Effect of Administration of Combined Enteral Lactoferrin and Probiotic On Invasive Fungal Infections In Preterm Neonates

The risk for invasive fungal infections is high in very low birth weight (VLBW) infants (< 1500 g) and highest for infants born at the youngest gestational ages who survive past the immediate postnatal period.

Invasive fungal infections (IFIs) represent an increasing cause of severe morbidity and mortality in most neonatal intensive care units.

Lactoferrin (LF) is secreted by epithelial cells into exocrine fluids: seminal fluid, tears, saliva, uterine secretions, and milk. LF is involved in innate immunity mechanisms with several documented anti-infective properties, including antifungal activity.

Probiotics are microorganisms that are believed to provide health benefits when consumed.

It is possible to adopt measures to modify the flora in our bodies and to replace the harmful microbes by useful microbes.

There are certain commercially available strains of probiotic bacteria from the Bifido bacterium and Lactobacillus genera when taken by mouth in daily doses possess treatment efficacy

Study Overview

• Status: Completed
• Conditions: Fungal Infection
• Intervention / Treatment: Drug: Lactoferrin Bovine; Combination product: Lactoferrin Bovine and probiotics; Other: Placebo

Detailed Description

Bovine LF alone or in combination of probiotics (Lactobacillus Delbrueckii and Lactobacillus Fermentum) can be used in prevention of invasive fungal infection in preterm neonates admitted to the NICU. So, this randomized interventional study aimed at evaluation of the efficacy and safety of enterally administered bovine LF alone or in combination of probiotics (Lactobacillus Delbrueckii and Lactobacillus Fermentum) in comparison to placebo in preterm neonates, through studying blood culture for fungal infection at enrollment, day 7, 14, 21 and 28 using Sabouraud agar for detecting Candida species and Hichrome agar to detect other fungal types ( primary outcome), and to compare length of hospital stay (LOS), use and duration of drug intake as antibiotics and inotropes, use and duration of mechanical ventilation, rate of increase of enteral feeding, time to reach full enteral intake, signs of feeding intolerance, complete blood count (CBC), C reactive protein (CRP), packed red blood cell transfusion (PRBCs) and mortality between the 3 groups as (secondary outcome).

• Study Type: Interventional
• Enrollment (Actual): 80
• Phase: Phase 1

Contacts and Locations

Study Locations

• Egypt
  • Cairo, Egypt, 11381
    • AIN shams university

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 day to 1 month (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 80 preterm
• ≤ 36 weeks gestational age
• >/ = 72 hours of life

Exclusion Criteria:

1. Nothing per os
2. Congenital anomalies.
3. Suspected inborn error of metabolism.
4. Prophylaxis antifungal drugs

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Lactoferrin Bovine group; Group A (20 preterm neonates) which will receive lactoferrin (100mg/day)	Drug: Lactoferrin Bovine; Lactoferrin granules (Pravotin®) in a dose of 100 mg /kg/day starting from birth to the 30th day of life for neonates in group A; Other Names: Pravotin®
Active Comparator: Lactoferrin Bovine with probiotics group; Group B (20 preterm neonates) which will receive lactoferrin (100mg/day) in combination with the probiotic	Combination product: Lactoferrin Bovine and probiotics; Lactoferrin granules (Pravotin®) in a dose of 100 mg /kg/day in combination with the probiotic Lactobacillus Delbrueckii and Lactobacillus Fermentum (Lacteol fort®) given in a dose of 5 billions starting from birth to the 30th day of life for neonates in group B; Other Names: Pravotin® plus Lacteol fort
Placebo Comparator: Placebo group; Group C (40 preterm neonates) which is a placebo group.	Other: Placebo; Placebo will be given starting from birth to the 30th day of life for neonates in group C.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with invasive fungal infection (IFI)	Efficacy of enteral lactoferrin either alone or in combination with the probiotic Lactobacillus Delbrueckii and Lactobacillus Fermentum in the prevention of invasive fungal infections in preterm infants through analyzing the incidence rates of invasive fungal infection (IFI) in all groups using Sabouraud agar for detecting Candida species and Hichrome agar to detect other fungal types.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patients who received packed RBC in each group	The number of patients who received packed RBC in each group from time of enrollment till the 30th day of life	30 days
Days on inotropic support in each group	Define how many days required for inotropic support in each group	12 months
Days on mechanical ventilation in each group	Define how many days required for mechanical ventilation support in each group	12 months
Days of NICU admission in each group	Define how many days patients in each group were admitted in the NICU	12 monthes
Number of participants with Necrotizing enterocolitis in each group	Define the rate of NEC occurrence in each group	12 months
Mortality in each group	Define the number of mortality in each group	12 months

Collaborators and Investigators

• Sponsor: Ain Shams University
• Investigators: Study Director: Hebatallah A Shaaban, MD, doctor

Study record dates

Study Major Dates

• Study Start (Actual): February 10, 2020
• Primary Completion (Actual): March 27, 2021
• Study Completion (Actual): April 27, 2021

Study Registration Dates

• First Submitted: October 17, 2017
• First Submitted That Met QC Criteria: March 12, 2022
• First Posted (Actual): March 16, 2022

Study Record Updates

• Last Update Posted (Actual): March 16, 2022
• Last Update Submitted That Met QC Criteria: March 12, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: Probiotic; Lactoferrin; Preterm
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Bacterial Infections and Mycoses; Infections; Communicable Diseases; Mycoses; Invasive Fungal Infections; Anti-Infective Agents; Lactoferrin
• Other Study ID Numbers: Pediatrics Dep-ASU

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No