Clinical trial NCT04931212: Fetoscopic Endoluminal Tracheal Occlusion (FETO) with Smart-TO
Official title: Fetoscopic Endoluminal Tracheal Occlusion (FETO) with Smart-TO Device in Fetuses with Congenital Diaphragmatic Hernia and Moderate to Severe Pulmonary Hypoplasia: Proof of Concept and Safety Evaluation.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Congenital Diaphragmatic Hernia
Keywords: Congenital diaphragmatic hernia
Fetal endoscopic tracheal occlusion
Smart-TO balloon
Proof of concept
Safety study
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2021-06-18
Enrollment: 23
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to make the proof of concept and to evaluate the safety of fetoscopic endoluminal tracheal occlusion (FETO) using Smart-TO device in fetuses with congenital diaphragmatic hernia and moderate to severe pulmonary hypoplasia

Detailed description: Congenital diaphragmatic hernia (CDH) leads to lung hypoplasia and impaired lung vasculature. Fetal lung growth may be stimulated by fetal endoscopic tracheal occlusion (FETO). In severe CDH, FETO may improve survival. In the moderate cases, the prematurity induced by the plug-unplug strategy limits the benefit from the lung growth induced by tracheal occlusion.

One of the main drawbacks of FETO is the need for in-utero reversal of tracheal occlusion by the balloon, as the current procedure involves re-establishment of patent airways either electively at 34 weeks' gestation or earlier if required, ideally at least 24 h before birth. Unfortunately, removal of the balloon is a difficult, invasive, and risky procedure. Furthermore, it requires a specialist team to be able to reverse the occlusion at all times. As a result, it is recommended that the patient stays close to a FETO center during the whole duration of the occlusion, which may limit the acceptability of FETO.

The Smart-TO balloon allows an easy, remotely controlled, and non-invasive reversal occlusion, so it allows to overcome issues related to the airway reestablishment. The technology solution is based on a magnetic valve that opens under the influence of the peripheral magnetic field around a magnetic resonance (MR) scanner. The opening of the valve induces the deflation of the balloon, which is then washed out by the fluid coming out from the lungs.

The purpose of this study is to make the proof of concept and to evaluate the safety of fetoscopic endoluminal tracheal occlusion (FETO) using Smart-TO device in fetuses with congenital diaphragmatic hernia and moderate to severe pulmonary hypoplasia. Secondary objectives include evaluation of prematurity, preterm premature rupture of membranes, lung growth, and survival at discharge in case of FETO with Smart-TO balloon.

FETO with Smart-TO balloon will be performed between 27 and 31wks + 6 days depending on the severity of pulmonary hypoplasia, according to the same technique that is used with the balloon usually used for FETO procedure. The unplug procedure will be performed between 34 and 34wks + 6 days or earlier if required. The patient will be asked to make a peripheral course around the MR scanner in order to open the magnetic valve and induce the deflation of the balloon. Ultrasound scan will be performed before and after the unplug procedure, in order to check the balloon did not deflate spontaneously at the time of the unplug, and to check the balloon deflates thanks to the magnetic fringe field of the MR scan. Expelling of the Smart-TO balloon outside the airways will be check at birth by a thorax X-ray.

Patients will be monitored during the whole duration of the study so serious unexpected or adverse reactions can be recorded.

Eligibility criteria: Inclusion Criteria:

* Patients aged 18 years or more, who are able to consent, and affiliated to social security
* Singleton pregnancy with fetus with isolated left-sided congenital diaphragmatic hernia (no additional malformation nor chromosomal abnormality) and:

Severe pulmonary hypoplasia defined as observed on expected 'lung-to-head ration' (O/E LHR) \<25% irrespective of the liver position as measured between 27wks and 29wks + 6 days Or Moderate pulmonary hypoplasia defined as O/E LHR 25-34.9% (liver up or down) or O/E LHR 35-44.9% with liver up as measured between 30wks and 31wks + 6 days

Exclusion Criteria:

* Maternal contraindication to fetoscopic surgery
* Preterm premature rupture of the membranes (PPROM) or condition strongly predisposing to PPROM or premature delivery
* Impossibility of remain close to the FETO center during the fetal occlusion period

Primary outcomes:
measure: Deflation of the Smart-TO balloon after exposure to the fringe field of the MRI
timeFrame: Between 34 and 34+6 amenorrhea weeks
measure: Expelling of the Smart-TO balloon outside the airways
timeFrame: At birth
Secondary outcomes:
measure: Serious unexpected or adverse reactions
timeFrame: From date of inclusion until discharge date from hospitalization of newborn, up 15 months
measure: Spontaneous deflation of the balloon
timeFrame: Between the FETO (27amenorrhea weeks) and the unplug procedure (34 amenorrhea weeks)
measure: Prematurity
timeFrame: At birth
measure: Preterm premature rupture of the membranes (PPROM)
timeFrame: from date of inclusion until delivery, up to 37 amenorrhea weeks
measure: Fetal lung growth
timeFrame: Before the unplug procedure
measure: Survival at discharge
timeFrame: From date of inclusion until discharge date from hospitalization of newborn, up to 6 months
measure: Survival at 6 months of age
timeFrame: 6 months after birth
measure: Oxygen dependence
timeFrame: 6 months after birth
Other outcomes:
Locations:
city: Clamart
country: France
facility: Hôpital Béclère
city: Le Kremlin-Bicêtre
country: France
facility: Hôpital Bicêtre
Study officials:
affiliation: Assistance Publique - Hôpitaux de Paris
name: Anne-Gael CORDIER, MD, PhD
role: STUDY_CHAIR
affiliation: University Hospital, Strasbourg, France
name: Nicolas SANANES, MD, PhD
role: STUDY_CHAIR
affiliation: AH-HP
name: Alexandra BENACHI, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: