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

• ClinicalTrials.gov Identifier: NCT04381728
• Recruitment Status: Completed
• First Posted: May 11, 2020
• Results First Posted: November 9, 2021
• Last Update Posted: November 9, 2021
• Sponsor: Womed
• Information provided by (Responsible Party): Womed

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Intrauterine Adhesion	Device: Womed Leaf	Not Applicable

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 23 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: PREvention of Intrauterine Adhesion After Hysteroscopic Surgery With Novel deGradable Film
• Actual Study Start Date: November 18, 2019
• Actual Primary Completion Date: March 15, 2021
• Actual Study Completion Date: March 15, 2021

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures :

1. Safety (Adverse Events) [ Time Frame: 30 days ]
   The number and severity of polymer film related adverse event
2. Efficacy (Rate of Patient With no IUA) [ Time Frame: At second look hysteroscopy between 4 and 8 weeks ]
   Freedom from intrauterine adhesion
3. Efficacy (Intrauterine Adhesion Severity According to AFS Classification) [ Time Frame: At second look hysteroscopy between 4 and 8 weeks ]

   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

4. Efficacy (Intrauterine Adhesion Severity According to ESGE Classification) [ Time Frame: At second look hysteroscopy between 4 and 8 weeks ]

   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

Secondary Outcome Measures :

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

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

Belgium

UZ Gent

Gent, Belgium

France

CHU Nîmes

Nîmes, France

CHU Bicêtre (APHP)

Paris, France

Netherlands

Bergman Clinics

Amsterdam, Netherlands

Zaans Medical Center

Amsterdam, Netherlands

Isala Zwolle

Zwolle, Netherlands

Sponsors and Collaborators

Womed

  Study Documents (Full-Text)

Documents provided by Womed:

Study Protocol  [PDF] April 27, 2020

No Statistical Analysis Plan (SAP) exists for this study.

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Womed
• ClinicalTrials.gov Identifier: NCT04381728
• Other Study ID Numbers: PREG1
• First Posted: May 11, 2020
• Results First Posted: November 9, 2021
• Last Update Posted: November 9, 2021
• Last Verified: November 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No
• Plan Description: No sharing of individual participant data is planed

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Womed:

myomectomy; Intrauterine adhesion; hysteroscopy

Additional relevant MeSH terms:

Tissue Adhesions; Cicatrix; Fibrosis; Pathologic Processes