Clinical trial NCT03355326
Conditions: Gastroschisis
Sponsor: Indiana University
Start date: 2017-10-01; Completion date: 2020-10-01
Enrollment: 16 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
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.

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.

Arms: arm 1: None arm 2: None
Interventions: intervention 1: Glycerin Suppository
Intervention descriptions: intervention 1: Glycerin suppository is given once daily beginning after conditions described are met and continued until discontinue conditions are met.

Protocol documents:
ICF_001.pdf: 
 
 
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INDIANA UNIVERSITY INFORMED CONSENT STATEMENT FOR 
 
Evaluation of Routine Administration of Glycerin Suppositories to Improve Bowel Function in 
Patients with Uncomplicated Gastroschisis 
 
 
 
Your child is invited to participate in a research study evaluating glycerin suppositories in treatment of children 
with gastroschisis.  He/she was selected as a possible subject because of this diagnosis.  The pediatric general 
surgery team at Riley Children’s Hospital is responsible for this study and is involved in the care of all neonates 
with this problem.  Please read this form and ask any questions you may have before agreeing to be in the study.  
 
The study is being led by Dr. Alan Ladd with the help of the rest of the pediatric general surgeons at Riley 
Children’s Hospital (Drs. Billmire, Burns, Gray, Landman, Markel, Rescorla, and Rouse).  It is internally funded 
by these physicians and the Indiana University School of Medicine Department of Surgery, Division of Pediatric 
General Surgery.  
 
 
STUDY PURPOSE 
 
Glycerin suppositories are often used in children with gastroschisis after abdominal wall closure with the goal of 
improving function of the intestines and decreasing the time it takes to start enteral feeds (i.e. using the intestines 
to absorb nutrition) and the time to reach goal feed volumes (i.e. the amount needed for your baby to grow 
appropriately).  Reducing this time has been shown to improve outcomes in babies with gastroschisis.  However, 
it is not known if using glycerin suppositories actually helps decrease this time.  The purpose of this study is to 
determine whether routine use of glycerin suppositories improves bowel function as measured by the time to first 
bowel movement after abdominal closure and time to full enteral feeds.   
 
 
NUMBER OF PEOPLE TAKING PART IN THE STUDY 
 
If you agree, your child will be one of approximately seventy subjects who will be participating in this research.  
One half of the patients will have a glycerin suppository administered daily beginning the day after their final 
surgery for gastroschisis, the other half will receive no glycerin suppositories at any point during their treatment.  
These two groups will then be compared based upon the factors mentioned above.  Your participation in this 
study will complete at the time of initial discharge from the hospital. 
 
 
PROCEDURES FOR THE STUDY 
 
If you agree to be in the study, you will do the following things: 
 
Your child will be randomly assigned to either receive daily glycerin suppositories as part of their treatment or 
receive no glycerin suppositories as part of their treatment. Suppository administration will begin the day after 
their final surgery until the day all needed nutrition is provided by breast milk and/or formula. The choice 
between breastmilk or formula will be left up to you/your child’s caretakers.  Additionally, a standard protocol for 
advancing feeds in babies with gastroschisis will be used.  This protocol has been approved for this study by all of 
the pediatric general surgeons at Riley Hospital for Children.  There will be no additional alterations in the 
treatment of your child compared to children with gastroschisis not involved in this study.    
 
 
RISKS OF TAKING PART IN THE STUDY 
 
While on the study, the risks, and side effects are: 
 


 
 
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-Injury to the rectum/large intestines while giving a suppository (while this has never occurred at Riley, it is a 
possible risk) 
-Discomfort with suppository administration and/irritation to the intestines and surrounding skin with 
administration of the glycerin suppositories 
 
-In premature neonates, necrotizing enterocolitis (a disease that causes lack of blood flow and injury to the 
intestines) has been reported after receiving glycerin suppositories.  Premature neonates are at increased risk for 
necrotizing enterocolitis and no study has definitively linked suppositories to an increased risk of necrotizing 
enterocolitis in this population.  This study will not include premature neonates and necroziting enterocolitis has 
not been reported in term neonates after receiving glycerin suppositories, but a possible increased risk cannot be 
excluded.  Necrotizing enterocolitis is higly variable disease process; ranging from clinically insignificant to fatal 
disease. 
 
-Loss of confidentiality with resultant difficulties in obtaining insurance and/or social/psychological stress to the 
patient and/or family 
 
-There also may be other side effects that we cannot predict.  
 
 
Measures that will be employed to minimize the risks and side effects listed above: 
 
-All infants with gastroschisis are already monitored for signs of necrotizing enterocolitis.  Any signs of 
enterocolitis (abdominal distention with associated fever/leukocytosis/other signs of infection) prompt additional 
work up.  Any child diagnosed with necrotizing enterocolitis will be removed from the study protocol (i.e. 
glycerin suppositories will be stopped if in treatment group) and treatment of necrotizing enterocolitis will begin.   
 
-While the possibility of rectal perforation/injury during administration of glycerin suppositories is possible, this 
has not been reported in the literature or occurred at our institution in children with gastroschisis.  Nurses will be 
instructed to notify the research coordinator/surgery team if any significant rectal bleeding occurs during/after 
administration or if difficulty placing the suppository is noted.  At that time it will be determined by the research 
team if the patient administration should be stopped (the patient will be removed from the study/protocol). 
 
-Social/legal: All information will be de-identified as early as possible within the data acquisition period (i.e. 
removal of medical record numbers, date of birth, date of admission, etc.) 
 
 
BENEFITS OF TAKING PART IN THE STUDY 
 
The benefits to participation that are reasonable to expect are: 
 
-If your child receives glycerin suppositories and this proves to be beneficial, they will have a proven decreased 
risk of problems during the hospitalization. 
 
-Your child will be aiding in the improved treatment of future children with gastroschisis regardless of the treatment 
group they are assigned. 
 
 
ALTERNATIVES TO TAKING PART IN THE STUDY 
 
Instead of being in the study, you have these options:   
 
-You may choose to not participate in this study and have your child’s feeding regimen and administration of 
glycerin suppositories determined by your personal surgeon. 
 
 
 


 
 
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CONFIDENTIALITY 
 
Efforts will be made to keep your personal information confidential.  We cannot guarantee absolute 
confidentiality.  Your personal information may be disclosed if required by law.  Your identity will be held in 
confidence in reports in which the study may be published and databases in which results may be stored.   
 
Organizations that may inspect and/or copy your research records for quality assurance and data analysis include 
groups such as the study investigator and his/her research associates, the Indiana University Institutional Review 
Board or its designees, and (as allowed by law) state or federal agencies, specifically the Food and Drug 
Administration (FDA) who may need to access your medical and/or research records. 
 
A description of this clinical trial will be available on ClinicalTrials.gov, as required by U.S. law. This website 
will not include information that can identify you. At most, the website will include a summary of the results. You 
can search this website at any time.  
 
WILL MY INFORMATION BE USED FOR RESEARCH IN THE FUTURE? 
 
Information collected from you for this study may be used for future research studies or shared with other 
researchers for future research.  If this happens, information which could identify you will be removed before any 
information is shared.  Since identifying information will be removed, we will not ask for your additional consent. 
 
COSTS 
 
Taking part in this study may lead to added costs to you or your insurance company.  You or your insurance 
company will be responsible for the following costs:   
 
-Potential increased cost related to medications.  No additional laboratory studies or additional analysis/work up 
will be necessary. 
 
PAYMENT 
 
You will not receive payment for taking part in this study.   
 
COMPENSATION FOR INJURY 
 
In the event of physical injury resulting from your participation in this research, necessary medical treatment will 
be provided to you and billed as part of your medical expenses.  Costs not covered by your health care insurer will 
be your responsibility.  Also, it is your responsibility to determine the extent of your health care coverage.  There 
is no program in place for other monetary compensation for such injuries.  However, you are not giving up any 
legal rights or benefits to which you are otherwise entitled.  If you are participating in research that is not 
conducted at a medical facility, you will be responsible for seeking medical care and for the expenses associated 
with any care received.   
 
FINANCIAL INTEREST DISCLOSURE 
 
None of the research personnel have financial interests.  
 
CONTACTS FOR QUESTIONS OR PROBLEMS 
 
For questions about the study or a research-related injury, contact a research member  at 317-274-4681.  If you 
cannot reach the researcher during regular business hours (i.e., 8 a.m.  to 5 p.m.), please call the IU Human 
Subjects Office at 317-278-3458 or 800-696-2949.  After business hours, please call the Riley Hospital for 
Children Surgeon’s Office 317-944-5000 and ask for the pediatric surgeon on-call. 
 
 


 
 
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For questions about your rights as a research participant, to discuss problems, complaints, or concerns about a 
research study, or to obtain information or offer input, contact the IU Human Subjects Office at 317-278-3458 or 
800-696-2949. 
 
VOLUNTARY NATURE OF THIS STUDY 
 
Taking part in this study is voluntary.  You may choose not to take part or may leave the study at any time.  
Leaving the study will not result in any penalty or loss of benefits to which you are entitled.  Your decision 
whether or not to participate in this study will not affect your current or future relations with Riley Hospital for 
Children or your child’s care teams.   
 
Your participation may be terminated by the investigator without regard to your consent in the following 
circumstances:  
 
-Your child has an adverse reaction to glycerin suppositories (such as an allergic reaction, intestinal injury, or 
other intolerance) or if they are unable to advance enteral feeds based upon the established protocol 
 
 
You will be told about new information that may affect your health, welfare, or willingness to stay in the study.  
This study may be terminated by Dr. Alan Ladd and/or your surgeon of record if information not available at the 
time of enrollment into this study suggests your child is at a greater than minimal risk as a result from 
participating in this study. 
 
USE OF SPECIMENS 
 
No specimens will be used in this study. 
 
SUBJECT’S CONSENT 
 
In consideration of all of the above, I give my consent for my child to participate in this research study.   
 
I will be given a copy of this informed consent document to keep for my records.   
 
Printed Name of Child: 
 
 
Child’s Date of Birth:  
 
 
 
Printed Name of Parent: 
 
 
Signature of Parent: 
Date: 
 
 
 
If two (2) parents are required to sign the consent document: 
 
Printed Name of Parent: 
 
 
Signature of Parent: 
Date: 
 
 
 
Printed Name of Person Obtaining Consent: 
 
 
Signature of Person Obtaining Consent: 
Date: 
 
 
 

Prot_SAP_002.pdf: 
 
 
NCT03355326 
4/1/2020 
 
 
Evaluation of Routine Administration of Glycerin Suppositories to Improve Bowel Function in Patients 
with Uncomplicated Gastroschisis 
 
NCT03355326 
 
Last date of Revision 5/7/2018 
Last date of Approval 4/1/2020 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
 
NCT03355326 
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Introduction/Background: 
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 is well established that bowel 
function after repair of gastroschisis is impaired due to the aforementioned pathologic 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.  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. 
 
Study Procedures: 
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) in neonates with uncomplicated 
gastroschisis.  Additional secondary outcomes that will be measured include time to first bowel 
movement, length of hospital stay, infectious complications, days on total parenteral nutrition (TPN), 
post-operative days on TPN, sequela of long term TPN administration, and post-operative complications. 
After obtaining consent, patients will be randomized (utilizing a block technique) into two 
groups: the treatment group and the control group.  Consent and randomization will occur the day of 
surgery or preceding surgery with the operating surgeon blind to the treatment arm prior to operation.  
A newly developed study-specific standardized feeding protocol that has been adopted by all pediatric 
general surgeons at Riley Hospital for Children will be used on all study participants.  Signs of feeding 
intolerance are outlined in the attached feeding protocol.  The treatment group will undergo 
administration of a glycerin suppository beginning the day after abdominal closure and daily until 
reaching full enteral feeds.  Time to first stool (secondary outcome) will also be monitored and recorded.  
Clinical nursing staff often will report very small bowel movements as “smears”.  These will be noted in 
the study database but will not be considered a first bowel movement.   If at any point during treatment 
the patient develops significant rectal bleeding, suppository administration will be discontinued, and the 
patient will be removed from the study.  The control group will not receive routine glycerin 
suppositories until full enteral feeds are obtained and will be based upon attending preference 
thereafter.  Weaning of TPN during advancement of enteral feeds will be based upon attending 
preference. Laboratory values routinely monitored for signs of malnutrition and TPN-induced cholestasis 


 
 
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(secondary outcome) will also be monitored/recorded, these labs are normally drawn in this patient 
population and no additional labs/blood draws will be required for this study 
 
Inclusion/Exclusion Criteria: 
Inclusion criteria: 
-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 or those known to impair intestinal motility 
-Identification of a secondary gastrointestinal abnormality requiring surgical intervention 
-Cyanotic heart disease 
 
Power Analysis/Recruitment Period 
Assuming the average time to full enteral feeds in the control group will be approximately 21 
days with a standard deviation of 3 days and a power (1-β) of 0.8, the study will need to enroll thirty-
seven (37) in each study arm to detect a difference of two days between groups (two sided test with an 
α = 0.05).  After reaching this enrollment, that data from each group will be analyzed for normality and if 
found to be normal, student’s t-tests will be performed to determine significance for the primary 
outcome variables.   If the resulting data is not normally distributed, Wilcoxon ranked-sum tests will be 
performed. Data analysis will be completed by Matthew Landman, M.D., M.P.H. 
The average number of uncomplicated gastroschisis patients admitted to Riley Hospital for 
Children is approximately 20 per year.  Assuming 80% enrollment (i.e. 44 patients enrolled) with an 85% 
retention rate to completion (i.e. 37 patients completing the study), the study period will be 
approximately 5.5 years.   
Participant Privacy/Data Safety 
All data obtained for use in this study will be abstracted from clinical (medical record) and 
entered on to a RedCap database built explicitly for this research study.  Data entry will occur on the 
private/encrypted pediatric general surgery research computer, which is available only in the Pediatric 
General Surgery office within the physical/technical infrastructure of Indiana University Health.  
Additionally these computers are independently password-protected and all access to the office is 


 
 
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limited to staff only and is continuously supervised.  All office doors are locked during non-business 
hours.  Patient names will never be used in the research database in order to help reduce the risk of loss 
of confidentiality.  All physical charts will be reviewed (if needed) in this office and only in this office and 
delivered immediately back to their respective sites upon completion of review.  Paper records will be 
locked within the pediatric general surgery research office at all times.