Fetal Endotracheal Occlusion for Congenital Diaphragmatic Hernia

Overseen By Brittany Gudanowski

Age: 18+

Sex: Female

Trial Phase: Academic

Sponsor: Alireza Shamshirsaz

Disqualifiers: Severe obesity, Preterm labor, Placental abnormalities, 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to explore whether Fetal Endotracheal Occlusion (FETO) can help babies with severe congenital diaphragmatic hernia (CDH) grow their lungs better before birth and improve their survival chances after birth. The study will assess the safety and feasibility of FETO as a treatment option. Pregnant participants diagnosed with severe CDH in their baby and who can stay near Boston Children's Hospital during the treatment period might be a good fit. As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research that could improve outcomes for future families facing similar challenges.

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 team or your doctor.

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

Research shows that Fetal Endotracheal Occlusion (FETO) is a promising treatment for severe congenital diaphragmatic hernia (CDH) in unborn babies. Studies have found that FETO can be a safe option for these cases. The procedure involves placing a small balloon in the baby's airway to help their lungs grow before birth.

Safety data from previous research indicate that FETO is generally well-tolerated. However, like any medical procedure, risks can occur. Some studies have reported complications, but these are usually manageable. This treatment is specifically for severe cases of CDH, where traditional care might not suffice.

Overall, FETO has shown good results for babies with severe CDH. Prospective trial participants should discuss potential risks and benefits with their healthcare provider for personalized guidance. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Fetal Endotracheal Occlusion (FETO) is unique because it directly addresses the lung development issues in babies with severe congenital diaphragmatic hernia (CDH) before birth. Unlike the standard of care, which often involves surgery after the baby is born and supportive treatments like ventilation, FETO is a prenatal intervention that temporarily blocks the fetus's trachea. This blockage encourages the lungs to expand and mature in the womb, potentially improving the baby's breathing ability once born. Researchers are excited about FETO because it offers a proactive way to tackle the root cause of complications from CDH, potentially leading to better outcomes for affected newborns.

What evidence suggests that Fetal Endotracheal Occlusion is effective for congenital diaphragmatic hernia?

Research shows that Fetal Endotracheal Occlusion (FETO), the treatment under study in this trial, is a promising approach for severe congenital diaphragmatic hernia (CDH). Studies indicate that FETO increases survival rates in babies with CDH. Data from the TOTAL trials found that survival improved by 25% in severe cases. This procedure aids lung development in the baby before birth. Previous patients demonstrated that FETO is a practical option with good results for severe CDH. ^{1 2 6 7 8}

Who Is on the Research Team?

Alireza Shamshirsaz, MD

Principal Investigator

Director, Maternal Fetal Care Center

Are You a Good Fit for This Trial?

This trial is for pregnant individuals carrying fetuses with severe congenital diaphragmatic hernia. Participants will be between 27 and nearly 30 weeks pregnant when undergoing the FETO procedure, and must be able to follow through with monitoring until their child turns two years old.

Inclusion Criteria

Singleton pregnancy

Patient has a support person who is able to stay with them for the duration of the pregnancy

Gestation at enrollment prior to 29 weeks 5 days

Exclusion Criteria

Additional fetal anomaly and chromosomal abnormalities by ultrasound, MRI, or echocardiogram that will significantly worsen prognosis

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

I have had a weak cervix, with or without a stitch.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

FETO Procedure

Participants undergo the Fetal Endotracheal Occlusion (FETO) procedure to promote lung growth

7-8 weeks

Weekly visits for monitoring

Balloon Removal

The FETO balloon is removed prior to delivery to allow lung maturation

1 week

Follow-up

Participants are monitored for safety and effectiveness after treatment, including neurodevelopmental assessments

Up to 2 years

What Are the Treatments Tested in This Trial?

Interventions

• Fetal Endotracheal Occlusion (FETO)

Trial Overview The study tests the FETO procedure's ability to promote lung growth in fetuses with CDH before birth and improve survival rates after birth. It involves a small group of 10 participants who will have the device placed and then removed several weeks later.

How Is the Trial Designed?

Group I: Fetal Endotracheal Occlusion (FETO) Experimental Treatment 1 Intervention

Participants with severe congenital diaphragmatic hernia will undergo the FETO therapy.

Fetal Endotracheal Occlusion (FETO) is already approved in European Union, United States for the following indications:

Approved in European Union as FETO for:

• Severe congenital diaphragmatic hernia (CDH)

Approved in United States as FETO for:

• Severe congenital diaphragmatic hernia (CDH)

Who Is Running the Clinical Trial?

Alireza Shamshirsaz

Lead Sponsor

Trials

1

Recruited

10+

Published Research Related to This Trial

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]

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]

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]

Fetal endoscopic tracheal occlusion (FETO) is a treatment for severe congenital diaphragmatic hernia that can lead to complications such as tracheomegaly in infants, as observed in a series of five cases.

This study highlights a new potential risk associated with FETO, suggesting that the compliant fetal airway may be damaged by balloon occlusion, warranting careful evaluation of the trachea in infants who underwent this procedure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tracheomegaly: a complication of fetal endoscopic tracheal occlusion in the treatment of congenital diaphragmatic hernia. McHugh, K., Afaq, A., Broderick, N., et al.[2021]

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]

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]

Foetoscopic endotracheal occlusion (FETO) for congenital diaphragmatic hernia (CDH) was successfully performed in 28 cases at a new center in Poland, achieving a neonatal survival rate of 46.4%, which aligns with results from other established centers.

Key factors influencing survival included the gestational age at delivery and the pulmonary response measured by the observed over expected lung area to head circumference ratio (o/e LHR), indicating that earlier intervention and better lung development are crucial for outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Foetoscopic endotracheal occlusion (FETO) for severe isolated left-sided congenital diaphragmatic hernia: single center Polish experience. Kosinski, P., Wielgos, M.[2018]

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]

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. 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.

3. 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 ...

4. 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, ...

5. mdpi.com mdpi.com/1422-0067/26/4/1639

Fetoscopic Endoluminal Tracheal Occlusion-Synergic ... The TOTAL trials demonstrated an increase in the survival rates by 25% in fetuses with severe CDH and by 13% in those with moderate CDH at discharge from the ...

6. nejm.org nejm.org/doi/full/10.1056/NEJMoa035005

A Randomized Trial of Fetal Endoscopic Tracheal ... Experimental and clinical data suggest that fetal endoscopic tracheal occlusion to induce lung growth may improve the outcome of severe congenital ...

7. tp.amegroups.org tp.amegroups.org/article/view/51975/html

Fetal endoscopic tracheal occlusion for congenital ... Fetal endoscopic tracheal occlusion for congenital diaphragmatic hernia: a narrative review of the history, current practice, and future directions.

8. cincinnatichildrens.org cincinnatichildrens.org/service/f/fetal-care/conditions/congenital-diaphragmatic-hernia/feto

Fetoscopic Endoluminal Tracheal Occlusion (FETO) for CDH FETO is a surgical procedure to treat the most severe cases of congenital diaphragmatic hernia (CDH) that are diagnosed in utero.