Heat Killed Probiotics in the Prevention of Necrotizing Enterocolitis

Shaare Zedek Medical Center

Status and phase: Unknown; Phase 2

Conditions: Necrotizing Enterocolitis; Enterocolitis, Necrotizing

Treatments: Dietary Supplement: Heat Inactivated probiotics; Dietary Supplement: Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT02796703

SZMC 0297-15

Details and patient eligibility

About

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.

Full 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

Enrollment: 450 estimated patients

Sex: All

Ages: 6 hours to 7 days old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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450 participants in 2 patient groups, including a placebo group

Control Group

Placebo Comparator group

Description:

Dietary Supplement: Placebo 2 cc/day of placebo diluted in mother's milk (when available) or premature formula.

Treatment:

Dietary Supplement: Placebo

Treatment Group

Active Comparator group

Description:

Dietary Supplement: Heat Inactivated Probiotics 1 tsp heat inactivated Biotikid powder will be diluted in 2 cc of mother's milk (when available) or premature formula.

Treatment:

Dietary Supplement: Heat Inactivated probiotics