Pilot Study: Lactoferrin for Prevention of Neonatal Sepsis (NEOLACTO)

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.

Study Overview

• Status: Completed
• Conditions: Sepsis
• Intervention / Treatment: Dietary supplement: lactoferrin; Dietary supplement: Maltodextrin

Detailed Description

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).

• Study Type: Interventional
• Enrollment (Actual): 190
• Phase: Phase 2

Contacts and Locations

Study Locations

• Peru
  • Lima, Peru, Lima13
    • Hospital Guillermo Almnara Irigoyen
  • Lima, Peru, Lima31
    • Hospital Nacional Cayetano Heredia
  • Lima
    • Callao, Lima, Peru, Callao2
      • Hospital Nacional Alberto Sabogal Sologuren

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 day to 3 days (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Neonates with a birth weight between 500g and 2500g
2. 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:

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 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).
5. Neonates whose parents decline to participate.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lactoferrin; Lactoferrin is a freeze-dried protein purified directly from fresh bovine milk.	Dietary supplement: lactoferrin; 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.; Other Names: Bovine lactoferrin
Placebo Comparator: maltodextrin; Maltodextrin is an inert sugar.	Dietary supplement: Maltodextrin; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Universidad Peruana Cayetano Heredia

Publications and helpful links

General Publications

• Manzoni P, Rinaldi M, Cattani S, Pugni L, Romeo MG, Messner H, Stolfi I, Decembrino L, Laforgia N, Vagnarelli F, Memo L, Bordignon L, Saia OS, Maule M, Gallo E, Mostert M, Magnani C, Quercia M, Bollani L, Pedicino R, Renzullo L, Betta P, Mosca F, Ferrari F, Magaldi R, Stronati M, Farina D; Italian Task Force for the Study and Prevention of Neonatal Fungal Infections, Italian Society of Neonatology. Bovine lactoferrin supplementation for prevention of late-onset sepsis in very low-birth-weight neonates: a randomized trial. JAMA. 2009 Oct 7;302(13):1421-8. doi: 10.1001/jama.2009.1403.
• Ochoa TJ, Zegarra J, Cam L, Llanos R, Pezo A, Cruz K, Zea-Vera A, Carcamo C, Campos M, Bellomo S; NEOLACTO Research Group. Randomized controlled trial of lactoferrin for prevention of sepsis in peruvian neonates less than 2500 g. Pediatr Infect Dis J. 2015 Jun;34(6):571-6. doi: 10.1097/INF.0000000000000593.

Study record dates

Study Major Dates

• Study Start: December 1, 2010
• Primary Completion (Actual): October 1, 2011
• Study Completion (Actual): December 1, 2011

Study Registration Dates

• First Submitted: December 20, 2010
• First Submitted That Met QC Criteria: December 20, 2010
• First Posted (Estimate): December 21, 2010

Study Record Updates

• Last Update Posted (Estimate): September 10, 2012
• Last Update Submitted That Met QC Criteria: September 7, 2012
• Last Verified: September 1, 2012

More Information

Terms related to this study

• Keywords: infections; prevention; sepsis; neonates; 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: SIDISI 56909; OPP1015669 (Other Grant/Funding Number: Gates Foundation)