PREvention of Intrauterine Adhesion After Hysteroscopic Surgery With Novel deGradable Film (PREG1)

Intrauterine adhesions (IUA) are the major long-term complication of intrauterine procedures and are associated with pelvic pain, menstrual disorders, obstetrical complication and infertility.

Womed Leaf is a medical device specifically designed for intrauterine use that prevents intra-uterine adhesions. It is a film that acts as a mechanical barrier to keep uterus walls separated during healing. It is then naturally discharged through the cervix and vagina in less than 30 days.

The PREG1 clinical investigation is designed to evaluate Womed Leaf safety under clinical conditions, in women scheduled for a hysteroscopic myomectomy as well as its efficacy.

Study Overview

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

Detailed Description

Intrauterine adhesions (IUA) are defined as "fibrous strings at opposing walls of the uterus and/or cervix leading to partial or complete obliteration of the cavity". IUAs are the major long-term complication of intrauterine procedures and are associated with pelvic pain, menstrual disorders, obstetrical complications and infertility.

Womed Leaf™ is a sterile, degradable polymer film specifically design for intrauterine use. It is inserter in the uterus like an intrauterine device. Once released it will self-deploy into the uterine cavity to form a mechanical barrier keeping uterus walls separated during healing, for several days, thus preventing the formation or recurrence of intrauterine adhesions. It is degraded and discharged naturally through the cervix and vagina in less than 30 days.

The PREG1 clinical investigation is a prospective multicenter, single arm study, designed to evaluate Womed Leaf safety under clinical conditions, in women scheduled for a hysteroscopic myomectomy as well as its efficacy in preventing IUA at second look hysteroscopy.

• Study Type: Interventional
• Enrollment (Actual): 23
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Belgium
  • Gent, Belgium
    • UZ Gent
• France
  • Nîmes, France
    • CHU Nîmes
  • Paris, France
    • CHU Bicêtre (APHP)
• Netherlands
  • Amsterdam, Netherlands
    • Bergman Clinics
  • Amsterdam, Netherlands
    • Zaans Medical Center
  • Zwolle, Netherlands
    • Isala Zwolle

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Women ≥ 40 years AND no childbearing wish, OR history of permanent sterilization;
• Subject scheduled for hysteroscopic myomectomy for one or more myoma(s) where one myoma is at least 10 mm in size (≥10mm) as estimated by pre-operative ultrasound measurement of the largest diameter,
• Hysterometry prior to device insertion ≥ 6cm and ≤ 9cm.
• Subjects who are willing to provide a written informed consent as approved by the applicable Ethics Committee prior to participating in this clinical investigation.
• Subjects who can comply with the study follow-up or other study requirements

Exclusion Criteria:

Pre-operative exclusion criteria:

• Current pregnancy
• Abnormal uterine cavity according to ESHRE classification I to VI, such as unicornis, bicornis, septate, duplex
• Known or suspected endometrial hyperplasia
• Medical history of cervical or endometrial cancer
• Active pelvic infection or medical history of pelvic peritonitis
• Intrauterine device in situ
• Known contraindication or hypersensitivity to PEO or PLA, and to medications such as aspirin….
• Concurrent medical condition with a life expectancy of less than 12 months
• Full endometrial ablation

Per-operative exclusion criteria:

• Adenomyosis
• Inflammation (endometritis)
• Abnormal uterine cavity
• Hysterometry < 6cm or >9cm
• Any complication during the intervention that is deemed to potentially interfere with the objective of the study by the investigator

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Womed Leaf; At the end of the hysteroscopic myomectomy, Womed Leaf is delivered in the uterus thanks to a 5mm diameter, flexible inserter. Then an endovaginal ultrasound will be performed to assess the positioning of the uterine film. Another ultrasound will be performed at 2 hours, prior to patient discharge in order to record images of the uterine film deployment. A second look hysteroscopy will performed at 4-8 weeks to evaluate the presence of intrauterine adhesion.

Device: Womed Leaf; Womed Leaf uterine film will be inserted immediately after the myomectomy, following per-operative hysterometry.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety (Adverse Events)	The number and severity of polymer film related adverse event	30 days
Efficacy (Rate of Patient With no IUA)	Freedom from intrauterine adhesion	At second look hysteroscopy between 4 and 8 weeks
Efficacy (Intrauterine Adhesion Severity According to AFS Classification)	Severity of IUAs according to American Fertility Society (AFS) classification systems of adhesions. Pronostic classification => Hysteroscopy score Stade I (mild) => 1-4 Stade II (moderate) => 5-8 Stade III (severe) => 9-12	At second look hysteroscopy between 4 and 8 weeks
Efficacy (Intrauterine Adhesion Severity According to ESGE Classification)	Severity of IUAs according to European Society of Gynecological Endoscopy (ESGE) classification systems of adhesions. I => Thin or filmy IUA easily ruptured by HSC sheath alone. Cornual areas normal II => Singular dense IUA connecting separate parts of the uterine cavity. Visualization of both tubal ostia possible. Cannot be ruptured by HSC sheath alone IIa => Occluding IUA only in the region of the internal cervical os. Upper uterine cavity normal III => Multiple dense IUA connecting separate parts of the uterine cavity. Unilateral obliteration of ostial areas of the tubes IV => Extensive dense IUA with (partial) occlusion of the uterine cavity. Both tubal ostial areas (partially) occluded Va => Extensive endometrial scarring and fibrosis in combination with grade I or grade II IUA with amenorrhea or pronounced hypomenorrhea Vb => Extensive endometrial scarring and fibrosis in combination with grade III or grade IV IUA with amenorrhea	At second look hysteroscopy between 4 and 8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Events	Number of adverse events (AE) at 30 days	30 days
Device Technical Success	Defined as the rate of success of the following 2 steps : insertion and release	During operation: T=0
Womed Leaf Residuals	Presence of Womed Leaf residuals in the uterus	At second look hysteroscopy: 4-8 weeks
Womed Leaf Discharge Feedback : Time Interval in Days Between Surgery and Discharge	Uterine film discharge experience as recalled by subject using a survey to be asked to the patient	At second look hysteroscopy: 4-8 weeks
Device Manipulation	Device manipulation duration from insertion to withdrawal.	During intervention: T=0
Womed Leaf Discharge Feedback Questionnaire (Polymer Tolerance Assessed on a Scale From 1 (no Discomfort) to 10 (Extremely Disturbing))	Uterine film discharge experience as recalled by subject using a survey to be asked to the patient	At second look hysteroscopy: 4-8 weeks

Collaborators and Investigators

• Sponsor: Womed

Publications and helpful links

General Publications

• Weyers S, Capmas P, Huberlant S, Dijkstra JR, Hooker AB, Hamerlynck T, Debras E, De Tayrac R, Thurkow AL, Fernandez H. Safety and Efficacy of a Novel Barrier Film to Prevent Intrauterine Adhesion Formation after Hysteroscopic Myomectomy: The PREG1 Clinical Trial. J Minim Invasive Gynecol. 2022 Jan;29(1):151-157. doi: 10.1016/j.jmig.2021.07.017. Epub 2021 Jul 31.

Study record dates

Study Major Dates

• Study Start (Actual): November 18, 2019
• Primary Completion (Actual): March 15, 2021
• Study Completion (Actual): March 15, 2021

Study Registration Dates

• First Submitted: April 28, 2020
• First Submitted That Met QC Criteria: May 5, 2020
• First Posted (Actual): May 11, 2020

Study Record Updates

• Last Update Posted (Actual): November 9, 2021
• Last Update Submitted That Met QC Criteria: November 8, 2021
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Keywords: hysteroscopy; Intrauterine adhesion; myomectomy
• Additional Relevant MeSH Terms: Pathologic Processes; Fibrosis; Cicatrix; Tissue Adhesions
• Other Study ID Numbers: PREG1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: No sharing of individual participant data is planed

Drug and device information, study documents

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