Clinical trial NCT02774746: Gastroschisis Outcomes of Delivery (GOOD) Study
Official title: Gastroschisis Outcomes of Delivery (GOOD) Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Gastroschisis
Lead sponsor: Medical College of Wisconsin
Sponsor class: OTHER
First posted: 2016-05-17
Enrollment: 800
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The objective of this study is to investigate the hypothesis that delivery at 35 0/7- 35 6/7 weeks in stable patients with gastroschisis is superior to observation and expectant management with a goal of delivery at 38 0/7 - 38 6/7 weeks. To test this hypothesis, we will complete a randomized, prospective, multi-institutional trial across NAFTNet-affiliated institutions. Patients may be enrolled in the study any time prior to 33 weeks, but will be randomized at 33 weeks to delivery at 35 weeks or observation with a goal of 38 weeks. The primary composite outcome will include stillbirth, neonatal death prior to discharge, respiratory morbidity, and need for parenteral nutrition at 30 days.

Detailed description: Gastroschisis is the most common congenital abdominal wall abnormality in which the intestines are outside of body floating in the amniotic fluid. This is diagnosed by prenatal ultrasound at 18-20 weeks gestation. Gastroschisis occurs in 1 out of every 4000 births and the incidence is increasing. The majority of patients with gastroschisis have an uncomplicated neonatal course and recover well after surgical repair. However, subsets of gastroschisis patients have more complicated courses due to loss of intestine or blockages of the intestine These infants have a higher risk of death and long-term morbidity. Additionally, gastroschisis patients have an increased risk of in-utero fetal demise or stillbirth.

The potential risk of pregnancy loss late in the third trimester has prompted some physicians to deliver gastroschisis patients prior to term. This results in an increased chance of additional prematurity-related complications. There is no consensus about the ideal time to deliver a baby with gastroschisis and practice patterns vary widely. It is unclear which offers the fetus a chance at a better outcome: early delivery to mitigate risk of stillbirth and intestinal injury versus delivery closer to term.

Retrospective data published show inconsistent results on outcomes with early delivery or later gestational age delivery in gastroschisis. There have been two randomized, prospective trials with delivery early versus awaiting spontaneous labor. The first included 42 patients rendering the study largely underpowered. There was a trend towards decreased length of hospital stay and earlier time to full enteral feeding in the early delivery group, but this did not reach statistical significance. The latest study was stopped early because of futility and an increased risk of sepsis in the early group. There was no increase in sepsis in the early group in the first trial, and the study design of this trial varies greatly from both studies.

Standard delivery times for uncomplicated gastroschisis are between 34 and 39 weeks gestation. As the current available literature does not adequately answer the question of optimal gestational age of delivery in patients with gastroschisis, the objective of this study is to investigate the hypothesis that delivery at 35 0/7 - 35 6/7 weeks in stable patients with gastroschisis is superior to observation and expectant management with a goal of delivery at 38 0/7 - 38 6/7 weeks. To test this hypothesis, we will complete a randomized, prospective, multi-institutional trial. Patients may be enrolled in the study any time prior to 33 weeks but will be randomized at 33 weeks to delivery at 35 weeks or observation with a goal of 38 weeks. The primary outcome will be based on a weighted composite comprised of intrauterine fetal demise, neonatal/infant death prior to discharge, respiratory morbidity, gastrointestinal morbidity, and sepsis. We will compare the rates of the composite outcome as well as the individual components to determine whether a significant difference between the two strategies can be detected. Secondary maternal outcomes include need for labor induction, need for cesarean section, and complications of delivery including infection, blood transfusions, and thromboembolic events. We will also evaluate antenatal test values, such as amniotic fluid index, estimated fetal weight, and intra- and extra-abdominal bowel dilation. Secondary neonatal outcomes include birth and discharge weight, central venous catheter days, sepsis, intestinal atresia, necrotizing enterocolitis, time to enteral autonomy, individual components of respiratory morbidity, need for caffeine, and length of stay.

Given the unprecedented patient data being collected for the randomized trial, we plan to leverage the infrastructure built for this study to generate the largest prospective, multicenter database of gastroschisis-related (maternal, fetal, and neonatal) outcomes in the United States. The database will provide data for future development of both hypotheses and study design regarding gastroschisis-related outcomes. The associated biobank will collect blood from the neonatal participants to be stored and analyzed in future research.

Eligibility criteria: Inclusion criteria:

To be eligible for study inclusion, subjects are required to meet the following criteria:

1. Speak English or Spanish
2. Age of ≥18 years old
3. Have a diagnosis of an isolated fetal gastroschisis confirmed via sonogram at ≤33 weeks gestation
4. Have a singleton pregnancy
5. Capable of providing written informed consent for study participation
6. Established Estimated Date of Confinement (EDC) prior to 22 0/7 weeks GA by last menstrual period (LMP) with ultrasound confirmation or ultrasound dating when LMP is unknown.

Exclusion criteria:

Subjects will be excluded from enrollment for any of the following criteria

1. Fetal anomaly unrelated to gastroschisis, such as a chromosomal abnormality or another congenital structural abnormality (if known; no additional testing required for research participation)
2. Severe intrauterine growth restriction / fetal growth restriction (defined as growth below the 5th percentile for gestational age)
3. Maternal history of previous stillbirth (intrauterine fetal demise)
4. Maternal history of spontaneous preterm (\<36 weeks) delivery
5. Maternal cervical length \< 25 mm prior to 24 weeks of gestation if documented
6. Maternal hypertension
7. Maternal insulin-dependent diabetes
8. Prenatal care initiated after 24 weeks of gestation
9. An active case of COVID-19 (confirmed by a positive test for COVID-19) that is not recovered (confirmed by a negative test for COVID-19) by the date of randomization
10. Unstable pregnancy defined as meeting any of the following criteria

    1. Abnormal amniotic fluid volume defined as oligohydramnios or polyhydramnios where the maximal vertical pocket (MVP) is \< 2 cm or \> 8 cm in the third trimester, respectively
    2. Umbilical artery Dopplers with S/D ratio or resistive index (RI) \> 97th percentile for age with or without absent or reversed end diastolic flow
    3. Non-stress test (NST) or biophysical profile (BPP) deemed non-reassuring by treating clinician
11. Concurrent enrollment in another study that requires either a treatment or intervention which would either alter the delivery plan or potentially influence the maternal, fetal, and neonatal outcomes of this study
12. Traditional surrogacy, gestational surrogacy, gestational carrier, or gestational surrogate
13. Incapable of providing informed consent
14. Are not their own legally authorized representative.

Primary outcomes:
measure: Comparison of the proportion of the primary weighted composite outcome (occurrence of any of the 5 clinical risks: IUFD, neonatal death, respiratory morbidity, GI morbidity, and sepsis) between groups as estimated from the ITT population.
timeFrame: NICU Discharge
Secondary outcomes:
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Phoenix Children's Hospital
state: Arizona
city: Loma Linda
country: United States
facility: Loma Linda University Children's Hospital
state: California
city: Stanford
country: United States
facility: Lucile Packard Children's Hospital Stanford
state: California
city: Aurora
country: United States
facility: Children's Hospital of Colorado
state: Colorado
city: Hartford
country: United States
facility: Connecticut Children's Medical Center
state: Connecticut
city: Wilmington
country: United States
facility: Nemours Children's Hospital, Delaware
state: Delaware
city: Tampa
country: United States
facility: University of South Florida & Tampa General Hospital
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Chicago
country: United States
facility: Ann & Robert H. Lurie Children's Hospital of Chicago
state: Illinois
city: Peoria
country: United States
facility: OSF St. Francis Medical Center
state: Illinois
city: Indianapolis
country: United States
facility: Riley Children's Hospital
state: Indiana
city: Lousiville
country: United States
facility: Norton Healthcare, Inc.
state: Kentucky
city: Baltimore
country: United States
facility: University of Maryland, Baltimore
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins Hospital
state: Maryland
city: Boston
country: United States
facility: Brigham and Women's Hospital & Boston Children's Hospital
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Ann Arbor
country: United States
facility: CS Mott Children's & Von Voigtlander Women's Hospital, Michigan Medicine
state: Michigan
city: Minneapolis
country: United States
facility: Children's MN, Midwest Fetal Care Center
state: Minnesota
city: Kansas City
country: United States
facility: Children's Mercy Hospital
state: Missouri
city: Saint Louis
country: United States
facility: St. Louis University, SSM Health Cardinal Glennon Children's Hospital & SSM Health St. Mary's Hospital
state: Missouri
city: Saint Louis
country: United States
facility: Washington University in St. Louis & St. Louis Children's Hospital
state: Missouri
city: New York
country: United States
facility: Columbia University Irving Medical Center
state: New York
city: New York
country: United States
facility: New York Presbyterian - Weill Cornell Medicine
state: New York
city: Rochester
country: United States
facility: University of Rochester Medical Center
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina Hospitals
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Providence
country: United States
facility: Women & Infants Hospital/Rhode Island Hospital (Hasbro Children's)
state: Rhode Island
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Fort Worth
country: United States
facility: Cook Children's Medical Center
state: Texas
city: Houston
country: United States
facility: The University of Texas Health Science Center at Houston
state: Texas
city: Houston
country: United States
facility: The Woman's Hospital of Texas / Obstetrix Maternal-Fetal Medicine Specialists of Houston
state: Texas
city: San Antonio
country: United States
facility: Christus Children's / Baylor College of Medicine
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah & Primary Children's Hospital
state: Utah
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
city: Madison
country: United States
facility: University of Wisconsin - Madison
state: Wisconsin
city: Milwaukee
country: United States
facility: Medical College of Wisconsin & Children's Wisconsin
state: Wisconsin
Study officials:
affiliation: Medical College of Wisconsin
name: Amy Wagner, MD
role: PRINCIPAL_INVESTIGATOR
References: