Fetal Endoscopic Tracheal Occlusion (FETO) Trial for Congenital Diaphragmatic Hernia (CDH)

This is a single site, single arm, non-randomized, pilot trial to assess the feasibility and safety of treating severe congenital diaphragmatic hernia (CDH) with Fetal Endoscopic Tracheal Occlusion (FETO) at Columbia University Irving Medical Center (CUIMC)/ NewYork-Presbyterian Hospital (NYP).

Study Overview

• Status: Not yet recruiting
• Conditions: Diaphragmatic Hernia
• Intervention / Treatment: Device: Placement of the GOLDBAL2 balloon

Detailed Description

Congenital diaphragmatic hernia (CDH) affects 1 in 2,200 to 5,000 live births per year. The defect in the fetal diaphragm allows abdominal organs (intestine, stomach, liver, spleen) to migrate into the thorax, hindering normal lung development. The herniated contents place pressure on the developing lungs and this may result in varying degrees of pulmonary hypoplasia and associated pulmonary hypertension; both of which may be lethal. In an attempt to prenatally quantify the impact of the herniated organs on underlying lung development, prognostic tools have been developed. The most widely used prognostic indicator is lung-to-head ratio (LHR) as measured by prenatal ultrasound. The lung contralateral to the diaphragmatic defect is measured in a transverse plane at the level of the four chamber heart and its area is divided by the fetal head circumference (LHR). The LHR is tracked through the pregnancy but seems to be most strongly correlated with outcomes in the early third trimester.

Fetuses with severe CDH have a high risk of mortality. The current standard of care treatment offers postnatal repair, which is associated with overall survival of 71% in all cases. A majority (68%) of fetuses are prenatally diagnosed, and the survival in this cohort is even lower at 65%. The severity of the defect can be measured prenatally by the degree of pulmonary hypoplasia, and the survival drops to below 30% for those with expected lung volumes below 30% of expected. The purpose of the FETO procedure in severe CDH patients is to improve prenatal lung growth in order to potentially increase neonatal survival.

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

Contacts and Locations

• Study Contact: Name: Amanda Alonso, MHA; Phone Number: 212-342-0261; Email: aa2974@cumc.columbia.edu

Study Locations

• United States
  • New York
    • New York, New York, United States, 11021
      • Columbia University Irving Medical Center/NewYork-Presbyterian
      • Contact: Amanda Alonso, MHA; Phone Number: 212-342-0261; Email: aa2974@cumc.columbia.edu
      • Principal Investigator: Vincent Duron, MD

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Provision of signed and dated informed consent form
2. Stated willingness to comply with all study procedures and availability (meets psychosocial criteria below) for the duration of the study
3. Pregnant women, age 18 years and older
4. Singleton pregnancy
5. No pathogenic variants on microarray or pathologic findings on karyotype; results by fluorescence in situ hybridization (FISH) will be acceptable if patient is >26 weeks
6. Fetal echocardiogram with changes expected with CDH and no major structural cardiac defects
7. Fetal CDH (left or right) with severe pulmonary hypoplasia, defined as o/e LHR <25% with liver up
8. Gestational age at FETO procedure: if o/e LHR <25%, will be done at 27 weeks plus 0 days to 29 weeks plus 6 days

9. Meets psychosocial criteria

   • Willing to reside within 30 minutes of NewYork-Presbyterian Sloane Hospital for Women/Columbia University Irving Medical Center (CUIMC) and ability to maintain follow up appointments. NYP/CUIMC will work with the study participant to assist in securing housing 30 minutes from the hospital if this is a challenge to her.
   • Patient has a support person (e.g. spouse, partner, friend, parent) that is available to stay with her for the duration of the pregnancy near NewYork-Presbyterian Sloane Hospital for Women/Columbia University Irving Medical Center (CUIMC)
   • Willing to comply with restrictions of daily living including inability to exercise, have intercourse, or return to work

Exclusion Criteria:

1. Multi-fetal pregnancy
2. History of latex allergy
3. History of preterm labor or incompetent cervix (requiring cerclage), short cervix (<20mm), or uterine anomaly predisposing to preterm labor

4. Psychosocial ineligibility

   • Inability to reside within 30 minutes of NewYork-Presbyterian Sloane Hospital for Women/Columbia University Irving Medical Center (CUIMC) 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 her as a potential candidate.
5. Bilateral CDH, unilateral CDH with o/e LHR > 25%, or unilateral CDH with o/e LHR <25% but liver completely down in abdomen
6. Additional fetal or genetic abnormalities that would impact care after delivery or be known to have an impact on outcome
7. Maternal contraindications to elective fetoscopic surgery
8. Significant placental abnormalities (abruption, chorioangioma, accreta) known at time of enrollment and/or surgery
9. Maternal-fetal Rh isoimmunization, Kell sensitization or neonatal alloimmune thrombocytopenia affecting the current pregnancy.Maternal 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
10. No safe or feasible fetoscopic approach to balloon placement
11. Uterine anomaly such as large or multiple fibroids or mullerian duct abnormality
12. Participation in another intervention study that influences maternal and fetal morbidity and mortality.

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: Treatment; GOLDBAL2 balloon will be placed for Fetus diagnosed with Congenital diaphragmatic hernia (CDH) at Gestational age of 27w0d - 29w6d and retrieved at Gestational age of 34w0d to 34w 6 days	Device: Placement of the GOLDBAL2 balloon; The Fetal Endoscopic Tracheal Occlusion (FETO) procedure using the Goldballoon Detachable Balloon (GOLDBAL2) along with the Delivery Microcatheter (BALTACCI-BDPE100) will be used to treat fetuses diagnosed with severe Congenital Diaphragmatic Hernia (CDH)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total number of subjects with successful placement of the balloon	Success will be defined as completion with direct visual placement above the carina and confirmation on ultrasound done during the procedure.	Up to 30 weeks
Total number of subjects with successful retrieval of the balloon	Success will be defined by retrieval prior to delivery, including safe retrieval during an ex-utero intrapartum therapy (EXIT) procedure.	Up to 35 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in fetal lung volume growth on prenatal MRI	Fetal MRI prior to balloon placement and 2nd fetal MRI at +/- 2 weeks of balloon retrieval will be performed to calculate the difference between the 1st and 2nd MRIs.	Baseline and up to 37 weeks
Change in fetal lung growth on prenatal ultrasound	Fetal ultrasound before balloon placement and immediately prior to balloon removal will be performed to calculate the different between the 2 ultrasounds.	Baseline and up to 35 weeks
Gestational age at delivery	Gestational age at delivery will be measured.	At the time of delivery (up to 40 weeks of gestation)
Total number of maternal complications	Maternal complications will be recorded and reviewed.	Up to 6 weeks post-delivery
Survival rate post-delivery	Survival rate will be measured at 180 days for those still hospitalized at the time point.	Up to 180 days post-delivery

Collaborators and Investigators

• Sponsor: Vincent Duron
• Investigators: Principal Investigator: Vincent Duron, MD, Columbia University

Study record dates

Study Major Dates

• Study Start (Estimated): November 1, 2023
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2027

Study Registration Dates

• First Submitted: April 26, 2022
• First Submitted That Met QC Criteria: April 26, 2022
• First Posted (Actual): April 29, 2022

Study Record Updates

• Last Update Posted (Actual): October 23, 2023
• Last Update Submitted That Met QC Criteria: October 20, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Fetal Endoscopic Tracheal Occlusion (FETO); Congenital diaphragmatic hernia (CDH)
• Additional Relevant MeSH Terms: Congenital Abnormalities; Pathological Conditions, Anatomical; Internal Hernia; Hernia; Hernias, Diaphragmatic, Congenital; Hernia, Diaphragmatic
• Other Study ID Numbers: AAAU1357

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