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Fluconazole Versus Micafungin in Neonates With Candidiasis (TINN)

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ClinicalTrials.gov Identifier: NCT02145832
Recruitment Status : Unknown
Verified May 2014 by Institut National de la Santé Et de la Recherche Médicale, France.
Recruitment status was:  Not yet recruiting
First Posted : May 23, 2014
Last Update Posted : May 23, 2014
Sponsor:
Information provided by (Responsible Party):
Institut National de la Santé Et de la Recherche Médicale, France

Brief Summary:

This study is designed to determine whether micafungin is as efficacious as the current standard of fluconazole, to 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.


Condition or disease Intervention/treatment Phase
Candidiasis Drug: Fluconazole Drug: Micafungin Phase 2 Phase 3

Detailed Description:

The epidemiology of candidiasis is rapidly changing; recent estimates are that nearly 50% of Candida bloodstream isolates are non-albicans Candida species requiring the use of treatments active against them.

Because of the high risk associated with candida infection in premature babies and fluconazole prophylaxis is now recommended in Neonatal Intensive Care Units (NICUs) with a high incidence in fungal infections. As candida infection is difficult to prove and requires an urgent treatment, in particular to avoid central nervous system (CNS) infection, treatment is often started in high risk patients when the infection is only suspected, i.e. on clinical arguments without waiting for positive cultures (10% of cases).

Fluconazole has not been approved for use in the treatment of neonatal candidiasis. In contrast, the efficacy of echinocandins for the treatment of invasive candidiasis has been suggested by pre-clinical and clinical studies.

Related to Micafungin, the available data suggest that only dosages that are greater than what currently recommended in infants (2 to 4 mg/kg/day) may ensure adequate coverage of the CNS, given that ability of low dosages of micafungin to penetrate the cerebrospinal compartment and to diffuse in the cerebrospinal fluid is deemed suboptimal.

The doses that will be administered are higher that currently used in order to optimize efficacy, and the concept of a loading dose that will be used for both drugs in this project, is present in antifungal treatment strategies for adults, but it has never been applied to infants and preterm neonates.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Fluconazole Versus Micafungin in Neonates With Suspected or Culture-proven Candidiasis: a Randomized Pharmacokinetic and Safety Study (TINN Project - Treat Infections iN Neonates)
Study Start Date : June 2014
Estimated Primary Completion Date : May 2015
Estimated Study Completion Date : May 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Yeast Infections

Arm Intervention/treatment
Experimental: Fluconazole

Fluconazole Kabi, Fresenius 2mg/ml

Fluconazole will be administered at a loading dose of 25 mg/kg on the first day and followed by a maintenance dose of 12 mg/kg or 20 mg/kg once daily, depending of corrected gestational age (GA) at the beginning of treatment:

  • 12 mg/kg/day for neonates corrected GA (GA + postnatal age) < 30 weeks
  • 20 mg/kg/day for neonates corrected GA (GA + postnatal age) ≥ 30 weeks

The infusion will last two hours.

Drug: Fluconazole
Other Name: Antifungal

Experimental: Micafungin

Mycamine 50mg - 10 mg/mL of micafungin

Micafungin will be administered as a loading dose of 15 mg/kg on the first day of treatment and followed by a maintenance dose of 10 mg/kg once daily.

The infusion will last two hours.

Drug: Micafungin
Other Name: Antifungal




Primary Outcome Measures :
  1. Area Under the Concentration / Minimal Inhibitory Concentration ratio (AUC/MIC ratio) [ Time Frame: One year ]
    AUC/MIC ratio in the two treated groups (both fluconazole and micafungin) is used as primary outcome. The theoretical "Minimum Inhibitory Concentration required to inhibit the growth of 90% of organisms" (MIC90s) against the common pathogens responsible for the infection to be treated will be used by opposition with the "real MIC90" of the agent really involved that is rarely isolated.



Information from the National Library of Medicine

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Ages Eligible for Study:   24 Weeks to 42 Weeks   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.
  5. And specifically for the French participants: infant shall be insured (Health Insurance) - able to understand and accept the study constraints

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
  9. Infants with baseline Candida spp. isolate resistant to fluconazole or micafungin according to "EUropean Committee on Antimicrobial Susceptibility Testing" and "Clinical and Laboratory Standards Institute" (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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02145832


Contacts
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Contact: Evelyne M Jacqz-Aigrain, MD PhD 00 33 1 40 03 21 50 evelyne.jacqzaigrain@gmail.com
Contact: Frederic Legrand, PhD frederic.legrand.rdb.aphp@gmail.com

Locations
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Belgium
Antwerp, Rocourt, Liège, Louvain, Namur, Belgium
France
Paris, Lyon, Saint-Pierre de la Réunion, France
Italy
Roma, Torino, Catania, Foggia, Reggio Emilia, Italy
Netherlands
Rotterdam, Amsterdam, Utrecht, Isala, Netherlands
Spain
Malaga, Salamanca, Spain
Sponsors and Collaborators
Institut National de la Santé Et de la Recherche Médicale, France
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Responsible Party: Institut National de la Santé Et de la Recherche Médicale, France
ClinicalTrials.gov Identifier: NCT02145832    
Other Study ID Numbers: C11-11
2012-001916-41 ( EudraCT Number )
First Posted: May 23, 2014    Key Record Dates
Last Update Posted: May 23, 2014
Last Verified: May 2014
Keywords provided by Institut National de la Santé Et de la Recherche Médicale, France:
TINN
Pharmacokinetic
Neonates
Antifungal
Fluconazole
Micafungin
Additional relevant MeSH terms:
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Candidiasis
Mycoses
Fluconazole
Micafungin
Antifungal Agents
Clotrimazole
Miconazole
Anti-Infective Agents
14-alpha Demethylase Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Steroid Synthesis Inhibitors
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Cytochrome P-450 CYP2C9 Inhibitors
Cytochrome P-450 CYP2C19 Inhibitors
Anti-Infective Agents, Local
Cytochrome P-450 CYP3A Inhibitors