Fetal treatment for congenital diaphragmatic hernia

Infant Survival and Long-term Outcome Following Fetoscopic Endoluminal Tracheal Occlusion in Severe Left and Right Congenital Diaphragmatic Hernia, A Phase III Trial

This study is testing a new way to treat congenital diaphragmatic hernia in unborn babies by placing a balloon in their airway to help their lungs grow before they are born.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 80 (estimated)
• Ages: 18 Years and up
• Sex: Female
• Sponsor: Children's Hospital of Philadelphia (Academic / other)
• Locations: 2 sites (Philadelphia, Pennsylvania and 1 other locations)
• Trial ID: NCT06884423 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the safety and efficacy of fetoscopic endoluminal tracheal occlusion (FETO) in treating congenital diaphragmatic hernia (CDH) in fetuses. Pregnant women with eligible singleton pregnancies will undergo a series of prenatal evaluations to determine candidacy for the intervention. If eligible, a balloon will be placed in the fetal airway to block it, allowing the lungs to grow before delivery. Participants will be closely monitored throughout the process at the Children's Hospital of Philadelphia.

Who should consider this trial

Good fit: Ideal candidates are pregnant women aged 18 and older with a singleton pregnancy diagnosed with isolated left or right congenital diaphragmatic hernia.

Not a fit: Patients who may not benefit include those with multiple pregnancies or those whose fetuses have additional congenital anomalies.

Why it matters

Potential benefit: If successful, this intervention could significantly improve lung development in fetuses with CDH, leading to better survival rates and health outcomes after birth.

How similar studies have performed: Previous studies have shown promise with similar fetal interventions, indicating potential for success in this approach.

Eligibility criteria

Inclusion Criteria:

1. Pregnant women age 18 years and older
2. Singleton pregnancy
3. Normal fetal karyotype with confirmation by culture results, whole exome sequencing (WES), whole genome sequencing (WGS), or chromosomal microarray with non-pathologic variants. Results by fluorescence in situ hybridization (FISH) will be acceptable if the patient is greater than 26 weeks.
4. Gestational age at enrollment is prior to 29 weeks 6 days
5. Liver is intrathoracic
6. Isolated left congenital diaphragmatic hernia (CDH) with observed/expected lung to head ratio (O/E LHR) of less than 30% at enrollment (18\^0 to 29\^5 weeks), or:
7. Isolated right CDH with O/E LHR equal to or less than 45% at enrollment (18\^0 to 29\^5 weeks).
8. Cervical length by transvaginal ultrasound equal to or greater than 20 mm within 24 hours of fetoscopic endoluminal tracheal occlusion (FETO) procedure
9. Patient meets psychosocial criteria
10. Informed consent

Exclusion Criteria:

1. Patient is less than 18 years of age
2. Multi-fetal pregnancy
3. History of natural rubber latex allergy
4. Preterm labor, cervix shortened (less than 20 mm at enrollment or within 24 hours of FETO balloon insertion procedure) or uterine anomaly strongly predisposing to preterm labor, placenta previa
5. Psychosocial ineligibility, precluding consent:

   * Inability to reside within 30 minutes of the Children's Hospital of Philadelphia (CHOP) and inability to comply with the travel for the follow-up requirements of the trial
   * Patient does not have a support person (e.g. spouse, partner, mother) available to stay with the patient for the duration of the pregnancy at CHOP
6. Bilateral CDH, isolated left sided CDH with O/E LHR greater than or equal to 30% (measured at 18\^0 to 29\^5 weeks), isolated right sided CDH with O/E LHR greater than 45% (measured at 180 to 295 weeks), as determined by ultrasound
7. No Liver herniation into thoracic cavity.
8. Additional fetal anomaly by ultrasound, magnetic resonance imaging (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).
9. Maternal contraindication to fetoscopic surgery or severe maternal medical condition in pregnancy
10. History of incompetent cervix with or without cerclage
11. Placental abnormalities (previa, abruption, accrete) known at time of enrollment.
12. Maternal-fetal Rh isoimmunization, Kell sensitization or neonatal alloimmune thrombocytopenia affecting the current pregnancy.
13. 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.
14. Uterine anomaly such as large or multiple fibroids or mullerian duct abnormality
15. There is no safe or technically feasible fetoscopic approach to balloon placement.
16. Participation in another intervention study that influences maternal and fetal morbidity and mortality or participation in this trial in a previous pregnancy.

Where this trial is running

Philadelphia, Pennsylvania and 1 other locations

• Children's Hospital of Philadelphia — Philadelphia, Pennsylvania, United States (Not_yet_recruiting)
• Children's Hospital of Philadelphia — Philadelphia, Pennsylvania, United States (Recruiting)

Study contacts

• Principal investigator: Holly L Hedrick, MD, FACS — Children's Hospital of Philadelphia
• Study coordinator: Holly L Hedrick, MD, FACS

Conditions Congenital Diaphragmatic Hernia; Pulmonary Hypoplasia; congenital diaphragmatic hernia; tracheal occlusion