The aim of this study is to assess the effects of mucous fistula refeeding in a prospective randomized trial. We hypothesize that MFR between enterostomy creation and enterostomy closure reduces the time to full enteral feeds after enterostomy…
ID
Source
Brief title
Condition
- Other condition
Synonym
Health condition
Enterostomy
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Time to full feeds (hours), defined as time from enterostomy closure to actual
enteral intake of the age-dependent caloric requirements per day for at least
24h and a concomitant reduction of parenteral fluids to < 20ml/kg/24h.
For determining the time to full enteral feeds, the feeding advancement will be
carried out according to the predefined nutritional protocol after 6-8
tolerated feedings in 3-4 hour intervals (24 hours). *Full feeds* is therefore
defined age-dependent as 90 or 120kcal/kg/24h (full feed kcal goal) actual
enteral intake [8, 9, 32, 33]. The nurses will document any increase and
decrease of nutrition precisely and daily controls will be carried out by the
responsible neonatologist and pediatric surgeon.
The decision about the full feed kcal goal is made before randomization by the
treating physician, depending on the birth weight of the infants and mother*s
gestation week at birth:
- The nutrition aim is 120 kcal/kg/24h for premature infants with a birth
weight < 1000g or premature infants with a birth weight >= 1000g and mother*s
gestation week at birth before 37+0.
- The nutrition aim is 90 kcal/kg/24h for born mature infants, e.g. mother*s
gestation week at birth at least 37+0.
In the case unforeseen circumstances lead to an unexpected maturation of the
infant, at the time of enterostomy closure an infant formerly classified as
*premature* can be re-classified as *mature*, following justified reasoning
concerning laboratory parameters and consultation
with the principal investigators. To rule out a biased decision by the
investigators, an independent reviewer will review these decisions at the end
of the study.
As the full feed kcal goal is implemented firstly in the study protocol version
3.0 the independent reviewer will also be provided with the data of patients
that were randomized before study protocol version 3.0 and that did not achieve
time to full feeds with the initial kcal goal of 120
kcal/kg/24h. On the basis of the individual patient information the independent
reviewer will assess the primary endpoint with respect to the specific kcal
goal defined above.
Secondary outcome
1) Reoperation.
2) Time to first bowel movement after enterostomy closure (mucous stool is
considered a bowel movement) Cleaning and changing of infants diapers will be
performed according to a fixed schedule in order to uniformly document the time
to first bowel movement following enterostomy
closure.
3) Postoperative weight gain (g/d) (daily documentations recommended, minimum
2x per week), regular Z-Score (standard deviation score) documentation [WHO -
weight-for-age] (daily documentations recommended, minimum 2x per week), This
will be carried out
according to a fixed schedule during morning rounds prior to feeding in an
unclothed status.
4) Days of postoperative total parenteral nutrition (> 20 ml/kg/24h) before and
after the 2nd operation (=ostomy takedown) (TPN) Days of postoperative total
parenteral nutrition (TPN) are counted, starting on the day of enterostomy
closure and ending on the day of full enteral nutrition. The parenteral
nutrition is manufactured by the hospital pharmacy on a daily basis, while
considering the
simultaneous enteral caloric intake.
5) Laboratory parameters indicating cholestasis (conjugated bilirubin, GGT,
ALT, AST, hemoglobin) and sodium resorption (sodium in urine).
Time points for harvesting of blood samples during clinical routine blood
withdrawal: Baseline at the time of randomization, then every 2 weeks until
enterostomy takedown, at the 3-months follow up and in cases of pathologic
clinical signs (jaundice, acholic stools).
6) Weight gain during the subsequent 5 days after reaching the primary endpoint.
7) Central venous line (CVL) duration (days) and number of CVL infections
(definition of infection: Neo-Kiss Guidelines).
8) Length of hospital stay (days).
9) Estimated ratio of the diameter of the two bowel loops which are anastomosed.
10) Time to full oral volume intake (based on age-dependent daily fluid
requirements), for at least 24h. The feeding advancement will be carried out
according to the predefined nutritional protocol. *Full oral volume intake* is
therefore defined as 150ml/kg/24h (premature infants) and 120ml/kg/24h (born
mature as well as corrected mature infants) actual enteral volume intake.
11) Assessment of safety: Assessment of possible (serious) adverse events
(AEs/SAEs) after randomization (e.g. death, sepsis, bowel perforation, stoma
prolapse, abscess).
Background summary
Enterostomies in infants may be created for different reasons. During the
presence of an enterostomy, the regular stool transfer is interrupted since the
distal part of the bowel (the part following the enterostomy) does not
participate in the processing of stool. Therefore, it does not contribute to
the resorption of enteral nutrients. As a consequence, these infants need
additional parenteral nutrition. Due to the negative side-effects of parenteral
nutrition all patients should return to enteral nutrition as soon as possible.
Consequently, many pediatric surgical centers worldwide routinely perform
mucous fistula refeeding (MFR) into the former unused bowel after enterostomy
creation because case reports and retrospective analyses show low complication
rates and faster postoperative weight gain. Several providers, however, shy
away from this approach because to date there is still no high-quality evidence
for the benefit of this treatment.
Study objective
The aim of this study is to assess the effects of mucous fistula refeeding in a
prospective randomized trial. We hypothesize that MFR between enterostomy
creation and enterostomy closure reduces the time to full enteral feeds after
enterostomy closure compared to standard care. Moreover, the side effects of
parenteral nutrition may be reduced and the postoperative hospital care of
infants undergoing ostomy closure shortened.
Study design
This is a randomized, multicenter (approx..=13), open-label, parallel group,
controlled research study to demonstrate that mucous fistula refeeding between
enterostomy creation and enterostomy closure reduces the time to full enteral
feeds after enterostomy closure compared to standard of care.
Intervention
All patients will receive standard care with standardized enterostomy creation
and closure and will be treated according to a standardized
feeding protocol.
Experimental intervention:
Perioperative mucous fistula refeeding between enterostomy creation and
enterostomy closure
Control intervention:
No perioperative mucous fistula refeeding between enterostomy creation and
enterostomy closure
Follow-up per patient:
3 months and 6 months postoperatively, following enterostomy closure (12-month
follow-up only applicable for patients that are recruited early
enough to complete this follow-up within the 48 month of overall study
duration). Duration of intervention per patient of the intervention group:
minimum 21 days/3 weeks until patient*s weight >2000g (averaged 6 weeks between
enterostomy creation and enterostomy closure).
Study burden and risks
In general, blood draws are safe from a medical point of view and no
significant problems are expected. The blood is taken from the vein with a
cannula. In principle, taking a blood sample is associated with only a very
small risk. These include temporary pain, bleeding and bruising (bruising). In
addition, there is a small risk of infection at the puncture site. In extremely
rare cases, errors in pricking, nerve damage (also chronic), inflammation of
the veins with the formation of blood clots (thrombosis), dizziness, anesthesia
and/or fainting may occur.
To avoid additional traumatization, an attempt is made to carry out the planned
examinations by means of the same blood samples during the course of the
examination. Only in rare cases is an additional blood sample necessary.
Liebigstrasse 20a
Leipzig 04103
DE
Liebigstrasse 20a
Leipzig 04103
DE
Listed location countries
Age
Inclusion criteria
1. Only infants younger than 366 days of age with status post ileostomy or
jejunostomy creation (double loop enterostomies and split enterostomies (with
mucous fistula)) will be included in the study to create a homogenous cohort of
patients with similar diseases (e.g. necrotizing enterocolitis [NEC], focal
intestinal perforation [FIP]). Also, infants of this age group are unique in
several respects such as the response to parenteral nutrition and its hepatic
toxicity resulting into neonatal cholestasis. The ostomy localization is
restricted to the jejunum and ileum. Therefore, the cohort of
patients shows a similar bowel length for fluid-, vitamin- and electrolyte
resorption.
2. All patients with meconium ileus are included into the study. If later
(required) diagnostics verify cystic fibrosis, the diagnostics as well as the
diagnosis need to be documented in the eCRF and in further analysis subgroups
will be established.
3. Signed written informed consent obtained by parents/legal guardians and
willingness
of parents/legal guardians to comply with treatment and follow-up procedures of
their
child.
Exclusion criteria
1. The resection of the ileocecal valve is an exclusion criterion because of
its association
with extensive bowel resection and therefore prolonged parenteral nutrition
[10].
2. Colostomy.
3. Patients with small bowel atresia are excluded because of prenatally
underdeveloped
bowel distal to the atresia.
4. Multiple ostomies (more than just an enterostomy and a mucous fistula).
5. Patients with chromosomal abnormalities (if known at the time of
randomization) are
excluded because of potential malabsorption and malnutrition due to an
underlying
syndrome.
6. Hirschsprung disease secondary exclusion.
7. Participation in another drug-intervention study.
8. Intestinal perforation due to congenital heart defects with impaired
hemodynamics.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| ClinicalTrials.gov | NCT03469609 |
| CCMO | NL80496.078.22 |