Evaluate Formation of IUAs After Third-generation Endometrial Ablation, With and Without Intrauterine Adhesion Barrier

Study Overview
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Brief Summary
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Evaluate the formation of adhesions after third-generation endometrial ablation, with and without the intrauterine adhesion barrier.

Detailed Description
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The application of endometrial ablation (EA) has significantly increased in the past 10 years. It is an effective treatment for heavy menstrual bleeding with functional aetiology. However, the risk of post-ablative intracavitary scarring after EA is significant and can lead to long term complications, and the possible delay in diagnosing endometrial cancer. CLEAN is a prospective, multi-center, randomized, controlled, two arm pilot clinical trial. The objective is to compare the formation of adhesions after third-generation endometrial ablation, with and without the intrauterine adhesion barrier. The study will be performed on women with heavy menstrual bleeding (menorrhagia) scheduled for thermal endometrial ablation with Novasure system (Hologic) A follow-up diagnostic hysteroscopy will be performed 4-8 weeks after the ablation procedure to determine the presence and severity of IUAs according to the American Fertility Society.

Official Title
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Evaluation of Adhesions Formation Using Conventional Third Generation Endometrial Ablation With and Without Postoperative Application of an Intrauterine Adhesion Barrier Film

Conditions
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Asherman Syndrome, Intrauterine Adhesion

Intervention / Treatment
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* Device: Womed Leaf


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient with refractory heavy menstrual bleeding scheduled for endometrial ablation with Novasure system Women 30 years old or older; Subjects who are willing to provide a written informed consent as approved by the applicable Ethics Committee / IRB prior to participating in this clinical investigation. Subjects who can comply with the study follow-up and other study requirements. Exclusion Criteria: Cavity length <4 or >8 Perforation during ablation procedure Previous adhesiolysis procedure or diagnosis of Asherman's disease. Abnormal uterine cavity at the time of ablation according to ESHRE classification I to V such as unicornis, bicornis, septate, duplex History of cervical or endometrial cancer Active pelvic infection or history of pelvic peritonitis Known contraindication or hypersensitivity to Womed Leaf component Current participation in another clinical investigation that has not yet received the primary endpoint Any other condition that makes participation in the study contrary to the patient's best interests.

Ages Eligible for Study
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Minimum Age: 30 Years

Sexes Eligible for Study
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Female

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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Womed Leaf group<br>Womed Leaf is inserted immediately after completion of the endometrial ablation. | Device: Womed Leaf<br>* Womed Leaf™ is a sterile, degradable film of poly(D,L-lactide) (PLA) and poly(ethylene oxide) (PEO). PEO is a biocompatible polymer with anti-adhesion and swelling properties. It is polymerized with hydrophobic PLA to form a degradable film. Womed Leaf™ is inserted in the uterine cavity by a gynaecologist surgeon with a 5 mm diameter flexible inserter. Once released, the film unfolds and grows into the uterine cavity to create a mechanical barrier and keep the uterine walls separated for approximately one week. It is then degraded and discharged naturally through the cervix.<br>|
| No Intervention: No adhesion prevention group<br>Standard of care: no IUA prevention, no placebo after ablation | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy endpoint: AFS scale; a discrete number | Focused on the intrauterine adhesion formation following Novasure (i.e. considering only extent of cavity involved and type of adhesions) Extent of IUA => 1 = less than 1/3 of the cavity involved and 4 = more than 2/3. Type of IUA => 1 = filmy and 4 = dense. Sum: 1 = very light adhesions and 12 = extremely severe adhesions obstructing the whole cavity. | 4-8 weeks after surgery | 
| Safety endpoint 1.1: Assessment of cavity findings | Ability to perform a biopsy anywhere within the uterine cavity | 4-8 weeks after surgery | 
| Safety endpoint 1.2: Assessment of cavity findings | Ability to adequately visualise the endometrium to evaluate for pathologic change | 4-8 weeks after surgery | 
| Safety endpoint 1.3: Assessment of cavity findings | Qualitative description of the endometrial cavity (i.e. presence of viable endometrium vs cicatricial/fibrotic tissue…) | 4-8 weeks after surgery | 
| Serious adverse events | Number of Serious Adverse Events and Serious Device-related Adverse Events such as postablation syndrome. | 3 months after surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Each component of AFS score at second look hysteroscopy | Extent of IUA => 1 = less than 1/3 of the cavity involved and 4 = more than 2/3. Type of IUA => 1 = filmy and 4 = dense. | 4-8 weeks after surgery | 
| Binary rate of intrauterine adhesions on hysteroscopy | Yes/ No intrauterine adhesions are present | 4-8 weeks after surgery | 
| Change in menstrual bleeding | Change in menstrual bleeding using Pictorial Blood Loss Assessment Chart | 3 months after surgery | 
| Level of dysmenorrhea | Painful cramping associated with menstruation; 0 = no symptoms and 5 = very severe symptoms | Before surgery and after 3 months | 
| Level of patient satisfaction on ablation procedure | On a scale from 0 to 5 from the worst to the best health care possible; 0 = worst health care possible and 5 = best health care possible | Immediately after the surgery | 
| Number of patients complaints | Number of patient complaints (i.e. complaints related to discharge or dyspareunia) | 3 months after surgery | 
| Number of subjects for whom a second ablation is possible | For each subject, the second look evaluator will assess whether it is possible to perform a second ablation if needed. | 4-8 weeks after surgery |