Intrauterine Adhesion
Conditions
Keywords
myomectomy, Intrauterine adhesion, hysteroscopy
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.
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.
Interventions
DEVICEWomed Leaf
Womed Leaf uterine film will be inserted immediately after the myomectomy, following per-operative hysterometry.
Sponsors
Womed
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
40 Years to 70 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety (Adverse Events) | 30 days | The number and severity of polymer film related adverse event |
| Efficacy (Rate of Patient With no IUA) | At second look hysteroscopy between 4 and 8 weeks | Freedom from intrauterine adhesion |
| 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 |
| 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
| Measure | Time frame | Description |
|---|---|---|
| Device Manipulation | During intervention: T=0 | Device manipulation duration from insertion to withdrawal. |
| Adverse Events | 30 days | Number of adverse events (AE) at 30 days |
| 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 |
| Device Technical Success | During operation: T=0 | Defined as the rate of success of the following 2 steps : insertion and release |
| Womed Leaf Residuals | At second look hysteroscopy: 4-8 weeks | Presence of Womed Leaf residuals in the uterus |
| 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 |
Countries
Belgium, France, Netherlands
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.
Participants by arm
| Arm | Count |
|---|---|
| Womed Leaf 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. | 23 |
| Total | 23 |
Baseline characteristics
| Characteristic | Womed Leaf | — |
|---|---|---|
| Age, Continuous | 47 years STANDARD_DEVIATION 6 | — |
| Mean number of tumor resected | 1.3 tumors resected STANDARD_DEVIATION 0.9 | — |
| Myoma type (FIGO classification) FIGO type 0 (pedunculated intracavitary) | 4 Participants | — |
| Myoma type (FIGO classification) FIGO type 1 (< 50% intramural) | 10 Participants | — |
| Myoma type (FIGO classification) FIGO type 2 (> 50% intramural) | 9 Participants | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Region of Enrollment Belgium | 4 participants | — |
| Region of Enrollment France | 12 participants | — |
| Region of Enrollment Netherlands | 7 participants | — |
| Sex: Female, Male Female | 23 Participants | — |
| Sex: Female, Male Male | 0 Participants | — |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 23 |
| other Total, other adverse events | 3 / 23 |
| serious Total, serious adverse events | 0 / 23 |
Outcome results
Primary
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
Time frame: At second look hysteroscopy between 4 and 8 weeks
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Womed Leaf | Efficacy (Intrauterine Adhesion Severity According to AFS Classification) | moderate adhesions | 1 Participants |
| Womed Leaf | Efficacy (Intrauterine Adhesion Severity According to AFS Classification) | mild adhesions | 2 Participants |
Primary
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
Time frame: At second look hysteroscopy between 4 and 8 weeks
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Womed Leaf | Efficacy (Intrauterine Adhesion Severity According to ESGE Classification) | Grade II | 1 Participants |
| Womed Leaf | Efficacy (Intrauterine Adhesion Severity According to ESGE Classification) | Grade III | 2 Participants |
Primary
Efficacy (Rate of Patient With no IUA)
Freedom from intrauterine adhesion
Time frame: At second look hysteroscopy between 4 and 8 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Womed Leaf | Efficacy (Rate of Patient With no IUA) | 20 Participants |
Primary
Safety (Adverse Events)
The number and severity of polymer film related adverse event
Time frame: 30 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Womed Leaf | Safety (Adverse Events) | 0 device related adverse event |
Secondary
Adverse Events
Number of adverse events (AE) at 30 days
Time frame: 30 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Womed Leaf | Adverse Events | 3 adverse events |
Secondary
Device Manipulation
Device manipulation duration from insertion to withdrawal.
Time frame: During intervention: T=0
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Womed Leaf | Device Manipulation | 2 minutes | Standard Deviation 0 |
Secondary
Device Technical Success
Defined as the rate of success of the following 2 steps : insertion and release
Time frame: During operation: T=0
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Womed Leaf | Device Technical Success | 23 Participants |
Secondary
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
Time frame: At second look hysteroscopy: 4-8 weeks
Population: 10 patients did not notice the discharge of the device
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Womed Leaf | Womed Leaf Discharge Feedback Questionnaire (Polymer Tolerance Assessed on a Scale From 1 (no Discomfort) to 10 (Extremely Disturbing)) | 1.9 scale from 1 (no discomfort) to 10 | Standard Deviation 1.8 |
Secondary
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
Time frame: At second look hysteroscopy: 4-8 weeks
Population: 10 patients did not notice the discharge of the device
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Womed Leaf | Womed Leaf Discharge Feedback : Time Interval in Days Between Surgery and Discharge | 6 days |
Secondary
Womed Leaf Residuals
Presence of Womed Leaf residuals in the uterus
Time frame: At second look hysteroscopy: 4-8 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Womed Leaf | Womed Leaf Residuals | 0 Participants |