Fetal Tracheal Balloon Study in Diaphragmatic Hernia

Study Overview
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Brief Summary
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The purpose of this phase 2 limited study is to examine whether prenatal intervention correct the lung underdevelopment associated with severe diaphragmatic hernia.

Detailed Description
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Congenital diaphragmatic hernia (CDH) has traditionally been associated with very high mortality rates. Most infants died of pulmonary hypoplasia and severe pulmonary hypertension. This led to correction of CDH and pulmonary hypoplasia before birth. Unfortunately, maternal morbidity of open fetal surgery was significant and fetal mortality was very high (>60%). Moreover, the results of postnatal therapy for CDH improved dramatically, from less than 20% survival several decades ago to more than 70% today. Fetal intervention has evolved as well, to a minimally invasive approach that involves a single endoscopic port and occlusion of the fetal trachea. While this has considerably decreased the morbidity and fetal mortality of the in utero procedure, its results do not exceed the overall (i.e., non-stratified) results of contemporary postnatal treatment. Most recently, a multicentric cooperative study under (Eurofoetus) has conducted a clinical trial comparing postnatal treatment with endoscopic fetal tracheal occlusion for the most severe forms of CDH. Results of the Eurofoetus trial and of a recent retrospective review involving European and North-American centers have shown the following: 1) It is possible to identify a specific subgroup of fetuses with CDH in whom survival can be predicted to be less than 10%, despite all current methods of postnatal treatment, 2) Survival of fetuses with predicted postnatal survival of 8% was >50% following endoscopic fetal tracheal occlusion, and 3) Fetal tracheal occlusion in that group resulted in an increase in lung size (LHR), from an average of 0.7 pre-intervention, to 1.7 post-intervention. Based on the available research literature, the results of the Eurofoetus trial, and this institution's experience with endoscopic fetal surgery, we hypothesize that in the highest risk group of fetuses with congenital diaphragmatic hernia, where chances of survival is estimated at less than 10%, endoscopic fetal tracheal occlusion in late second trimester, with reversal of occlusion in mid-third trimester, allows catch-up lung growth and maturation and converts the condition into one with intermediate to good prognosis (predicted survival 50-60%). We propose to offer this form of treatment, under an FDA-approved Investigational Device Exemption (G080077), to eligible patients, on a case-by-case basis, after discussion before a multidisciplinary board.

Official Title
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Phase 2 Fetal Tracheal Balloon (IDE G080077) Study in Diaphragmatic Hernia

Conditions
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Diaphragmatic Hernia, Lung Disease

Intervention / Treatment
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* Device: Fetal tracheal obstruction with detachable balloon (device)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Singleton pregnancies Isolated congenital diaphragmatic hernia Normal karyotype (amniocentesis) Initial diagnosis before 26 weeks gestation Competent cervix Severity of CDH: lung-to-head ratio (LHR) ≤0.8 at 22-26 weeks gestation Liver herniation in the chest Informed consent Exclusion Criteria: Preterm labor, premature rupture of membranes or amniotic leak Significant maternal morbidity Minor (<18 years)

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Detachable balloon<br>Intervention: Fetuses treated with endoscopic tracheal occlusion | Device: Fetal tracheal obstruction with detachable balloon (device)<br>* Fetal tracheal obstruction with detachable balloon (device): Endoscopic placement of a detachable balloon in the fetal trachea at 28-30 weeks gestation. - Ultrasound-guided puncture of balloon or, if not feasible, repeat endoscopic tracheoscopy with puncture and retrieval of the balloon at 34 weeks gestation.<br>* Other names: Goldvalve Balloon, nFocus Neuromedical, Inc.;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Newborn Survival at Birth |  | Newborn period (1 day) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Newborn Survival at 30 Days |  | 30 days | 
| Maternal Complications |  | Intervention to 30 days postpartum | 
| Fetal Morbidity | Fetal morbidity, fetal mortality | Intervention to delivery | 
| Number of Participants With In Utero Lung Growth (LHR) >1.4 | Inclusion criterion for the study is LHR<0.9 (extreme pulmonary hypoplasia). Given that LHR is relatively constant during 2nd and 3rd trimester of gestation, In utero lung growth is defined as LHR>1.4 (definition of mild/moderate pulmonary hypoplasia) within 2 weeks of intervention. Outcome measure = number of participants with LHR>1.4 at 2 weeks post-intervention | Intervention to 2 weeks post-intervention | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diaphragm, Trachea, Lung development, Lung growth, Tracheal occlusion, ECMO, Neonatal death