North American Fetal Therapy Network for Long-term Outcome Following Fetoscopic Endoluminal Tracheal Occlusion in Severe Left and Right Congenital Diaphragmatic Hernia

Official title

North American Fetal Therapy Network Prospective Registry for Long-term Outcome Following Fetoscopic Endoluminal Tracheal Occlusion in Severe Left and Right Congenital Diaphragmatic Hernia

Overview

The purpose of this study is to evaluate successful placement and removal of Fetoscopic Endoluminal Tracheal Occlusion (FETO) device in cases of intrathoracic liver herniation with isolated left congenital diaphragmatic hernia (LCDH) with Observed/Expected (O/E) Lung to Head Circumference Ratio (LHR) \< 30% or isolated right congenital diaphragmatic hernia (RCDH) with O/E LHR \< 45%,to compare survival to discharge from the neonatal intensive care units (NICU), between fetuses with intrathoracic liver herniation and isolated LCDH with O/E LHR \< 30% that receive FETO procedure performed at 27 weeks 0 days to 29weeks 6 days of gestation to those with intrathoracic liver herniation, isolated LCDH and o/e LRH \< 30% that undergo expectant management, to compare the neonatal survival rate to discharge from the neonatal intensive care units (NICU), between fetuses with intrathoracic liver herniation, isolated RCHD with o/e LHR \< 45% that undergo FETO procedure performed at 27 weeks 0 days to 29 weeks 6 days gestation to those with intrathoracic liver herniation, isolated RCHD and o/e LHR \< 45% that elect to proceed with expectant management, to evaluate the frequency of maternal and fetal complications associated with FETO procedure, to evaluate whether the FETO procedure is associated with reduced long-term mortality and morbidities in isolated LCDH survivors with o/e LHR \<30% when compared to isolated LCDH with o/e LRH \<30% that undergo expectant management where all fetuses were found to have intrathoracic liver herniation and to evaluate whether the FETO procedure is associated with reduced long-term mortality and morbidities in isolated RCDH survivors with o/e LHR ≤ 45% when compared to isolated RCHD with LHR \< 45% that undergo expectant management where all fetuses were found to have intrathoracic liver herniation

Interventions

• Device Fetal Treatment arm (FETO Group)
  Participants will undergo FETO surgery at at 27 weeks 0 days - 29 weeks 6 days gestation.Balloon insertion into the fetal trachea will be performed. This will be followed by weekly \\ ultrasound monitoring and MRI at 3 weeks following FETO insertion and removal of the balloon which will be performed at at 34 weeks 0 days to 34 weeks 6 days. Planned delivery will occur after 37 weeks. The follow-up phase will be conducted from birth to 24 months of age

Primary outcome measures

• Number of neonates that survived [Time frame: from delivery to hospital discharge (up to 12 months)]
• Number of Successful placement of FETO device [Time frame: 10-60 minutes after surgery begins]
• Number of Successful removal of FETO device [Time frame: immediately after the procedure (about 1 hour after start of surgery)]
• FETO procedure complications [Time frame: end of study (24 months)]

Secondary outcome measures (12)

• Number of infants that survived [Time frame: 6 months]
• Number of infants that survived [Time frame: 12 months]
• Number of infants that survived [Time frame: 18 months]
• Number of infants that survived [Time frame: 24 months]
• Number of infants that show presence of pulmonary hypertension [Time frame: 6 months]
• Number of infants that show presence of pulmonary hypertension [Time frame: 12 months]
• Number of infants that show presence of pulmonary hypertension [Time frame: 18 months]
• Number of infants that show presence of pulmonary hypertension [Time frame: 24 months]
• Number of infants that show need for supplemental oxygen [Time frame: 6 months]
• Number of infants that show need for supplemental oxygen [Time frame: 12 months]
• Number of infants that show need for supplemental oxygen [Time frame: 18 months]
• Number of infants that show need for supplemental oxygen [Time frame: 24 months]

Eligibility criteria

Inclusion criteria

• Pregnant women who are able to consent
• Singleton pregnancy
• Normal Karyotype, chromosomal microanalysis (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 is prior to 296 wks.
• Intrathoracic liver herniation
• Isolated left CDH with o/e LHR < 30% at enrollment (180 to 295 wks.). or
• Isolated RCDH with o/e LHR < 45% at enrollment (180 to 295 wks.)
• Cervical length by transvaginal ultrasound > 20 mm within 24 hours prior to FETO procedure
• Patient meets psychosocial criteria
• Informed consent understood

Exclusion criteria

• History of natural rubber latex allergy
• Preterm labor, cervix shortened (<20 mm at enrollment or within 24 hours of FETO balloon insertion procedure) or uterine anomaly strongly predisposing to preterm labor, placenta previa.
• Psychosocial ineligibility, precluding consent:

• Inability to reside within 30 minutes of University of Texas Health Science Center at Houston Fetal Center
• The 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 UTHealth Houston Fetal Center
• Bilateral CDH, isolated left sided CDH with O/E LHR ≥ 30% (measured at 180 to 295 weeks), isolated right sided CDH with O/E LHR > 45% (measured at 180 to 295 weeks), as determined by ultrasound
• No liver herniation into thoracic cavity
• Additional fetal anomaly and chromosomal abnormalities by ultrasound, MRI, or echocardiogram at the fetal treatment center. Exclude chromosomal abnormalities, associated anomalies recognized to alter survival prognosis (i.e., CDH and congenital heart disease) or presence of an underlying genetic syndrome (i.e., Fryns).
• Maternal contraindication to fetoscopic surgery or severe maternal medical condition in pregnancy
• 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 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
• Uterine anomalies such as large or multiple fibroids or Mullerian duct abnormality
• There is no safe or technically feasible fetoscopic approach to balloon placement
• 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

• The University of Texas Health Science Center at Houston — Houston

Identifiers

NCT: NCT06739356 · HSC-MS-24-0984

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗