Comparison of prophylactic effect of synbiotic on necrotizing enterocolitis, sepsis and hyperbilirubinemia with placebo on very low birth weight infants
Objective: Prebiotics are synergistic with probiotics and enhance survival probiotic bacteria in human milk. The goal of this study was to investigate the efficacy of synbiotic preparation in preventing necrotizing enterocolitis, sepsis, and hyperbilirubinemia in very low birth weight infants. Design: A prospective, double blinded, randomized, placebo controlled trial. Setting: Single center in Istanbul, Turkey. Patients: Infants (n: 220) were born ≤32 gestational age, ≤1500 g birth weight. Interventions: Very low birth weight infants who started enteral feeding were randomized either to receive daily feeding supplementation with synbiotic (NBL ATP 1/2 sachet every 12 hours) or placebo until discharge. The sample was randomized via computer centre. Main outcome measures: Necrotizing enterocolitis (Bell’s stage ≥2), sepsis, and hyperbilirubinemia.
General information
Acronym
IRCT registration information
IRCT registration number:IRCT2013062710279N3
Registration date:2015-01-18, 1393/10/28
Registration timing:retrospective
Last update:
Update count:0
Registration date
2015-01-18, 1393/10/28
Registrant information
Name
Ozge Serce Pehlevan
Name of organization / entity
Zeynep Kamil Maternity and Children Education and Training Hospital
Country
Turkey
Phone
08 60 193 612 0900
Email address
ozge.serce@marmara.edu.tr
Recruitment status
Recruitment complete
Funding source
NBL Pharmacy
Expected recruitment start date
2012-10-01, 1391/07/10
Expected recruitment end date
2013-10-01, 1392/07/09
Actual recruitment start date
empty
Actual recruitment end date
empty
Trial completion date
empty
Scientific title
Comparison of prophylactic effect of synbiotic on necrotizing enterocolitis, sepsis and hyperbilirubinemia with placebo on very low birth weight infants
Public title
Outcome of synbiotics on necrotizing enterocolitis, sepsis
Purpose
Prevention
Inclusion/Exclusion criteria
Inclusion criteria: Very low birth weight infants (gestational age: ≤32 weeks; birth weight: ≤1500 g) who survived to feed enterally (minimum age: first postnatal day, maximum age: 10 days). Exclusion criteria: Infants who had severe asphyxia (stage III), major congenital anomalies, those who had been fasted for more than 3 weeks, died within the first postnatal 14 days.
Age
From 1 day old to 1 month old
Gender
Both
Phase
3
Groups that have been masked
No information
Sample size
Target sample size:
210
Randomization (investigator's opinion)
Randomized
Randomization description
Blinding (investigator's opinion)
Double blinded
Blinding description
Placebo
Used
Assignment
Parallel
Other design features
The event rate was determined by unpublished data based on
2009–2010 of our NICU. Our recent event rate for NEC or sepsis was
31% and for death or NEC was 35% in our NICU (for NEC alone 17%, for
sepsis alone 19%, and for death alone 18%). With the α-error set at
0.05 and the β-error set at 0.2, and an absolute reduction in the incidence
of either NEC/sepsis or NEC/death of 50%, the number of infants
needed to verify our hypothesis was 104 for NEC or sepsis and 92 for
NEC or death for each group. The infants enrolled in the study were
assigned randomly to the intervention or control group prospectively after informed
parental consent was obtained. Randomization was performed
by using sequential numbers generated at the computer center.
Secondary Ids
empty
Ethics committees
1
Ethics committee
Name of ethics committee
Ministry of Health of Turkey, General Directorate of Pharmaceuticals and Pharmacy
Street address
No 5, 2176 Sok., Söğütözü Mah.
City
Ankara
Postal code
06520
Approval date
2012-07-20, 1391/04/30
Ethics committee reference number
17
Health conditions studied
1
Description of health condition studied
Necrotizing enterocolitis
ICD-10 code
p77
ICD-10 code description
Necrotizing enterocolitis of fetus and newborn
2
Description of health condition studied
Sepsis
ICD-10 code
P36
ICD-10 code description
Bacterial sepsis of newborn
3
Description of health condition studied
Hyperbilirubinemia
ICD-10 code
P59.3
ICD-10 code description
Neonatal jaundice from breast milk inhibitor
Primary outcomes
1
Description
Necrotizing enterocolitis
Timepoint
Starts at the same time with the intervention
Method of measurement
Patients' medical records
2
Description
Sepsis
Timepoint
Starts at the same time with the intervention
Method of measurement
Patients' medical records
3
Description
Hyperbilirubinemia
Timepoint
Starts at the same time with the intervention
Method of measurement
Serum sample
Secondary outcomes
1
Description
Weight gain per week
Timepoint
Starts on the 7th day of intervention
Method of measurement
Patients' medical records
2
Description
Time to reach full enteral feeding
Timepoint
Starts at the same time with the intervention
Method of measurement
Patients medical records
3
Description
Mortality until hospital discharge
Timepoint
Starts at the same time with the intervention
Method of measurement
Patients' medical records
4
Description
Length of hospitalization
Timepoint
Starts at the same time with the intervention
Method of measurement
Patients' medical records
5
Description
Neurocognitive development
Timepoint
18 months corrected age
Method of measurement
Bayley test
Intervention groups
1
Description
The intervention group received synbiotic preparation (Probiotic ATP, NBL, 1/2 sachet per dose twice daily) which were added to breast milk or formula until discharge.
Category
Treatment - Drugs
2
Description
The control group received placebo (distilled water; 1 cc per dose twice daily) which were added to breast milk or formula until discharge.
Category
Placebo
Recruitment centers
1
Recruitment center
Name of recruitment center
Zeynep Kamil Maternity and Children's Education and Training Hospital