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

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

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

Study Overview

• Status: Completed
• Conditions: Asherman Syndrome; Intrauterine Adhesion
• Intervention / Treatment: Device: Womed Leaf

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 1
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Netherlands
  • Eindhoven, Netherlands, 5623EJ
    • Catharina Hospital
  • Weert, Netherlands, 6001BE
    • St. Jans Gasthuis

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 28 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Womed Leaf group; Womed Leaf is inserted immediately after completion of the endometrial ablation.	Device: Womed Leaf; 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.
No Intervention: No adhesion prevention group; Standard of care: no IUA prevention, no placebo after ablation

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Remko P. Bosgraaf
• Investigators: Principal Investigator: Remko Bosgraaf, Catharina Ziekenhuis Eindhoven

Study record dates

Study Major Dates

• Study Start (Actual): November 11, 2022
• Primary Completion (Actual): February 5, 2024
• Study Completion (Actual): February 5, 2024

Study Registration Dates

• First Submitted: May 29, 2022
• First Submitted That Met QC Criteria: June 8, 2022
• First Posted (Actual): June 10, 2022

Study Record Updates

• Last Update Posted (Estimated): February 7, 2024
• Last Update Submitted That Met QC Criteria: February 5, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Fibrosis; Cicatrix; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Genital Diseases, Female; Tissue Adhesions; Gynatresia
• Other Study ID Numbers: CLEAN

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

The anonymized data will become available and reusable for other researchers upon reasonable request according to GCP and FAIR principles. All research data will be handled confidentially in accordance with legislation and conditions imposed by Autoriteit Persoonsgegevens.

Individual participant data that underlie the result that will be reported in an article and study protocol may be made available to researchers who provide a methodologically sound proposal, immediately after article publication and during 5 years

• IPD Sharing Time Frame: Immediately after article publication and during 5 years
• IPD Sharing Access Criteria: Researchers who provide a methodologically sound proposal
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No