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Bovine Lactoferrin and Neonatal Survival in Low Birth Weight Babies.

Phase 3
Conditions
Necrotizing Enterocolitis
Neonatal Sepsis
Interventions
Combination Product: bLF (Bovine lactoferrin)
Drug: Glucon-D 99.4% (Placebo)
Registration Number
NCT03431558
Lead Sponsor
Aga Khan University
Brief Summary

Pakistan has the third highest number of neonatal deaths worldwide. During the last two decades (1990-2013), neonatal mortality rate in the country has declined by only 1.0% per year. Severe infection is the second most leading cause of neonatal mortality, account for 28% of all deaths in Pakistan. Majority of neonatal deaths occur in infants who LBW (birth weight \<2500g) and LBW comprises of both preterm / small for gestational age newborns. Breastfeeding helps protect infants from infections by serving as a source of nutrition uncontaminated by environmental pathogens. The protection is due to the multiple anti-infective, anti-inflammatory, and immuno regulatory factors transmitted through milk including secretory antibodies, glycan's, Lactoferrin, leukocytes, cytokines \& other components produced by the mother's immune system.

Reduction in neonatal infections and deaths is the aim of this study. The study is being conducted at the Aga Khan University in collaboration with University of Sydney.

Detailed Description

Globally, severe infection is the second leading cause of neonatal mortality. It is one of the indirect leading causes of death in a world. According to Annual report, 28% neonatal deaths were due to preterm baby, 26% due to severe infection , 23% due to asphyxia and 7% neonatal tetanus. Every year, three - fourth deaths occurred in first week and four million babies die each year within first four weeks of birth, whereas, 99% of cases were reported by low and middle income countries.Severe infections are the second major cause of death among neonates in Pakistan. Breastfeeding helps to protect infants from infections due to the multiple anti-infective, anti-inflammatory, and immuno regulatory factors such as secretory antibodies, glycan, Lactoferrin etc. Lactoferrin, the second most abundant protein in human milk has multiple putative functions. A trial in Italy found that the incidence of late-onset sepsis and sepsis related deaths were significantly lower in very LBW infants who were given daily (Bovine Lactoferrin) bLF compared to placebo. One small trial from India, found there was a 79% reduction in neonatal infections in LBW infants who received daily bovine Lactoferrin (bLF) from birth until 28 days. Evidence gaps remain about the appropriate daily prophylactic dose, the optimal method to deliver, and the effectiveness of bLF to prevent neonatal sepsis in LBW infants in low \& middle-income countries.The overall goal of the project is to improve newborn survival among low birth weight (LBW) Pakistani infants through provision of a daily prophylactic dose of bLF. The project aim is to prevent neonatal infections, as opposed to the current approach which treats neonatal infections when they occur. The current approach depends on early detection of infections in newborns through post-natal care and treatment with antibiotics, with the potential risk of inappropriate use of antibiotics.A two stage study will be conducted including formative research followed by RCT to evaluate the appropriate daily dose of bLF. At the end of the study the investigators will have developed and tested an appropriate method to deliver bLF to newborns at home \& identified the most appropriate dose of bLF to prevent neonatal sepsis in LBW newborns.

This study will be conducted at the Aga Khan University and Hospital, Karachi in two phases. A qualitative study will be conducted followed by a RCT. 300 LBW new born babies will be recruited;all standard operating procedures will be followed for administration of bLF to the neonates. Each arm of the study will be allocated 100 newborns.

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
300
Inclusion Criteria

Neonates with:

birth weight ≤ 2500 g and ≥ 1000 grams. gestational age ≥ to 28 +0 weeks to 36+6. family planned on staying in the study area for at least 1 month • parents/ caretaker willing to provide consent. newborn initiated enteral feeding via (gavage feeding with expressed breast milk or formula, direct breast feeding or cup and spoon feeding at or within 48 hours of birth.)

Exclusion Criteria

Neonate with congenital anomalies. early-onset sepsis. birth weight less than 1000 g. gestational age less than or equal to 27weeks+6 days. history of Chorioamnionitis or maternal group B streptococcus colonization. Reversed or absent end-diastolic flow on maternal umbilical artery Doppler where available.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Group 2bLF (Bovine lactoferrin)bLF (Bovine Lactoferrin plus Glucan D 99.4%) Dose: 300mg Frequency: a single daily dose mixed with milk (preferentially breast milk otherwise formula milk). Duration: 1 month
Group 1bLF (Bovine lactoferrin)bLF (Bovine Lactoferrin plus Glucan D 99.4%) Dose: 150 mg Frequency: a single daily dose mixed with milk (preferentially breast milk otherwise formula milk). Duration: 1 month
Group 3Glucon-D 99.4% (Placebo)Placebo: Only Glucan-D (99.4% glucoseDose: 150 mg Frequency: a single daily dose mixed with milk (preferentially breast milk otherwise formula milk). Duration: 1 month
Primary Outcome Measures
NameTimeMethod
Late onset sepsis (LOS) in Low Birth Weight.1 month

Reduction in late onset sepsis (LOS) in Low Birth Weight babies.

Optimal dosage of bLF1 month

Deduce optimal dosage of bLF in LBW babies.

Secondary Outcome Measures
NameTimeMethod
Necrotizing Enterocolitis in LBW babies1 month

Incidence of Necrotizing Enterocolitis in Low Birth Weight babies

Neonatal Mortality at 1 month of life.1 month

Incidence of Neonatal Mortality at 1 month of life.

Trial Locations

Locations (1)

Aga Khan University Hospital

🇵🇰

Karachi, Sindh, Pakistan

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