Fetoscopic Endoluminal Tracheal Occlusion

Study Overview
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Brief Summary
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The purpose of this research study is to see if the FETO surgery and FETO release (surgery to remove the device) works and is safe for babies with severe right or left Congenital Diaphragmatic Hernia (CDH). CDH is a condition in which a hole in the baby's diaphragm allows the abdominal organs to move into the chest and limit lung growth. The goal of the FETO device is to block the airway with a balloon-type device, allowing fluid to build up and help the unborn baby's lungs grow. Bigger lungs may improve the baby's quality of life.

Detailed Description
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Despite advances in prenatal diagnosis and postnatal therapies, including extracorporeal membrane oxygenation (ECMO), inhaled nitric oxide therapy, and ventilator strategies that minimize ventilator-induced lung injury, morbidity and mortality rates for babies with severe CDH remain high. Data from Children's Hospital of Philadelphia (CHOP) between January 2006 and December 2010 for prenatal and postnatal care for 64 patients with isolated left CDH showed overall survival was 63%. Survival was 33% in patients requiring the use ECMO. Immediate morbidity/mortality is related to the severity of the pulmonary hypoplasia caused by the mass effect of the herniated abdominal contents on the developing lungs. Quantifying the severity of pulmonary hypoplasia has been performed using the observed/expected lung to head circumference ratio (O/E LHR). It is a tool validated in 354 fetuses with unilateral isolated CDH evaluated between 18 and 38 weeks gestation. For O/E LHR < 25%, survival was dismal at 1/9 or 11% (CHOP experience, not published). Published data from an interdisciplinary follow-up program at CHOP shows striking morbidities in neuromuscular tone and neurodevelopmental status. The rationale for fetal therapy in severe CDH is to improve fetal lung growth and therefore neonatal survival. Prenatal tracheal occlusion obstructs the normal egress of lung fluid during pulmonary development leading to increased lung tissue stretch, increased cell proliferation, and accelerated lung growth. European colleagues have developed foregut endoscopy and techniques to position and remove endoluminal tracheal balloons in utero. Recently, the Belgium group published summary results of FETO showing an improved survival in 175 patients with isolated left CDH from 24% to 49%. The investigators goal with this pilot study is to study the feasibility of implementing FETO therapy in the most severe group of fetuses with left CDH (O/E< 25%; O/E < 30%) and right CDH (O/E < 45%).

Official Title
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Pilot Trial of Fetoscopic Endoluminal Tracheal Occlusion (FETO) in Severe Right and Left Congenital Diaphragmatic Hernia (CDH)

Conditions
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Congenital Diaphragmatic Hernia

Intervention / Treatment
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* Device: Fetoscopic Endoluminal Tracheal Occlusion (FETO)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pregnant women age 18 years and older, who are able to consent Singleton pregnancy Fetal Normal Karyotype Fetal Diagnosis of Isolated Left or Right CDH with liver up Gestation at enrollment prior to 29 wks plus 6 days SEVERE pulmonary hypoplasia with Ultra Sound L-sided O/E LHR < 25% or R-sided O/E LHR <45% Exclusion Criteria: Pregnant women <18 years of age. Maternal contraindication to fetoscopic surgery or severe maternal medical condition in pregnancy Technical limitations precluding fetoscopic surgery Rubber latex allergy Preterm labor, cervix shortened (<15 mm at enrollment or within 24 hours of FETO balloon insertion procedure) or uterine anomaly strongly predisposing to preterm labor, placenta previa Psychosocial ineligibility, precluding consent Inability to remain at FETO site during time period of tracheal occlusion, delivery and postnatal care

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fetuses with Left CDH (O/E LHR < 25%)<br>Fetuses with Left CDH (O/E LHR < 25%) will receive Fetoscopic Endoluminal Tracheal Occlusion (FETO) | Device: Fetoscopic Endoluminal Tracheal Occlusion (FETO)<br>* This study will position and remove an endoluminal tracheal balloon in utero (FETO) to study the feasibility of implementing FETO therapy in the most severe group of fetuses with left CDH (O/E < 25%; O/E LHR < 30 %) and right CDH (O/E LHR < 45%).<br>* Other names: BALTACCIBDPE100: Catheter System;|
| Experimental: Fetuses with L- sided CDH with O/E LHR <30%.<br>Fetuses with Left CDH (O/E LHR < 30%) will receive Fetoscopic Endoluminal Tracheal Occlusion (FETO) | Device: Fetoscopic Endoluminal Tracheal Occlusion (FETO)<br>* This study will position and remove an endoluminal tracheal balloon in utero (FETO) to study the feasibility of implementing FETO therapy in the most severe group of fetuses with left CDH (O/E < 25%; O/E LHR < 30 %) and right CDH (O/E LHR < 45%).<br>* Other names: BALTACCIBDPE100: Catheter System;|
| Experimental: Fetuses with R- sided CDH with O/E LHR < 45%<br>Fetuses with Right CDH (O/E LHR < 45%) will receive Fetoscopic Endoluminal Tracheal Occlusion (FETO) | Device: Fetoscopic Endoluminal Tracheal Occlusion (FETO)<br>* This study will position and remove an endoluminal tracheal balloon in utero (FETO) to study the feasibility of implementing FETO therapy in the most severe group of fetuses with left CDH (O/E < 25%; O/E LHR < 30 %) and right CDH (O/E LHR < 45%).<br>* Other names: BALTACCIBDPE100: Catheter System;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Successful placement of Balt Goldbal2 balloon | The feasibility of performing the procedure and managing the pregnancy during the period of tracheal occlusion | 7 weeks after placement | 
| Successful removal of Balt Goldbal2 balloon | The feasibility of the removal of the device prior to delivery | Within 5 weeks prior to delivery | 
| Gestational age at delivery |  | At delivery | 
| Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] | Incidence of Maternal complications: preterm labor, premature rupture of membranes, oligohydramnios, polyhydramnios, chorioamnionitis) | After Insertion of Balloon to delivery- (from 27 weeks gestational age up to 39 weeks gestational age) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Survival at Discharge or at 6 months if still hospitalized |  | Discharge up to 180 days post delivery | 
| Lung Volume Measurement |  | 7 weeks after placement of balloon | 
| Lung Head Ratio Measurement |  | 7 weeks after placement of balloon | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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tracheal occlusion, FETO, Congenital Diaphragmatic Hernia