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

10 Participants Needed

Trial Summary

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 data supports the effectiveness of the treatment Fetal Endotracheal Occlusion (FETO) for Congenital Diaphragmatic Hernia?

Research indicates that Fetal Endoscopic Tracheal Occlusion (FETO) can improve lung growth and development in babies with severe congenital diaphragmatic hernia, potentially increasing their chances of survival. However, there are concerns about complications like preterm delivery and tracheal issues. ^{1 2 3 4 5}

Is fetal endotracheal occlusion (FETO) generally safe for humans?

Fetal endotracheal occlusion (FETO) is a promising treatment for congenital diaphragmatic hernia, but it has some risks, including preterm delivery and potential tracheal complications like tracheomegaly (enlarged trachea) and tracheomalacia (softening of the trachea). ^{1 2 4 6 7}

How is the treatment Fetal Endotracheal Occlusion (FETO) unique for congenital diaphragmatic hernia?

Fetal Endotracheal Occlusion (FETO) is unique because it involves placing a balloon in the fetus's trachea (windpipe) to help the lungs grow better before birth, which is different from other treatments that might not directly target lung development. ^{1 2 3 8 9}

What is the purpose of this trial?

The goal of this pilot trial is to learn more about the role of Fetal Endotracheal Occlusion (FETO) as an intervention in fetuses with severe congenital diaphragmatic hernia (CDH). The research team will investigate the feasibility and safety of the FETO procedure, as well as determine whether FETO can improve lung growth before birth, and survival after birth. This study will enroll 10 pregnant participants to undergo the FETO procedure at a gestational age of 27 weeks 0 days to 29 weeks 6 days. The participant will be monitored for a few weeks, and then the FETO removal procedure will be performed ideally at 34 weeks 0 days to 34 weeks 6 days, but may be indicated earlier as determined by the Maternal Fetal care team. The pregnant participant and their baby will continue to be monitored during delivery and up until the child reaches 2 years of age.

Research Team

Alireza Shamshirsaz, MD

Principal Investigator

Director, Maternal Fetal Care Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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) 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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Severe diaphragmatic hernia treated by fetal endoscopic tracheal occlusion. [2022]

2. Germany pubmed.ncbi.nlm.nih.gov

Tracheomegaly: a complication of fetal endoscopic tracheal occlusion in the treatment of congenital diaphragmatic hernia. [2021]

3. England pubmed.ncbi.nlm.nih.gov

Impact of fetal endoscopic tracheal occlusion in fetuses with congenital diaphragmatic hernia and moderate lung hypoplasia. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Prevalence of symptomatic tracheal morbidities after fetoscopic endoluminal tracheal occlusion: a systematic review and meta-analysis. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Randomized Trial of Fetal Surgery for Moderate Left Diaphragmatic Hernia. [2022]

6. Australia pubmed.ncbi.nlm.nih.gov

Feasibility and outcomes of fetoscopic endoluminal tracheal occlusion for severe congenital diaphragmatic hernia: A Japanese experience. [2020]

7. Switzerland pubmed.ncbi.nlm.nih.gov

A novel translational model of percutaneous fetoscopic endoluminal tracheal occlusion - baboons (Papio spp.). [2021]

8. Switzerland 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. [2016]

9. England pubmed.ncbi.nlm.nih.gov

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