Mucous Fistula Refeeding Reduces the Time From Enterostomy Closure to Full Enteral Feeds (MUC-FIRE Trial)

Study Overview
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Brief Summary
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The primary objective of this study is 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.

Detailed Description
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Enterostomies in children may be created for different reasons. During the presence of an enterostomy the regular stool transfer is interrupted as the distal part of the bowel (the part following the enterostomy) does not participate in the circulation of stool. Therefore it does not contribute to the resorption of enteral contents. As a consequence these children 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.The aim of this study is to assess the effects of mucous fistula refeeding in a randomized, prospective trial. We hypothesize that MFR between enterostomy creation and enterostomy closure reduces the time to full enteral feeds after enterostomy closure compared to the group without refilling. Moreover, the side effects of parenteral nutrition may be reduced and the postoperative hospital care of infants undergoing ostomy closure shortened.

Official Title
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A Randomized Multicenter Open-label Controlled Trial to Show That Mucous Fistula Refeeding Reduces the Time From Enterostomy Closure to Full Enteral Feeds (MUCous FIstula REfeeding (MUC-FIRE) Trial)

Conditions
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Enterostomy

Intervention / Treatment
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* Other: mucous fistula refeeding


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Infants < 366 days, Ileostomy / Jejunostomy, double loop enterostomies and split enterostomies (with mucous fistula) 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: resection of ileocecal valve, colostomy, small bowel atresia, multiple ostomies (more than just an enterostomy and a mucous fistula), chromosomal abnormalities (if known at the time of randomization), Hirschsprung's disease, participation in another drug-intervention study Intestinal perforation due to a hemodynamic heart defect

Ages Eligible for Study
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Maximum Age: 12 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Multicenter, open-label, randomized, parallel group, controlled trial
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Perioperative mucous fistula refeeding<br>Perioperative mucous fistula refeeding between enterostomy creation and enterostomy closure | Other: mucous fistula refeeding<br>* Transfer of infants' own stool<br>|
| No Intervention: No mucous fistula refeeding<br>No perioperative mucous fistula refeeding | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to full enteral feeds (hours) | Time to full feeds (hours), defined as time to actual enteral intake of the age-dependent caloric requirements per day (defined as 90 or 120kcal/kg/24h) for at least 24 hours and a concomitant reduction of parenteral fluids to <20ml/kg/24h. 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, mother's gestation week at birth at least 37+0. | week 4 to week 12 daily | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to first 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 | Week 4 to week 12 daily | 
| Thriving | Measurement of body weight | Week 1 to week 12 daily; follow-up (month 3, 6, 12) | 
| Z-Score (standard deviation score) | Measurement of weight [weight for age, World Health Organization (WHO)] | Week 1 to week 12 daily, follow-up (month 3, 6, 12) | 
| Number of days of postoperative total parenteral nutrition (TPN) | Calculation of days of postoperative TPN starts on the day of operation and ends on the day of full enteral nutrition | Week 2 to week 12 daily, follow-up (month 3, 6, 12) | 
| Laboratory parameter indicating cholestasis | Measurement of conjugated Bilirubin (µmol/l) | Week 1 to week 12 daily, follow-up (month 3) | 
| Assessment of adverse events (AEs) | Adverse events will be collected by the investigator either based on the information provided spontaneously by the parents of patient or evaluated by non-suggestive questions. | Week 1 to week 12 daily, follow-up (month 3, 6, 12) | 
| Assessment of serious adverse events (SAEs) | Adverse events will be collected by the investigator either based on the information provided spontaneously by the parents of patient or evaluated by non-suggestive questions. | Week 1 to week 12 daily, follow-up (month 3, 6, 12) | 
| Postoperative weight gain (g/d) | Weight gain during the subsequent 5 days after reaching the primary endpoint following enterostomy closure | week 4 to week 12 | 
| Central venous line (CVL) | duration (days) and number of CVL infections (definition of infection: Neo-Kiss Guidelines) | Week 1 to week 12 | 
| hospitalisation | Length of hospital stay (days) | week 1 to week 12 | 
| jump in caliber | Estimated ratio of the diameter of the two bowel loops which are anastomosed. | week 5 | 
| Sodium resorption | Sodium in Urine (mmol/l) | Week 1 to week 12 daily, follow-up (month 3) | 
| Status of liver enzymes | Gamma-Glutamyltransferase (GGT) , Alanine-Aminotransferase (ALT) , Aspartate-Aminotransferase (AST) (µkat/l) | Week 1 to week 12 daily, follow-up (month 3) | 
| Laboratory parameters | Haemoglobin (g/dl) | Week 1 to week 12 daily, follow-up (month 3) | 
| Time to full volume intake per day (in hours) | Time to full age-dependent volume intake per day (defined as 150ml/kg/24h for premature infants and 120ml/kg/24h for mature born infants as well as corrected mature infants) (in hours). The volume aim is 150 ml/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 volume aim is 120 ml/kg/24h for born mature infants, mother's gestation week at birth at least 37+0. | week 4 to week 12 daily | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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infants, necrotizing enterocolitis (NEC), focal intestinal perforation (FIP), enterostomy creation, bowel reanastomosis, enteral feeding, caloric intake, parenteral nutrition, complication rate, reduction of hospital expenses, length of hospital stay, refeeding