Contact information
Type
Scientific
Primary contact
Dr Paolo Manzoni
ORCID ID
Contact details
Neonatology and Neonatal Intensive Care Unit
Saint Anna Hospital
C. Spezia 60
Torino
10126
Italy
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manzonipaolo@hotmail.it
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
N/A
Study information
Scientific title
Prophylaxis with lactoferrin and lactobacillusGG in Very Low Birth Weight (VLBW) neonates in Neonatal Intensive Care Unit (NICU): a double-blind, multicentre, placebo-controlled, randomised trial
Acronym
LF+LGG/PRETERMS
Study hypothesis
To evaluate the efficacy of lactoferrin (LF) (alone, or in combination with lactobacillusGG [LGG]) in prevention of bacterial and fungal colonization and infection, and Necrotising EnteroColitis (NEC), in preterm very low birth weight (i.e., <1500 g at birth) infants in NICUs.
Disease/condition/study domain:
1. Colonization by Candida species
2. Invasive infection by Candida species
3. Colonization by bacterial (Gram+ and Gram-) species
4. Invasive infection by bacterial (Gram+ and Gram-) species
5. NEC (surgical stages)
Ethics approval
Ethical Committee of the Saint Anna Foundation (Fondazione Crescere Insieme al Santa Anna - ONLUS) on behalf of each participating institution, 18/06/2007
Study design
Multicentre prospective randomised double-blind placebo-controlled trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Not specified
Trial type
Prevention
Patient information sheet
Not available in web format, please use the contact details to request a patient information sheet
Condition
Bacterial and fungal colonization and infection, and Necrotising EnteroColitis (NEC) in Very Low Birth Weight (VLBW) neonates
Intervention
The regimens in the two intervention groups will be:
Group A: LactobacillusGG, 6 x 109 Colony-Forming Units (CFU)/day (Dicoflor 60®, Dicofarm spa, Italy) plus Lactoferrin 100 mg (LF100®, Dicofarm spa, Italy), to be started within the first 36 h of life: single administration (added to prepared milk or to 1 ml of a 5% glucose solution), daily for 4 or 6 weeks.
Group B: Lactoferrin 100 mg (LF100®, Dicofarm spa, Italy), to be started within the first 36 h of life: single administration (added to prepared milk or to 1 ml of a 5% glucose solution), daily for 4 or 6 weeks.
The regimen in the placebo group will be:
Group C: Addition of 2 ml of 5% glucose solution to milk feeding, daily for 4 or 6 weeks.
Six weeks (in infants with birth weight less than 1000 g, i.e. Extremely Low Birth Weight [ELBW]) and four weeks (in the infants with birth weight 1001 g to 1500 g) are chosen as the duration of therapy on the basis of the currently published data, unless earlier discharge.
Neonates not feeding in the first 36 hours will receive the drug(s)/placebo by oral/naso-gastric tube and can be enrolled in the absence of gastric instability and/or repeated gastric residuals or vomit.
If they repeatedly display gastric instability, gastric residuals or vomit, they may be enrolled at any point during the first week of life, depending on the first "efficacious" feedings. The day of life on which they first received the drugs(s)/placebo will be recorded in the database, and their statistics will be limited to the days of administration exposure to intervention.
Intervention type
Drug
Phase
Not Applicable
Drug names
LactobacillusGG , lactoferrin
Primary outcome measure
Evaluation of the effectiveness of LF (alone, or in combination with the probiotic LGG) compared to placebo in the prevention of Bacterial and fungal colonization and infection, and of necrotizing enterocolitis (NEC), in the preterm very low birth weight neonates admitted to the participant NICUs. This will be based on the following outcome measures:
1. Assessment of the incidence of Gram-positive , Gram-negative and Candida sepsis prior to discharge
2. Mortality (overall, bacterial sepsis- and Candida-attributable) prior to discharge
3. Rate of progression from fungal colonization to fungal infection prior to discharge
4. Ligation of patent ductus arteriosus prior to discharge
5. Threshold retinopathy of prematurity requiring surgery at discharge
6. Severe (grade 3-4) intraventricular haemorrhage at discharge
7. Bronchopulmonary dysplasia at discharge
8. Incidence of organ locations (major complications) in infected patients prior to discharge
9. Absence of changes in the relative frequencies of the various Candida sub-species isolated at discharge
Secondary outcome measures
No secondary outcome measures
Overall trial start date
01/10/2007
Overall trial end date
31/07/2008
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
All neonates with birth weight <1500 g (i.e. VLBW) born within the study period, whether at one of the eighteen participating institutions or elsewhere, were eligible for the study.
Participant type
Patient
Age group
Neonate
Gender
Both
Target number of participants
219
Participant exclusion criteria
1. Parental refusal
2. Admission after 12 hours of life
3. Death prior to 72 hours of life
4. Ongoing systemic antifungal management
5. Ongoing antifungal prophylaxis
Recruitment start date
01/10/2007
Recruitment end date
31/07/2008
Locations
Countries of recruitment
Italy
Trial participating centre
Saint Anna Hospital
Torino
10126
Italy
Sponsor information
Organisation
Saint Anna Foundation (Fondazione Crescere Insieme al Santa Anna [ONLUS]) (Italy)
Sponsor details
Corso Spezia 60
Torino
10126
Italy
-
d.farina@infinito.it
Sponsor type
Charity
Website
Funders
Funder type
Industry
Funder name
Dicofarm S.p.A. will supply the LF, the LGG and placebo, and will provide financial support with a grant, but will not be involved in the concept, design, enrolment, data collection, analysis and interpretation of its results, and decision inherent the publication of the results.
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Basic results (scientific)
Publication list
2009 results in: http://www.ncbi.nlm.nih.gov/pubmed/19809023
2012 results in: http://www.ncbi.nlm.nih.gov/pubmed/22184648
2014 results in: http://www.ncbi.nlm.nih.gov/pubmed/24709463
2018 secondary analysis in: http://www.ncbi.nlm.nih.gov/pubmed/29198543
Publication citations
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Results
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, , Bovine lactoferrin supplementation for prevention of late-onset sepsis in very low-birth-weight neonates: a randomized trial., JAMA, 2009, 302, 13, 1421-1428, doi: 10.1001/jama.2009.1403.
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Results
Manzoni P, Stolfi I, Messner H, Cattani S, Laforgia N, Romeo MG, Bollani L, Rinaldi M, Gallo E, Quercia M, Maule M, Mostert M, Decembrino L, Magaldi R, Mosca F, Vagnarelli F, Memo L, Betta PM, Stronati M, Farina D, , Bovine lactoferrin prevents invasive fungal infections in very low birth weight infants: a randomized controlled trial., Pediatrics, 2012, 129, 1, 116-123, doi: 10.1542/peds.2011-0279.
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Results
Manzoni P, Meyer M, Stolfi I, Rinaldi M, Cattani S, Pugni L, Romeo MG, Messner H, Decembrino L, Laforgia N, Vagnarelli F, Memo L, Bordignon L, Maule M, Gallo E, Mostert M, Quercia M, Bollani L, Pedicino R, Renzullo L, Betta P, Ferrari F, Alexander T, Magaldi R, Farina D, Mosca F, Stronati M, Bovine lactoferrin supplementation for prevention of necrotizing enterocolitis in very-low-birth-weight neonates: a randomized clinical trial, Early Hum Dev, 2014, 90, Suppl 1, S60-S65, doi: 10.1016/S0378-3782(14)70020-9.