Condition category
Neonatal Diseases
Date applied
20/08/2007
Date assigned
06/09/2007
Last edited
15/02/2012
Prospective/Retrospective
Prospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

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
manzonipaolo@hotmail.it

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

N/A

Study information

Scientific title

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. Approved on 18th 2007 June.

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 below 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 Specified

Drug names

lactobacillusGG , lactoferrin

Primary outcome measures

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

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

Neonatology and Neonatal Intensive Care Unit
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

http://www.fondazionesantanna.it/

Funders

Funder type

Hospital/treatment centre

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

Results - basic reporting

Publication summary

1. 2009 results in http://www.ncbi.nlm.nih.gov/pubmed/19809023
2. 2012 results in http://www.ncbi.nlm.nih.gov/pubmed/22184648

Publication citations

  1. 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.

  2. 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.

Additional files

Editorial Notes