Pilot Study: Lactoferrin for Prevention of Neonatal Sepsis

Study Overview
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Brief Summary
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We will test the hypothesis that bovine lactoferrin supplementation prevents serious infections in preterm infants. We will conduct a randomized placebo-controlled double blind study in 190 premature infants <2500 gm in 5 Neonatal Intermediate and Intensive Care Units in Lima, Peru to determine whether bovine lactoferrin prevents the first episode of late-onset sepsis.

Detailed Description
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Lactoferrin is an iron chelating protein with multiple physiological functions (anti-microbial, anti-inflammatory and immunomodulatory) and is one of the most important proteins present in mammalian milk. We hypothesize that lactoferrin as an oral supplement given daily to low birth weight will improve their health by mimicking their protective role in milk. There is extensive literature showing in vitro and in animal models the benefits of lactoferrin. However, there are few clinical trials designed to translate this knowledge into patient care. We will conduct a pilot randomized, double-blinded placebo-controlled trial comparing daily supplementation with bovine lactoferrin versus placebo in neonates to reduce the incidence of sepsis in the first month of life. We will enroll 190 neonates with a birth weight less than 2,500 g, younger than 3 days of age in the neonatal intensive care unit of 5 pediatric hospitals in Lima, after informed consent of both parents. Infants will be followed in the hospital until death or discharge and then at home up to 1 month of age. Bovine lactoferrin will be used in this trial (200 mg/Kg per day). Although bovine and human lactoferrin are not identical, their bioactivity is quite comparable. Maltodextrin (an inert sugar) will be used for controls. The primary study outcome will be the number of first late-onset sepsis episodes (occurring >72h after birth with isolation of any pathogen in blood or cerebrospinal fluid).

Official Title
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Pilot Study: Lactoferrin for Prevention of Neonatal Sepsis

Conditions
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Sepsis

Intervention / Treatment
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* Dietary Supplement: lactoferrin
* Dietary Supplement: Maltodextrin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Neonates with a birth weight between 500g and 2500g Neonates born in, or referred to the Neonatal Intermediate and Intensive Care Units of one of the participating hospitals in the first 72 hours of life. Exclusion Criteria: Neonates with underlying gastrointestinal problems that prevent oral intake. Neonates with predisposing conditions that profoundly affect growth and development (chromosomal abnormalities, structural brain anomalies, severe congenital abnormalities) Neonates with a family background of cow milk allergy Neonates that, according to the investigator criteria, will not have the chance to complete the subsequent study visits (patients that before one month old would not be living in Lima). Neonates whose parents decline to participate.

Ages Eligible for Study
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Minimum Age: 24 Hours
Maximum Age: 72 Hours

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: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lactoferrin<br>Lactoferrin is a freeze-dried protein purified directly from fresh bovine milk. | Dietary Supplement: lactoferrin<br>* Infants will receive oral bovine lactoferrin (200 mg/Kg/day divided in three dosis) for 4 weeks. Lactoferrin will be dissolved in human milk or infant formula or in a 5% glucose solution. Each dose will be dissolved in a small volume so the maximum lactoferrin concentration will be 25mg/mL.<br>* Other names: Bovine lactoferrin;|
| Placebo Comparator: maltodextrin<br>Maltodextrin is an inert sugar. | Dietary Supplement: Maltodextrin<br>* Infants will receive oral maltodextrin (200mg/Kg/day in three divided dosis) for 4 weeks. Maltodextrin will be dissolved in human milk or infant formula or in a 5% glucose solution. Each dose will be dissolved in a small volume so the maximum maltodextrin concentration will be 25mg/mL.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of confirmed episodes of late-onset sepsis. | Number of confirmed episodes of late-onset sepsis in the first month of life | 1 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Gram positive and Gram negative bacterial and fungal bouts of sepsis, pneumonia, diarrhea and mortality | Incidence of Gram positive and Gram negative bacterial and fungal bouts of sepsis, pneumonia, diarrhea and mortality in the first month of life. | 1 month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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lactoferrin, sepsis, neonates, prevention, infections