## Protocol Section
### Identification Module
**NCT ID:** NCT04963179

**Acronym:** PREG2

**Brief Title:** PREvention of Intrauterine Adhesion After Adhesiolysis With Novel Tri-block deGradable Polymer Film.

**Official Title:** PREvention of Intrauterine Adhesion After Adhesiolysis With Novel Tri-block deGradable Polymer Film.

#### Organization Study ID Info
**ID:** PREG2
#### Organization
**Class:** INDUSTRY
**Full Name:** Womed
### Status Module
#### Completion Date
**Date:** 2025-01

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-02-14

**Type:** ACTUAL

**Last Update Submit Date:** 2024-02-12

**Overall Status:** ACTIVE_NOT_RECRUITING

#### Primary Completion Date
**Date:** 2023-11-11

**Type:** ACTUAL

#### Start Date
**Date:** 2021-11-29

**Type:** ACTUAL

**Status Verified Date:** 2024-02

#### Study First Post Date
**Date:** 2021-07-15
**Type:** ACTUAL
**Study First Submit Date:** 2021-07-05
**Study First Submit QC Date:** 2021-07-05
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** INDUSTRY

**Name:** Womed

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

### Description Module

**Brief Summary:** 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

**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.

### Conditions Module

**Conditions:**

- Asherman Syndrome

- Intrauterine Adhesion

**Keywords:**

- Asherman Syndrome

- Intrauterine adhesion

- Hysteroscopy

- Adhesiolysis

- Adhesion prevention

- Infertility

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** PARALLEL

##### Masking Info

**Masking:** DOUBLE

**Who Masked:**

- PARTICIPANT

- OUTCOMES_ASSESSOR

**Primary Purpose:** PREVENTION

#### Enrollment Info

**Count:** 160

**Type:** ACTUAL

**Phases:**

- NA

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** IUA prevention: The novel intrauterine barrier film (Womed Leaf) is inserted immediately after completion of the hysteroscopic adhesiolysis

**Intervention Names:**

- Device: Womed Leaf

**Label:** Womed Leaf

**Type:** EXPERIMENTAL

#### Arm Group 2

**Description:** No IUA prevention - no placebo after adhesiolysis

**Label:** Control

**Type:** NO_INTERVENTION

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Womed Leaf

**Description:** 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.

**Name:** Womed Leaf

**Type:** DEVICE

### Outcomes Module

#### Primary Outcomes

**Description:** Change of AFS score between pre-adhesiolysis and second-look hysteroscopy (AFS) score

**Measure:** Efficacy - IUA severity

**Time Frame:** At second look hysteroscopy between 4 and 8 weeks

**Description:** Adverse events up to second look hysteroscopy.

**Measure:** Safety - Adverse events

**Time Frame:** At second look hysteroscopy between 4 and 8 weeks

#### Secondary Outcomes

**Description:** Percentage of patients who have improved from severe to mild adhesions or from severe to no adhesions or from moderate to no adhesions

**Measure:** High-responder rate

**Time Frame:** At second look hysteroscopy between 4 and 8 weeks

**Description:** Average of AFS score component "extent of cavity involved"

**Measure:** Change of "extent of cavity involved" component

**Time Frame:** At second look hysteroscopy between 4 and 8 weeks

**Description:** Average of AFS score component "extent of cavity involved"

**Measure:** Change in "extent of cavity involved" component between post-adhesiolysis and second look hysteroscopy

**Time Frame:** At second look hysteroscopy between 4 and 8 weeks

**Description:** Average of AFS score

**Measure:** AFS score

**Time Frame:** At second look hysteroscopy between 4 and 8 weeks

**Description:** Average of the change of the AFS score component "Extent of IUA"

**Measure:** Change of extent of IUA AFS score component

**Time Frame:** At second look hysteroscopy between 4 and 8 weeks

**Description:** Average of the change of the AFS score component "type of IUA"

**Measure:** Change of type of IUA AFS score component

**Time Frame:** At second look hysteroscopy between 4 and 8 weeks

**Description:** Average of the change of the AFS score component "Menstrual Pattern"

**Measure:** Menstrual pattern AFS score component

**Time Frame:** At second look hysteroscopy between 4 and 8 weeks

**Description:** Percentage of patients who have AFS \< 5

**Measure:** Percentage of patients who have Mild adhesions or no adhesion

**Time Frame:** At second look hysteroscopy between 4 and 8 weeks

**Description:** Rate of patients who don't have adhesion

**Measure:** Freedom from IUA

**Time Frame:** At second look hysteroscopy between 4 and 8 weeks

**Description:** Rate of ECGE stage

**Measure:** ESGE stage

**Time Frame:** At second look hysteroscopy between 4 and 8 weeks

**Description:** Level of post-operative pain on a numeric rating scale, with 0 = no pain and 10 = the worst pain.

**Measure:** Level of post-operative pain

**Time Frame:** At second look hysteroscopy between 4 and 8 weeks

**Description:** Level of discomfort related to vaginal discharge on a numeric rating scale, with 0 = no discomfort and 10 = extremely disturbing

**Measure:** Level of discomfort related to vaginal discharge

**Time Frame:** At second look hysteroscopy between 4 and 8 weeks

**Description:** Timing of vaginal discharge as recalled by the patient

**Measure:** Timing of vaginal discharge

**Time Frame:** At second look hysteroscopy between 4 and 8 weeks

**Description:** Duration of the vaginal discharge as recalled by the patient

**Measure:** Duration of the vaginal discharge

**Time Frame:** At second look hysteroscopy between 4 and 8 weeks

**Description:** Qualitative description of the vaginal discharge as recalled by the patient

**Measure:** Qualitative description of the vaginal discharge

**Time Frame:** At second look hysteroscopy between 4 and 8 weeks

**Description:** Change of menstrual pattern

**Measure:** Change of menstrual pattern

**Time Frame:** At second look hysteroscopy between 4 and 8 weeks, 1 year, 2 years

**Description:** Reintervention rate, during second look hysteroscopy or scheduled later up to one year

**Measure:** Reintervention rate

**Time Frame:** At second look hysteroscopy or scheduled later up to one year

**Description:** Number of adhesiolysis procedures after second look to one year

**Measure:** Number of adhesiolysis procedures

**Time Frame:** After second look to one year

**Description:** Pregnancy rate defined as presence of foetal sac or heartbeat by ultrasound at 1 year and 2 years, whether spontaneous or IVF

**Measure:** Pregnancy rate

**Time Frame:** 1 year, 2 years

**Description:** Live birth rate at 1 year and 2 years

**Measure:** Live birth rate

**Time Frame:** 1 year and 2 years

**Description:** Pregnancy complication rate

**Measure:** Pregnancy complication rate

**Time Frame:** 2 years

**Description:** Time to pregnancy (i.e. time between the second look hysteroscopy and pregnancy start)

**Measure:** Time to pregnancy

**Time Frame:** 2 years

**Description:** IUA severity according to Chinese scoring system (for patients enrolled in China only)

**Measure:** IUA severity according to Chinese scoring system

**Time Frame:** At second look hysteroscopy between 4 and 8 weeks

**Description:** Percentage of patients with an improvement of one clinical category i.e from Severe to Moderate or from Moderate to Mild

**Measure:** Responder rate

**Time Frame:** At second look hysteroscopy between 4 and 8 weeks

### Eligibility Module

**Eligibility Criteria:** 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

**Minimum Age:** 18 Years

**Sex:** FEMALE

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Locations

**Location 1:**

**City:** Gent

**Country:** Belgium

**Facility:** Gent UZ

**Zip:** 9000

**Location 2:**

**City:** Guangzhou

**Country:** China

**Facility:** Guangdong Maternal and Child Health Hospital

**Location 3:**

**City:** Hangzhou

**Country:** China

**Facility:** Women's Hospital School Of Medicine Zhejiang University

**Location 4:**

**City:** Shanghai

**Country:** China

**Facility:** The Obstetrics & Gynecology Hospital Affiliated to Fudan University

**Location 5:**

**City:** Ostrava

**Country:** Czechia

**Facility:** Gynprenatal

**Location 6:**

**City:** Le Kremlin-Bicêtre

**Country:** France

**Facility:** CHU Bicêtre

**Zip:** 94270

**Location 7:**

**City:** Lille

**Country:** France

**Facility:** CHU de Lille

**Zip:** 59000

**Location 8:**

**City:** Marseille

**Country:** France

**Facility:** Hopital La Conception

**Zip:** 13005

**Location 9:**

**City:** Paris

**Country:** France

**Facility:** CHU Lariboisière

**Zip:** 75010

**Location 10:**

**City:** Rennes

**Country:** France

**Facility:** Clinique Mutualiste La sagesse

**Zip:** 35043

**Location 11:**

**City:** Napoli

**Country:** Italy

**Facility:** A.O.U Federico II

**Zip:** 80131

**Location 12:**

**City:** Torino

**Country:** Italy

**Facility:** Aso Mauriziano Umberto I

**Location 13:**

**City:** Barcelona

**Country:** Spain

**Facility:** Hospital Clinic Barcelonna

**Location 14:**

**City:** Madrid

**Country:** Spain

**Facility:** Ramon y Cajal Hospital

**Zip:** 28034

**Location 15:**

**City:** Lausanne

**Country:** Switzerland

**Facility:** Centre Hospitalier Universitaire Vaudois

**Zip:** 1011

### IPD Sharing Statement Module

**Access Criteria:** researchers who provide a methodologically sound proposal

**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

**Info Types:**

- STUDY_PROTOCOL

**IPD Sharing:** YES

**Time Frame:** immediately after article publication and during 5 years

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000010335

- Term: Pathologic Processes

- ID: D000002921

- Term: Cicatrix

- ID: D000005355

- Term: Fibrosis

- ID: D000005831

- Term: Genital Diseases, Female

- ID: D000052776

- Term: Female Urogenital Diseases

- ID: D000005261

- Term: Female Urogenital Diseases and Pregnancy Complications

- ID: D000091642

- Term: Urogenital Diseases

- ID: D000091662

- Term: Genital Diseases

### Condition Browse Module - Browse Branches

- Abbrev: BC23

- Name: Symptoms and General Pathology

- Abbrev: All

- Name: All Conditions

- Abbrev: BXS

- Name: Urinary Tract, Sexual Organs, and Pregnancy Conditions

- Abbrev: Rare

- Name: Rare Diseases

### Condition Browse Module - Browse Leaves

- ID: M16355

- Name: Syndrome

- Relevance: LOW

- As Found: Unknown

- ID: M10290

- Name: Infertility

- Relevance: LOW

- As Found: Unknown

- ID: M3620

- Name: Tissue Adhesions

- Relevance: HIGH

- As Found: Adhesion

- ID: M9269

- Name: Gynatresia

- Relevance: HIGH

- As Found: Asherman Syndrome

- ID: M6160

- Name: Cicatrix

- Relevance: LOW

- As Found: Unknown

- ID: M8485

- Name: Fibrosis

- Relevance: LOW

- As Found: Unknown

- ID: M8943

- Name: Genital Diseases, Female

- Relevance: LOW

- As Found: Unknown

- ID: M2876

- Name: Genital Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M2875

- Name: Urogenital Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M27093

- Name: Female Urogenital Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M14127

- Name: Pregnancy Complications

- Relevance: LOW

- As Found: Unknown

- ID: M8399

- Name: Female Urogenital Diseases and Pregnancy Complications

- Relevance: LOW

- As Found: Unknown

- ID: T509

- Name: Asherman's Syndrome

- Relevance: HIGH

- As Found: Asherman Syndrome

### Condition Browse Module - Meshes

- ID: D000006175

- Term: Gynatresia

- ID: D000000267

- Term: Tissue Adhesions

### Misc Info Module

- Version Holder: 2024-05-24
