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

Study Overview
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Brief Summary
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Despite advances in prenatal diagnosis and postnatal therapies, including ECMO (Extracorporeal Membrane Oxygenation), inhaled nitric oxide therapy, and ventilator strategies that minimize ventilator-induced lung injury, morbidity and mortality rates for babies with severe CDH remain high. The rationale for fetal therapy in severe CDH is to promote adequate lung growth for 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. The investigator's goal with this pilot study is to study the feasibility of implementing Fetoscopic Endoluminal Tracheal Occlusion (FETO) therapy in the most severe group of fetuses with left CDH (LHR O/E < 25%).

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

Conditions
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Congenital Diaphragmatic Hernia

Intervention / Treatment
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* Device: Fetoscopic Endoluminal Tracheal Occlusion Surgery


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pregnant women age 18 years and older Singleton pregnancy Normal fetal karyotype with confirmation by culture results. Results by fluorescence in situ hybridization (FISH) will be acceptable if the patient is > 26 weeks Isolated Left CDH with liver up Gestation age at enrollment prior to 29 wks plus 6 days SEVERE pulmonary hypoplasia with US LHR O/E < 25% (measured at 180 to 295 weeks) at the time of surgery Gestational age at FETO procedure 27 weeks 0 days to 29 weeks 6 days as determined by clinical information (LMP) and evaluation of first ultrasound Family meets psychosocial criteria Pre-authorization from third-party payor for fetal intervention OR the ability to self-pay for study treatment. For all patients without insurance or the means to pay for the procedure, an attempt will be made to obtain Medicaid. Insurers that have denied payment have noted that this remains an experimental procedure. As this is a feasibility study and not being offered as either standard of care or as a prospective randomized control trial to determine efficacy, the investigators do not feel that there is a breach of ethical standards. Informed consent Exclusion Criteria: Failure to meet all inclusion criteria Patient < 18 years of age Multi-fetal pregnancy 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 Family does not meet psychosocial criteria. Reasons for exclusion include: insufficient social support, inability to understand requirements of the study, inability to reside in or near San Francisco. Right sided CDH or bilateral CDH, isolated left sided with LHR O/E < 25% (measured at 180 to 295 weeks) as determined by ultrasound Additional fetal anomaly by ultrasound, MRI, or echocardiogram at the fetal treatment center. Exclude chromosomal abnormalities, associated anomalies recognized to alter survival prognosis (ie. CDH and congenital heart disease) or presence of an underlying genetic syndrome (ie. Fryns). No cases will be removed post hoc if abnormalities are discovered in the course of post-operative monitoring Maternal contraindication to fetoscopic surgery or severe maternal medical condition in pregnancy History of incompetent cervix with or without cerclage Placental abnormalities (previa, abruption, accrete) known at time of enrollment Maternal-fetal Rh isoimmunization, Kell sensitization or neonatal alloimmune thrombocytopenia affecting the current pregnancy Maternal HIV, Hepatitis-B, Hepatitis-C status positive because of the increased risk of transmission to the fetus during maternal-fetal surgery. If the patient's HIV or Hepatitis status is unknown, the patient must be tested and found to have negative results before enrollment Uterine anomaly such as large or multiple fibroids or mullerian duct abnormality There is no safe or technically feasible fetoscopic approach to balloon placement Participation in another intervention study that influences maternal and fetal morbidity and mortality or participation in this trial in a previous pregnancy

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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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Device - FETO<br>Fetoscopic Endoluminal Tracheal Occlusion (FETO) surgery and removal of balloon using the BALT GOLDBAL2 balloon and BALTACCIBDPE100 catheter. | Device: Fetoscopic Endoluminal Tracheal Occlusion Surgery<br>* Fetoscopic Endoluminal Tracheal Occlusion (FETO) surgery will be completed at 27 weeks 0 days - 29 weeks 6 days gestation. Fetoscopic removal of the balloon occlusion will be performed at 34 weeks 0 days to 34 weeks 6 days gestation.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of effective placements of balloon to occlude trachea via fetoscopy | Number of effective placements of balloon to occlude trachea via fetoscopy by performing Fetoscopic Endoluminal Tracheal Occlusion (FETO) in fetuses with severe left congenital diaphragmatic hernia (CDH), as defined by lung to head ratio (LHR) Observed/Expected < 25% | Between 27 and 29 weeks gestation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of fetal lung growth after FETO as measured by lung volume. | Fetal lung growth as measured by lung volume. | Between 27 and 34 weeks gestation | 
| Rate of fetal lung growth after FETO as measured by Lung to head circumference ratio | Fetal lung growth as measured by Lung to head circumference ratio (LHR) measurements. | Between 27 and 34 weeks gestation | 
| Determine survival rate of FETO patients | Survival at 6 months after birth. | 6 months after birth |