Fetal Repair of Complex Gastroschisis: a Safety and Feasibility Trial

Not Applicable

Recruiting

• Conditions: Gastroschisis
• Interventions: Device: fetoscopy

• Registration Number: NCT05704257
• Lead Sponsor: Baylor College of Medicine

Brief Summary

The goal of this clinical trial is to evaluate the safety and feasibility of fetal repair of complex gastroschisis (GS) via a fetoscopic surgical approach by assessing maternal, fetal, neonatal, and infant outcomes in a cohort of 10 patients. The hypothesis is that in utero repair of GS will reduce postnatal mortality and morbidity in complex GS infants with minimal maternal and fetal risk.

Detailed Description

Gastroschisis is a congenital abdominal wall defect by which the intestinal structures eviscerate from the abdomen, with a current prevalence of 4.9 per 10,000 pregnancies in the United States. Not only is it the most common abdominal wall defect, but the incidence of GS has increased by nearly 30% in the US (Jones et al., 2016) and 25 % in Europe (EUROCAT, 2021) between 2006 and 2012 for reasons that are still unknown. Two subtypes of the disease have been identified - simple and complex GS. Simple GS presents as an otherwise healthy bowel that may have an inflammatory peel over the bowel surface. By contrast, complex GS is characterized by serious bowel complications, such as bowel volvulus, atresia, stenosis, necrosis, and perforation.

Participants will be offered the minimally invasive in-utero repair technique as an alternative to the traditional standard postnatal GS surgical repair. During surgery, the mother's uterus is opened using the standard laparotomy approach that we currently use in our open fetal surgeries and fetoscopic spina bifida repair through an exteriorized uterus, and then fetal surgeons repair the fetus' defect. The uterus is closed, and the pregnancy continues. When babies are treated in this way, they may be less likely to be born with their intestines coming out of their belly and if this is the case, they may be less likely to have other problems that occur with gastroschisis because the intestines are not covered.

All participants will be closely followed with ultrasound and consultation after the surgery. Delivery will be scheduled at Texas Children's Hospital, and the infants will be followed for 12 months by our research team.

Study Timeline

• Study First Submitted: 2023-01-03
• Study First Submitted QC: 2023-01-20
• Study First Posted: 2023-01-30
• Study Start: 2023-10-20
• Status Verified: 2024-10
• Last Update Submitted: 2024-10-24
• Last Update Posted: 2024-10-28
• Primary Completion: 2029-12
• Study Completion: 2029-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Female
• Target Recruitment: 10

Inclusion Criteria

1. Pregnant women - maternal age 18 years or older and capable of consenting for her own participation in this study

2. Singleton pregnancy

3. Sonographic evidence of gastroschisis (exteriorization of bowel content outside the fetal abdominal cavity into the amniotic cavity)

4. Intraabdominal bowel dilation ≥ 10 mm at 20-24 weeks GA reviewed by prenatal ultrasound

5. Absence of significant associated anomalies* diagnosed on prenatal ultrasound or MRI

6. Gestational age at the time of the procedure will be between 20 0/7 weeks and 25 6/7 weeks

7. Absence of chromosomal and clinically significant abnormalities, i.e., normal karyotype and/or normal chromosomal microarray (CMA) by invasive testing (amniocentesis or Chorionic Villus Sampling (CVS)). If there is a balanced translocation with normal CMA with no other anomalies the candidate can be included. Results by fluorescence in situ hybridization (FISH) will be accepted, if the candidate's gestation age is ≥ 22 0/7 weeks. Patients declining invasive testing will be excluded

8. The family has considered and declined the option of termination of the pregnancy at less than 24 weeks and of standard postnatal treatment

9. The family meets psychosocial criteria (sufficient social support, ability to understand the requirements of the study)

10. Parental/guardian permission (informed consent) for follow up of the child after birth

    • Significant associated anomalies are defined as such anomalies that would, in and of themselves, be life limiting or life threatening. A minor anomaly, such as a small VSD or ASD not deemed to be life limiting or threatening, or a cleft lip or other such anomaly, unless part of a genetic syndrome, will not disqualify the patient.

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Exclusion Criteria

1. Significant fetal anomaly unrelated to gastroschisis
2. Evidence of bowel perforation (presence of intraabdominal bowel calcification on ultrasonography)
3. Increased risk for preterm labor including short cervical length (≤ 2.0 cm), history of incompetent cervix with or without cerclage, and previous preterm birth in a singleton pregnancy (other than a patient delivered for a non-repeating medical or surgical indication)
4. Placental abnormalities (previa, abruption, accreta) known at time of enrollment
5. Pre-pregnancy body-mass index (BMI) ≥40
6. Contraindications to surgery including previous hysterotomy (whether from a previous classical cesarean, uterine anomaly such as an arcuate or bicornuate uterus, major myomectomy resection, or previous fetal surgery) in active uterine segment
7. Technical limitations precluding fetoscopic surgery, such as extensive uterine fibroids, fetal membrane separation, or uterine anomalies
8. Maternal-fetal Rh alloimmunization, Kell sensitization, or neonatal alloimmune thrombocytopenia affecting the current pregnancy.
9. 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
10. Maternal medical condition that is a contraindication to surgery or general anesthesia
11. Low amniotic fluid volume (Amniotic Fluid Index less than 6 cm) if deemed to be due to fetal anomaly, poor placental perfusion or function, or membrane rupture. Low amniotic fluid volume that responds to maternal hydration is not an exclusion criterion
12. Patient does not have a support person (i.e., spouse, partner, or mother) available to support her for the duration of the pregnancy
13. Inability to comply with the travel and follow-up requirements of the trial
14. Patient scores as severely depressed on the Edinburgh Postnatal Depression Scale (EPDS)
15. Patients that are enrolled or have been enrolled in any another intervention study that affects the mother or fetus
16. Maternal hypersensitivity to any of the entities associated w/ AlloDerm™. The use of AlloDerm™ Regenerative Tissue Matrix distributed by Allergan Aesthetics is contraindicated for patients sensitive to any of the antibiotics listed on the AlloDerm package, i.e., Gentamycin, Cefoxitin, Lincomycin, Polymyxin B and Vancomycin or Polysorbate 20

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
fetoscopic surgical repair	fetoscopy	Single arm study. All patients will receive the fetoscopic repair.

Primary Outcome Measures

Name	Time	Method
Successful Repair of Complex Gastroschisis	At end of surgical repair	Success of primary skin closure after complete bowel reduction.

Secondary Outcome Measures

Name	Time	Method
Respiratory Distress Syndrome	At the time of discharge from the NICU, an average of 1.5 months	As measured by presence in medical record
Time to initiation of enteral feeds (days)	At hospital discharge, an average of 1.5 months	The number of days until initiation of enteral feeding
Preterm Birth	At delivery	Number of patients that deliver at \< 37 weeks gestation
Time on total parenteral nutrition (TPN) (days)	At hospital discharge, an average of 1.5 months	The number of days on total parenteral nutrition (TPN)
Intracranial hemorrhage	During first month of life	Measured as presence in neonate during first month by MRI and/or ultrasound.
Intrauterine Fetal Death (IUFD)	At delivery	Demise of fetus while still in the womb
Necrotizing Enterocolitis	At hospital discharge, an average of 1.5 months	As measured by presence in medical record
Central Line Associated Bloodstream Infection (CLABSI)	12 months of age	As measured by presence in medical record ≤12 months
Survival at 12 months	12 months of age	Number of patients alive at 12 months of age
Short Bowel Syndrome	At hospital discharge, an average of 1.5 months	As measured by presence in medical record
Length of Hospital Stay	At the time of discharge from the NICU, an average of 1.5 months	Length of stay in the hospital measured in days
Retinopathy of Prematurity	At the time of discharge from the NICU, an average of 1.5 months	Postnatal grade classification presence of grade III or higher using standardized system (yes/no)
Bronchopulmonary Dysplasia	At the time of discharge from the NICU, an average of 1.5 months	As measured by presence in medical record
Need for Gastroschisis related surgery	12 months of age	As measured by presence in medical record ≤12 months
Neuro-developmental Outcome at 12 months	12 months of age	As measured by the Capute Scales at 12 months
Small Bowel Obstruction	12 months of age	As measured by presence in medical record ≤12 months

Trial Locations

Locations (1)

Texas Children's Hospital; 🇺🇸 Houston, Texas, United States