FETO for Congenital Diaphragmatic Hernia

Overseen By James Santanelli, MS, MPH

Age: 18+

Sex: Female

Trial Phase: Academic

Sponsor: Timothy Crombleholme

Disqualifiers: Maternal contraindication, Preterm labor, Placenta previa, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

15 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a treatment called FETO (Fetoscopic Endoluminal Tracheal Occlusion) to help babies with severe congenital diaphragmatic hernia (CDH) develop their lungs better before birth. CDH occurs when an opening in the diaphragm allows organs to move into the chest, hindering proper lung development. The trial aims to improve newborn survival by promoting sufficient lung growth for post-birth function. It seeks pregnant women carrying a single baby with specific types of CDH, who can remain in the hospital throughout treatment and delivery. As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research that could significantly enhance newborn survival rates.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What prior data suggests that Fetoscopic Endoluminal Tracheal Occlusion (FETO) is safe for treating congenital diaphragmatic hernia?

Research shows that Fetoscopic Endoluminal Tracheal Occlusion (FETO) might be an option for babies with severe congenital diaphragmatic hernia (CDH). CDH occurs when a hole in the diaphragm allows organs to move into the chest, affecting lung growth.

Studies have found that FETO does not significantly increase survival rates by six months after birth, possibly due to side effects like premature rupture of membranes (PPROM), which can lead to early delivery. However, FETO can still aid lung growth by placing a balloon in the unborn baby's airway, helping the lungs develop while the baby is in the womb.

The treatment is considered feasible regarding safety, but it carries risks like any procedure. Prospective trial participants should consider these risks and discuss them with their healthcare provider. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about Fetoscopic Endoluminal Tracheal Occlusion (FETO) for treating congenital diaphragmatic hernia (CDH) because it offers a unique approach compared to standard treatments, which typically involve postnatal surgery and intensive care. FETO involves a minimally invasive procedure where a balloon is placed in the fetus's trachea to promote lung growth before birth, addressing the condition at its root. This method could potentially improve lung function and overall outcomes for babies with CDH, offering hope for better survival rates and quality of life compared to traditional methods that address the symptoms after birth.

What evidence suggests that Fetoscopic Endoluminal Tracheal Occlusion (FETO) is effective for congenital diaphragmatic hernia?

Research has shown that Fetoscopic Endoluminal Tracheal Occlusion (FETO) can be a promising treatment for severe congenital diaphragmatic hernia (CDH). This trial will evaluate FETO, a less invasive type of fetal surgery that aims to help the baby's lungs grow and improve survival chances. Studies have reported good outcomes for babies with CDH who underwent FETO. Specifically, data from trials showed a significant increase in survival rates after the procedure. Overall, FETO is considered a good option for improving lung development and survival in severe CDH cases. ^{1 2 6 7 8}

Who Is on the Research Team?

Timothy Crombleholme, MD

Principal Investigator

Connecticut Children's Medical Center

Are You a Good Fit for This Trial?

This trial is for pregnant women aged 18 and older with a single pregnancy, who can consent to treatment. It's not for those under 18, with conditions that make fetoscopic surgery risky or impossible, latex allergy, high risk of preterm labor, placenta previa, certain types of diaphragmatic hernia or major associated anomalies.

Inclusion Criteria

You are pregnant with one fetus.

I am a pregnant woman, 18 or older, and can give consent.

Exclusion Criteria

I am at high risk for early labor due to a short cervix or uterine issues.

Psychosocial ineligibility, precluding consent

I have a health condition that prevents me from having surgery during pregnancy.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

FETO Procedure

Fetoscopic Endoluminal Tracheal Occlusion (FETO) is performed to promote lung growth in fetuses with severe left congenital diaphragmatic hernia

2 weeks

Postnatal Follow-up

Participants are monitored for neonatal survival and postnatal mechanical ventilator support

12 weeks

Regular monitoring until discharge

What Are the Treatments Tested in This Trial?

Interventions

• Fetoscopic Endoluminal Tracheal Occlusion (FETO)

Trial Overview The trial tests Fetoscopic Endoluminal Tracheal Occlusion (FETO) in severe congenital diaphragmatic hernia (CDH). The goal is to improve lung growth before birth to increase the chances of newborn survival.

How Is the Trial Designed?

Group I: Fetoscopic Endoluminal Tracheal Occlusion (FETO) Experimental Treatment 1 Intervention

An un-blinded non-randomized single arm pilot study of FETO in fetuses with congenital diaphragmatic hernia (CDH)

Fetoscopic Endoluminal Tracheal Occlusion (FETO) is already approved in United States, European Union for the following indications:

Approved in United States as FETO for:

• Severe congenital diaphragmatic hernia (CDH)

Approved in European Union as FETO for:

• Severe congenital diaphragmatic hernia (CDH)

Who Is Running the Clinical Trial?

Timothy Crombleholme

Lead Sponsor

Trials

1

Recruited

20+

Published Research Related to This Trial

The study successfully established a percutaneous fetoscopic endoluminal reversible tracheal occlusion (FETO) model in non-human primates, which is crucial for improving fetal outcomes in cases of congenital diaphragmatic herniation.

The FETO procedure did not result in any complications such as bleeding or premature fetal membrane rupture, and it led to a significant increase in tracheal width in the treated group compared to controls, indicating its potential efficacy in mimicking human conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A novel translational model of percutaneous fetoscopic endoluminal tracheal occlusion - baboons (Papio spp.). Mari, G., Deprest, J., Schenone, M., et al.[2021]

In a study of 18 children with severe congenital diaphragmatic hernia (CDH) who underwent fetoscopic endoluminal tracheal occlusion (FETO), long-term survival rates were comparable to a non-FETO group, with 67% surviving at 5 years.

Despite improvements in pulmonary morbidity and gastroesophageal reflux disease, many FETO patients continued to require bronchodilators and feeding tubes, indicating ongoing health challenges even after the procedure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Morbidity in children after fetoscopic endoluminal tracheal occlusion for severe congenital diaphragmatic hernia: Results from a multidisciplinary clinic. Sferra, SR., Nies, MK., Miller, JL., et al.[2023]

Fetal endoscopic tracheal occlusion (FETO) was performed successfully in 210 cases of congenital diaphragmatic hernia (CDH), with a high success rate of balloon placement (96.7%) and a median procedure duration of 10 minutes.

While FETO is associated with a significant risk of spontaneous preterm prelabor rupture of membranes (47.1%) and preterm delivery, it notably improves survival rates for affected fetuses, increasing survival from 24.1% to 49.1% for left-sided CDH and from 0% to 35.3% for right-sided CDH.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Severe diaphragmatic hernia treated by fetal endoscopic tracheal occlusion. Jani, JC., Nicolaides, KH., Gratacós, E., et al.[2022]

In a trial involving 196 women, fetoscopic endoluminal tracheal occlusion (FETO) did not show a significant improvement in survival rates for infants with moderate congenital diaphragmatic hernia compared to expectant care, with 63% survival in the FETO group versus 50% in the control group (P=0.06).

FETO was associated with higher risks of preterm birth and prelabor rupture of membranes (44% vs. 12% and 64% vs. 22%, respectively), indicating potential safety concerns despite no serious maternal complications reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized Trial of Fetal Surgery for Moderate Left Diaphragmatic Hernia. Deprest, JA., Benachi, A., Gratacos, E., et al.[2022]

A systematic review of 10 studies involving 449 infants who underwent fetoscopic endoluminal tracheal occlusion (FETO) for congenital diaphragmatic hernia (CDH) found that 6% of infants born alive and 12% of those who survived to discharge experienced symptomatic tracheal complications.

These complications ranged from mild symptoms like barking cough to severe issues requiring tracheostomy, highlighting the need for ongoing monitoring of FETO survivors and the development of devices that reduce tracheal injury.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prevalence of symptomatic tracheal morbidities after fetoscopic endoluminal tracheal occlusion: a systematic review and meta-analysis. Tho, ALW., Rath, CP., Tan, JKG., et al.[2023]

Fetoscopic endoluminal tracheal occlusion (FETO) is a feasible and safe procedure for treating severe congenital diaphragmatic hernia (CDH), with successful balloon insertion in all 11 cases studied, and no severe maternal adverse events reported.

The procedure resulted in a 45% survival rate at 90 days of age and at discharge for the treated fetuses, indicating its potential effectiveness in promoting fetal lung growth in cases of isolated left-sided CDH.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasibility and outcomes of fetoscopic endoluminal tracheal occlusion for severe congenital diaphragmatic hernia: A Japanese experience. Wada, S., Ozawa, K., Sugibayashi, R., et al.[2020]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11627046/

Feasibility, safety, and outcome of fetoscopic endoluminal ... Our data have shown that FETO represents a viable option for severe type of CDH fetuses with reasonable outcome.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06946576

Safety and Efficacy of Fetoscopic Endoluminal Tracheal ... The purpose of this study is to evaluate the safety and efficacy of Fetoscopic Endoluminal Tracheal Occlusion (FETO) in cases of severe Congenital Diaphragmatic ...

3. childrenscolorado.org childrenscolorado.org/advances-answers/recent-articles/fetoscopic-endoluminal-tracheal-occlusion/

FETO for Congenital Diaphragmatic Hernia FETO is a minimally invasive fetal surgery aimed to enhance lung growth and improve survival for patients with severe congenital diaphragmatic hernia (CDH).

4. karger.com karger.com/fdt/article/doi/10.1159/000546839/929109/Fetoscopic-Endoluminal-Tracheal-Occlusion-in

Fetoscopic Endoluminal Tracheal Occlusion in Congenital ... The primary outcome was survival, correlated with lung growth and prematurity. Results: Among 4,524 CDH patients, 106 (2.3%) received FETO; ...

5. obgyn.onlinelibrary.wiley.com obgyn.onlinelibrary.wiley.com/doi/full/10.1002/pd.6803

Fetal Endoscopic Tracheal Occlusion (FETO) for Left and ... Data from the TOTAL (tracheal occlusion to accelerate lung growth) trials have demonstrated significant improvement in survival following fetal ...

6. chop.edu chop.edu/news/childrens-hospital-philadelphia-researchers-find-specialized-procedure-boosts-survival-infants

Children's Hospital of Philadelphia In fetoscopic endoluminal tracheal occlusion, a balloon is placed in the unborn baby's airway. Fluid builds and the lungs grow before the ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S1028455924002912

Outcomes of fetuses with severe diaphragmatic hernia after ... The mortality rate of CDH is as high as 30 %–40 %, it even reaches to 100 % of severe CDH (O/E LHR was 15 %–25 %) [2]. Fetal endoluminal tracheal occlusion ( ...

8. ajog.org ajog.org/article/S0002-9378(22)00944-9/fulltext

Fetoscopic endoluminal tracheal occlusion (FETO) versus ... FETO does not lead to significantly increased six-month survival potentially due to increased rates of PPROM, earlier gestational age at delivery and lower ...