Safety and Efficacy of FETO in CDH: A Phase III Trial

NCT ID: NCT06884423

Last Updated: 2025-07-25

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 80 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-04-07
• Study Completion Date: 2032-04-30

Brief Summary

Congenital diaphragmatic hernia (CDH) is a birth defect characterized by the development of a hole in the diaphragm, the breathing muscle that separates the chest from the abdomen. As a result, organs in the abdomen can move into the chest and press on the developing lungs. This prevents the lungs from growing and developing normally.

In severe cases, CDH can lead to serious disease and death at birth. For these babies, treatment before birth may allow the lungs to grow enough before birth so these children are capable of surviving and thriving.

Detailed Description

All patients will complete a standard prenatal evaluation at the Children's Hospital of Philadelphia (CHOP) Center for Fetal Diagnosis and Treatment (CFDT) to determine if they are candidates for this study. The standard clinical assessments include medical history and physical exam, level II ultrasound, fetal echocardiogram, fetal magnetic resonance imaging (MRI), and a psychosocial assessment.

If determined eligible for fetoscopic endoluminal tracheal occlusion (FETO) intervention, patients will be extensively counseled by the CFDT Team and those who choose to participate will provide written, informed consent for study enrollment.

Up to 40 maternal/fetal dyads will be enrolled in the intervention arm of this study. The pregnant patient and fetus will undergo two procedures. A balloon will be placed in the fetal airway between 27+0/7 - 29+6/7 gestational age. The balloon blocks the airway and remains in place until balloon removal. The timing for balloon removal will be determined by the CFDT Management Team and can occur between 34 +0/7 - 34+6/7 gestational age.

Pregnant patients enrolled in the intervention arm of study must remain near the fetal center, under close supervision, from the time of balloon placement through delivery in the CHOP Garbose Family Special Delivery Unit.

Weekly prenatal monitoring will occur after the first procedure at the CFDT, and planned delivery will occur in the Garbose Family Special Delivery Unit at term.

Postnatal stabilization and subsequent surgery to repair the diaphragm will take place at CHOP.

Up to 40 maternal/fetal dyads which meet criteria according to defect side, observed/expected lung to head ratio (O/E LHR), and liver position, but undergo expectant management rather than FETO intervention, will be enrolled in the control arm of this study.

Infants in both the intervention arm and the control arm will be followed at CHOP at 6 months, 12 months, 18 months, and 24 months of age through the CHOP Pulmonary Hypoplasia Program.

Conditions

Congenital Diaphragmatic Hernia; Pulmonary Hypoplasia

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

FETO in CDH

Fetoscopic Endoluminal Tracheal Occlusion (FETO) will be performed by placing a detachable balloon inside the fetal airway and removing the balloon after several weeks. Devices: GoldBAL2 Detachable Balloon and BALTACCIBDPE100 Delivery Catheter. Assignment will be non-randomized. 40 maternal/fetal dyads will be enrolled in this arm.

Group Type: EXPERIMENTAL

FETO with GoldBAL2 Balloon and BALTACCIBDPE100 Catheter

Intervention Type: DEVICE

Fetoscopic Endoluminal Tracheal Occlusion (FETO) in CDH with GoldBAL2 Detachable Balloon and BALTACCIBDPE100 Delivery Catheter

Expectant Management in CDH

The control arm includes patients eligible for FETO according to side of defect, O/E LHR, and liver position who undergo expectant management rather than FETO intervention. Assignment will be non-randomized. 40 maternal/fetal dyads will be enrolled in this arm.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

FETO with GoldBAL2 Balloon and BALTACCIBDPE100 Catheter

Fetoscopic Endoluminal Tracheal Occlusion (FETO) in CDH with GoldBAL2 Detachable Balloon and BALTACCIBDPE100 Delivery Catheter

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

1. Pregnant women age 18 years and older

2. Singleton pregnancy

3. Normal fetal karyotype with confirmation by culture results, whole exome sequencing (WES), whole genome sequencing (WGS), or chromosomal microarray with non-pathologic variants. Results by fluorescence in situ hybridization (FISH) will be acceptable if the patient is greater than 26 weeks.

4. Gestational age at enrollment is prior to 29 weeks 6 days

5. Liver is intrathoracic

6. Isolated left congenital diaphragmatic hernia (CDH) with observed/expected lung to head ratio (O/E LHR) of less than 30% at enrollment (18^0 to 29^5 weeks), or:

7. Isolated right CDH with O/E LHR equal to or less than 45% at enrollment (18^0 to 29^5 weeks).

8. Cervical length by transvaginal ultrasound equal to or greater than 20 mm within 24 hours of fetoscopic endoluminal tracheal occlusion (FETO) procedure

9. Patient meets psychosocial criteria

10. Informed consent

Exclusion Criteria

1. Patient is less than 18 years of age

2. Multi-fetal pregnancy

3. History of natural rubber latex allergy

4. Preterm labor, cervix shortened (less than 20 mm at enrollment or within 24 hours of FETO balloon insertion procedure) or uterine anomaly strongly predisposing to preterm labor, placenta previa

5. Psychosocial ineligibility, precluding consent:

• Inability to reside within 30 minutes of the Children's Hospital of Philadelphia (CHOP) and inability to comply with the travel for the follow-up requirements of the trial
• Patient does not have a support person (e.g. spouse, partner, mother) available to stay with the patient for the duration of the pregnancy at CHOP

6. Bilateral CDH, isolated left sided CDH with O/E LHR greater than or equal to 30% (measured at 18^0 to 29^5 weeks), isolated right sided CDH with O/E LHR greater than 45% (measured at 180 to 295 weeks), as determined by ultrasound

7. No Liver herniation into thoracic cavity.

8. Additional fetal anomaly by ultrasound, magnetic resonance imaging (MRI), or echocardiogram at the fetal treatment center. Exclude chromosomal abnormalities, associated anomalies recognized to alter survival prognosis (ie. CDH and congenital heart disease) or presence of an underlying genetic syndrome (ie. Fryns).

9. Maternal contraindication to fetoscopic surgery or severe maternal medical condition in pregnancy

10. History of incompetent cervix with or without cerclage

11. Placental abnormalities (previa, abruption, accrete) known at time of enrollment.

12. Maternal-fetal Rh isoimmunization, Kell sensitization or neonatal alloimmune thrombocytopenia affecting the current pregnancy.

13. Maternal HIV, Hepatitis-B, Hepatitis-C status positive because of the increased risk of transmission to the fetus during maternal-fetal surgery. If the patient's HIV or Hepatitis status is unknown, the patient must be tested and found to have negative results before enrollment.

14. Uterine anomaly such as large or multiple fibroids or mullerian duct abnormality

15. There is no safe or technically feasible fetoscopic approach to balloon placement.

16. Participation in another intervention study that influences maternal and fetal morbidity and mortality or participation in this trial in a previous pregnancy.

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Holly L Hedrick, MD

OTHER

Sponsor Role: lead

Responsible Party

Holly L Hedrick, MD

Sponsor-Investigator, Attending Surgeon, Professor of Surgery

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Holly L Hedrick, MD, FACS

Role: PRINCIPAL_INVESTIGATOR

Children's Hospital of Philadelphia

Locations

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Site Status: NOT_YET_RECRUITING

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Holly L Hedrick, MD, FACS

Role: CONTACT

hedrick@chop.edu

1-800-468-8376

Annaliese Aarthun

Role: CONTACT

aarthuna@chop.edu

Facility Contacts

Holly L Hedrick, MD, FACS

Role: primary

hedrick@chop.edu

1-800-468-8376

Annaliese Aarthun

Role: backup

aarthuna@chop.edu

References

Danzer E, Hedrick HL. Controversies in the management of severe congenital diaphragmatic hernia. Semin Fetal Neonatal Med. 2014 Dec;19(6):376-84. doi: 10.1016/j.siny.2014.10.001. Epub 2014 Nov 7.

Reference Type: BACKGROUND

PMID: 25454678 (View on PubMed)

Deprest JA, Gratacos E, Nicolaides K, Done E, Van Mieghem T, Gucciardo L, Claus F, Debeer A, Allegaert K, Reiss I, Tibboel D. Changing perspectives on the perinatal management of isolated congenital diaphragmatic hernia in Europe. Clin Perinatol. 2009 Jun;36(2):329-47, ix. doi: 10.1016/j.clp.2009.03.004.

Reference Type: BACKGROUND

PMID: 19559323 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 19658113 (View on PubMed)

Style CC, Olutoye OO, Belfort MA, Ayres NA, Cruz SM, Lau PE, Shamshirsaz AA, Lee TC, Olutoye OA, Fernandes CJ, Cortes MS, Keswani SG, Espinoza J. Fetal endoscopic tracheal occlusion reduces pulmonary hypertension in severe congenital diaphragmatic hernia. Ultrasound Obstet Gynecol. 2019 Dec;54(6):752-758. doi: 10.1002/uog.20216. Epub 2019 Nov 4.

Reference Type: BACKGROUND

PMID: 30640410 (View on PubMed)

Russo FM, Cordier AG, Basurto D, Salazar L, Litwinska E, Gomez O, Debeer A, Nevoux J, Patel S, Lewi L, Pertierra A, Aertsen M, Gratacos E, Nicolaides KH, Benachi A, Deprest J. Fetal endoscopic tracheal occlusion reverses the natural history of right-sided congenital diaphragmatic hernia: European multicenter experience. Ultrasound Obstet Gynecol. 2021 Mar;57(3):378-385. doi: 10.1002/uog.23115.

Reference Type: BACKGROUND

PMID: 32924187 (View on PubMed)

Deprest JA, Nicolaides KH, Benachi A, Gratacos E, Ryan G, Persico N, Sago H, Johnson A, Wielgos M, Berg C, Van Calster B, Russo FM; TOTAL Trial for Severe Hypoplasia Investigators. Randomized Trial of Fetal Surgery for Severe Left Diaphragmatic Hernia. N Engl J Med. 2021 Jul 8;385(2):107-118. doi: 10.1056/NEJMoa2027030. Epub 2021 Jun 8.

Reference Type: BACKGROUND

PMID: 34106556 (View on PubMed)

Deprest J, Brady P, Nicolaides K, Benachi A, Berg C, Vermeesch J, Gardener G, Gratacos E. Prenatal management of the fetus with isolated congenital diaphragmatic hernia in the era of the TOTAL trial. Semin Fetal Neonatal Med. 2014 Dec;19(6):338-48. doi: 10.1016/j.siny.2014.09.006. Epub 2014 Nov 11.

Reference Type: BACKGROUND

PMID: 25447987 (View on PubMed)

Related Links

https://www.chop.edu/centers-programs/center-fetal-diagnosis-and-treatment

CHOP Center for Fetal Diagnosis and Treatment

https://www.chop.edu/centers-programs/pulmonary-hypoplasia-program

CHOP Pulmonary Hypoplasia Program

Other Identifiers

G140236

Identifier Type: OTHER

Identifier Source: secondary_id

24-022603

Identifier Type: -

Identifier Source: org_study_id