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

• Sponsor: Womed (Industry)
• Overall Status: Completed
• CT.gov ID: NCT04381728
• Collaborator: (none)
• Enrollment: 23
• Locations: 6
• Arm: 1
• Actual Duration (Months): 15.9
• Patients Per Site: 3.8
• Patients Per Site Per Month: 0.2

Study Details

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	N/A

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
• 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: Nov 18, 2019
• Actual Primary Completion Date: Mar 15, 2021
• Actual Study Completion Date: Mar 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) [30 days]

   The number and severity of polymer film related adverse event

2. Efficacy (Rate of Patient With no IUA) [At second look hysteroscopy between 4 and 8 weeks]

   Freedom from intrauterine adhesion

3. Efficacy (Intrauterine Adhesion Severity According to AFS Classification) [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) [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 [30 days]

   Number of adverse events (AE) at 30 days

2. Device Technical Success [During operation: T=0]

   Defined as the rate of success of the following 2 steps : insertion and release

3. Womed Leaf Residuals [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 [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 [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)) [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

Criteria

• Ages Eligible for Study: 40 Years to 70 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

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

	Site	City	State	Country	Postal Code
1	UZ Gent	Gent		Belgium
2	CHU Nîmes	Nîmes		France
3	CHU Bicêtre (APHP)	Paris		France
4	Bergman Clinics	Amsterdam		Netherlands
5	Zaans Medical Center	Amsterdam		Netherlands
6	Isala Zwolle	Zwolle		Netherlands

Sponsors and Collaborators

• Womed

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - Apr 27, 2020

More Information

Publications

None provided.

• Responsible Party: Womed
• ClinicalTrials.gov Identifier: NCT04381728
• Other Study ID Numbers: PREG1
• First Posted: May 11, 2020
• Last Update Posted: Nov 9, 2021
• Last Verified: Nov 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• 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

Study Results

Participant Flow

Recruitment Details	Six centers in France, Belgium and the Netherlands participated in the trial. Between November 2019 and January 2021, 23 patients were enrolled into the study.

Arm/Group Title	Womed Leaf
Arm/Group Description	At the end of the hysteroscopic myomectomy, Womed Leaf was delivered in the uterus thanks to a 5mm diameter, flexible inserter. Then an endovaginal ultrasound was performed to assess the positioning of the uterine film. Another ultrasound was performed at 2 hours, prior to patient discharge in order to record images of the uterine film deployment. A second look hysteroscopy was performed at 4-8 weeks to evaluate the presence of intrauterine adhesion.
Period Title: Overall Study
STARTED	23
COMPLETED	23
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Womed Leaf
Arm/Group Description	At the end of the hysteroscopic myomectomy, Womed Leaf was delivered in the uterus thanks to a 5mm diameter, flexible inserter. Then an endovaginal ultrasound was performed to assess the positioning of the uterine film. Another ultrasound was performed at 2 hours, prior to patient discharge in order to record images of the uterine film deployment. A second look hysteroscopy was performed at 4-8 weeks to evaluate the presence of intrauterine adhesion.
Overall Participants	23
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	47 (6)
Sex: Female, Male (Count of Participants)
Female	23 100%
Male	0 0%
Race and Ethnicity Not Collected (Count of Participants)
Region of Enrollment (participants) [Number]
Netherlands	7 30.4%
Belgium	4 17.4%
France	12 52.2%
Myoma type (FIGO classification) (Count of Participants)
FIGO type 0 (pedunculated intracavitary)	4 17.4%
FIGO type 1 (< 50% intramural)	10 43.5%
FIGO type 2 (> 50% intramural)	9 39.1%
Mean number of tumor resected (tumors resected) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [tumors resected]	1.3 (0.9)

Outcome Measures

1. Primary Outcome

Title	Safety (Adverse Events)
Description	The number and severity of polymer film related adverse event
Time Frame	30 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Womed Leaf
Arm/Group Description	At the end of the hysteroscopic myomectomy, Womed Leaf was delivered in the uterus thanks to a 5mm diameter, flexible inserter. Then an endovaginal ultrasound was performed to assess the positioning of the uterine film. Another ultrasound was performed at 2 hours, prior to patient discharge in order to record images of the uterine film deployment. A second look hysteroscopy was performed at 4-8 weeks to evaluate the presence of intrauterine adhesion.
Measure Participants	23
Number [device related adverse event]	0

2. Primary Outcome

Title	Efficacy (Rate of Patient With no IUA)
Description	Freedom from intrauterine adhesion
Time Frame	At second look hysteroscopy between 4 and 8 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Womed Leaf
Arm/Group Description	At the end of the hysteroscopic myomectomy, Womed Leaf was delivered in the uterus thanks to a 5mm diameter, flexible inserter. Then an endovaginal ultrasound was performed to assess the positioning of the uterine film. Another ultrasound was performed at 2 hours, prior to patient discharge in order to record images of the uterine film deployment. A second look hysteroscopy was performed at 4-8 weeks to evaluate the presence of intrauterine adhesion.
Measure Participants	23
Count of Participants [Participants]	20 87%

3. Primary Outcome

Title	Efficacy (Intrauterine Adhesion Severity According to AFS Classification)
Description	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
Time Frame	At second look hysteroscopy between 4 and 8 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Womed Leaf
Arm/Group Description	At the end of the hysteroscopic myomectomy, Womed Leaf was delivered in the uterus thanks to a 5mm diameter, flexible inserter. Then an endovaginal ultrasound was performed to assess the positioning of the uterine film. Another ultrasound was performed at 2 hours, prior to patient discharge in order to record images of the uterine film deployment. A second look hysteroscopy was performed at 4-8 weeks to evaluate the presence of intrauterine adhesion.
Measure Participants	23
mild adhesions	2 8.7%
moderate adhesions	1 4.3%

4. Primary Outcome

Title	Efficacy (Intrauterine Adhesion Severity According to ESGE Classification)
Description	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
Time Frame	At second look hysteroscopy between 4 and 8 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Womed Leaf
Arm/Group Description	At the end of the hysteroscopic myomectomy, Womed Leaf was delivered in the uterus thanks to a 5mm diameter, flexible inserter. Then an endovaginal ultrasound was performed to assess the positioning of the uterine film. Another ultrasound was performed at 2 hours, prior to patient discharge in order to record images of the uterine film deployment. A second look hysteroscopy was performed at 4-8 weeks to evaluate the presence of intrauterine adhesion.
Measure Participants	23
Grade II	1 4.3%
Grade III	2 8.7%

5. Secondary Outcome

Title	Adverse Events
Description	Number of adverse events (AE) at 30 days
Time Frame	30 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Womed Leaf
Arm/Group Description	At the end of the hysteroscopic myomectomy, Womed Leaf was delivered in the uterus thanks to a 5mm diameter, flexible inserter. Then an endovaginal ultrasound was performed to assess the positioning of the uterine film. Another ultrasound was performed at 2 hours, prior to patient discharge in order to record images of the uterine film deployment. A second look hysteroscopy was performed at 4-8 weeks to evaluate the presence of intrauterine adhesion.
Measure Participants	23
Number [adverse events]	3

6. Secondary Outcome

Title	Device Technical Success
Description	Defined as the rate of success of the following 2 steps : insertion and release
Time Frame	During operation: T=0

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Womed Leaf
Arm/Group Description	At the end of the hysteroscopic myomectomy, Womed Leaf was delivered in the uterus thanks to a 5mm diameter, flexible inserter. Then an endovaginal ultrasound was performed to assess the positioning of the uterine film. Another ultrasound was performed at 2 hours, prior to patient discharge in order to record images of the uterine film deployment. A second look hysteroscopy was performed at 4-8 weeks to evaluate the presence of intrauterine adhesion.
Measure Participants	23
Count of Participants [Participants]	23 100%

7. Secondary Outcome

Title	Womed Leaf Residuals
Description	Presence of Womed Leaf residuals in the uterus
Time Frame	At second look hysteroscopy: 4-8 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Womed Leaf
Arm/Group Description	At the end of the hysteroscopic myomectomy, Womed Leaf was delivered in the uterus thanks to a 5mm diameter, flexible inserter. Then an endovaginal ultrasound was performed to assess the positioning of the uterine film. Another ultrasound was performed at 2 hours, prior to patient discharge in order to record images of the uterine film deployment. A second look hysteroscopy was performed at 4-8 weeks to evaluate the presence of intrauterine adhesion.
Measure Participants	23
Count of Participants [Participants]	0 0%

8. Secondary Outcome

Title	Womed Leaf Discharge Feedback : Time Interval in Days Between Surgery and Discharge
Description	Uterine film discharge experience as recalled by subject using a survey to be asked to the patient
Time Frame	At second look hysteroscopy: 4-8 weeks

Outcome Measure Data

Analysis Population Description

10 patients did not notice the discharge of the device

Arm/Group Title	Womed Leaf
Arm/Group Description	At the end of the hysteroscopic myomectomy, Womed Leaf was delivered in the uterus thanks to a 5mm diameter, flexible inserter. Then an endovaginal ultrasound was performed to assess the positioning of the uterine film. Another ultrasound was performed at 2 hours, prior to patient discharge in order to record images of the uterine film deployment. A second look hysteroscopy was performed at 4-8 weeks to evaluate the presence of intrauterine adhesion.
Measure Participants	13
Median (Full Range) [days]	6

9. Secondary Outcome

Title	Device Manipulation
Description	Device manipulation duration from insertion to withdrawal.
Time Frame	During intervention: T=0

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Womed Leaf
Arm/Group Description	At the end of the hysteroscopic myomectomy, Womed Leaf was delivered in the uterus thanks to a 5mm diameter, flexible inserter. Then an endovaginal ultrasound was performed to assess the positioning of the uterine film. Another ultrasound was performed at 2 hours, prior to patient discharge in order to record images of the uterine film deployment. A second look hysteroscopy was performed at 4-8 weeks to evaluate the presence of intrauterine adhesion.
Measure Participants	23
Mean (Standard Deviation) [minutes]	2 (0)

10. Secondary Outcome

Title	Womed Leaf Discharge Feedback Questionnaire (Polymer Tolerance Assessed on a Scale From 1 (no Discomfort) to 10 (Extremely Disturbing))
Description	Uterine film discharge experience as recalled by subject using a survey to be asked to the patient
Time Frame	At second look hysteroscopy: 4-8 weeks

Outcome Measure Data

Analysis Population Description

10 patients did not notice the discharge of the device

Arm/Group Title	Womed Leaf
Arm/Group Description	At the end of the hysteroscopic myomectomy, Womed Leaf was delivered in the uterus thanks to a 5mm diameter, flexible inserter. Then an endovaginal ultrasound was performed to assess the positioning of the uterine film. Another ultrasound was performed at 2 hours, prior to patient discharge in order to record images of the uterine film deployment. A second look hysteroscopy was performed at 4-8 weeks to evaluate the presence of intrauterine adhesion.
Measure Participants	13
Mean (Standard Deviation) [scale from 1 (no discomfort) to 10]	1.9 (1.8)

Adverse Events

Time Frame	30 days after hysteroscopic myomectomy and device insertion
Arm/Group Title	Womed Leaf
Arm/Group Description	At the end of the hysteroscopic myomectomy, Womed Leaf was delivered in the uterus thanks to a 5mm diameter, flexible inserter. Then an endovaginal ultrasound was performed to assess the positioning of the uterine film. Another ultrasound was performed at 2 hours, prior to patient discharge in order to record images of the uterine film deployment. A second look hysteroscopy was performed at 4-8 weeks to evaluate the presence of intrauterine adhesion.
All Cause Mortality
	Womed Leaf
	Affected / at Risk (%)	# Events
Total	0/23 (0%)
Serious Adverse Events
	Womed Leaf
	Affected / at Risk (%)	# Events
Total	0/23 (0%)
Other (Not Including Serious) Adverse Events
	Womed Leaf
	Affected / at Risk (%)	# Events
Total	3/23 (13%)
General disorders
renal colic	1/23 (4.3%)
Surgical and medical procedures
Bleeding	1/23 (4.3%)
Hematoma	1/23 (4.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.