Clinical trial NCT03421002: Determination of Levels of Micafungin in Neonates Suffering From Systemic Candidiasis and/or Candida Meningitis
Official title: Determination of Plasmatic and CSF Levels of High Doses of Micafungin in Neonates Suffering From Systemic Candidiasis and/or Candida Meningitis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Candidiasis, Systemic
Candida Meningitis
Keywords: candida meningitis
Mycamine
candidiasis, systemic
micafungin
Lead sponsor: Astellas Pharma Inc
Sponsor class: INDUSTRY
Collaborators: name: IRCCS, Ospedale Pediatrico Bambino Gesu
First posted: 2018-02-05
Enrollment: 35
Sex: ALL
Minimum age (years): 1
Maximum age (years): 180
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The primary purpose of this study is to evaluate the pharmacokinetic profile of micafungin administered to neonates suffering from systemic candidiasis. This study will also evaluate the proportion of success and of failure of the therapy with micafungin among treated neonates and will identify a conversion factor to relate plasma levels of micafungin into capillary and venous blood measured through blood samples from the heel and from a peripheral vein, collected simultaneously. Safety of micafungin in neonates will also be assessed.


Eligibility criteria: Inclusion Criteria:

* Infection by systemic candidiasis Systemic candidiasis is diagnosed in case of worsening of clinical conditions while on therapy with antibiotics, in case of isolation of candida from at least one sample collected from a normally sterile site (Blood, CSF, Urine, Peritoneal Fluid) and/or from at least two non contiguous sites (tracheal aspirate, gastric aspirate, faeces) and/or positivity to candida through polymerase chain reaction (PCR)(Septifast test), associated with at least one clinical symptom (fever or hypothermia, mottled skin, feeding difficulties, muscular hypotonia or hypertonia, apnoea crisis, bradycardia, tachycardia, hypotension, dyspnea, polypnea, desaturation) and one laboratory symptom (white blood cell \[WBC\] ≤5000/mm3 or WBC ≥20.000/mm3, immature to total neutrophil ratio \[I/T ratio\] \>2, Platelet count ≤100.000/mm3, C-reactive Protein \>0,5 mg/dL, Standard Base Excess \>-7 mmol/L, CSF pleocytosis-cells ≥ 6) and/or positivity to test Enzyme Linked Immuno-Sorbent Assay (ELISA) for the mannan antigen (≥125 pg/ml).
* Neonates affected by candida meningitis and/or hydrocephalus due to candida infection and/or bearing external ventricular derivation, until enrollment of at least 4 subjects with this characteristics.
* Parents of neonates, or legal representative, able to consent and comply with protocol requirements.
* Survival expectation not inferior to 3 days.

Exclusion Criteria:

* Acute hepatopathy (ammonium \> 200 µg/dL) or chronic hepatopathy.
* Known allergy or hypersensitivity to echinocandins or any of the excipients present in the formulation of the investigational product.

Primary outcomes:
measure: Concentration of Micafungin in Blood
timeFrame: Predose and after 1, 3, and 8 hours post-dose on one of treatment days from Day 3 to Day 10
measure: Concentration of Micafungin in Cerebral Spinal Fluid (CSF)
timeFrame: Predose and after 1, 3, and 8 hours post-dose on one of treatment days from Day 3 to Day 10
Secondary outcomes:
measure: Percentage of Participants with a Response at End of Treatment (EOT) - Success of Therapy (SOT)
timeFrame: Up to day 14
measure: Percentage of Participants with A Response at EOT - Failure of Therapy (FOT)
timeFrame: Up to day 14
measure: Number of Participants with Adverse Events (AEs)
timeFrame: From the first dose of study drug administration up 72 hours after the last dose, up to 17 days
measure: Comparison of Capillary and Venous Plasma Concentrations of Micafungin
timeFrame: Predose and after 1, 3, and 8 hours post-dose on one of treatment days from Day 3 to Day 10
Other outcomes:
Locations:
city: Rome
country: Italy
facility: Site IT39001
city: Rome
country: Italy
facility: Site IT39002
Study officials:
affiliation: Astellas Pharma Global Development, Inc.
name: Executive Medical Director
role: STUDY_DIRECTOR
References:
citation: Auriti C, Goffredo BM, Ronchetti MP, Piersigilli F, Cairoli S, Bersani I, Dotta A, Bagolan P, Pai MP. High-Dose Micafungin in Neonates and Young Infants with Invasive Candidiasis: Results of a Phase 2 Study. Antimicrob Agents Chemother. 2021 Mar 18;65(4):e02494-20. doi: 10.1128/AAC.02494-20. Print 2021 Mar 18.