Clinical Trial Details
— Status: Terminated
Administrative data
| NCT number |
NCT03355326 |
| Other study ID # |
IU-IRB-1611267731 |
| Secondary ID |
|
| Status |
Terminated |
| Phase |
Phase 4
|
| First received |
|
| Last updated |
|
| Start date |
October 1, 2017 |
| Est. completion date |
October 1, 2020 |
Study information
| Verified date |
September 2021 |
| Source |
Indiana University |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial 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.
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.
