Heat Killed Probiotics in the Prevention of Necrotizing Enterocolitis

Necrotizing Enterocolitis Clinical Trial

Official title:

Heat Killed Probiotics in the Prevention of Necrotizing Enterocolitis (NEC) in Premature Neonates

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT02796703
• Other study ID #: SZMC 0297-15
• Status: Not yet recruiting
• Phase: Phase 2
• First received: May 22, 2016
• Last updated: June 15, 2016
• Start date: June 2016
• Est. completion date: September 2020

Study information

• Verified date: June 2016
• Source: Shaare Zedek Medical Center
• Contact: Cathy Hammerman, MD
• Phone: 0508685238
• Email: cathyh[@]ekmd.huji.ac.il
• Is FDA regulated: No
• Health authority: Israel: Ministry of Health
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 450
• Est. completion date: September 2020
• Est. primary completion date: July 2020
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 7 Days

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Enterocolitis
• Enterocolitis, Necrotizing
• Necrotizing Enterocolitis

Intervention

Dietary Supplement:
• Heat Inactivated probiotics
Biotikid, a probiotic mixture, will be heated to 100 degrees Centigrade for 10 minutes to inactivate and then 1 tsp will be diluted in milk and give with feeds to treatment group
• Placebo
2 cc of milk will be given to control group

Locations

Country	Name	City	State
Israel	Neonatal Intensive Care Unit - Shaare Zedek Medical Center	Jerusalem

Sponsors (1)

Lead Sponsor	Collaborator
Shaare Zedek Medical Center

Country where clinical trial is conducted

Israel, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Necrotizing Enterocolitis, Bell Stage 2 or above, or Death	Necrotizing Enterocolitis diagnosis will be based on clinical and radiographic criteria	Birth until 40 weeks post-conceptional age	No
Secondary	Increased Urine IFABP Levels		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	No
Secondary	Increased Fecal Calprotectin Levels		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	No