FETO for Congenital Diaphragmatic Hernia

Overseen By Rebecca M Johnson, MS

Age: 18 - 65

Sex: Female

Trial Phase: Academic

Sponsor: Michael A Belfort

Disqualifiers: Preterm labor, Preeclampsia, Uterine anomaly, 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: 3

80 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. However, if you have an allergy or previous adverse reaction to a study medication, you may be excluded from participating.

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

Research suggests that FETO can improve lung growth and development in fetuses with severe congenital diaphragmatic hernia, potentially increasing survival rates, especially in cases with moderate lung underdevelopment. ^{1 2 3 4 5}

Is FETO generally safe for humans?

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 3 6 7}

How does the treatment FETO differ from other treatments for congenital diaphragmatic hernia?

FETO is unique because it involves placing a balloon in the fetus's trachea (windpipe) to block it, which helps the lungs grow better before birth. This approach is different from other treatments that typically focus on managing the condition after birth. ^{2 3 5 8 9}

What is the purpose of this trial?

Congenital diaphragmatic hernia (CDH) occurs when the diaphragm fails to fully fuse and leaves a portal through which abdominal structures can migrate into the thorax. In the more severe cases, the abdominal structures remain in the thoracic cavity and compromise the development of the lungs. Infants born with this defect have a decreased capacity for gas exchange; mortality rates after birth have been reported between 40-60%. Now that CDH can be accurately diagnosed by mid-gestation, a number of strategies have been developed to repair the hernia and promote lung tissue development. Fetal tracheal occlusion (FETO), using a fetoscopically delivered and removed balloon device, has been used to temporarily occlude the trachea and increase lung distension in CDH to allow the lungs to develop and has been shown to increase survival at birth. The role of FETO in the resolution of pulmonary hypertension in fetuses with severe left- and right- sided CDH remains unclear. Our recent observation that FETO is associated with a higher proportion of infants who resolve their pulmonary hypertension by the age of 1 year as compared with those who have not had FETO, is based on a retrospective cohort study, which, as with any such design, has some intrinsic limitations. Thus, a prospective cohort study that is appropriately powered to confirm or disprove this encouraging observation is needed. If our preliminary observation is confirmed, resolution of PH by the age of 1 year could be added to the benefits of the FETO procedure in severe left and right-sided CDH cases. The investigators will perform 40 FETO procedures on fetuses diagnosed prenatally with severe right- or left-sided CDH, and outcome data will be compared with that of a control group of severe right- or left-sided CDH who will not undergo the FETO procedure because of medical or social issues. Because the prevalence of left-sided CDH is higher than right-side CDH, the investigators will perform 25 FETO procedures in left sided CDH and 15 in right-sided CDH, and these outcomes will be compared to a cohort of 40 non FETO cases.

Research Team

Michael Belfort, MD PhD

Principal Investigator

Baylor College of Medicine - Texas Children's Hospital

Eligibility Criteria

This trial is for pregnant women aged 18-45 with a single pregnancy and a fetus diagnosed with severe left or right-sided CDH. The fetus should be between 28 to almost 32 weeks old, have normal heart function or minor issues not affecting outcome, and the mother must stay in Houston post-procedure until delivery. Exclusions include latex allergy, surgery risks, fetal genetic anomalies impacting survival, maternal BMI over 40, or high risk of fetal hemophilia.

Inclusion Criteria

Fetuses should be between 28 weeks and 31 weeks and 6 days of gestational age.

My unborn baby has been diagnosed with severe CDH, with significant liver herniation and low lung volume.

I am healthy enough to undergo surgery.

Exclusion Criteria

My unborn baby has been diagnosed with a genetic condition that could affect survival.

There are signs of a serious known syndrome on the ultrasound or MRI.

I have had preterm labor, preeclampsia, or a large fibroid tumor in my current pregnancy.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

FETO Procedure

Fetal endotracheal occlusion (FETO) procedure is performed using a fetoscopically delivered balloon device to temporarily occlude the trachea and increase lung distension.

1 week

1 visit (in-person)

Postoperative Monitoring

Serial measurements of sonographic lung volume and LHR, amniotic fluid level, and membrane status are monitored weekly. Comprehensive ultrasonography for fetal growth is performed every four weeks.

Up to 10 weeks

Weekly visits (in-person)

Balloon Retrieval

The balloon is retrieved no later than 36+6/7 weeks of gestation. The patient remains within 30 minutes of the hospital until retrieval.

1 week

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after delivery, with regular check-ups at 6 weeks, 3 months, 6 months, 1 year, and 2 years to assess the baby's breathing and development.

2 years

Multiple visits (in-person or virtual)

Treatment Details

Interventions

• Fetal Endotracheal Occlusion (FETO)

Trial Overview The study tests FETO using a balloon device inserted fetoscopically to treat severe congenital diaphragmatic hernia (CDH) in fetuses. It aims to improve lung development and resolve pulmonary hypertension by comparing outcomes of 40 FETO procedures against non-FETO cases due to medical/social reasons.

Participant Groups

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

Placement and retrieval of the GoldBAL4 or GoldBAL2 Detachable balloon using the plug/unplug method, using BALTACCIDBPE100 Delivery Catheter.

Group II: non-FETO Active Control 1 Intervention

The control group will consist of patients who did not undergo the FETO procedure who fit the same fetal inclusion/exclusion criteria as our FETO subjects and will be matched by variables including maternal age, body mass index, gestational age, severity of CDH and site of CDH (left- or right-sided).

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?

Michael A Belfort

Lead Sponsor

Trials

5

Recruited

510+

Baylor College of Medicine

Collaborator

Trials

1,044

Recruited

6,031,000+

Findings from Research

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]

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]

Fetal endoscopic tracheal occlusion (FETO) significantly improved survival rates in fetuses with severe left-sided congenital diaphragmatic hernia (CDH), with a survival rate of 32% compared to 0% in those managed expectantly.

The procedure was safely performed in 25 fetuses, with no technical issues, and resulted in earlier delivery at a median gestational age of 35.3 weeks compared to 37.7 weeks for the expectantly managed group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Survival outcome in severe left-sided congenital diaphragmatic hernia with and without fetal endoscopic tracheal occlusion in a country with suboptimal neonatal management. Cruz-Martínez, R., Martínez-Rodríguez, M., Gámez-Varela, A., et al.[2021]

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]

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]

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) 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]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

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

2. England pubmed.ncbi.nlm.nih.gov

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

3. Germany pubmed.ncbi.nlm.nih.gov

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

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

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

5. England pubmed.ncbi.nlm.nih.gov

Survival outcome in severe left-sided congenital diaphragmatic hernia with and without fetal endoscopic tracheal occlusion in a country with suboptimal neonatal management. [2021]

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. England pubmed.ncbi.nlm.nih.gov

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

8. England pubmed.ncbi.nlm.nih.gov

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

9. 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]