Fluconazole versus Micafungin in neonates with suspected or culture-proven Candidiasis: a randomized  pharmacokinetic and safety study

Study Objective 

This study is designed to determine whether micafungin is as efficacious as the current standard of fluconazole, as well as, compare the safety of the two drugs in the treatment of proven neonatal candidiasis.

It is also designed to further elucidate the pharmacokinetics of the two products in the growing and developing neonate and premature infant.

This is a phase 2-3, randomized study which will take place in around 15 centres across France, Belgium, The Netherlands and Spain. The study is set-up within a European project funded by the European Commission, the Health Co-operation Work Program of the 7th Framework Program. The coordinating investigator for the Project is Prof. Evelyne Jacqz-Aigrain (Hôpital Robert Debré, Paris, France) and the academic sponsor is the INSERM (Institut National de la Santé et de la Recherche Médicale).

Participation conditions

Inclusion criteria

1. Neonates and infants between 24 up to 42 weeks gestational age AND with a post-natal age of 48 hours of life up to day of life (DOL) 120 at the time of culture acquisition.

2. Requiring antifungal therapy according to medical decision by the attending physician for microbiologically documented or clinically suspected candida infection independently from the availability of any positive culture for Candida spp

3. Written informed consent from the parents or the legally authorized representative must be obtained prior to entry.

4. Infant must have sufficient venous access to permit administration of study medication and monitoring of safety variables.

Exclusion criteria

1. Infant exposed to fluconazole or micafungin prophylaxis prior to inclusion

2. Infant who has received more than 48 hours of systemic antifungal therapy (any product) prior to the first dose of study drug for treatment of the current Candida infection.

3. Infant with a concomitant medical condition, whose participation, in the opinion of the Investigator and/or medical advisor, may create an unacceptable additional risk.

4. Infant previously enrolled in this study.

5. Infant who is co-infected with a non-Candida fungal organism.

6. Neonates with isolated candiduria

7. Infant with any history of a hypersensitivity or severe vasomotor reaction to any echinocandin or fluconazole product

8. Infant with pre-existing hepatic or renal disease

Infants with baseline Candida spp. isolate resistant to fluconazole or micafungin according to EUCAST/CLSI clinical breakpoints or with an isolate for which treatment with an alternative antifungal agent is indicated, i.e. there is insufficient evidence that the species in question is a good target for therapy with either fluconazole or micafungin.

Centers managed by the CIEC:

Belgium:

Cliniques Universitaires Saint Luc- UCL, Brussels
CHC St Vincent, Rocourt
CHR de Namur, Namur
CHR de la Citadelle, Liège
Universitair Ziekenhuis Antwerpen (UZA), Antwerp

The Netherlands:

Erasmus MC-Sophia Children’s Hospital, Rotterdam
Sophia Hospital, Isala Clinics, Zwolle
VU University Medical center, Amsterdam
Wilhelmina Children's Hospital, University Medical Center, Utrecht