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Fluconazole Versus Micafungin in Neonates With Candidiasis (TINN)

Primary Purpose

Candidiasis

Status

Unknown status

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

Fluconazole

Micafungin

About this trial

This is an interventional treatment trial for Candidiasis focused on measuring TINN, Pharmacokinetic, Neonates, Antifungal, Fluconazole, Micafungin

Eligibility Criteria

24 Weeks - 42 Weeks (Child)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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.
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
Written informed consent from the parents or the legally authorized representative must be obtained prior to entry.
Infant must have sufficient venous access to permit administration of study medication and monitoring of safety variables.
And specifically for the French participants: infant shall be insured (Health Insurance) - able to understand and accept the study constraints

Exclusion Criteria:

Infant exposed to fluconazole or micafungin prophylaxis prior to inclusion
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.
Infant with a concomitant medical condition, whose participation, in the opinion of the Investigator and/or medical advisor, may create an unacceptable additional risk.
Infant previously enrolled in this study.
Infant who is co-infected with a non-Candida fungal organism.
Neonates with isolated candiduria
Infant with any history of a hypersensitivity or severe vasomotor reaction to any echinocandin or fluconazole product
Infant with pre-existing hepatic or renal disease
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.

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Fluconazole

Micafungin

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Area Under the Concentration / Minimal Inhibitory Concentration ratio (AUC/MIC ratio)

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.

Secondary Outcome Measures

Full Information

NCT ID

NCT02145832

First Posted

May 15, 2014

Last Updated

May 20, 2014

Sponsor

Institut National de la Santé Et de la Recherche Médicale, France

1. Study Identification

Unique Protocol Identification Number

NCT02145832

Brief Title

Fluconazole Versus Micafungin in Neonates With Candidiasis

Acronym

TINN

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 Type

Interventional

2. Study Status

Record Verification Date

May 2014

Overall Recruitment Status

Unknown status

Study Start Date

June 2014 (undefined)

Primary Completion Date

May 2015 (Anticipated)

Study Completion Date

May 2017 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Institut National de la Santé Et de la Recherche Médicale, France

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Candidiasis

Keywords

TINN, Pharmacokinetic, Neonates, Antifungal, Fluconazole, Micafungin

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2, Phase 3

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

100 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Fluconazole

Arm Type

Experimental

Arm Description

Arm Title

Micafungin

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Fluconazole

Other Intervention Name(s)

Antifungal

Intervention Type

Drug

Intervention Name(s)

Micafungin

Other Intervention Name(s)

Antifungal

Primary Outcome Measure Information:

Title

Area Under the Concentration / Minimal Inhibitory Concentration ratio (AUC/MIC ratio)

Description

Time Frame

One year

10. Eligibility

Sex

All

Minimum Age & Unit of Time

24 Weeks

Maximum Age & Unit of Time

42 Weeks

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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. 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 Written informed consent from the parents or the legally authorized representative must be obtained prior to entry. Infant must have sufficient venous access to permit administration of study medication and monitoring of safety variables. And specifically for the French participants: infant shall be insured (Health Insurance) - able to understand and accept the study constraints Exclusion Criteria: Infant exposed to fluconazole or micafungin prophylaxis prior to inclusion 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. Infant with a concomitant medical condition, whose participation, in the opinion of the Investigator and/or medical advisor, may create an unacceptable additional risk. Infant previously enrolled in this study. Infant who is co-infected with a non-Candida fungal organism. Neonates with isolated candiduria Infant with any history of a hypersensitivity or severe vasomotor reaction to any echinocandin or fluconazole product Infant with pre-existing hepatic or renal disease 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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Evelyne M Jacqz-Aigrain, MD PhD

Phone

00 33 1 40 03 21 50

evelyne.jacqzaigrain@gmail.com

First Name & Middle Initial & Last Name or Official Title & Degree

Frederic Legrand, PhD

frederic.legrand.rdb.aphp@gmail.com

Facility Information:

City

Antwerp, Rocourt, Liège, Louvain, Namur

Country

Belgium

City

Paris, Lyon, Saint-Pierre de la Réunion

Country

France

City

Roma, Torino, Catania, Foggia, Reggio Emilia

Country

Italy

City

Rotterdam, Amsterdam, Utrecht, Isala

Country

Netherlands

City

Malaga, Salamanca

Country

Spain

12. IPD Sharing Statement

Learn more about this trial

Fluconazole Versus Micafungin in Neonates With Candidiasis

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