Early Versus Late Lactoferrin in Prevention of Neonatal Sepsis

Systematic Randomized , Single Blinded, Placebo-Controlled Trial of Early Versus Late Lactoferrin in Prevention of Neonatal Sepsis

The present study was designed to evaluate the effectiveness of oral lactoferrin in prevention of neonatal sepsis with comparison early (1st day) versus late (48-72 hours) Lactoferrin administration, Secondary aim was to study effect of Lactoferrin administration on serum Ferritin and follow up long term outcome (Bronchopulmonary dysplasia, retinopathy of prematurity and necrotizing enterocolitis.

Study Overview

• Status: Completed
• Conditions: Neonatal Sepsis
• Intervention / Treatment: Drug: Lactoferrin; Drug: Placebo (for Lactoferrin)

Detailed Description

This study was carried out on 180 preterm neonates(< 37 weeks of gestation counting from the first day of the Last Menstrual Period and confirmed by Ballard score) admitted to the Neonatal Intensive Care Units of Ain Shams University Hospitals in the period from August 2014 to December 2015.

Enrolled subjects were further randomly subdivided into three groups according to the dose regimen of Lactoferrin supplementation.

• Group A: (60 preterm neonates) who received oral Lactoferrin supplementation in a dose of 100 mg/day starting on day 1 and continue for 4-6 weeks.
• Group B: (60 preterm neonates) who received oral Lactoferrin supplementation in a dose of 100 mg/day starting on day 3 (48hrs-72hrs) of life and continue for 4-6 weeks.
• Group C: (60 preterm neonates) who match the subjected neonates, received placebo in form of distilled water.

• Study Type: Interventional
• Enrollment (Actual): 180
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 3 days (CHILD)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Neonates with a < 37 weeks of gestation counting from the first day of the Last Menstrual Period.
2. Preterm neonates are breast fed, artificially fed or on total parenteral nutrition.
3. Preterm neonates born in, or referred to our Neonatal Intensive Care Unit in the first day of life free from infection and not fed.

Exclusion Criteria:

1. Neonates with underlying gastrointestinal problems that prevent oral intake.
2. Neonates with predisposing conditions that profoundly affect growth and development (chromosomal abnormalities, structural brain anomalies, severe congenital abnormalities).
3. Neonates with a family background of cow milk allergy.
4. Neonates who will not have the chance to complete the study time (who will be referred to another hospitals).
5. Neonates with early onset sepsis.
6. Neonates whose parents decline to participate.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Early Lactoferrin Group; Oral Bovine Lactoferrin 100 mg/day once starting on day 1 of life and continued for 4-6 weeks.	Drug: Lactoferrin; Other Names: Bovine Lactoferrin
EXPERIMENTAL: Late Lactoferrin Group; Oral Bovine Lactoferrin 100 mg/day once starting on day 3 of life and continued for 4-6 weeks.	Drug: Lactoferrin; Other Names: Bovine Lactoferrin
ACTIVE_COMPARATOR: Placebo Group; placebo in form of distilled water once starting on day 1 of life and continued for 4-6 weeks.	Drug: Placebo (for Lactoferrin); placebo in form of distilled water

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Evaluate the effectiveness of oral Lactoferrin in prevention of neonatal sepsis according to Tollner score, hematological scoring system (HSS) and positive blood culture.	4-6 weeks of life
Compare early (1st day) versus late (48-72 hours) Lactoferrin administration on neonatal sepsis according to Tollner score, hematological scoring system (HSS) and positive blood culture	4-6 weeks of life

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effect of Lactoferrin supplementation on long term complications	Long term complications as: Broncho-Pulmonary Dysplasia using clinical symptoms and signs and chest X ray findings. Retinopathy of Prematurity using the International Classification of Retinopathy of Prematurity (ICROP). Necrotizing Enterocolitis using Modified Bell's criteria for staging Necrotizing Enterocolitis.	4-6 weeks of life
any reported side effects for Bovine Lactoferrin		4-6 weeks of life

Collaborators and Investigators

• Sponsor: Ain Shams University
• Investigators: Study Director: Ghada I Ghad, Professor, Ain Shams University

Publications and helpful links

General Publications

• Kaur G, Gathwala G. Efficacy of Bovine Lactoferrin Supplementation in Preventing Late-onset Sepsis in low Birth Weight Neonates: A Randomized Placebo-Controlled Clinical Trial. J Trop Pediatr. 2015 Oct;61(5):370-6. doi: 10.1093/tropej/fmv044. Epub 2015 Jul 29.
• Manzoni P, Meyer M, Stolfi I, Rinaldi M, Cattani S, Pugni L, Romeo MG, Messner H, Decembrino L, Laforgia N, Vagnarelli F, Memo L, Bordignon L, Maule M, Gallo E, Mostert M, Quercia M, Bollani L, Pedicino R, Renzullo L, Betta P, Ferrari F, Alexander T, Magaldi R, Farina D, Mosca F, Stronati M. Bovine lactoferrin supplementation for prevention of necrotizing enterocolitis in very-low-birth-weight neonates: a randomized clinical trial. Early Hum Dev. 2014 Mar;90 Suppl 1:S60-5. doi: 10.1016/S0378-3782(14)70020-9.

Study record dates

Study Major Dates

• Study Start: August 1, 2014
• Primary Completion (ACTUAL): December 1, 2015
• Study Completion (ACTUAL): October 1, 2016

Study Registration Dates

• First Submitted: October 27, 2016
• First Submitted That Met QC Criteria: November 5, 2016
• First Posted (ESTIMATE): November 9, 2016

Study Record Updates

• Last Update Posted (ESTIMATE): November 9, 2016
• Last Update Submitted That Met QC Criteria: November 5, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Keywords: Late onset sepsis; Bovine Lactoferrin
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Infant, Newborn, Diseases; Sepsis; Toxemia; Neonatal Sepsis; Anti-Infective Agents; Lactoferrin
• Other Study ID Numbers: FMASU M.S 23/2016

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED