Prospective Registry for Long-term Outcomes Following FETO in Severe Left and Right CDH

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

This registry study aims to confirm that FETO increases neonatal survival to discharge and reduces long-term morbidity in fetuses with isolated left CDH and o/e LHR \< 30%, or isolated right CDH and o/e LHR ≤ 45%, compared to those receiving standard care. This prospective registry plans to enroll 80 pregnant women (40 treatment/40 control) with fetuses diagnosed with isolated CDH, and the children will be followed for up to 24 months.

Detailed description

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 between 27 weeks + 0 days to 29 weeks + 6 days gestation. The FETO intervention involves two procedures: (1) inserting a balloon into the fetal trachea, and (2) removing the balloon before delivery. After the first FETO procedure, participants will be monitored weekly by ultrasound. Removal of the balloon will be performed at 34 weeks + 0 days to 34 weeks + 6 days gestation. Planned delivery will occur after 37 weeks. The follow-up phase will be conducted f

Primary outcome measures

• 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)]
• Number of FETO procedure complications [Time frame: End of study (24 months)]
• Number of neonates that survived [Time frame: From delivery to hospital discharge]

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 age 18 years and older
• 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 gestation.
• Gestational age at enrollment is prior to 29 weeks + 6 days gestation.
• Intrathoracic liver herniation:

• Isolated left CDH with o/e LHR < 30% at enrollment (18wks + 0 days to 29wks + 5 days gestation).
• Isolated right CDH with o/e LHR ≤ 45% at enrollment (18wks + 0 days to 29wks + 5 days gestation).
• Cervical length by transvaginal ultrasound ≥ 20 mm within 24 hours prior to FETO procedure.
• Patient meets psychosocial criteria.
• Informed consent understood.

Exclusion criteria

• Patient < 18 years of age
• Multi-fetal pregnancy
• 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 Johns Hopkins Hospital Center for Fetal Therapy.
• 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 Johns Hopkins Hospital Center for Fetal Therapy.
• Bilateral CDH, isolated left sided CDH with O/E LHR ≥ 30% (18wks + 0 days to 29wks + 5 days gestation), isolated right sided CDH with O/E LHR > 45% (18wks + 0 days to 29wks + 5 days gestation), 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

• Johns Hopkins Hospital — Baltimore

Identifiers

NCT: NCT07166172 · IRB00495298

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗