Clinical trial NCT02796703: Heat Killed Probiotics in the Prevention of Necrotizing Enterocolitis
Official title: Heat Killed Probiotics in the Prevention of Necrotizing Enterocolitis (NEC) in Premature Neonates
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Necrotizing Enterocolitis
Enterocolitis, Necrotizing
Lead sponsor: Shaare Zedek Medical Center
Sponsor class: OTHER
First posted: 2016-06-13
Enrollment: 450
Sex: ALL
Minimum age (years): 6
Maximum age (years): 7
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Prophylactic probiotics have been shown to decrease the incidence of Necrotizing Enterocolitis (NEC) in premature neonates. However, there is some resistance to giving live bacteria to small babies. Based on animal data, the investigators hypothesized that heat inactivated probiotics would also reduce NEC.

Detailed description: Preterm neonates, \<1500 gm birth weight will potentially be candidates for study and will be recruited when they begin enteral feeding. The infants will be prospectively and randomly assigned to one of two groups:

1. Treatment group - to receive daily inactivated probiotic prophylaxis starting with the initiation of feeds. 1 tsp powder will be diluted in 2 cc of mother's milk when possible or in Similac Special Care formula 24 cal when mother's milk is not available; and
2. Control group - to receive 2 cc/day of placebo similarly diluted. Supplements will be continued until the infant tolerates enteral feeds of 100 cc/kg/day or reaches 35 weeks post conceptual age (whichever comes LAST). Biotikid, a probiotic mixture, will be heated to 100 degrees C for 10 minutes. Babies will be followed clinically for signs of NEC, and with urine intestinal fatty acid binding protein (IFABP) and fecal calprotectin levels.

The investigators primary aim is to demonstrate that premature neonates who are treated prophylactically with heat inactivated probiotics will have less necrotizing enterocolitis when compared to age matched infants given placebo.

The investigators secondary objectives are to demonstrate the following:

* That the decrease in NEC will coincide with improved intestinal barrier integrity, as reflected by levels of:
* I-FABP in urine
* Fecal Calprotectin

Eligibility criteria: Inclusion Criteria:

* Preterm neonates
* ≤1500 gm birth weight

Exclusion Criteria:

* Infants who are not deemed likely to survive more than one week;
* Infants who are not started on enteral feeds by one week of age;
* Infants who have significant congenital malformations or other gastrointestinal problem

Primary outcomes:
measure: Necrotizing Enterocolitis, Bell Stage 2 or above, or Death
timeFrame: Birth until 40 weeks post-conceptional age
Secondary outcomes:
measure: Increased Urine IFABP Levels
timeFrame: Weekly, from date of randomization until full enteral feeds (100 cc/kg/day) achieved or until death or necrotizing enterocolitis is diagnosed, whichever comes first until 37 weeks postconceptional age
measure: Increased Fecal Calprotectin Levels
timeFrame: Weekly, from date of randomization until full enteral feeds (100 cc/kg/day) achieved or until death or necrotizing enterocolitis is diagnosed, whichever comes first until 37 weeks postconceptional age
Other outcomes:
Locations:
city: Jerusalem
country: Israel
facility: Neonatal Intensive Care Unit - Shaare Zedek Medical Center
Study officials:
affiliation: Shaare Zedek Medical Center
name: Cathy Hammerman, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Awad H, Mokhtar H, Imam SS, Gad GI, Hafez H, Aboushady N. Comparison between killed and living probiotic usage versus placebo for the prevention of necrotizing enterocolitis and sepsis in neonates. Pak J Biol Sci. 2010 Mar 15;13(6):253-62. doi: 10.3923/pjbs.2010.253.262.