Diaphragmatic Hernia, Lung Disease
Conditions
Keywords
Diaphragm, Trachea, Lung development, Lung growth, Tracheal occlusion, ECMO, Neonatal death
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.
Interventions
DEVICEFetal tracheal obstruction with detachable balloon (device)
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.
Sponsors
Rhode Island Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Newborn Survival at Birth | Newborn period (1 day) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
United States
Participant flow
Pre-assignment details
1 participant met inclusion criteria and was enrolled, but was excluded immediately before intervention (active labor), and was therefore excluded from the trial.
Participants by arm
| Arm | Count |
|---|---|
| Detachable Balloon Fetuses treated with endoscopic tracheal occlusion
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. | 2 |
| Total | 2 |
Baseline characteristics
| Characteristic | Detachable Balloon |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants |
| Region of Enrollment United States | 2 participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 2 |
| serious Total, serious adverse events | 0 / 2 |
Outcome results
Primary
Newborn Survival at Birth
Time frame: Newborn period (1 day)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Detachable Balloon | Newborn Survival at Birth | 1 Participants |
Secondary
Fetal Morbidity
Fetal morbidity, fetal mortality
Time frame: Intervention to delivery
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Detachable Balloon | Fetal Morbidity | 1 Participants |
Secondary
Maternal Complications
Time frame: Intervention to 30 days postpartum
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Detachable Balloon | Maternal Complications | 0 occurrences |
Secondary
Newborn Survival at 30 Days
Time frame: 30 days
Population: 1 of 2 enrolled participants (fetuses) survived until birth (Primary outcome). This 1 participant (infant) also survived at 30 days (secondary outcome).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Detachable Balloon | Newborn Survival at 30 Days | 1 Participants |
Secondary
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
Time frame: Intervention to 2 weeks post-intervention
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Detachable Balloon | Number of Participants With In Utero Lung Growth (LHR) >1.4 | 1 Participants |