Condition category
Neonatal Diseases
Date applied
19/09/2006
Date assigned
25/09/2006
Last edited
19/09/2007
Prospective/Retrospective
Retrospectively 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 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 (DIFLUCANĀ®; 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

  1. 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.

  2. 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.

Additional files

Editorial Notes