Back to resultsDetermination of Levels of Micafungin in Neonates Suffering From Systemic Candidiasis and/or Candida Meningitis
Primary Purpose
Candidiasis, Systemic, Candida Meningitis
Status
Completed
Phase
Phase 2
Locations
Italy
Study Type
Interventional
Intervention
Micafungin
Sponsored by
About this trial
This is an interventional treatment trial for Candidiasis, Systemic focused on measuring candida meningitis, Mycamine, candidiasis, systemic, micafungin
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.
Sites / Locations
- Site IT39001
- Site IT39002
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Micafungin
Arm Description
Participants will receive micafungin 8 mg/kg per day via intravenous infusion for approximately 1 hour. Micafungin will be administered for a minimum of 14 days until 1 of the following conditions applied: •Negative results (absence of Candida growth) from at least 2 consecutive blood cultures and/or resolution of clinical and laboratory symptoms and reduction of mannan antigen blood level (< 125 pg/mL) are obtained. •In case of meningitis, hydrocephalus and external ventricular derivation, negative results (absence of Candida growth) from at least 2 consecutive cerebral spinal fluid (CSF) cultures associated with resolution of clinical and laboratory symptoms. •Interruption (including addition or switch to another antifungal agent or dosage change of micafungin) due to demonstration of therapy failure.
Outcomes
Primary Outcome Measures
Concentration of Micafungin in Blood
Concentration will be determined from the pharmacokinetic (PK) blood samples collected via capillary micro-method (draws from the heel).
Concentration of Micafungin in Cerebral Spinal Fluid (CSF)
Concentration will be determined from the from the CSF samples collected.
Secondary Outcome Measures
Percentage of Participants with a Response at End of Treatment (EOT) - Success of Therapy (SOT)
For systemic candidiasis (SC) participants, SOT will be determined by survival associated with negative Candida test results of 2 consecutive blood cultures, completed at start of treatment, or resolution of clinical & laboratory symptoms together with reduction of mannan antigen blood level (MABL) (<125 pg/ml). For Candida meningitis (CM), SOT will be determined by survival associated with negative Candida test results of at least 2 consecutive CSF cultures, completed at start of treatment and resolution of clinical and lab symptoms. For hydrocephalus due to Candida infection (CI) and/or external ventricular derivation (EVD), SOT will be determined by survival associated with negative Candida test results of at least 2 consecutive CSF cultures, completed at start of treatment.
Percentage of Participants with A Response at EOT - Failure of Therapy (FOT)
For SC participants, FOT will be determined by death due to Candida sepsis, by confirmation of persistence of positive Candida test results from 1 blood culture completed by need to add/switch to another antifungal agent (AA) and/or change of micafungin dose for resolution of infection at any time or by the persistence of Candida colonization in different indicated sites associated with persistence of clinical and lab symptoms and with high (MABL) (≥ 125 pg/ml). For CM, FOT will be determined by death due to CM, by persistence of CI from confirmation of positive CSF culture or by need to add/switch to another AA or dose change of micafungin for resolution of CI at any time. For hydrocephalus due to CI and/or EVD, FOT will be determined by death due to CI, by need to add/switch to another AA or dose change of micafungin for resolution of CI at any time or by persistence of CI from confirmation of positive CSF culture.
Number of Participants with Adverse Events (AEs)
An adverse event (AE) will be defined as any untoward medical occurrence in a participant administered a study drug or who will undergo study procedures which may not necessarily have a causal relationship with this treatment. This includes abnormal laboratory tests, vital signs, electrocardiogram data or physical examinations that are defined as AEs if the abnormality will induce clinical signs or symptoms, require active intervention, interruption or discontinuation of study drug or may be clinically significant in the investigator's opinion. The following standard with 3 grades will be used to measure the severity of AEs, including abnormal clinical laboratory values: ● Mild: No disruption of normal daily activities ● Moderate: Affected normal daily activities ● Severe: Inability to perform daily activities. A treatment-emergent adverse event (TEAE) will be defined as an AE observed after starting administration of the test drug/comparative drug.
Comparison of Capillary and Venous Plasma Concentrations of Micafungin
Micafungin concentrations will be determined from the PK blood samples collected via both capillary micro-method (draws from the heel) and venous methods.
Full Information
NCT ID
NCT03421002
First Posted
January 9, 2018
Last Updated
April 15, 2019
Sponsor
Astellas Pharma Global Development, Inc.
Collaborators
IRCCS, Ospedale Pediatrico Bambino Gesu
1. Study Identification
Unique Protocol Identification Number
NCT03421002
Brief Title
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
2. Study Status
Record Verification Date
April 2019
Overall Recruitment Status
Completed
Study Start Date
May 30, 2015 (Actual)
Primary Completion Date
April 10, 2018 (Actual)
Study Completion Date
April 10, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Astellas Pharma Global Development, Inc.
Collaborators
IRCCS, Ospedale Pediatrico Bambino Gesu
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Candidiasis, Systemic, Candida Meningitis
Keywords
candida meningitis, Mycamine, candidiasis, systemic, micafungin
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
35 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Micafungin
Arm Type
Experimental
Arm Description
Participants will receive micafungin 8 mg/kg per day via intravenous infusion for approximately 1 hour. Micafungin will be administered for a minimum of 14 days until 1 of the following conditions applied: •Negative results (absence of Candida growth) from at least 2 consecutive blood cultures and/or resolution of clinical and laboratory symptoms and reduction of mannan antigen blood level (< 125 pg/mL) are obtained. •In case of meningitis, hydrocephalus and external ventricular derivation, negative results (absence of Candida growth) from at least 2 consecutive cerebral spinal fluid (CSF) cultures associated with resolution of clinical and laboratory symptoms. •Interruption (including addition or switch to another antifungal agent or dosage change of micafungin) due to demonstration of therapy failure.
Intervention Type
Drug
Intervention Name(s)
Micafungin
Other Intervention Name(s)
Mycamine
Intervention Description
Participants will receive micafungin 8 mg/kg per day via intravenous infusion for approximately 1 hour.
Primary Outcome Measure Information:
Title
Concentration of Micafungin in Blood
Description
Concentration will be determined from the pharmacokinetic (PK) blood samples collected via capillary micro-method (draws from the heel).
Time Frame
Predose and after 1, 3, and 8 hours post-dose on one of treatment days from Day 3 to Day 10
Title
Concentration of Micafungin in Cerebral Spinal Fluid (CSF)
Description
Concentration will be determined from the from the CSF samples collected.
Time Frame
Predose and after 1, 3, and 8 hours post-dose on one of treatment days from Day 3 to Day 10
Secondary Outcome Measure Information:
Title
Percentage of Participants with a Response at End of Treatment (EOT) - Success of Therapy (SOT)
Description
For systemic candidiasis (SC) participants, SOT will be determined by survival associated with negative Candida test results of 2 consecutive blood cultures, completed at start of treatment, or resolution of clinical & laboratory symptoms together with reduction of mannan antigen blood level (MABL) (<125 pg/ml). For Candida meningitis (CM), SOT will be determined by survival associated with negative Candida test results of at least 2 consecutive CSF cultures, completed at start of treatment and resolution of clinical and lab symptoms. For hydrocephalus due to Candida infection (CI) and/or external ventricular derivation (EVD), SOT will be determined by survival associated with negative Candida test results of at least 2 consecutive CSF cultures, completed at start of treatment.
Time Frame
Up to day 14
Title
Percentage of Participants with A Response at EOT - Failure of Therapy (FOT)
Description
For SC participants, FOT will be determined by death due to Candida sepsis, by confirmation of persistence of positive Candida test results from 1 blood culture completed by need to add/switch to another antifungal agent (AA) and/or change of micafungin dose for resolution of infection at any time or by the persistence of Candida colonization in different indicated sites associated with persistence of clinical and lab symptoms and with high (MABL) (≥ 125 pg/ml). For CM, FOT will be determined by death due to CM, by persistence of CI from confirmation of positive CSF culture or by need to add/switch to another AA or dose change of micafungin for resolution of CI at any time. For hydrocephalus due to CI and/or EVD, FOT will be determined by death due to CI, by need to add/switch to another AA or dose change of micafungin for resolution of CI at any time or by persistence of CI from confirmation of positive CSF culture.
Time Frame
Up to day 14
Title
Number of Participants with Adverse Events (AEs)
Description
An adverse event (AE) will be defined as any untoward medical occurrence in a participant administered a study drug or who will undergo study procedures which may not necessarily have a causal relationship with this treatment. This includes abnormal laboratory tests, vital signs, electrocardiogram data or physical examinations that are defined as AEs if the abnormality will induce clinical signs or symptoms, require active intervention, interruption or discontinuation of study drug or may be clinically significant in the investigator's opinion. The following standard with 3 grades will be used to measure the severity of AEs, including abnormal clinical laboratory values: ● Mild: No disruption of normal daily activities ● Moderate: Affected normal daily activities ● Severe: Inability to perform daily activities. A treatment-emergent adverse event (TEAE) will be defined as an AE observed after starting administration of the test drug/comparative drug.
Time Frame
From the first dose of study drug administration up 72 hours after the last dose, up to 17 days
Title
Comparison of Capillary and Venous Plasma Concentrations of Micafungin
Description
Micafungin concentrations will be determined from the PK blood samples collected via both capillary micro-method (draws from the heel) and venous methods.
Time Frame
Predose and after 1, 3, and 8 hours post-dose on one of treatment days from Day 3 to Day 10
10. Eligibility
Sex
All
Minimum Age & Unit of Time
1 Day
Maximum Age & Unit of Time
180 Days
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Executive Medical Director
Organizational Affiliation
Astellas Pharma Global Development, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
Site IT39001
City
Rome
ZIP/Postal Code
00146
Country
Italy
Facility Name
Site IT39002
City
Rome
ZIP/Postal Code
00186
Country
Italy
12. IPD Sharing Statement
Plan to Share IPD
No
IPD Sharing Plan Description
Access to anonymized individual participant level data will not be provided for this trial as it meets one or more of the exceptions described on www.clinicalstudydatarequest.com under "Sponsor Specific Details for Astellas."
Citations:
PubMed Identifier
33558294
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.
Results Reference
derived
Links:
URL
https://astellasclinicalstudyresults.com/study.aspx?ID=312
Description
Link to Results on the Astellas Clinical Study Results website
Learn more about this trial
Determination of Levels of Micafungin in Neonates Suffering From Systemic Candidiasis and/or Candida Meningitis
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