A Pilot Study on the Role of Fetal Endotracheal Occlusion (FETO) in Fetuses With Severe Congenital Diaphragmatic Hernia

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Congenital Diaphragmatic Hernia
• Intervention / Treatment: Device: Fetal Endotracheal Occlusion (FETO)

Detailed Description

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 diaphragmatic hernia (CDH). CDH is a condition in which the diaphragm fails to completely close, leaving a gap through which abdominal organs can herniate and slide into and out of the chest. In severe cases, abdominal organs move into the chest and stay there, putting pressure on the heart and lungs and potentially causing the disruption or deformation of these structures. Impaired development of the lungs can often lead to a condition known as pulmonary hypertension, a form of high blood pressure that damages the heart. Pulmonary hypoplasia and pulmonary hypertension can be lethal. Congenital diaphragmatic hernia (CDH) affects 1 in 2,200 to 5,000 live births per year.

FETO will be performed with the goal of promoting lung growth and improving neonatal outcomes. FETO is a minimally invasive procedure in which a balloon device is inserted into the trachea of the fetus. The devices involved are the Goldballoon Detachable Balloon (GOLDBAL2) along with the Delivery Microcatheter (BALTACCI-BDPE100). The balloon would be left in place for several weeks and allow the lungs to grow, after which it would be removed, enabling the lungs to mature before birth. Participants will continue to be monitored up until the child reaches 2 years of age in order to assess mental and physical development after FETO.

• Study Type: Interventional
• Enrollment (Estimated): 10
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Brittany Gudanowski; Phone Number: 617-919-6658; Email: Brittany.Gudanowski@childrens.harvard.edu

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Boston Children's Hospital
      • Contact: Brittany Gudanowski; Phone Number: 617-919-6658; Email: Brittany.Gudanowski@childrens.harvard.edu
      • Contact: Maternal Fetal Care Center; Phone Number: 617-355-6512; Email: MFCCFetalResearchStudies-dl@childrens.harvard.edu
      • Principal Investigator: Alireza Shamshirsaz, MD
      • Sub-Investigator: Eyal Krispin, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Pregnant patient 18 and older who is able to consent
• Singleton pregnancy
• Ability to reside within 30 minutes of Boston Children's Hospital for the duration of the FETO intervention, from the time of balloon placement until balloon removal
• Patient has a support person who is able to stay with them for the duration of the pregnancy

Fetal:

• Reassuring genetic analysis demonstrated by either normal Karyotype, normal fluorescence in situ hybridization (FISH) for chromosomes 13, 18, 21, X and Y, or chromosomal microarray (CMA) with non-pathologic variants
• Diagnosis of isolated left CDH with liver up
• Gestation at enrollment prior to 29 weeks 5 days
• SEVERE pulmonary hypoplasia with ultrasound Observed/Expected Lung-to-Head Ratio (O/E LHR) < 25%

Exclusion Criteria:

• Maternal contraindication to fetoscopic surgery or severe maternal medical condition in pregnancy
• Technical limitations precluding fetoscopic surgery, including uterine anomaly such as large or multiple fibroids, or Mullerian duct anomaly
• Latex allergy
• Preterm labor, shortened cervix (<20mm at enrollment or within 24 hours of FETO balloon insertion procedure) or uterine anomaly strongly predisposing to preterm labor, placenta previa
• Severe maternal obesity pre-pregnancy (BMI > 40)
• Psychosocial ineligibility, precluding consent, as determined by clinic social worker during review
• Inability to remain at FETO site during time period of tracheal occlusion, delivery, and postnatal care
• Right-sided or bilateral, left-sided CDH O/E LHR > 25% on ultrasound
• Additional fetal anomaly and chromosomal abnormalities by ultrasound, MRI, or echocardiogram that will significantly worsen prognosis
• History of incompetent cervix with or without cerclage
• Placental abnormalities (previa, abruption, accreta) known at time of enrollment
• Maternal-fetal RH isoimmunization, Kell sensitization, or neonatal alloimmune thrombocytopenia affecting the current pregnancy
• Maternal HIV, Hepatitis B, Hepatitis C status positive

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Fetal Endotracheal Occlusion (FETO); Participants with severe congenital diaphragmatic hernia will undergo the FETO therapy.

Device: Fetal Endotracheal Occlusion (FETO); The FETO insertion procedure will be performed between gestational age 27 weeks 0 days and 29 weeks and 6 days. The Goldballoon Detachable Balloon (GOLDBAL2) will be inserted in the airway of the fetus using the Delivery Microcatheter (BALTACCI-BDPE100). The fetal tracheal balloon will be removed between 34 weeks 0 days and 34 weeks 6 days gestation or earlier as indicated.; Other Names: FETO; Fetoscopic Endoluminal Tracheal Occlusion; Fetal Tracheal Occlusion; BALT GOLDBALLOON: GoldBAL2

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Successful Ballon Placement	Defined as direct visualization of balloon deployment above the carina at the time of FETO procedure	Gestational age of 27 weeks 0 days to 29 weeks 6 days
Successful Balloon Removal	Removal of the balloon prior to delivery, ideally during 34 weeks gestation	Prior to delivery, ideally at 34 weeks
Balloon placement operative time	Length of FETO procedure for successful balloon placement	Gestational age of 27 weeks 0 days to 29 weeks 6 days
Balloon removal operative time	Length of FETO procedure for successful balloon removal	Prior to delivery, ideally at 34 weeks
Type of FETO release	Emergent or non-emergent FETO release	Prior to delivery, ideally at 34 weeks
Maternal Complications	Maternal complications include: preterm labor, premature rupture of membranes, oligohydramnios, polyhydramnios, chorioamnionitis	From balloon placement to delivery
Gestational age at delivery	Gestational age at delivery will be recorded	At delivery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fetal lung volume	Fetal lung volume will be monitored on ultrasound	Once per week from balloon placement to removal. This measure will be recorded at earliest gestational age of 27 weeks 0 days, and latest at 34+6/7 weeks' gestation.
O/E LHR	Prenatal ultrasound will measure the observed-to-expected lung to head ratio (o/e LHR) at weekly visits while the balloon is in place and after balloon removal. Fetal lung growth will be calculated as the difference between the o/e LHR pre-balloon placement and the o/e LHR after balloon removal.	Calculated at balloon removal, ideally at 34 weeks gestation
Infant survival	Survival at discharge from the hospital, or at 6 months of age if still hospitalized	At hospital discharge or 6 months of age, whichever comes first. Hospital discharge typically occurs at 2-3 months of age
Oxygen dependency	Infant dependency on oxygen as defined by Bancalari 2001	At time of discharge, on average at 2-3 months of age
Number of infants requiring ECMO	Use of ECMO support will be documented	Birth to 6 months
NICU stay	Number of days spent in the neonatal intensive care unit	From birth until discharge, at an average of 2-3 months of age
Ventilator support	Number of days on ventilator support	Up to 2 years of age
Presence of periventricular leukomalacia	Incidence of periventricular leukomalacia at <2 months postnatally	From birth until 2 months of age
Presence of neonatal sepsis	Incidence of neonatal sepsis	From birth until 1 month of age
Presence of intraventricular hemorrhage	Incidence of intraventricular hemorrhage (grade 0-III)	Up to 2 years of age
Retinopathy of prematurity	Incidence of retinopathy of prematurity (grade III or higher)	From birth to 1 month of age
Presence of gastro-esophageal reflux	Incidence of gastro-esophageal reflux	From birth until 2 years of age
CDH repair type	CDH repair type will be documented as patch or muscle flap	Postnatal, at time of CDH repair, typically within 2 weeks of birth
Pulmonary function	Pulmonary function	At discharge around 2-3 months and at one year of age
Infant Neurodevelopment	Neurodevelopmental testing of the infant using the Bayley-4	At 6 months, 12 months, and 24 months of age
Route of delivery	Delivery route will be recorded	At delivery
Maternal hospitalization	Total days of maternal hospital stay after delivery	From delivery until discharge, around 2-3 months of age

Collaborators and Investigators

• Sponsor: Alireza Shamshirsaz
• Investigators: Principal Investigator: Alireza Shamshirsaz, MD, Director, Maternal Fetal Care Center

Publications and helpful links

General Publications

• Jani JC, Nicolaides KH, Gratacos E, Valencia CM, Done E, Martinez JM, Gucciardo L, Cruz R, Deprest JA. Severe diaphragmatic hernia treated by fetal endoscopic tracheal occlusion. Ultrasound Obstet Gynecol. 2009 Sep;34(3):304-10. doi: 10.1002/uog.6450.
• Deprest J, Jani J, Gratacos E, Vandecruys H, Naulaers G, Delgado J, Greenough A, Nicolaides K; FETO Task Group. Fetal intervention for congenital diaphragmatic hernia: the European experience. Semin Perinatol. 2005 Apr;29(2):94-103. doi: 10.1053/j.semperi.2005.04.006.
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Study record dates

Study Major Dates

• Study Start (Estimated): March 1, 2024
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): August 30, 2030

Study Registration Dates

• First Submitted: October 26, 2023
• First Submitted That Met QC Criteria: February 26, 2024
• First Posted (Actual): February 28, 2024

Study Record Updates

• Last Update Posted (Actual): February 28, 2024
• Last Update Submitted That Met QC Criteria: February 26, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Hernia; Fetoscopic Endoluminal Tracheal Occlusion; Fetal Endoscopic Tracheal Occlusion; Hernias, Diaphragmatic, Congenital
• Additional Relevant MeSH Terms: Congenital Abnormalities; Pathological Conditions, Anatomical; Internal Hernia; Hernia; Hernias, Diaphragmatic, Congenital; Hernia, Diaphragmatic
• Other Study ID Numbers: IRB-P00045047

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes