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

Study Overview
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Brief Summary
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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

Detailed Description
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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).

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

Conditions
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Fungal Infection

Intervention / Treatment
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* Drug: Lactoferrin Bovine
* Combination Product: Lactoferrin Bovine and probiotics
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 80 preterm ≤ 36 weeks gestational age >/ = 72 hours of life Exclusion Criteria: Nothing per os Congenital anomalies. Suspected inborn error of metabolism. Prophylaxis antifungal drugs

Ages Eligible for Study
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Minimum Age: 1 Day
Maximum Age: 30 Days

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Lactoferrin Bovine group<br>Group A (20 preterm neonates) which will receive lactoferrin (100mg/day) | Drug: Lactoferrin Bovine<br>* 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<br>* Other names: Pravotin®;|
| Active Comparator: Lactoferrin Bovine with probiotics group<br>Group B (20 preterm neonates) which will receive lactoferrin (100mg/day) in combination with the probiotic | Combination Product: Lactoferrin Bovine and probiotics<br>* 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<br>* Other names: Pravotin® plus Lacteol fort;|
| Placebo Comparator: Placebo group<br>Group C (40 preterm neonates) which is a placebo group. | Other: Placebo<br>* Placebo will be given starting from birth to the 30th day of life for neonates in group C.<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lactoferrin, Probiotic, Preterm