Bovine Lactoferrin and Neonatal Survival in Low Birth Weight Babies.

Necrotizing Enterocolitis Clinical Trial

Official title:

Can Bovine Lactoferrin Prevent Neonatal Infections in Low Birth Weight Babies in Karachi, Sindh, Pakistan.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03431558
• Other study ID #: SLAB
• Status: Recruiting
• Phase: Phase 3
• Start date: May 1, 2018
• Est. completion date: May 2020

Study information

• Verified date: April 2020
• Source: Aga Khan University
• Contact: Sajid B Soofi, MBBS,FCPS,
• Phone: +922134864798
• Email: sajid.soofi[@]aku.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 300
• Est. completion date: May 2020
• Est. primary completion date: May 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: N/A to 72 Hours

Eligibility

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.

Related Conditions & MeSH terms

• Birth Weight
• Enterocolitis
• Enterocolitis, Necrotizing
• Necrotizing Enterocolitis
• Neonatal Sepsis

Intervention

Combination Product:
• bLF (Bovine lactoferrin)
BLF administration in two different strengths (150 & 300mg) will be given on the third day of life with a single daily dose mixed with milk for 1 month.

Drug:
• Glucon-D 99.4% (Placebo)
This group will be given 100mg Glucon-D (99.4% glucose) placebo which will be similar in shape, color to the bLF.

Locations

Country	Name	City	State
Pakistan	Aga Khan University Hospital	Karachi	Sindh

Sponsors (3)

Lead Sponsor	Collaborator
Aga Khan University	United States Agency for International Development (USAID), University of Sydney

Country where clinical trial is conducted

Pakistan, 

References & Publications (9)

Anderson BF, Baker HM, Dodson EJ, Norris GE, Rumball SV, Waters JM, Baker EN. Structure of human lactoferrin at 3.2-A resolution. Proc Natl Acad Sci U S A. 1987 Apr;84(7):1769-73. — View Citation

Farnaud S, Evans RW. Lactoferrin--a multifunctional protein with antimicrobial properties. Mol Immunol. 2003 Nov;40(7):395-405. Review. — View Citation

Hug L, Sharrow D, You D. Levels & trends in child mortality: report 2017. Estimates developed by the UN Inter-agency Group for Child Mortality Estimation. 2017.

Khan A, Kinney MV, Hazir T, Hafeez A, Wall SN, Ali N, Lawn JE, Badar A, Khan AA, Uzma Q, Bhutta ZA; Pakistan Newborn Change and Future Analysis Group. Newborn survival in Pakistan: a decade of change and future implications. Health Policy Plan. 2012 Jul;27 Suppl 3:iii72-87. doi: 10.1093/heapol/czs047. — View Citation

Kramer MS. Determinants of low birth weight: methodological assessment and meta-analysis. Bull World Health Organ. 1987;65(5):663-737. Review. — View Citation

Lawn JE, Cousens S, Zupan J; Lancet Neonatal Survival Steering Team. 4 million neonatal deaths: when? Where? Why? Lancet. 2005 Mar 5-11;365(9462):891-900. — View Citation

Morrow AL, Rangel JM. Human milk protection against infectious diarrhea: implications for prevention and clinical care. Semin Pediatr Infect Dis. 2004 Oct;15(4):221-8. Review. — View Citation

Rahman S, Hameed A, Roghani MT, Ullah Z. Multidrug resistant neonatal sepsis in Peshawar, Pakistan. Arch Dis Child Fetal Neonatal Ed. 2002 Jul;87(1):F52-4. — View Citation

The World Bank. Mortality rate, neonatal (per 1,000 live births) [29/02/2016]. Available from: http://data.worldbank.org/indicator/SH.DYN.NMRT.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Late onset sepsis (LOS) in Low Birth Weight.	Reduction in late onset sepsis (LOS) in Low Birth Weight babies.	1 month
Primary	Optimal dosage of bLF	Deduce optimal dosage of bLF in LBW babies.	1 month
Secondary	Necrotizing Enterocolitis in LBW babies	Incidence of Necrotizing Enterocolitis in Low Birth Weight babies	1 month
Secondary	Neonatal Mortality at 1 month of life.	Incidence of Neonatal Mortality at 1 month of life.	1 month

External Links

•   The World Bank Mortality rate ,Neonatal (per,1000 live births) 29/02/2016
•   United.Nations Sustainable development goals