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Bovine Lactoferrin and Neonatal Survival in Low Birth Weight Babies.

Primary Purpose

Neonatal Sepsis, Necrotizing Enterocolitis

Status
Unknown status
Phase
Phase 3
Locations
Pakistan
Study Type
Interventional
Intervention
bLF (Bovine lactoferrin)
Glucon-D 99.4% (Placebo)
Sponsored by
Aga Khan University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Neonatal Sepsis focused on measuring Bovine Lactoferrin, Neonatal infection, Low Birth Weight

Eligibility Criteria

48 Hours - 72 Hours (Child)All SexesAccepts Healthy Volunteers

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.

Sites / Locations

  • Aga Khan University HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Placebo Comparator

Arm Label

Group 1

Group 2

Group 3

Arm Description

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

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

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

Outcomes

Primary Outcome Measures

Late onset sepsis (LOS) in Low Birth Weight.
Reduction in late onset sepsis (LOS) in Low Birth Weight babies.
Optimal dosage of bLF
Deduce optimal dosage of bLF in LBW babies.

Secondary Outcome Measures

Necrotizing Enterocolitis in LBW babies
Incidence of Necrotizing Enterocolitis in Low Birth Weight babies
Neonatal Mortality at 1 month of life.
Incidence of Neonatal Mortality at 1 month of life.

Full Information

First Posted
February 6, 2018
Last Updated
April 8, 2020
Sponsor
Aga Khan University
Collaborators
University of Sydney, United States Agency for International Development (USAID)
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1. Study Identification

Unique Protocol Identification Number
NCT03431558
Brief Title
Bovine Lactoferrin and Neonatal Survival in Low Birth Weight Babies.
Official Title
Can Bovine Lactoferrin Prevent Neonatal Infections in Low Birth Weight Babies in Karachi, Sindh, Pakistan.
Study Type
Interventional

2. Study Status

Record Verification Date
April 2020
Overall Recruitment Status
Unknown status
Study Start Date
May 1, 2018 (Actual)
Primary Completion Date
May 2020 (Anticipated)
Study Completion Date
May 2020 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Aga Khan University
Collaborators
University of Sydney, United States Agency for International Development (USAID)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Neonatal Sepsis, Necrotizing Enterocolitis
Keywords
Bovine Lactoferrin, Neonatal infection, Low Birth Weight

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Model Description
Group 1: bLF (150 mg) will be administered after 48 hours of age with a single daily dose mixed with milk (preferentially breast milk otherwise premature formula milk). Group 2: bLF will be administered (300mg) after 48 hours of life with a single daily dose mixed with milk (preferentially breast milk otherwise premature formula milk). Group 3: Placebo will be administered after 48 hours of life (Placebo will be physically identical to the bLF mixed with breast milk or premature formula milk).
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
Randomization will be carried out by Data management unit and all investigators /dispensers and participants will be masked to the randomization. Clinical Trial Unit (CTU) of the Aga khan university will dispense the randomized supplemnt/placebo
Allocation
Randomized
Enrollment
300 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Group 1
Arm Type
Experimental
Arm Description
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
Arm Title
Group 2
Arm Type
Experimental
Arm Description
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
Arm Title
Group 3
Arm Type
Placebo Comparator
Arm Description
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
Intervention Type
Combination Product
Intervention Name(s)
bLF (Bovine lactoferrin)
Other Intervention Name(s)
bLF
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Glucon-D 99.4% (Placebo)
Other Intervention Name(s)
Placebo
Intervention Description
This group will be given 100mg Glucon-D (99.4% glucose) placebo which will be similar in shape, color to the bLF.
Primary Outcome Measure Information:
Title
Late onset sepsis (LOS) in Low Birth Weight.
Description
Reduction in late onset sepsis (LOS) in Low Birth Weight babies.
Time Frame
1 month
Title
Optimal dosage of bLF
Description
Deduce optimal dosage of bLF in LBW babies.
Time Frame
1 month
Secondary Outcome Measure Information:
Title
Necrotizing Enterocolitis in LBW babies
Description
Incidence of Necrotizing Enterocolitis in Low Birth Weight babies
Time Frame
1 month
Title
Neonatal Mortality at 1 month of life.
Description
Incidence of Neonatal Mortality at 1 month of life.
Time Frame
1 month

10. Eligibility

Sex
All
Minimum Age & Unit of Time
48 Hours
Maximum Age & Unit of Time
72 Hours
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Sajid B Soofi, MBBS,FCPS,
Phone
+922134864798
Ext
4798
Email
sajid.soofi@aku.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Asghar Ali, MRA,MBA
Phone
92 213 493 0051
Ext
2279
Email
asghar.ali@aku.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Shabina Ariff, MBBS,FCPS
Organizational Affiliation
Aga Khan University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Michael J Dibley, MB BS, MPH
Organizational Affiliation
University of Sydney
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Almas Aamir, MSC
Organizational Affiliation
Aga Khan University
Official's Role
Study Director
Facility Information:
Facility Name
Aga Khan University Hospital
City
Karachi
State/Province
Sindh
ZIP/Postal Code
74800
Country
Pakistan
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Shabina Associate Professor
Phone
+92 21 34864357
Ext
4357
Email
Shabina.ariff@aku.edu
First Name & Middle Initial & Last Name & Degree
Dr. Saajid B Soofi Soofi, FCPS MBBS
Phone
+92 21 99244230
Ext
8186
Email
Sajid.soofi@aku.edu
First Name & Middle Initial & Last Name & Degree
Neeloy A Alam
First Name & Middle Initial & Last Name & Degree
William T Mordi

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
22692418
Citation
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.
Results Reference
background
PubMed Identifier
15752534
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. doi: 10.1016/S0140-6736(05)71048-5.
Results Reference
background
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.
Results Reference
background
PubMed Identifier
14568385
Citation
Farnaud S, Evans RW. Lactoferrin--a multifunctional protein with antimicrobial properties. Mol Immunol. 2003 Nov;40(7):395-405. doi: 10.1016/s0161-5890(03)00152-4.
Results Reference
background
PubMed Identifier
3470756
Citation
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. doi: 10.1073/pnas.84.7.1769.
Results Reference
background
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.
Results Reference
background
PubMed Identifier
3322602
Citation
Kramer MS. Determinants of low birth weight: methodological assessment and meta-analysis. Bull World Health Organ. 1987;65(5):663-737.
Results Reference
background
PubMed Identifier
12091293
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. doi: 10.1136/fn.87.1.f52.
Results Reference
background
PubMed Identifier
15494945
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. doi: 10.1053/j.spid.2004.07.002.
Results Reference
background
PubMed Identifier
33704071
Citation
Ariff S, Soofi S, Aamir A, D'Almeida M, Aziz Ali A, Alam A, Dibley M. Bovine Lactoferrin to Prevent Neonatal Infections in Low-Birth-Weight Newborns in Pakistan: Protocol for a Three-Arm Double-Blind Randomized Controlled Trial. JMIR Res Protoc. 2021 Mar 11;10(3):e23994. doi: 10.2196/23994.
Results Reference
derived
Links:
URL
http://data.worldbank.org/indicator/SH.DYN.NMRT
Description
The World Bank Mortality rate ,Neonatal (per,1000 live births) 29/02/2016
URL
http://www.un.org/sustainabledevelopment/health
Description
United.Nations Sustainable development goals

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Bovine Lactoferrin and Neonatal Survival in Low Birth Weight Babies.

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