Gastroschisis Outcomes of Delivery (GOOD) Study

Gastroschisis Clinical Trial

Official title:

Gastroschisis Outcomes of Delivery (GOOD) Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02774746
• Other study ID #: 898740-1
• Status: Recruiting
• Phase: Phase 3
• Start date: February 23, 2018
• Est. completion date: March 31, 2027

Study information

• Verified date: May 2024
• Source: Medical College of Wisconsin
• Contact: Maddie Rundell, BS
• Phone: 414-337-7032
• Email: mrundell[@]childrenswi.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 800
• Est. completion date: March 31, 2027
• Est. primary completion date: March 31, 2027
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Gastroschisis

Intervention

Other:
• 35-week delivery
Induction at 35 weeks gestational age
• 38-week delivery
Observation to spontaneous delivery or induction at 38 weeks gestational age

Locations

Country	Name	City	State
United States	CS Mott Children's & Von Voigtlander Women's Hospital, Michigan Medicine	Ann Arbor	Michigan
United States	Emory University	Atlanta	Georgia
United States	Children's Hospital of Colorado	Aurora	Colorado
United States	Johns Hopkins Hospital	Baltimore	Maryland
United States	University of Maryland, Baltimore	Baltimore	Maryland
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Brigham and Women's Hospital & Boston Children's Hospital	Boston	Massachusetts
United States	University of North Carolina Hospitals	Chapel Hill	North Carolina
United States	University of Virginia	Charlottesville	Virginia
United States	Ann & Robert H. Lurie Children's Hospital of Chicago	Chicago	Illinois
United States	Cleveland Clinic	Cleveland	Ohio
United States	Cook Children's Medical Center	Fort Worth	Texas
United States	Connecticut Children's Medical Center	Hartford	Connecticut
United States	The University of Texas Health Science Center at Houston	Houston	Texas
United States	The Woman's Hospital of Texas / Obstetrix Maternal-Fetal Medicine Specialists of Houston	Houston	Texas
United States	Riley Children's Hospital	Indianapolis	Indiana
United States	Children's Mercy Hospital	Kansas City	Missouri
United States	Loma Linda University Children's Hospital	Loma Linda	California
United States	Norton Healthcare, Inc.	Louisville	Kentucky
United States	Medical College of Wisconsin & Children's Wisconsin	Milwaukee	Wisconsin
United States	Children's MN, Midwest Fetal Care Center	Minneapolis	Minnesota
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Columbia University Irving Medical Center	New York	New York
United States	New York Presbyterian - Weill Cornell Medicine	New York	New York
United States	OSF St. Francis Medical Center	Peoria	Illinois
United States	Phoenix Children's Hospital	Phoenix	Arizona
United States	Oregon Health and Science University	Portland	Oregon
United States	Women & Infants Hospital/Rhode Island Hospital (Hasbro Children's)	Providence	Rhode Island
United States	University of Rochester Medical Center	Rochester	New York
United States	St. Louis University, SSM Health Cardinal Glennon Children's Hospital & SSM Health St. Mary's Hospital	Saint Louis	Missouri
United States	Washington University in St. Louis & St. Louis Children's Hospital	Saint Louis	Missouri
United States	University of Utah & Primary Children's Hospital	Salt Lake City	Utah
United States	Christus Children's / Baylor College of Medicine	San Antonio	Texas
United States	Lucile Packard Children's Hospital Stanford	Stanford	California
United States	University of South Florida & Tampa General Hospital	Tampa	Florida
United States	Nemours Children's Hospital, Delaware	Wilmington	Delaware

Sponsors (1)

Lead Sponsor	Collaborator
Medical College of Wisconsin

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	The primary outcome is the weighted composite endpoint combining the following five clinical risks: intrauterine fetal demise, neonatal death prior to NICU discharge, sepsis, respiratory morbidity, and gastrointestinal morbidity. Mortality (intrauterine or neonatal death) will be considered an exclusive event.; The composite endpoint score for each subject will be computed as the sum of the weights corresponding to the events observed in the subject. The mean composite score will be compared between groups as defined by the ITT population using a two-sided test at a 4.58% nominal significance level. The nominal significance level will be adjusted based on the timing of the interim analysis if different from the original plan. This test is asymptotically equivalent to a t-test performed on the composite endpoint score. We will report the estimated difference in the weighted endpoint score along with the estimated confidence interval using the nominal significance level.	NICU Discharge