CandidiasisPhase 2/3TINNNCT02145832
Fluconazole Versus Micafungin in Neonates With Candidiasis
A Phase 2/3 study testing Fluconazole and Micafungin in people with Candidiasis, run by Institut National de la Santé Et de la Recherche Médicale, France at 5 sites in 5 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 24 to 42 weeks
- Conditions the study is for
- Candidiasis
- What is being tested?
- Fluconazole and Micafungin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 5 sitesin 5 countries
- Study dates
- Oct 2014to Nov 2015
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 24 to 42 weeks
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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
Who cannot join
- 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
Show all 9Show fewer
- 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.
Trial locations and contacts
5 sites in 5 countries.
5 sites in 5 countries
About this study
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)
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.
Read the 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.
- Conditions
- Candidiasis
- Being tested
- Fluconazole, Micafungin
- Keywords
- TINN, Pharmacokinetic, Neonates, Antifungal, Fluconazole, Micafungin
- Medical subject headings
- Candidiasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FluconazoleDrug
Also called Antifungal
MicafunginDrug
Also called Antifungal
| Study group | Role | What they receive |
|---|---|---|
| Fluconazole | Experimental | 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. Receives: Drug: Fluconazole |
| Micafungin | Experimental | 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. Receives: Drug: Micafungin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: One year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 May 2014 (estimated)
- Study startOct 2014
- Primary completionNov 2015
- Study completionNov 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for CandidiasisStudies of the same condition, open and under way.
- More trials run by Institut National de la Santé Et de la Recherche Médicale, FranceThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Sponsor type
- Other government
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02145832
- Sponsor's protocol ID
- C11-11
- Other IDs
- 2012-001916-41
- Acronym
- TINN
- Status last verified
- Jan 2025
- First submitted
- 15 May 2014
- Last updated
- 4 Sep 2025
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Leroux S, Jacqz-Aigrain E, Elie V, Legrand F, Barin-Le Guellec C, Aurich B, Biran V, Dusang B, Goudjil S, Coopman S, Garcia Sanchez R, Zhao W, Manzoni P; FP7 TINN (Treat Infections in NeoNates) consortium. Pharmacokinetics and safety of fluconazole and micafungin in neonates with systemic candidiasis: a randomized, open-label clinical trial. Br J Clin Pharmacol. 2018 Sep;84(9):1989-1999. doi: 10.1111/bcp.13628. Epub 2018 Jun 21.
PubMed 29744900
Study at a glance
From the registry record, last updated by the sponsor on 4 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT02145832
- Acronym / sponsor ID
- TINN / C11-11
- Conditions
- Candidiasis
- Keywords
- TINN, Pharmacokinetic, Neonates, Antifungal, Fluconazole, Micafungin
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Institut National de la Santé Et de la Recherche Médicale, FranceOther government
- Study start
- Oct 2014 (actual)
- Primary completion
- Nov 2015 (actual)
- Study completion
- Nov 2015 (actual)
- First posted
- 23 May 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Fluconazole | Experimental | Drug: FluconazoleFluconazole 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. |
| Micafungin | Experimental | Drug: MicafunginMycamine 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. |
Who may qualify
- Ages
- 24 to 42 weeks
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (9 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| FluconazoleAlso: Antifungal | Drug | Fluconazole |
| MicafunginAlso: Antifungal | Drug | Micafungin |
Primary outcome
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.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Sep 2025.
- Results publication: PubMed 29744900Leroux S, Jacqz-Aigrain E, Elie V, Legrand F, Barin-Le Guellec C, Aurich B, Biran V, Dusang B, Goudjil S, Coopman S, Garcia Sanchez R, Zhao W, Manzoni P; FP7 TINN (Treat Infections in NeoNates) consortium. Pharmacokinetics and safety of fluconazole and micafungin in neonates with systemic candidiasis: a randomized, open-label clinical trial. Br J Clin Pharmacol. 2018 Sep;84(9):1989-1999. doi: 10.1111/bcp.13628. Epub 2018 Jun 21.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
5 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Fluconazole and Micafungin in people with Candidiasis, run by Institut National de la Santé Et de la Recherche Médicale, France at 5 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in Belgium, France, Italy, Netherlands, Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Area Under the Concentration / Minimal Inhibitory Concentration ratio (AUC/MIC ratio) (time frame: One year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02145832, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Sep 2025.