Prophylactic fluconazole is effective in preventing fungal colonisation and infection in preterm neonates: a multicentre, randomised trial in Italy

• Register: ISRCTN
• Last refreshed on: 13 January 2015
• Main ID: ISRCTN85753869
• Date of registration: 25/09/2006
• Prospective Registration: No
• Primary sponsor: Saint Anna Foundation (Fondazione Crescere Insieme al Santa Anna [ONLUS]) (Italy)
• Public title: Prophylactic fluconazole is effective in preventing fungal colonisation and infection in preterm neonates: a multicentre, randomised trial in Italy
• Date of first enrolment: 01/05/2004
• Target sample size: 267
• Recruitment status: Completed
• URL: http://isrctn.com/ISRCTN85753869
• Study type: Interventional
• Study design: Multicentre, prospective, randomised, double-blind, placebo-controlled trial (Treatment)

Countries of recruitment

Italy

Contacts

• Name: Paolo Manzoni

Key inclusion & exclusion criteria

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.
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)

Age minimum:
Age maximum:
Gender: Both

Health Condition(s) or Problem(s) studied

Neonatal fungal infection
Neonatal Diseases
Neonatal fungal infection

Intervention(s)

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.

Primary Outcome(s)

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(s)

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

Secondary ID(s)

N/A

Source(s) of Monetary Support

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.