Fetal Tracheal Balloon Study in Diaphragmatic Hernia

Phase 2

Terminated

Conditions: Diaphragmatic Hernia
Lung Disease

Interventions: Device: Fetal tracheal obstruction with detachable balloon (device)

Registration Number: NCT00966823

Lead Sponsor: Rhode Island Hospital

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: TERMINATED

Sex: Female

Target Recruitment: 3

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)

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Detachable balloon	Fetal tracheal obstruction with detachable balloon (device)	Intervention: Fetuses treated with endoscopic tracheal occlusion

Primary Outcome Measures

Name	Time	Method
Newborn Survival at Birth	Newborn period (1 day)

Secondary Outcome Measures

Name	Time	Method
Newborn Survival at 30 Days	30 days
Maternal Complications	Intervention to 30 days postpartum
Fetal Morbidity	Intervention to delivery	Fetal morbidity, fetal mortality
Number of Participants With In Utero Lung Growth (LHR) >1.4	Intervention to 2 weeks post-intervention	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