Determination of Levels of Micafungin in Neonates Suffering from Systemic Candidiasis and/or Candida meningitis.

Determination of Plasmatic and CSF Levels Of High Doses Of Micafungin in Neonates Suffering from Systemic Candidiasis and/or Candida meningitis.

Status

Active, not recruiting

Phases

Phase 2

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2014-003087-20-IT

Enrollment

Registered

2014-08-26

Start date

2014-11-12

Completion date

Unknown

Last updated

2022-04-04

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Systemic Candidiasis and/or Candida Meningitis MedDRA version: 17.0 Level: LLT Classification code 10027238 Term: Meningitis fungal NOS System Organ Class: 100000004862 MedDRA version: 17.0 Level: HLT Classification code 10027237 Term: Meningeal fungal infections System Organ Class: 100000004852 MedDRA version: 17.0 Level: LLT Classification code 10042941 Term: Systemic fungal infection NOS System Organ Class: 100000004862

Interventions

Trade Name: Mycamine Pharmaceutical Form: Powder for solution for infusion INN or Proposed INN: MICAFUNGIN CAS Number: 235114-32-6 Concentration unit: mg/kg milligram(s)/kilogram Concentration type: e

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: 1. Infection by systemic Candidiasis, definite or suspected. a) Definite systemic Candidiasis is diagnosed in case of isolation of Candida from at least one sample collected from a normally sterile site (Blood, CSF, Urine, Peritoneal Fluid) and/or positivity to Candida through 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 (WBC =5000/mm3 or WBC =20.000/mm3, 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). b) Suspected systemic Candidiasis is diagnosed in case of worsening of clinical conditions while on therapy with antibiotics, isolation of Candida from at least two non contiguous sites (tracheal aspirate, gastric aspirate, faeces) 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 (WBC =5000/mm3 or WBC =20.000/mm3, 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 positivity to test ELISA for the mannan antigen (=250 pg/ml). 2. Neonates affected by definite or suspected Candida meningitis and/or hydrocephalus due to Candida infection and/or bearing external ventricular derivation, until enrolment of 4 subjects with this characteristics. 3. Parents of neonates, or their legal representative, able to consent and comply with protocol requirements. 4. Survival expectation not inferior to 3 days. Are the trial subjects under 18? yes Number of subjects for this age range: 30 F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range

Exclusion criteria

Exclusion criteria: 1. Hepatic acute or chronic insufficiency with at least one of the following abnormal parameters: a. Ammonium > 85 µg/dL b. ALT/GPT > 40 UI/L c. AST/GOT > 40 UI/L d. Direct Bilirubin > 2mg/dL 2. Baseline INR >5% 3. Known allergy or hypersensitivity to echinocandins or any of the excipients present in the formulation of the IMP. 4. Micafungin infusion already started. 5. Neonates affected by definite or suspected Candida meningitis and/or hydrocephalus due to Candida infection and/or bearing external ventricular derivation, if already 4 subjects with this characteristics have been enrolled into the study.

Design outcomes

Secondary

Measure	Time frame
Secondary end point(s): 1) To evaluate the percentage of success and failure of therapy with micafungin, among treated patients, on the basis of the following definitions: - In case of definite or suspected sepsis, the success of the therapy will be determined by survival associated with the negative results to Candida test of two consecutive blood cultures, performed starting from the beginning of treatment, or, only in case of suspected sepsis, determined by resolution of clinical and laboratory symptoms together with reduction of mannan antigen blood level (<250 pg/ml). - In case of definite or suspected sepsis, the failure of the therapy will be determined by death due to Candida sepsis, by confirmation of persistence of positive result to Candida test at 14th (± 2days) day from one blood culture performed in the previous days, by the need to add or switch to another antifungal agent and/or change of micafungin dosage for the resolution of infection at any time or, only in case of suspected sepsis, by the persistence of Candida colonization in the different indicated sites associated with the persistence of clinical and laboratory symptoms and with high blood level of the mannan antigen (=250 pg/ml) at 14th day (± 2days) from the start of the therapy. - In case of Candida meningitis, the success of the therapy will be determined by survival associated with the negative results to Candida test of at least three consecutive CSF cultures, performed starting from the beginning of treatment, and resolution of clinical and laboratory symptoms. - In case of Candida meningitis, the failure of the therapy will be determined by death due to Candida meningitis, by persistence of Candida infection as resulted from confirmation of positive CSF culture after the 14th day of therapy (± 2days) or by the need to add or switch to another antifungal agent or dosage change of micafungin for the resolution of Candida infection at any time. - In case of neonates with hydrocep	—

Measure

Time frame

Secondary end point(s): 1) To evaluate the percentage of success and failure of therapy with micafungin, among treated patients, on the basis of the following definitions: - In case of definite or suspected sepsis, the success of the therapy will be determined by survival associated with the negative results to Candida test of two consecutive blood cultures, performed starting from the beginning of treatment, or, only in case of suspected sepsis, determined by resolution of clinical and laboratory symptoms together with reduction of mannan antigen blood level (<250 pg/ml). - In case of definite or suspected sepsis, the failure of the therapy will be determined by death due to Candida sepsis, by confirmation of persistence of positive result to Candida test at 14th (± 2days) day from one blood culture performed in the previous days, by the need to add or switch to another antifungal agent and/or change of micafungin dosage for the resolution of infection at any time or, only in case of suspected sepsis, by the persistence of Candida colonization in the different indicated sites associated with the persistence of clinical and laboratory symptoms and with high blood level of the mannan antigen (=250 pg/ml) at 14th day (± 2days) from the start of the therapy. - In case of Candida meningitis, the success of the therapy will be determined by survival associated with the negative results to Candida test of at least three consecutive CSF cultures, performed starting from the beginning of treatment, and resolution of clinical and laboratory symptoms. - In case of Candida meningitis, the failure of the therapy will be determined by death due to Candida meningitis, by persistence of Candida infection as resulted from confirmation of positive CSF culture after the 14th day of therapy (± 2days) or by the need to add or switch to another antifungal agent or dosage change of micafungin for the resolution of Candida infection at any time. - In case of neonates with hydrocep

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Primary

Measure	Time frame
Main Objective: To study the pharmacokinetic profile of micafungin administered, at a dose of 8 mg/Kg/day, to neonates suffering from definite or suspected systemic Candidiasis. ;Secondary Objective: • To evaluate the proportion of success and of failure of the therapy with micafungin among treated neonates • To 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 • To evaluate the safety of Micafungin in neonates ;Primary end point(s): • Quantification of micafungin levels into blood, through samples collected with capillary micro-method (draws from the heel). Blood draws are to be taken before infusion with the IMP and after 1, 2 and 8 hours from the end of the intravenous infusion, in one of the treatment days starting from the third and within the tenth. • Quantification of micafungin levels in the cerebrospinal fluid, through samples collected from 4 neonates with Candida meningitis, hydrocephalus due to Candida infection and/or with external ventricular derivation. CSF draws are to be taken before infusion with the IMP and after 1, 2 and 8 hours from the end of the intravenous infusion, in one of the treatment days starting from the third and within the tenth.;Timepoint(s) of evaluation of this end point: Between third and tenth day of therapy.	—

Measure

Time frame

Main Objective: To study the pharmacokinetic profile of micafungin administered, at a dose of 8 mg/Kg/day, to neonates suffering from definite or suspected systemic Candidiasis. ;Secondary Objective: • To evaluate the proportion of success and of failure of the therapy with micafungin among treated neonates • To 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 • To evaluate the safety of Micafungin in neonates ;Primary end point(s): • Quantification of micafungin levels into blood, through samples collected with capillary micro-method (draws from the heel). Blood draws are to be taken before infusion with the IMP and after 1, 2 and 8 hours from the end of the intravenous infusion, in one of the treatment days starting from the third and within the tenth. • Quantification of micafungin levels in the cerebrospinal fluid, through samples collected from 4 neonates with Candida meningitis, hydrocephalus due to Candida infection and/or with external ventricular derivation. CSF draws are to be taken before infusion with the IMP and after 1, 2 and 8 hours from the end of the intravenous infusion, in one of the treatment days starting from the third and within the tenth.;Timepoint(s) of evaluation of this end point: Between third and tenth day of therapy.

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Countries

Italy

Contacts

Public ContactCinzia Auriti

IRCCS Ospedale Pediatrico Bambino Gesù

+390668592347

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026