Evaluation of Glycerin Suppositories to Improve Bowel Function in Gastroschisis

September 15, 2021 updated by: Alan P. Ladd, Indiana University

Evaluation of Routine Administration of Glycerin Suppositories to Improve Bowel Function in Patients With Uncomplicated Gastroschisis

Gastroschisis is a congenital defect of the abdominal wall that leads to evisceration of various amounts of the abdominal organs. The mainstay of therapy is restoring continuity of the abdominal wall, either through primary closure or with a synthetic graft when primary closure is not feasible.

It has been established that bowel function after repair of gastroschisis is impaired due to the aforementioned pathological processes. Previous studies have shown that the time from surgery to attaining full nutrition through enteral means is a predictor for morbidity in this population. Therefore, numerous therapeutic interventions have been proposed to help hasten bowel function and decrease the time to tolerance of total enteral nutrition. A common, but unproven, technique is the use of glycerin suppositories to stimulate bowel function. The concept of glycerin suppositories is that stimulating colonic activity through the use of the suppository will stimulate small intestinal function. The underlying concept is that improved bowel motility and reduced time to full enteral feeds will reduce the morbidity associated with this disease. While the formation/evacuation of stools is most easily monitored, the main purpose of using these suppositories is to hasten tolerance of nutrition through enteral means.

While the practice of using glycerin suppositories is common in neonates, there is no literature or best-practice guidelines advocating for (or against) their use. A single previous prospective study utilizing glycerin suppositories in premature, low birth weight neonates failed to show any benefit in improving time to tolerate full enteral feeds. At this time, this is the only study investigating the use of glycerin suppositories in any neonatal population, and due to the indications (i.e. premature and low birth weight infants without surgical disease), the findings are not applicable to neonates with gastroschisis. To the authors' knowledge, there are no previous studies or current ongoing studies examining this question. Given this lack of information regarding the efficacy of glycerin suppositories, there is a significant variation in practice among practicing surgeons, including timing of initial administration, frequency of use, and indication to discontinue. Indeed the spectrum ranges from some surgeons who never use glycerin suppositories, to some who prescribe them daily for all gastroschisis patients immediately following surgery.

The purpose of this study will be to determine whether routine use of glycerin suppositories improves bowel function as measured by time to full enteral feeds (primary outcome: defined as enteral feed volume >120mL/kg/day with appropriate weight gain (20-30g/day for two consecutive days)) in neonates with uncomplicated gastroschisis after complete reduction of abdominal viscera. Secondary outcomes include time to first bowel movement and incidence/severity of TPN-induced cholestasis in the study groups.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

Gastroschisis is a congenital defect of the abdominal wall that leads to evisceration of various amounts of the abdominal organs. The mainstay of therapy is restoring continuity of the abdominal wall, either through primary closure or with a synthetic graft when primary closure is not feasible. Closure of the abdominal cavity is confounded by prenatal loss of abdominal domain coupled by resultant swelling of the abdominal viscera due to prenatal exposure to amniotic fluid. Additionally, some patients with gastroschisis have other concomitant abnormalities of the bowel (termed complicated gastroschisis) that require additional surgical intervention.

It has been established that bowel function after repair of gastroschisis is impaired due to the aforementioned pathological processes. Previous studies have shown that the time from surgery to attaining full nutrition through enteral means is a predictor for morbidity in this population. Therefore, numerous therapeutic interventions have been proposed to help hasten bowel function and decrease the time to tolerance of total enteral nutrition. A common, but unproven, technique is the use of glycerin suppositories to stimulate bowel function. The concept of glycerin suppositories is that stimulating colonic activity through the use of the suppository will stimulate small intestinal function. The underlying concept is that improved bowel motility and reduced time to full enteral feeds will reduce the morbidity associated with this disease. While the formation/evacuation of stools is most easily monitored, the main purpose of using these suppositories is to hasten tolerance of nutrition through enteral means.

While the practice of using glycerin suppositories is common in neonates, there is no literature or best-practice guidelines advocating for (or against) their use. A single previous prospective study utilizing glycerin suppositories in premature, low birth weight neonates failed to show any benefit in improving time to tolerate full enteral feeds. At this time, this is the only study investigating the use of glycerin suppositories in any neonatal population, and due to the indications (i.e. premature and low birth weight infants without surgical disease), the findings are not applicable to neonates with gastroschisis. To the authors' knowledge, there are no previous studies or current ongoing studies examining this question. Given this lack of information regarding the efficacy of glycerin suppositories, there is a significant variation in practice among practicing surgeons, including timing of initial administration, frequency of use, and indication to discontinue. Indeed the spectrum ranges from some surgeons who never use glycerin suppositories, to some who prescribe them daily for all gastroschisis patients immediately following surgery.

The purpose of this study will be to determine whether routine use of glycerin suppositories improves bowel function as measured by time to full enteral feeds (primary outcome: defined as enteral feed volume >120mL/kg/day with appropriate weight gain (20-30g/day for two consecutive days)) in neonates with uncomplicated gastroschisis after complete reduction of abdominal viscera. Secondary outcomes include time to first bowel movement and incidence/severity of TPN-induced cholestasis in the study groups.

Individuals will be followed from the time of consultation by the Pediatric General Surgery service (i.e. at the time of birth) until initial discharge. Neonates undergo abdominal wall closure and reach full nutrition (via either full enteral, total parenteral nutrition, or a combination of both) prior to discharge.

Patients will approached by a study coordinator (Daisy Nunez or Robert Vandewalle) regarding enrollment, which will occur on the day of, or prior to completion of surgical intervention. Randomization into treatment/control arm, utilizing a block technique, will occur after completion of surgical intervention. While the operating surgeon will technically be unaware of the treatment arm of the patient at the time of surgery, neither the medical staff, study participants/families, or study staff be blinded for this study.

After closure of the abdominal wall children will be cared for according to the same standards used in previous/non-trial patients. The only exception is that the control-group patients will not be allowed to be administered glycerin suppositories at anytime and the treatment- group will receive glycerin suppositories (based upon previously established institutional pharmacy dosing protocols) from the first day after abdominal wall closure until they reach full enteral feeds (as defined as 120mL/kg/d with appropriate weight gain) which will be determined by the surgeon of record. Initiation and advancement of enteral feeds will be based upon on protocol developed for this study and agreed upon the study surgeons, who are responsible for nutritional management of these patients (see attached feeding protocol). Signs of feeding intolerance are outline in the attached feeding protocol. Additional metrics will be recorded in the study data sheet (see attached data collection sheet) this information is routinely collected as a part of normal care for patients with gastroschisis but otherwise no additional interventions will be a part of the study protocol. Because the most common morbidities associated with gastroschisis center on infectious complications and those related to prolonged parenteral nutrition, general indicators for these complications (i.e. laboratory and clinical variables) will be recorded as well.

The electronic patient chart will be reviewed on each patient each weekday of the patient's hospital admission (i.e. real time data collection) and the surgery team/study coordinator will contact the attending of record and/or nursing staff for clarification of any missing data. Both study coordinators will review the dataset independently on a weekly basis to help ensure fidelity of the database and data will be backed up on a twice a week basis.

No additional intervention, interaction, or follow up will be completed after the neonate is discharged from their initial admission as part of this study.

Identified barriers to enrollment included timing of delivery/transfer to Riley Hospital for proper enrollment. This will be addressed by the investigators reviewing the general surgery census list on a daily basis to identify patients early and provide time for patient/family consideration for enrollment. Additional enrollment barriers include language barriers which will be addressed with interpreter requests when available and translator phone when live interpreters are not available and/or not feasible.

Study Type

Interventional

Enrollment (Actual)

16

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Riley Hospital for Children

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 day to 1 year (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Diagnosis of uncomplicated gastroschisis
  • Gestational age >33 weeks at time of delivery
  • Weight >1900g at time of delivery
  • Transfer of patient to Riley Hospital for Children prior to any abdominal surgery

Exclusion Criteria:

  • Neurological Congenital malformations and/or those known to impair intestinal motility
  • Additional congenital gastrointestinal abnormalities requiring surgical intervention
  • Congenital Cyanotic heart disease
  • Surgical Closure of abdominal wall defect with prosthetic material (e.g. prosthetic or bio-prosthetic mesh)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Glycerin Suppository Group
Glycerin suppository is given once daily beginning after conditions described are met and continued until discontinue conditions are met.
No Intervention: Non-suppository Group

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time to Full Enteral Feeds
Time Frame: 2 months
time from study start time to goal full feeds by enteral route (per oral (PO), orogastric (OG), gastrostomy tube (gtube)).
2 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time to First Bowel Movement
Time Frame: 1 month
time from study start time after closure to first bowel movement
1 month
Hospital Length of Stay
Time Frame: ~3 months
time from admission (birth) to hospital discharge
~3 months
Days on Total Parenteral Nutrition (TPN)
Time Frame: 2 months
total time that patient required Total Parenteral Nutrition (TPN) feeds
2 months
Number of Participants With Sequela of Long Term Total Parenteral Nutrition (TPN) Administration
Time Frame: ~3 months
Any complications related to TPN administration, including TPN-induced cholestasis and hyperbilirubinemia
~3 months
Number of Participants With Infectious Complications
Time Frame: ~3 months
Any complications related to infections during the admission after start of study; these include infections such as line infections, wound infections, pneumonia, and urinary tract infection (UTI)
~3 months
Number of Participants With Post-operative Complications
Time Frame: ~3 months
Any complications during the admission after start of study; these include anything including infections, necrotizing enterocolitis (NEC), small bowel obstruction (SBO), and Total Parenteral Nutrition (TPN)-induced cholestasis.
~3 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Alan Ladd, M.D., Program Director, Department of General Surgery, Divison of Pediatric Surgery

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 1, 2017

Primary Completion (Actual)

October 1, 2020

Study Completion (Actual)

October 1, 2020

Study Registration Dates

First Submitted

October 24, 2017

First Submitted That Met QC Criteria

November 27, 2017

First Posted (Actual)

November 28, 2017

Study Record Updates

Last Update Posted (Actual)

October 12, 2021

Last Update Submitted That Met QC Criteria

September 15, 2021

Last Verified

September 1, 2021

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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