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

Official title

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

Overview

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.

Interventions

• 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.

Primary outcome measures

• Compare neonatal survival to discharge in LCDH [Time frame: 6-12 months (birth to discharge)]
• Compare neonatal survival to discharge in RCDH [Time frame: 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 [Time frame: 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 [Time frame: Removal prior to delivery at approximately 34 weeks of gestation]
• Number of FETO procedure complications [Time frame: Balloon placement to delivery (27 weeks up to delivery approximately 40 weeks)]

Secondary outcome measures (12)

• Fetal lung growth difference on MRI via o/e Total Fetal Lung Volume (TFLV) (FETO Intervention Arm) [Time frame: 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) [Time frame: 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 [Time frame: After birth at 6,12, 18, and 24 months (+ 2 months) of corrected age]
• Presence of pulmonary hypertension [Time frame: After birth at 6,12, 18, and 24 months (+ 2 months) of corrected age]
• Presence of need for supplemental oxygen [Time frame: After birth at 6,12, 18, and 24 months (+ 2 months) of corrected age]
• Periventricular leukomalacia at <2 months postnatally [Time frame: After birth at 2 months]
• Infant sepsis [Time frame: After birth at 6,12, 18, and 24 months (+ 2 months) of corrected age]
• Intraventricular hemorrhage (grade 0-III) [Time frame: After birth at 6,12, 18, and 24 months (+ 2 months) of corrected age]
• Retinopathy of prematurity (grade 3 or higher) [Time frame: After birth at 6,12, 18, and 24 months (+ 2 months) of corrected age]
• Gastroesophageal reflux [Time frame: After birth at 6,12, 18, and 24 months (+ 2 months) of corrected age]
• Number and cause of infant hospital readmissions [Time frame: After birth at 6,12, 18, and 24 months (+ 2 months) of corrected age]
• Long-term outcome measure childhood growth failure [Time frame: After birth at 6,12, 18, and 24 months (+ 2 months) of corrected age]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 1 center

• University of Michigan — Ann Arbor

Identifiers

NCT: NCT07577414 · HUM00265099

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗