Congenital Diaphragmatic Hernia
Conditions
Keywords
Pregnant, Fetal Endoscopic tracheal occlusion, Standard of Care arm, Goldballoon Detachable Balloon (GOLDBAL2)
Brief summary
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
This will take place between gestation of 27w0d - 29w6d. The balloon will be removed at approximately 34 weeks gestation.
Sponsors
Dr Erin Perrone
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Participants will choose between 2 courses of care. One group is the FETO surgery Intervention Arm and the other group is the Expectant Management Arm. It is expected that there will be 20 participants in each group.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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:
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of FETO procedure complications | Balloon placement to delivery (27 weeks up to delivery approximately 40 weeks) | FETO procedure complications include: Failure of the FETO insertion procedure; FETO device dislodgement potentially requiring a second FETO insertion; Fetal intraoperative injury; Procedural hemorrhage: Bleeding from insertion site or Abruptions; Post-procedural hemorrhage; Preterm premature rupture of membranes; Preterm delivery; Chorioamnion separation; Chorioamnionitis; Polyhydramnios; Oligohydramnios; Emergent removal due to obstetrical complication; Failed percutaneous or fetoscopic removal requiring cesarean section or Ex-Utero Intrapartum Therapy(EXIT) procedure for removal; Neonatal death due to asphyxia if delivery before FETO removal; Non-reassuring fetal heart rate monitoring. |
| Compare neonatal survival to discharge in LCDH | 6-12 months (birth to discharge) | — |
| Compare neonatal survival to discharge in RCDH | 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 | 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 | Removal prior to delivery at approximately 34 weeks of gestation | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Presence of need for supplemental oxygen | After birth at 6,12, 18, and 24 months (+ 2 months) of corrected age | — |
| Periventricular leukomalacia at <2 months postnatally | After birth at 2 months | — |
| Infant sepsis | After birth at 6,12, 18, and 24 months (+ 2 months) of corrected age | — |
| Intraventricular hemorrhage (grade 0-III) | After birth at 6,12, 18, and 24 months (+ 2 months) of corrected age | — |
| Retinopathy of prematurity (grade 3 or higher) | After birth at 6,12, 18, and 24 months (+ 2 months) of corrected age | — |
| Gastroesophageal reflux | After birth at 6,12, 18, and 24 months (+ 2 months) of corrected age | — |
| Number and cause of infant hospital readmissions | After birth at 6,12, 18, and 24 months (+ 2 months) of corrected age | — |
| Long-term outcome measure childhood growth failure | After birth at 6,12, 18, and 24 months (+ 2 months) of corrected age | Childhood growth failure: weight gain velocity or decline \>2 in weight, for length Z score. |
| Recurrence of CDH repair | After birth at 6,12, 18, and 24 months (+ 2 months) of corrected age | — |
| Bowel obstruction | After birth at 6, 12, 18, and 24 months (+ 2 months) of corrected age | — |
| Neurodevelopmental delay | 24 months (+ 2 months) of corrected age | Bayley Scales of Infant and Toddler Development- III(BSID)\>2 Standard deviation (SD) below mean, or other categorization at 24 months |
| Bronchopulmonary dysplasia | After birth at 6,12, 18, and 24 months (+ 2 months) of corrected age | — |
| Fetal lung growth difference on MRI via o/e Total Fetal Lung Volume (TFLV) (FETO Intervention Arm) | Baseline (prior to balloon placement) and approximately 2 weeks after balloon retrieval | Fetal MRI done prior to balloon placement and again done at approximately 2 weeks of balloon retrieval. Fetal lung growth (difference between 1st and 2nd MRIs will be calculated for FETO intervention arm only). |
| Fetal lung growth difference based on prenatal ultrasound via o/e LHR (Both Arms) | Baseline (prior to balloon placement) and immediately prior to balloon removal and SOC arm 29 + 1 week and 34 +1 week | Prenatal ultrasound (US) will measure the o/e LHR at weekly visits while the balloon is in place (FETO intervention arm) or at routine visits per standard of care (SOC) (expectant arm). Fetal lung growth will be calculated as the difference between the o/e LHR pre- balloon placement (or 29 + 1 week in control) and the o/e LHR immediately prior to balloon removal/puncture (or 34 + 1 week in control). |
| Long-term outcome measure infant survival rate | After birth at 6,12, 18, and 24 months (+ 2 months) of corrected age | — |
| Presence of pulmonary hypertension | After birth at 6,12, 18, and 24 months (+ 2 months) of corrected age | Determination of the ratio of the tricuspid regurgitation jet (estimation of the right ventricular systolic pressure) to systemic blood pressure where the is an objective measurement used to estimate the pulmonary artery pressure. Will be recorded as absent/none, systemic or suprasystemic. |
Countries
United States
Contacts
CONTACTIrene Carter
CONTACTErin Perrone, MD
PRINCIPAL_INVESTIGATORErin Perrone, MD
University of Michigan
Outcome results
None listed