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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a treatment called Fetal Endotracheal Occlusion (FETO) for babies with congenital diaphragmatic hernia (CDH), a condition where abdominal organs move into the chest and hinder lung development. The trial aims to determine if using a tiny balloon to block the trachea while the baby is still in the womb can enhance lung growth and reduce high blood pressure in the lungs after birth. Pregnant women carrying a single baby diagnosed with severe CDH and willing to stay in Houston for the procedure and delivery may be suitable candidates for this trial. As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research that could significantly improve outcomes for babies with CDH.

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 prior data suggests that the FETO procedure is safe for treating congenital diaphragmatic hernia?

Research has shown that Fetal Endotracheal Occlusion (FETO) is a safe treatment for severe congenital diaphragmatic hernia (CDH) in unborn babies. Studies have found that FETO can increase survival rates at birth. Data from the TOTAL trials, a series of studies on FETO, showed significant improvements in these outcomes.

FETO is generally well-tolerated. The procedure involves placing a small balloon in the unborn baby's airway to aid lung development, which is later removed. While any procedure carries some risk, FETO has been used for over 30 years, and current research suggests it is a reasonable option for severe CDH cases. It is important to discuss potential risks with a healthcare provider to make the best decision for the baby. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Fetal Endotracheal Occlusion (FETO) is unique because it offers a prenatal intervention for congenital diaphragmatic hernia (CDH), where most treatments occur post-birth. FETO involves placing a detachable balloon in the fetus's trachea to promote lung growth, which is different from standard surgical repairs typically done after delivery. Researchers are excited about FETO because it allows for early intervention, potentially improving lung development and survival rates even before the baby is born.

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

Research has shown that a procedure called fetal endotracheal occlusion (FETO) can improve survival rates for babies with congenital diaphragmatic hernia (CDH) at birth. FETO temporarily blocks the windpipe, aiding lung growth and function. In this trial, some participants will undergo the FETO procedure, while others will join a non-FETO control group. Specifically, babies with severe CDH who underwent FETO were more likely to overcome high blood pressure in the lungs by their first birthday compared to those who did not. A review of multiple studies also found that FETO could enhance survival rates for babies with CDH. While FETO shows promise, further research is needed to understand its long-term benefits. ^{2 5 6 7 8}

Who Is on the Research Team?

Michael Belfort, MD PhD

Principal Investigator

Baylor College of Medicine - Texas Children's Hospital

Are You a Good Fit for This Trial?

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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]

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]

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]

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]

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/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.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06281717?cond=(DIAPHRAGMATIC%20HERNIA)%20OR%20(ZFPM2)&rank=9

Fetal Endotracheal Occlusion (FETO) in Fetuses with ... The goal of this study is to learn more about the role of Fetal Endotracheal Occlusion (FETO) as an intervention in fetuses with isolated severe congenital ...

3. obgyn.onlinelibrary.wiley.com obgyn.onlinelibrary.wiley.com/doi/10.1002/uog.26164

Fetal endoscopic tracheal occlusion for congenital ... We conducted a systematic review and meta-analysis including the latest evidence to assess the overall effects of FETO on clinical outcomes of CDH.

4. 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.

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

Fetoscopic Endoluminal Tracheal Occlusion-Synergic ... This scoping review aimed to uncover all potential materno-fetal procedure-related risks, challenges, and pitfalls while highlighting the innovative solutions ...

6. 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.

7. 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 ...

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.