by the patient at baseline and at
EOS.
3. To evaluate pain intensity after treatment, a Numeric Rating Scale (NRS) *
with 0 representing no pain and 10 representing unbearable pain * will be used,
at discharge, after 24 hours and after 1 week from discharge.
4. To evaluate the procedural ease of use, a questionnaire will be completed by
the Investigator on the day of treatment.
5. To monitor menstrual changes (menstrual frequency, duration, regularity), a
menstrual calendar will be used by the patient from V-1 to EOS.
6. To evaluate the need for surgical or medical intervention to treat AUB after
EA with the ATTTVAS, any surgical or medical intervention required to treat AUB
after EA will be recorded.
7. To evaluate patient*s satisfaction with the ATTTVAS, a 5-Likert Scale will
be used at discharge and at EOS.
8. To evaluate PI*s satisfaction with the ATTTVAS, a 5-Likert Scale will be
used at discharge and at EOS.
Safety Endpoints
9. Monitoring of clinical parameters and vital signs over the duration of the
study.
10. Monitoring of device deficiencies before, during and after the use of the
device.
11. Monitoring of adverse events and serious adverse events unrelated to study
device over the duration of the study.
12. Monitoring of concomitant medications over the duration of the study.
Background summary
Abnormal uterine bleeding (AUB) is defined as *flow outside of normal volume,
duration, regularity, or frequency* [1]. AUB can be acute or chronic. 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 [2]. 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* [2].
Causes of AUB are classified as polyps, adenomyosis, leiomyomas (AUB-L),
malignancy and premalignant conditions, coagulopathy (AUB-C), ovulatory
disorders (AUB-O), endometrial disorders (AUB-E), iatrogenic, and **not
classified** [3]. AUB affects approximatively one in four women between 30 and
50 years of age, with serious implications on woman's quality of life (QoL)
[4], [5].
Endometrial ablation (EA) is a minimally invasive, surgical treatment for women
suffering from AUB. 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. The procedure was designed to treat heavy menstrual bleeding in
women refractory to medical therapy (or not willing to undergo hormonal
treatment) and not caused by structural uterine pathology [6]. EA has become an
alternative to hysterectomy in the treatment of AUB because it is less invasive
and has a shorter recovery period [7].
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 [6]. 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
water vapor endometrial ablation [8]. NREA technologies require short surgical
time and can also be performed in the outpatient setting [6].
Water vapor EA is one of the newest approaches in the field. Currently the only
FDA-approved system of this kind is AEGEA Water Vapor Ablation System (AEGEA
Medical, Menlo Park CA) [9].
In this context, the Aqua Therapeutics Thermal Therapy Vapor Ablation System
(ATTTVAS; AQUA Therapeutics Inc.) is a novel software-controlled device
designed to ablate uterine tissue using water 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.
References
1. A. Khafaga and S. R. Goldstein, *Abnormal Uterine Bleeding,* Obstetrics and
Gynecology Clinics of North America, vol. 46, no. 4. W.B. Saunders, pp. 595-
605, Dec. 01, 2019. doi: 10.1016/j.ogc.2019.07.001.
2. V. Jain, R. R. Chodankar, J. A. Maybin, and H. O. D. Critchley, *Uterine
bleeding: how understanding endometrial physiology underpins menstrual health,*
Nature Reviews Endocrinology, vol. 18, no. 5. Nature Research, pp. 290-308, May
01, 2022. doi: 10.1038/s41574-021-00629-4.
3. K. A. Matteson et al., *A systematic review comparing hysterectomy with
less-invasive treatments for abnormal uterine bleeding,* Journal of Minimally
Invasive Gynecology, vol. 19, no. 1. pp. 13-28, Jan. 2012. doi:
10.1016/j.jmig.2011.08.005.
4. T. J. Oderkerk et al., *Endometrial ablation plus levonorgestrel releasing
intrauterine system versus endometrial ablation alone in women with heavy
menstrual bleeding: study protocol of a multicentre randomised controlled
trial; MIRA2 trial,* BMC Womens Health, vol. 22, no. 1, Dec. 2022, doi:
10.1186/s12905-022-01843-6.
5. V. Kumar, R. Chodankar, and J. K. Gupta, *Endometrial ablation for heavy
menstrual bleeding,* Women*s Health, vol. 12, no. 1. Future Medicine Ltd., pp.
45-52, Jan. 01, 2016. doi: 10.2217/whe.15.86.
6. P. Laberge et al., *Endometrial Ablation in the Management of Abnormal
Uterine Bleeding,* Journal of Obstetrics and Gynaecology Canada, vol. 37, no.
4, pp. 362-376, 2015, doi: 10.1016/S1701-2163(15)30288-7.
7. P. Beelen et al., *Prognostic Factors for the Failure of Endometrial
Ablation: A Systematic Review and Meta-analysis,* Obstetrics and Gynecology,
vol. 134, no. 6. Lippincott Williams and Wilkins, pp. 1269-1281, Dec. 01, 2019.
doi: 10.1097/AOG.0000000000003556.
8. M. Bofill Rodriguez, A. Lethaby, M. Grigore, J. Brown, M. Hickey, and C.
Farquhar, *Endometrial resection and ablation techniques for heavy menstrual
bleeding,* Cochrane Database of Systematic Reviews, vol. 2019, no. 1. John
Wiley and Sons Ltd, Jan. 22, 2019. doi: 10.1002/14651858.CD001501.pub5.
9. N. Leyland and M. Harris, *Water vapor endometrial ablation for heavy
menstrual bleeding: 36-month follow-up of a prospective, multicenter pivotal
clinical trial,* Int J Womens Health, vol. 13, pp. 169-176, 2021, doi:
10.2147/IJWH.S279864.
Study objective
Primary Objective
To evaluate the safety of the Aqua Therapeutics Thermal Therapy Vapor Ablation
System (ATTTVAS).
Secondary Objectives
1. To evaluate the change of menstrual blood loss (MBL).
2. To evaluate the effect of MBL on the quality of life (QoL).
3. To evaluate pain intensity after treatment.
4. To evaluate procedure difficulty.
5. To evaluate menstrual changes (menstrual frequency, duration, regularity).
6. To evaluate the need for surgical or medical intervention to treat AUB after
EA with the ATTTVAS.
7. To evaluate patient*s satisfaction with the ATTTVAS.
8. To evaluate PI*s satisfaction with the ATTTVAS.
9. To evaluate additional safety parameters.
Study design
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.
Intervention
For each patient, a total of 6 visits (5 on-site and 1 remote) will be planned.
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, patients will also complete the Menorrhagia Impact
Questionnaire (MIQ).
At V1, enrolled Subjects will undergo EA with the ATTTVAS. EA must be performed
within 15 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 is planned when the clinical data collected from V-1 to EOS
(included) for the first 5 patients will be available. The primary aim of the
interim analysis will be to evaluate the safety of the medical device.
During the interim analysis, the enrollment of patients will stop. The results
of the interim analysis will be submitted to the Ethic Committee (EC) and
Competent Authority (CA). If there will be no objections by EC/CA after the
evaluation of the interim clinical investigation report, the enrollment and the
study activities will continue.
Study burden and risks
The expected benefits following the endometrial ablation procedure with the
ATTTVAS are as follows:
- Reduction in the amount of blood lost during periods.
- Reduction in the duration of periods, or absence of blood loss between
periods, or absence of periods.
After ablation surgery, it is normal to experience mild vaginal bleeding or
discharge that may last for several weeks after the procedure. The most common
side effects are pelvic pain, cramps, nausea, and vomiting that usually
disappear within 12 to 24 hours. The serious side effects associated with the
procedure include perforation of the uterus, bleeding following the procedure,
retention of menstrual blood inside your uterine cavity, pelvic infections, and
fever.
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Age
Inclusion criteria
1. Signed patient informed consent form (ICF).
2. Females aged >= 30 years and <= 55 years at baseline with no desire to
conceive, with or without simple endometrial hyperplasia (without atypia).
3. Diagnosis of AUB.
4. Premenopausal (follicle-stimulating hormone level <= 40 mIU/mL), women who
don*t want to receive hormonal treatment or who have failed to respond to
hormonal treatment.
5. Pictorial Blood Loss Assessment Chart (PBAC) score >=150 at baseline.
6. Normal endometrial biopsy.
7. Negative PAP test.
8. Willingness to follow all study procedures, including attending all site
visits, tests, and examinations.
Exclusion criteria
1. BMI >=35
2. Postmenopausal status.
3. Undiagnosed vaginal bleeding.
4. A patient with a history of a prior completed endometrial ablation procedure
and/or endometrial resection (including endometrial ablation/resection
performed immediately prior to the ATTTVAS Ablation Treatment) regardless of
the modality by which it was performed.
5. Previous uterine surgery.
6. Uterine cavity-length <4 cm or >6 cm (without cervix length).
7. Willing to avoid the use of vaginal ring, hormonal intrauterine device
(concomitant IUD such as Essure is not allowed prior to the ATTTVAS Ablation
Treatment), oral contraceptives during the study period.
8. Pregnant or breastfeeding.
9. Less than 1-year post-partum.
10. Any contraindication to endometrial ablation.
11. History of previous classical cesarean section or transmural myomectomy,
including hysteroscopic and/or laparoscopic myomectomy performed immediately
prior to the ATTTVAS Ablation Treatment).
12. Confirmed pelvic inflammatory disease, active/acute endometritis, sexually
transmitted disease, bacteremia, sepsis, other active local and/or systemic
infection.
13. Active genital or urinary tract infection (e.g., cervicitis, vaginitis,
endometritis, salpingitis or cystitis) at the time of treatment.
14. Congenital malformation of the uterus, fibroid(s) distorting the uterine
cavity, or large endometrial polyp(s).
15. Congenital malformations of the female genital tract.
16. Subjects with suspected or known coagulopathies or receiving
anticoagulation therapy.
17. A patient currently on medications that could thin the myometrial muscle,
such as long-term steroid use (except for inhaler or nasal therapy for asthma).
18. Documented cervical dysplasia, complex or atypical endometrial hyperplasia,
abdominal or pelvic cancer.
19. Presence of any relevant severe condition or clinically relevant abnormal
laboratory parameters that in the opinion of the Investigator may interfere
with the participation to the study.
20. Presence of any relevant severe organic, systemic, or metabolic disease
(particularly significant history of cardiac, renal, neurological, psychiatric,
oncology, endocrinology, metabolic or hepatic disease), or abnormal laboratory
values that will be deemed clinically significant in Investigator*s opinion.
21. Active malignant neoplasm of any type, or history of a malignancy (patients
with a history of other malignancies that have been surgically removed and who
have no evidence of recurrence for at least five years before study enrollment
are also acceptable).
22. Participation in another investigational study within the previous 30 days.
23. Recent history or suspicion of alcohol abuse or drug addiction.
24. Inability to follow study procedures.
25. History of allergic reactions to propofol and/or fentanyl.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL84185.000.24 |