Contact information
Type
Scientific
Primary contact
Dr Paolo Manzoni
ORCID ID
Contact details
Neonatology and Hospital NICU
C. Spezia 60
Torino
10126
Italy
+39 (0) 113 134 304
manzonipaolo@hotmail.it
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
N/A
Study information
Scientific title
Acronym
Study hypothesis
To evaluate the efficacy of fluconazole prophylaxis in prevention of fungal colonisation and infection (colonisation by Candida spp., or invasive infection caused by Candida spp.) in preterm very low birth weight (i.e., less than 1500 g at birth) infants in Neonatal Intensive Care Units (NICUs).
Ethics approval
Ethics Board of the Fondazione Crescere Insieme al Sant'Anna-ONLUS approved of the study on the 15/04/2004. The Fondazione is a Charity and Scientific Foundation of the Sant' Anna Hospital Institution.
Each participating Institution reviewed the protocol and was notified of the Fondazione's approval:
1. Policlinico Umberto I^ of Rome
2. Carlo Poma Hospital of Mantua
3. Mangiagalli Hospital of Milan
4. S. Matteo Hospital of Pavia
5. Arcispedale of Reggio Emilia
6. Fatebenefratelli Hospital of Benevento
7. Department of Pediatrics, University of Messina
8. Department of Pediatrics, University of Bologna
Study design
Multicentre, prospective, randomised, double-blind, placebo-controlled trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Condition
Neonatal fungal infection
Intervention
The regimens in the two intervention groups was 6 and 3 mg/kg of fluconazole (DIFLUCAN®; Pfizer Italia S.p.A.; Latina/Roma; Italy) every third day for the first two weeks, then every other day.
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 to 1500 g) were chosen as the duration of therapy on the basis of the currently published data, unless earlier discharge or need for systemic antifungal therapy due to the onset of proven or presumed invasive fungal infection.
Prophylaxis started from day of life three via a single dose intravenously or orally (via orogastric tube), depending on the availability of a venous line and/or the tolerance of oral feeding. Infants in the control group received placebo (1 ml saline) in the same way.
Intervention type
Drug
Phase
Not Specified
Drug names
Fluconazole prophylaxis
Primary outcome measures
The primary objective of the study was to evaluate the effectiveness of 3 and 6 mg/kg fluconazole compared with placebo in the prevention of Candida colonisation and infection in the preterm very low birth weight neonates admitted to the participant NICUs.
Secondary outcome measures
1. Assessment of the incidence of Gram-positive and Gram-negative sepsis
2. Mortality (overall and Candida-attributable)
3. Rate of progression from colonisation to infection
4. Necrotising enterocolitis
5. Ligation of patent ductus arteriosus
6. Threshold retinopathy of prematurity requiring surgery
7. Severe (grade 3-4) intraventricular haemorrhage
8. Bronchopulmonary dysplasia
9. Alteration of liver function as measured by serum AST, ALT, direct bilirubin and gamma-Glutamyl Transferase (gGT) values at baseline and at the end of all administrations
Overall trial start date
01/05/2004
Overall trial end date
31/07/2005
Reason abandoned
Eligibility
Participant inclusion criteria
All neonates with birth weight less than 1500 g (i.e. Very Low Birth Weight [VLBW]) born within the study period, whether at one of the eight Institutions or elsewhere, were eligible for the study.
Participant type
Patient
Age group
Neonate
Gender
Both
Target number of participants
267
Participant exclusion criteria
1. Parental refusal
2. Admission after 72 hours of life
3. Death prior to 72 hours of life
4. Liver failure (defined as three-fold elevation of Aspartate Aminotransferase [AST] and/or Alanine Aminotransferase [ALT] above the reference values)
Recruitment start date
01/05/2004
Recruitment end date
31/07/2005
Locations
Countries of recruitment
Italy
Trial participating centre
Neonatology and Hospital NICU
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
+39 (0)113 134 300
ggomirato@hotmail.com
Sponsor type
Charity
Website
Funders
Funder type
Industry
Funder name
Pfizer Italia S.p.A. (Italy) - supplied study drugs, provided financial support with a grant, but was not involved in the concept, design, enrolment, data collection, analysis and interpretation of its 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
Results in:
1. http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=retrieve&db=pubmed&list_uids=17568029
2. http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=retrieve&db=pubmed&list_uids=16326690
Publication citations
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Manzoni P, Stolfi I, Pugni L, Decembrino L, Magnani C, Vetrano G, Tridapalli E, Corona G, Giovannozzi C, Farina D, Arisio R, Merletti F, Maule M, Mosca F, Pedicino R, Stronati M, Mostert M, Gomirato G, , , A multicenter, randomized trial of prophylactic fluconazole in preterm neonates., N. Engl. J. Med., 2007, 356, 24, 2483-2495, doi: 10.1056/NEJMoa065733.
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Manzoni P, Arisio R, Mostert M, Leonessa M, Farina D, Latino MA, Gomirato G, Prophylactic fluconazole is effective in preventing fungal colonization and fungal systemic infections in preterm neonates: a single-center, 6-year, retrospective cohort study., Pediatrics, 2006, 117, 1, e22-32, doi: 10.1542/peds.2004-2227.