Safety and Efficacy of Fetoscopic Endoluminal Tracheal Occlusion (FETO) in Congenital Diaphragmatic Hernia (CDH)

Infant Survival and Long-term Outcome Following Fetoscopic Endoluminal Tracheal Occlusion in Severe Left and Right Congenital Diaphragmatic Hernia, A Phase III Trial

The purpose of the study is to determine if babies with left or right-sided CDH that undergo the FETO procedure survive more often and have fewer long-term complications than babies that have similar left or right-sided CDH that elect not to have the FETO procedure performed during pregnancy.

Study Overview

• Status: Recruiting
• Conditions: Congenital Diaphragmatic Hernia
• Intervention / Treatment: Device: FETO with Goldballoon Detachable Balloon (GOLDBAL2) along with the Delivery Microcatheter (BALTACCI-BDPE100)

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Erin Perrone, MD; Phone Number: 734-936-8464; Email: eperrone@med.umich.edu
• Study Contact Backup: Name: Irene Carter; Phone Number: 734-615-3883; Email: irenestc@med.umich.edu

Study Locations

• United States
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Recruiting
      • University of Michigan
      • Contact: Irene Carter; Phone Number: 734-615-3883; Email: irenestc@med.umich.edu
      • Principal Investigator: Erin Perrone, MD

Participation Criteria

Eligibility Criteria

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

Description

FETO Intervention Arm: Inclusion Criteria:

• Provision of signed and dated informed consent form
• Stated willingness to comply with all study procedures and availability (meets psychosocial criteria below) for the duration of the study
• Pregnant women, age 18 years and older
• Singleton pregnancy
• Normal fetal karyotype, Chromosomal Microarray (CMA) with non-pathologic variants, Whole Exome Sequencing (WES) or Whole Genome Sequencing (WGS). Results by fluorescence in situ hybridization (FISH) will be acceptable if the patient is >26 weeks.
• Gestational age at enrollment prior to 29w6d

• Fetal CDH with intrathoracic liver herniation with either:

  • Isolated left CDH with Observed/Expected (o/e) Lung to Head Ratio (LHR) <30% at enrollment (18w0d-29w5d)
  • Isolated right CDH with o/e LHR <45% at enrollment (18w0d-29w5d)
• Cervical length by transvaginal ultrasound >20 mm within 24hours of FETO procedure

• Meets psychosocial criteria

  • Willing to reside within 30 minutes of Von Voigtlander Women's Hospital and ability to maintain follow up appointments
  • Patient has a support person (e.g. spouse, partner, friend, parent) that is available to stay with participant for the duration of the pregnancy near Von Voigtlander Women's Hospital
  • Willing to comply with restrictions of daily living including inability to exercise, have intercourse, or return to work (work from home approved by Principal Investigator is okay)

Expectant Management Arm: Inclusion Criteria:

• Provision of signed and dated informed consent form
• Stated willingness to comply with all study procedures and availability (meets psychosocial criteria below) for the duration of the study
• Pregnant women, age 18 years and older
• Singleton pregnancy
• Normal fetal karyotype, CMA with non-pathologic variants, WES or WGS. Results by fluorescence in situ hybridization (FISH) will be acceptable if the patient is >26 weeks. (non-intervention arm can have karyotype or microarray prenatally or postnatally)
• Gestational age at enrollment prior to 29w6d
• Fetal CDH with intrathoracic liver herniation with either:
• Isolated left CDH with o/e LHR <30% at enrollment (18w0d-29w5d)
• Isolated right CDH with o/e LHR <45% at enrollment (18w0d-29w5d)

• Meets psychosocial criteria

  • Ability to maintain follow up appointments

FETO Intervention Arm: Exclusion Criteria:

• Patient <18 years of age
• Multi-fetal pregnancy
• History of natural rubber latex allergy
• Preterm labor, short cervix (<20mm within 24 hours of FETO balloon insertion procedure), or uterine anomaly strongly predisposing to preterm labor, placenta previa
• History of incompetent cervix with or without cerclage

• Psychosocial ineligibility

  • Inability to reside within 30 minutes of Von Voigtlander Women's Hospital or inability to maintain follow up appointments
  • Social work will meet with each patient to evaluate the social situation and support system. Identifiable issues of social instability or compliance with the protocol will exclude participant as a potential candidate (per protocol).
• Bilateral CDH, isolated Left Congenital Diaphragmatic Hernia (LCDH) with o/e LHR > 30% (measured at 180 to 295 weeks), isolated Right Congenital Diaphragmatic Hernia (RCDH) with o/e LHR >45% (measured at 180 to 295 weeks) as determined by ultrasound
• No liver herniation into the thoracic cavity.
• Additional fetal anomaly or genetic/chromosomal abnormalities recognized to alter survival prognosis (i.e., congenital heart disease) or presence of an underlying genetic syndrome (i.e. Fryns) by ultrasound, MRI or echocardiogram at the fetal treatment center.
• Maternal contraindications to elective fetoscopic surgery or severe maternal medical condition in pregnancy
• Placental abnormalities (previa, abruption, accreta) known at time of enrollment and/or surgery
• Maternal-fetal Rh isoimmunization, Kell sensitization, or neonatal alloimmune thrombocytopenia affecting the current pregnancy
• Maternal Human Immunodeficiency Virus (HIV), Hepatitis B with positive surface antigen, Hepatitis C with presence of virus in maternal blood due to risk of fetal transmission during the procedure. If the patient's HIV or Hepatitis status is unknown, the patient must be tested and found to have negative results before enrollment
• No safe or technically feasible fetoscopic approach to balloon placement
• Uterine anomalies such as large fibroids or Mullerian duct abnormality
• Participation in another intervention study that influences maternal and fetal morbidity and mortality or participation in this trial in a previous pregnancy

Expectant Management Arm: Exclusion Criteria:

• Patient <18 years of age
• Multi-fetal pregnancy
• Preterm labor, short cervix (<20mm), or uterine anomaly strongly predisposing to preterm labor, placenta previa
• History of incompetent cervix with or without cerclage

• Psychosocial ineligibility

  • Inability to maintain follow up appointments
  • Social work will meet with each patient to evaluate the social situation and support system. Identifiable issues of social instability or compliance with the protocol will exclude participant as a potential candidate.
• Bilateral CDH, isolated LCDH with o/e LHR > 30% (measured at 180 to 295 weeks), isolated RCDH with o/e LHR >45% (measured at 180 to 295 weeks), or any isolated CDH without intrathoracic liver herniation as determined by ultrasound
• Additional fetal anomaly or genetic/chromosomal abnormalities recognized to alter survival prognosis (i.e. congenital heart disease) or presence of an underlying genetic syndrome (i.e. Fryns) by ultrasound, Magnetic Resonance Imaging (MRI) or echocardiogram at the fetal treatment center Placental abnormalities (per protocol)
• Participation in another intervention study that influences maternal and fetal morbidity and mortality or participation in this trial in a previous pregnancy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: FETO surgery Intervention Arm; Eligible participants that choose the FETO Intervention Arm, will undergo two surgeries, one to place the balloon and a second to remove the balloon before delivery.	Device: FETO with Goldballoon Detachable Balloon (GOLDBAL2) along with the Delivery Microcatheter (BALTACCI-BDPE100); This will take place between gestation of 27w0d - 29w6d. The balloon will be removed at approximately 34 weeks gestation.
No Intervention: Expectant Management Arm; Participants choose to undergo the expectant management, or routine care, of carrying a baby with Congenital Diaphragmatic Hernia (CDH). Participants will undergo a comprehensive fetal evaluation at Michigan Medicine's Fetal Diagnosis and Treatment Center (FDTC) to confirm the diagnosis and severity of the CDH. Eligibility will be based on the results of the clinical assessment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Compare neonatal survival to discharge in LCDH		6-12 months (birth to discharge)
Compare neonatal survival to discharge in RCDH		6-12 months (birth to discharge)
Number of successful placements the of FETO balloon Gestational age of 27 weeks 0 days gestation to 29 weeks 6 days gestation		27weeks 0 days gestation to 29 weeks 6 days gestation
Number of successful retrievals/puncture of the FETO balloon Gestational age of 33 weeks 0 days to 35 weeks 0 days		Removal prior to delivery at approximately 34 weeks of gestation
Number of FETO procedure complications	FETO procedure complications include: Failure of the FETO insertion procedure; FETO device dislodgement potentially requiring a second FETO insertion; Fetal intraoperative injury; Procedural hemorrhage: Bleeding from insertion site or Abruptions; Post-procedural hemorrhage; Preterm premature rupture of membranes; Preterm delivery; Chorioamnion separation; Chorioamnionitis; Polyhydramnios; Oligohydramnios; Emergent removal due to obstetrical complication; Failed percutaneous or fetoscopic removal requiring cesarean section or Ex-Utero Intrapartum Therapy(EXIT) procedure for removal; Neonatal death due to asphyxia if delivery before FETO removal; Non-reassuring fetal heart rate monitoring.	Balloon placement to delivery (27 weeks up to delivery approximately 40 weeks)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fetal lung growth difference on MRI via o/e Total Fetal Lung Volume (TFLV) (FETO Intervention Arm)	Fetal MRI done prior to balloon placement and again done at approximately 2 weeks of balloon retrieval. Fetal lung growth (difference between 1st and 2nd MRIs will be calculated for FETO intervention arm only).	Baseline (prior to balloon placement) and approximately 2 weeks after balloon retrieval
Fetal lung growth difference based on prenatal ultrasound via o/e LHR (Both Arms)	Prenatal ultrasound (US) will measure the o/e LHR at weekly visits while the balloon is in place (FETO intervention arm) or at routine visits per standard of care (SOC) (expectant arm). Fetal lung growth will be calculated as the difference between the o/e LHR pre- balloon placement (or 29 + 1 week in control) and the o/e LHR immediately prior to balloon removal/puncture (or 34 + 1 week in control).	Baseline (prior to balloon placement) and immediately prior to balloon removal and SOC arm 29 + 1 week and 34 +1 week
Long-term outcome measure infant survival rate		After birth at 6,12, 18, and 24 months (+ 2 months) of corrected age
Presence of pulmonary hypertension	Determination of the ratio of the tricuspid regurgitation jet (estimation of the right ventricular systolic pressure) to systemic blood pressure where the is an objective measurement used to estimate the pulmonary artery pressure. Will be recorded as absent/none, systemic or suprasystemic.	After birth at 6,12, 18, and 24 months (+ 2 months) of corrected age
Presence of need for supplemental oxygen		After birth at 6,12, 18, and 24 months (+ 2 months) of corrected age
Periventricular leukomalacia at <2 months postnatally		After birth at 2 months
Infant sepsis		After birth at 6,12, 18, and 24 months (+ 2 months) of corrected age
Intraventricular hemorrhage (grade 0-III)		After birth at 6,12, 18, and 24 months (+ 2 months) of corrected age
Retinopathy of prematurity (grade 3 or higher)		After birth at 6,12, 18, and 24 months (+ 2 months) of corrected age
Gastroesophageal reflux		After birth at 6,12, 18, and 24 months (+ 2 months) of corrected age
Number and cause of infant hospital readmissions		After birth at 6,12, 18, and 24 months (+ 2 months) of corrected age
Long-term outcome measure childhood growth failure	Childhood growth failure: weight gain velocity or decline >2 in weight, for length Z score.	After birth at 6,12, 18, and 24 months (+ 2 months) of corrected age
Recurrence of CDH repair		After birth at 6,12, 18, and 24 months (+ 2 months) of corrected age
Bowel obstruction		After birth at 6, 12, 18, and 24 months (+ 2 months) of corrected age
Neurodevelopmental delay	Bayley Scales of Infant and Toddler Development- III(BSID)>2 Standard deviation (SD) below mean, or other categorization at 24 months	24 months (+ 2 months) of corrected age
Bronchopulmonary dysplasia		After birth at 6,12, 18, and 24 months (+ 2 months) of corrected age

Collaborators and Investigators

• Sponsor: Dr Erin Perrone
• Investigators: Principal Investigator: Erin Perrone, MD, University of Michigan

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): April 1, 2030
• Study Completion (Estimated): April 1, 2031

Study Registration Dates

• First Submitted: May 3, 2026
• First Submitted That Met QC Criteria: May 3, 2026
• First Posted (Actual): May 11, 2026

Study Record Updates

• Last Update Posted (Actual): June 4, 2026
• Last Update Submitted That Met QC Criteria: June 3, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Pregnant; Fetal Endoscopic tracheal occlusion; Standard of Care arm; Goldballoon Detachable Balloon (GOLDBAL2)
• Additional Relevant MeSH Terms: Internal Hernia; Pathological Conditions, Anatomical; Congenital Abnormalities; Hernia; Hernia, Diaphragmatic; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Pathological Conditions, Signs and Symptoms; Hernias, Diaphragmatic, Congenital
• Other Study ID Numbers: HUM00265099

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