Fetal Repair of Complex Gastroschisis: A Safety and Feasibility Trial

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.

Study Overview

• Status: Recruiting
• Conditions: Gastroschisis
• Intervention / Treatment: Device: fetoscopy

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 Type: Interventional
• Enrollment (Estimated): 10
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Becky Johnson; Phone Number: 832-826-7451; Email: rj2@bcm.edu
• Study Contact Backup: Name: Sundeep Keswani, MD; Phone Number: 832-824-0462; Email: sgkeswan@texaschildrens.org

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • Texas Children's Hospital
      • Sub-Investigator: Roopali Donepudi, MD
      • Contact: Becky Johnson; Phone Number: 832-826-7451; Email: rj2@bcm.edu
      • Sub-Investigator: Luc Joyeux, MD, PhD
      • Contact: Sundeep Keswani, MD
      • Sub-Investigator: Michael A Belfort, MD, PhD
      • Sub-Investigator: Larry Hollier Jr., MD
      • Sub-Investigator: Timothy Lee, MD
      • Sub-Investigator: Alice King, MD
      • Sub-Investigator: Magdalena Sanz Cortes, MD, PhD
      • Sub-Investigator: Ahmed Nassr, MD, PhD
      • Sub-Investigator: Jonathan Castillo Porter, MD, MPH
      • Sub-Investigator: Caitlin Sutton, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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. 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.

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Device Feasibility
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: fetoscopic surgical repair; Single arm study. All patients will receive the fetoscopic repair.	Device: fetoscopy; The fetoscopic arm is described above. All patients will have a laparotomy, exteriorization of the uterus, and a fetoscopic repair of the gastroschisis.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Successful Repair of Complex Gastroschisis	Success of primary skin closure after complete bowel reduction.	At end of surgical repair

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Baylor College of Medicine
• Investigators: Principal Investigator: Sundeep Keswani, MD, Baylor College of Medicine and Texas Children's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): October 20, 2023
• Primary Completion (Estimated): December 1, 2029
• Study Completion (Estimated): December 1, 2029

Study Registration Dates

• First Submitted: January 3, 2023
• First Submitted That Met QC Criteria: January 20, 2023
• First Posted (Actual): January 30, 2023

Study Record Updates

• Last Update Posted (Actual): November 7, 2023
• Last Update Submitted That Met QC Criteria: November 3, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Gastroschisis; Abdominal Wall Defect
• Additional Relevant MeSH Terms: Congenital Abnormalities; Musculoskeletal Diseases; Pathological Conditions, Anatomical; Hernia, Abdominal; Musculoskeletal Abnormalities; Hernia; Gastroschisis
• Other Study ID Numbers: H-51929

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes