Fetal Endoscopic Tracheal Occlusion for Congenital Diaphragmatic Hernia

(FETO Trial)

Age: 18 - 65

Sex: Female

Trial Phase: Academic

Sponsor: Mauro H. Schenone

Disqualifiers: Multi-fetal pregnancy, Latex allergy, Preterm labor, 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

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the safety and effectiveness of a procedure called Fetal Endoscopic Tracheal Occlusion (FETO) at Mayo Clinic. The goal is to aid lung development in unborn babies diagnosed with severe congenital diaphragmatic hernia (CDH), a condition where a hole in the diaphragm allows organs to move into the chest, potentially affecting lung growth. This trial suits pregnant women carrying a single baby with severe left-sided CDH who can remain near Mayo Clinic for follow-ups. As an unphased trial, it offers a unique opportunity to contribute to pioneering research that could improve outcomes for future patients with CDH.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. It's best to discuss your specific medications with the trial team to get a clear answer.

What prior data suggests that this procedure is safe for fetuses with congenital diaphragmatic hernia?

Research has shown that the Fetal Endoscopic Tracheal Occlusion (FETO) procedure offers a promising option for babies with severe congenital diaphragmatic hernia (CDH). Studies have demonstrated that FETO can be performed safely and leads to better short-term outcomes for these babies.

For instance, one study found that FETO improves lung development, which is crucial for survival after birth. This procedure is generally well-tolerated, but it is important to note that, like any surgery, it carries some risks. However, evidence suggests that the benefits, such as improved lung function and potentially reduced need for medical support after birth, can outweigh these risks.

Overall, FETO appears to be a safe option for enhancing the health of babies diagnosed with severe CDH before birth. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Fetal Endoscopic Tracheal Occlusion (FETO) is unique because it offers a direct, surgical approach to enhance lung development in fetuses with congenital diaphragmatic hernia (CDH), a condition where the diaphragm doesn't form properly, allowing abdominal organs to move into the chest cavity and hinder lung growth. Unlike traditional treatments which may focus on postnatal care, such as surgery after birth, FETO is performed in utero between 27 and 30 weeks of gestation, aiming to improve lung growth before birth. Researchers are excited about FETO because it temporarily blocks the trachea, which can increase lung fluid pressure and promote lung expansion and development, potentially improving outcomes for babies born with this challenging condition.

What evidence suggests that the FETO procedure is effective for congenital diaphragmatic hernia?

Research has shown that fetal endoscopic tracheal occlusion (FETO) can help babies with severe congenital diaphragmatic hernia (CDH). Participants in this trial will undergo the FETO procedure. Studies from the TOTAL trials indicated that FETO significantly increases survival chances for these babies. The procedure aids lung growth before birth, which is crucial for survival. Previous data confirmed that FETO is a good option for severe CDH cases, yielding positive results. Overall, FETO offers a promising way to improve survival chances for affected babies. ^{1 2 6 7 8}

Who Is on the Research Team?

Mauro Schenone, MD

Principal Investigator

Mayo Clinic

Are You a Good Fit for This Trial?

This trial is for pregnant individuals with a fetus diagnosed with severe left-sided congenital diaphragmatic hernia (CDH) and poor lung development. Eligible participants must be able to give informed consent, have had appropriate counseling, carry a single pregnancy with normal fetal genetics, and be able to stay near the Mayo Clinic for the duration of the pregnancy.

Inclusion Criteria

Patient is willing and able to give informed consent

Singleton pregnancy

My unborn baby has a severe left-sided diaphragmatic hernia.

Exclusion Criteria

Maternal-fetal Rh isoimmunization, Kell sensitization or neonatal alloimmune thrombocytopenia affecting the current pregnancy

It's not safe or possible for me to have a balloon placed via fetoscopy.

Participation in another intervention study that influences maternal and fetal morbidity and mortality or participation in this trial in a previous pregnancy

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

FETO Procedure

Participants undergo fetal endoscopic tracheal occlusion (FETO) surgical procedure between 27 weeks 0 days and 29 weeks 6 days gestation

3 weeks

Balloon Retrieval

Antenatal removal of the balloon is performed

Up to 34 weeks gestation

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments of fetal oxygen dependency, pulmonary hypertension, and other complications

Up to 24 months post partum

What Are the Treatments Tested in This Trial?

Interventions

• Fetal Endoscopic Tracheal Occlusion

Trial Overview The trial tests Fetoscopic Endoluminal Tracheal Occlusion (FETO), using specialized instruments like a fetoscope and detachable balloon to improve lung growth in fetuses with CDH. The procedure's safety and effectiveness are being studied at Mayo Clinic.

How Is the Trial Designed?

Group I: FETO Group Experimental Treatment 3 Interventions

Participants will undergo fetal endoscopic tracheal occlusion (FETO) surgical procedure between 27 weeks 0 days and 29 weeks 6 days gestation.

Fetal Endoscopic Tracheal Occlusion 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?

Mauro H. Schenone

Lead Sponsor

Trials

2

Recruited

100+

Published Research Related to This Trial

Fetal Endoscopic Tracheal Occlusion (FETO) significantly improved survival rates at 28 days and reduced the length of ventilatory support in neonates with congenital diaphragmatic hernia (CDH) and moderate lung hypoplasia, based on a study of 58 cases (29 treated with FETO and 29 controls).

While the overall survival at 6 months was not significantly different, the FETO group had a lower gestational age at delivery and a shorter NICU stay, indicating that FETO may reduce neonatal respiratory morbidity in affected fetuses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of fetal endoscopic tracheal occlusion in fetuses with congenital diaphragmatic hernia and moderate lung hypoplasia. Cruz-Martínez, R., Shazly, S., Martínez-Rodríguez, M., et al.[2022]

Fetal endoscopic tracheal occlusion (FETO) using a 1.0-mm fetoscope was successfully performed in 16 fetuses with severe congenital diaphragmatic hernia (CDH), leading to a significant increase in neonatal survival rates (52.9% in the FETO group vs. 5.6% in the control group).

The study also found that FETO reduced the incidence of severe pulmonary arterial hypertension in infants, with 47.1% of the FETO group affected compared to 88.9% in the control group, indicating a potential improvement in neonatal outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison between fetal endoscopic tracheal occlusion using a 1.0-mm fetoscope and prenatal expectant management in severe congenital diaphragmatic hernia. Ruano, R., Duarte, SA., Pimenta, EJ., et al.[2016]

Fetal tracheal occlusion, performed using advanced fetoscopic techniques, has been shown to accelerate lung growth and correct severe lung underdevelopment (pulmonary hypoplasia) in fetuses with congenital diaphragmatic hernia.

This innovative approach, referred to as 'Fetendo,' demonstrates the potential of fetoscopy not just for diagnosis but also for effective treatment in fetal medicine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fetendo-clip: a fetal endoscopic tracheal clip procedure in a human fetus. VanderWall, KJ., Skarsgard, ED., Filly, RA., et al.[2019]

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 randomized trial involving 24 pregnant women with fetuses diagnosed with severe congenital diaphragmatic hernia, fetal endoscopic tracheal occlusion did not improve survival rates compared to standard postnatal care, with survival rates of 73% and 77% respectively.

The intervention group experienced significantly more complications, including premature rupture of membranes and earlier delivery, indicating that tracheal occlusion may pose additional risks without providing survival benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized trial of fetal endoscopic tracheal occlusion for severe fetal congenital diaphragmatic hernia. Harrison, MR., Keller, RL., Hawgood, SB., 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]

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]

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. 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 ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04583644?term=AREA%5BConditionSearch%5D(FETO%20CDH)&rank=5

Pilot Trial of Fetoscopic Endoluminal Tracheal Occlusion ... The investigator's goal with this pilot study is to study the feasibility of implementing Fetoscopic Endoluminal Tracheal Occlusion (FETO) therapy in the most ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8192998/

Fetal endoscopic tracheal occlusion for congenital ... Fetal intervention for fetuses with congenital diaphragmatic hernia (CDH) has been investigated for over 30 years and is summarized in this manuscript.

5. nejm.org nejm.org/doi/full/10.1056/NEJMoa2027030

Randomized Trial of Fetal Surgery for Severe Left ... Previous studies have suggested that FETO improves survival among infants with congenital diaphragmatic hernia. Two small, single-center, ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03138863

Study Details | NCT03138863 | Fetal Endoscopic Tracheal ... The purpose of this research is to gather information on the safety and effectiveness of a new procedure called Fetoscopic Endoluminal Tracheal Occlusion ...

7. annsaudimed.net annsaudimed.net/doi/abs/10.5144/0256-4947.2024.408

Feasibility, safety, and outcome of fetoscopic endoluminal ... FETO represents a viable option for severe type of CDH fetuses with reasonable outcomes. FETO performance in low volume centers may be feasible ...

8. mayoclinic.org mayoclinic.org/medical-professionals/obstetrics-gynecology/news/multisite-study-finds-feto-associated-with-reduced-postbirth-ecmo-for-fetuses-with-cdh/mac-20575537

Multisite study finds FETO associated with reduced ... A North American multisite study of fetoscopic endoluminal tracheal occlusion (FETO) for fetuses with severe, left-sided congenital diaphragmatic hernia (CDH)