PREvention of Intrauterine Adhesion After Adhesiolysis With Novel Tri-block deGradable Polymer Film. (PREG2)

PREG2 is a randomized controlled trial that aims to evaluate efficacy in preventing intrauterine adhesion recurrence after hysteroscopic adhesiolysis of a novel intrauterine barrier film named Womed Leaf

Study Overview

• Status: Active, not recruiting
• Conditions: Asherman Syndrome; Intrauterine Adhesion
• Intervention / Treatment: Device: Womed Leaf

Detailed Description

PREG2 is a prospective, multi-center, randomized, controlled, two arm clinical study. The objective is to evaluate the efficacy of Womed Leaf in preventing intrauterine adhesion recurrence after adhesiolysis compared to adhesiolysis alone.

The study will be performed on women with moderate or severe adhesions (AFS score >=5) scheduled for adhesiolysis. Indeed, the risk of intrauterine adhesion is very high (up to 60%) in this population of patients.

A follow-up diagnostic hysteroscopy will be performed 6-8 weeks after the adhesiolysis procedure to determine the presence and severity of IUAs according to the American Fertility Society and European Society of Gynecologic Endoscopy classification systems of adhesions. Fertility-related outcome will include live pregnancy at 1 year and 2 years and will be reported as secondary endpoints. 154 women are planned to be included in the PREG2 study.

• Study Type: Interventional
• Enrollment (Actual): 160
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Belgium
  • Gent, Belgium, 9000
    • Gent UZ
• China
  • Guangzhou, China
    • Guangdong Maternal and Child Health Hospital
  • Hangzhou, China
    • Women's Hospital School of Medicine Zhejiang University
  • Shanghai, China
    • The Obstetrics & Gynecology Hospital Affiliated to Fudan University
• Czechia
  • Ostrava, Czechia
    • Gynprenatal
• France
  • Le Kremlin-Bicêtre, France, 94270
    • CHU Bicêtre
  • Lille, France, 59000
    • CHU de Lille
  • Marseille, France, 13005
    • Hopital La Conception
  • Paris, France, 75010
    • CHU Lariboisière
  • Rennes, France, 35043
    • Clinique Mutualiste la Sagesse
• Italy
  • Napoli, Italy, 80131
    • A.O.U Federico II
  • Torino, Italy
    • Aso Mauriziano Umberto I
• Spain
  • Barcelona, Spain
    • Hospital Clinic Barcelonna
  • Madrid, Spain, 28034
    • Ramón y Cajal Hospital
• Switzerland
  • Lausanne, Switzerland, 1011
    • Centre Hospitalier Universitaire Vaudois

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Women with moderate or severe intrauterine adhesions according to the AFS classification, i.e AFS score >=5, confirmed by hysteroscopy right before adhesiolysis
• Scheduled for hysteroscopic adhesiolysis
• Age above or equal to 18
• Subjects who are willing to provide a written informed consent.
• Subjects who can comply with the study follow-up (second look hysteroscopy) and other study requirements
• Subjects who agree to refrain from intercourse or use a reliable form of barrier contraception to prevent unintended pregnancy until the follow-up hysteroscopy.
• Subjects who agree to avoid all intrauterine devices (IUDs) until the follow-up hysteroscopy.

Exclusion Criteria:

Pre-operative criteria

• Post menopause
• Pregnant (confirmed by a positive pregnancy test) or lactating
• Abnormal uterine cavity according to ESHRE classification I to V such as unicornis, bicornis, septate, duplex
• Known or suspected endometrial hyperplasia
• History of cervical or endometrial cancer
• Active pelvic infection or history of pelvic peritonitis
• History of endometrial ablation
• 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.

Intra-operative criteria, post adhesiolysis:

• Perforation during adhesiolysis
• Uterine depth < 5cm or > 10cm

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Womed Leaf; IUA prevention: The novel intrauterine barrier film (Womed Leaf) is inserted immediately after completion of the hysteroscopic adhesiolysis	Device: Womed Leaf; Womed Leaf™ device is composed of a uterine anti-adhesion film pre-loaded inside a flexible inserter. Womed Leaf™ is inserted in the uterine cavity by the gynecologist surgeon as a film folded into a 5 mm diameter flexible inserter. Once released, the film will unfold and swell into the uterine cavity to keep uterus walls separated during approximately 5 days. It is degraded and discharged naturally through the cervix and vagina in less than 30 days.
No Intervention: Control; No IUA prevention - no placebo after adhesiolysis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy - IUA severity	Change of AFS score between pre-adhesiolysis and second-look hysteroscopy (AFS) score	At second look hysteroscopy between 4 and 8 weeks
Safety - Adverse events	Adverse events up to second look hysteroscopy.	At second look hysteroscopy between 4 and 8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to pregnancy	Time to pregnancy (i.e. time between the second look hysteroscopy and pregnancy start)	2 years
High-responder rate	Percentage of patients who have improved from severe to mild adhesions or from severe to no adhesions or from moderate to no adhesions	At second look hysteroscopy between 4 and 8 weeks
Change of "extent of cavity involved" component	Average of AFS score component "extent of cavity involved"	At second look hysteroscopy between 4 and 8 weeks
Change in "extent of cavity involved" component between post-adhesiolysis and second look hysteroscopy	Average of AFS score component "extent of cavity involved"	At second look hysteroscopy between 4 and 8 weeks
AFS score	Average of AFS score	At second look hysteroscopy between 4 and 8 weeks
Change of extent of IUA AFS score component	Average of the change of the AFS score component "Extent of IUA"	At second look hysteroscopy between 4 and 8 weeks
Change of type of IUA AFS score component	Average of the change of the AFS score component "type of IUA"	At second look hysteroscopy between 4 and 8 weeks
Menstrual pattern AFS score component	Average of the change of the AFS score component "Menstrual Pattern"	At second look hysteroscopy between 4 and 8 weeks
Percentage of patients who have Mild adhesions or no adhesion	Percentage of patients who have AFS < 5	At second look hysteroscopy between 4 and 8 weeks
Freedom from IUA	Rate of patients who don't have adhesion	At second look hysteroscopy between 4 and 8 weeks
ESGE stage	Rate of ECGE stage	At second look hysteroscopy between 4 and 8 weeks
Level of post-operative pain	Level of post-operative pain on a numeric rating scale, with 0 = no pain and 10 = the worst pain.	At second look hysteroscopy between 4 and 8 weeks
Level of discomfort related to vaginal discharge	Level of discomfort related to vaginal discharge on a numeric rating scale, with 0 = no discomfort and 10 = extremely disturbing	At second look hysteroscopy between 4 and 8 weeks
Timing of vaginal discharge	Timing of vaginal discharge as recalled by the patient	At second look hysteroscopy between 4 and 8 weeks
Duration of the vaginal discharge	Duration of the vaginal discharge as recalled by the patient	At second look hysteroscopy between 4 and 8 weeks
Qualitative description of the vaginal discharge	Qualitative description of the vaginal discharge as recalled by the patient	At second look hysteroscopy between 4 and 8 weeks
Change of menstrual pattern	Change of menstrual pattern	At second look hysteroscopy between 4 and 8 weeks, 1 year, 2 years
Reintervention rate	Reintervention rate, during second look hysteroscopy or scheduled later up to one year	At second look hysteroscopy or scheduled later up to one year
Number of adhesiolysis procedures	Number of adhesiolysis procedures after second look to one year	After second look to one year
Pregnancy rate	Pregnancy rate defined as presence of foetal sac or heartbeat by ultrasound at 1 year and 2 years, whether spontaneous or IVF	1 year, 2 years
Live birth rate	Live birth rate at 1 year and 2 years	1 year and 2 years
Pregnancy complication rate	Pregnancy complication rate	2 years
IUA severity according to Chinese scoring system	IUA severity according to Chinese scoring system (for patients enrolled in China only)	At second look hysteroscopy between 4 and 8 weeks
Responder rate	Percentage of patients with an improvement of one clinical category i.e from Severe to Moderate or from Moderate to Mild	At second look hysteroscopy between 4 and 8 weeks

Collaborators and Investigators

• Sponsor: Womed

Study record dates

Study Major Dates

• Study Start (Actual): November 29, 2021
• Primary Completion (Actual): November 11, 2023
• Study Completion (Estimated): January 1, 2025

Study Registration Dates

• First Submitted: July 5, 2021
• First Submitted That Met QC Criteria: July 5, 2021
• First Posted (Actual): July 15, 2021

Study Record Updates

• Last Update Posted (Actual): February 14, 2024
• Last Update Submitted That Met QC Criteria: February 12, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Infertility; Adhesiolysis; Intrauterine adhesion; Asherman Syndrome; Hysteroscopy; Adhesion prevention
• 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: PREG2

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: 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
• product manufactured in and exported from the U.S.: No