Clinical trial NCT05789940: Hysteroscopy vs. Endouterine Aspiration in the Management of Trophoblastic Retention
Official title: Hysteroscopy Versus Endouterine Aspiration in the Management of Trophoblastic Retention: A Prospective Randomized Multicenter Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Miscarriage
Keywords: Miscarriage
Hysteroscopy
Aspiration
Fertility
Synechiae
Lead sponsor: University Hospital, Montpellier
Sponsor class: OTHER
First posted: 2023-03-29
Enrollment: 220
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 42
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Introduction: Incomplete early miscarriage is defined as early miscarriage with persistent intrauterine material on ultrasound. Intrauterine retention of trophoblastic debris is not an uncommon phenomenon. These retentions may initially be asymptomatic but are often responsible for persistent metrorrhagia and endometritis. This symptomatology often accentuates the psychological distress of patients mourning the pregnancy. Incomplete miscarriages are mainly managed by the gynecological emergency department. The recommendations of the Collège National des Gynécologues et Obstétriciens Français (CNGOF) suggest as a first line of treatment: either surgical management or expectant care. The choice between the two is left to the discretion of the doctor and the patient. there are no clear recommendations as to the choice between hysteroscopy and aspiration. Within the teams, the choice is often made according to the habits and protocols of the service, according to the equipment available and the skills of the gynaecologists.

Aim: The main objective is to compare the efficacy of management by endo-uterine aspiration vs. management by hysteroscopy of trophoblastic retention after early miscarriage, at 6 weeks after surgery, by endovaginal ultrasound.

Methods: This is a prospective, multicenter, randomized, open-label, two-arms, parallel therapeutic clinical trial comparing hysteroscopy versus endouterine aspiration for the management of trophoblastic retention after spontaneous miscarriage.

Patients will be randomized (110 per arm) after verification of eligibility criteria and signature of consent, on the day of the operation:

* Arm A: 110 patients treated by operative hysteroscopy
* Arm B: 110 patients treated by endo-uterine aspiration

Detailed description: Introduction: Incomplete early miscarriage is defined as early miscarriage with persistent intrauterine material on ultrasound. Intrauterine retention of trophoblastic debris is not an uncommon phenomenon. These retentions may initially be asymptomatic but are often responsible for persistent metrorrhagia and endometritis. This symptomatology often accentuates the psychological distress of patients mourning the pregnancy. Incomplete miscarriages are mainly managed by the gynecological emergency department. The recommendations of the Collège National des Gynécologues et Obstétriciens Français (CNGOF) suggest as a first line of treatment: either surgical management or expectant care. The choice between the two is left to the discretion of the doctor and the patient. there are no clear recommendations as to the choice between hysteroscopy and aspiration. Within the teams, the choice is often made according to the habits and protocols of the service, according to the equipment available and the skills of the gynaecologists.

Aim: The main objective is to compare the efficacy of management by endo-uterine aspiration versus management by hysteroscopy of trophoblastic retention after early miscarriage, at 6 weeks after surgery, by endovaginal ultrasound.

The secondary objectives are:

* the comparison of the rate of complications of the two techniques, during and after surgery
* the comparison of the rate of recourse to a second line surgical management between the two arms,
* the comparison of the rate of synechiae diagnosed by hysterosonography between the two techniques at 6 weeks after surgery,
* the comparison of the time to conception in the two arms during the 2 years after surgery
* the comparison of the fertility rate at 2 years after surgery in the two arms.

Methods: This is a prospective, multicenter, randomized, open-label, two-arms, parallel therapeutic clinical trial comparing hysteroscopy versus endouterine aspiration for the management of trophoblastic retention after spontaneous miscarriage.

Patients will be randomized (110 per arm) after verification of eligibility criteria and signature of consent, on the day of the operation:

* Arm A: 110 patients treated by operative hysteroscopy
* Arm B: 110 patients treated by endo-uterine aspiration Randomization will be stratified by center, age (\<35 years, 35 years and over), size of trophoblastic retention (\<30mm, 30mm and over) and scheduled by random size block. It will be centralized (Ennov-clinical software) and parameterized by the Unité́ de Recherche Clinique \& Biostatistiques of the Montpellier University Hospital.

Statistics: The effectiveness of operative hysteroscopy is expected to be 100%, and that of aspiration 90%. To show this difference with an alpha risk of 5%, and with a power of 90%, 98 patients per arm will have to be analysed (exact binomial distribution calculation, epiR package of R implemented in biostatgv). To take into account a 10% loss of sight rate, 220 patients will be recruted.

Patients will be included in the study on the morning of the procedure, after verification of the selection criteria.

The expected number of lost to follow-up is estimated at 10%; in fact, the main criterion is evaluated relatively early (6 weeks), in patients having a desire for pregnancy and therefore relatively compliant, the rate of lost to follow-up will be a fairly low.

A flow-chart will be constructed to describe the evolution of the populations during the study. It will detail the causes of non-inclusion and the causes of loss to follow-up.

All study data will be described according to the randomization arm, in the randomized population: mean, standard deviation, median and quartiles, extrema and number of missing data for quantitative variables, numbers and percentages of each modality for qualitative data.

The clinical comparability of the randomized population and the ITT population for the primary endpoint will be assessed.

Primary analysis:

The uterine vacuity rate will be compared between the two arms in the ITT population for the primary endpoint by a Chi-square test or by a Fisher exact test if the conditions for Chi-square validity are not met. The significance level was set at 5%, two-sided.

Secondary endpoint analysis:

The rates of complications, use of second-line surgical management, synechiae, and fertility at 2 years after surgery will be compared between the two arms in their respective ITT populations, by a Chi-square test or by a Fisher's exact test if the conditions for the validity of Chi-square are not met.

The time to conception will be compared between the two arms of the randomized population by a log-rank test.

Within this family of endpoints, the alpha risk will be controlled by a Hochberg procedure.

Visit 1: Pre-operative consultation between 1 and 21 days before the operation

* Clinical examination performed as part of routine care: measurement of blood pressure and pulse, temperature, speculum examination to ensure the absence of significant bleeding indicating emergency surgical management.
* Diagnosis of trophoblastic retention by endovaginal ultrasound

At the end of the consultation:

* Verification of eligibility criteria
* Oral information on the study and information leaflet given to the patient
* Collection of informed and written consent after a reflection period
* Collection of the following data:
* Demographic data
* History, smoking habits and concomitant treatments
* Pregnancy data leading to the current miscarriage
* Results of pelvic ultrasound

Intervention (D0):

* Verification of eligibility criteria and randomization on the morning of the procedure
* Surgical management of trophoblastic retention by operative hysteroscopy (Arm A) or endo-uterine aspiration (Arm B)
* Collection of adverse events during the operation and before the patient is discharged

Visit 2: Consultation at 6 weeks after surgery +/- 7 days

This consultation will be performed by an investigator trained in pelvic ultrasound and hysterosonography, blinded to the allocated procedure:

* Plasma HCG measurement before hysterosonography to ensure that there is no current pregnancy
* Endovaginal ultrasound to check uterine vacuity
* Hysterosonography for the diagnosis of uterine synechia
* Collection of complications and adverse events after surgery

Visit 3: Telephone consultation at 6 months +/- 15 days after surgery

Carried out by the clinical research associate (CRA):

* Evaluation of fertility by questionnaire
* Evaluation of the time to conception if pregnancy in progress A letter will be sent to the patient if she cannot be reached by phone (questionnaire + return envelope)

Visit 4: Telephone consultation at 12 months +/- 1 month after surgery

Carried out by the CRA:

* Evaluation of fertility by questionnaire.
* Evaluation of the time to conception if pregnancy in progress. A letter will be sent to the patient if she cannot be reached by phone (questionnaire + return envelope)

Visit 5: Telephone consultation at 24 months (+/- 2 months) after surgery

Carried out by the CRA:

* Evaluation of fertility by questionnaire
* Evaluation of the time to conception if pregnancy in progress A letter will be sent to the patient if she cannot be reached by phone (questionnaire + return envelope). The patients will be followed until a pregnancy is obtained with a term greater than or equal to 24 weeks of amenorrhea or over a maximum period of 26 months after the surgery.

Eligibility criteria: Inclusion Criteria:

* Management for trophoblastic retention after early spontaneous miscarriage (\<14 weeks of amenorrhea)
* Diagnosis of intrauterine trophoblastic retention by endovaginal pelvic ultrasound
* Shared decision for surgical management
* Current pregnancy desire

Exclusion Criteria:

* Known uterine malformation
* Patient who has received surgical treatment for current intrauterine retention
* Trophoblastic retention after elective termination, late miscarriage and postpartum
* Patient with an intrauterine device (IUD)
* Pregnancy obtained by medically assisted procreation
* Indication for emergency surgical management for haemostatic purposes
* Failure to obtain free, informed and written consent after a period of reflection
* Person not affiliated or beneficiary of a national health insurance system
* Person protected by law, under guardianship or curatorship
* Person participating in other interventional research involving the human person

Primary outcomes:
measure: Uterine vacuity
timeFrame: 6 weeks after surgery
Secondary outcomes:
measure: Difference between the two arms in complication rates
timeFrame: During surgery and 6 weeks after surgery
measure: Difference between the two arms in the rate of second line surgical management
timeFrame: During surgery
measure: Difference between the two arms in synechia rates
timeFrame: 6 weeks after surgery
measure: Difference between the two arms in mean time to conception
timeFrame: 6, 12 and 24 months after surgery
measure: Difference between the two arms in pregnancy rates
timeFrame: 6, 12 and 24 months after surgery
Other outcomes:
Locations:
city: Bordeaux
country: France
facility: CHU de Bordeaux - Hôpital Pellegrin
city: Montpellier
country: France
facility: CHU de Montpellier - Hôpital Arnaud de Villeneuve
city: Nice
country: France
facility: CHU de Nice - Hôpital Archet II
city: Nîmes
country: France
facility: CHU de Nîmes - Hôpital Carémeau
Study officials:
affiliation: CHU de Montpellier
name: Martha DURAES, MD
role: STUDY_DIRECTOR
References: