Candidiasis, SystemicPhase 2NCT03421002
Determination of Levels of Micafungin in Neonates Suffering From Systemic Candidiasis and/or Candida Meningitis
A Phase 2 study testing Micafungin in people with Candidiasis, Systemic and Candida Meningitis, run by Astellas Pharma Global Development, Inc. at 2 sites in Italy.
Trial 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… Read more about this study
- Who is it for?
- Ages 1 day to 180 days
- Conditions the study is for
- Candidiasis, Systemic, Candida Meningitis
- What is being tested?
- Micafungin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 35 participants
- Where
- 2 sitesItaly
- Study dates
- 30 May 2015to 10 Apr 2018
- Phase
- Phase 2
- 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 1 day to 180 days
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
2 sites in 1 country.
About this study
Official title: Determination of Plasmatic and CSF Levels of High Doses of Micafungin in Neonates Suffering From Systemic Candidiasis and/or Candida Meningitis
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.
- Conditions
- Candidiasis, Systemic, Candida Meningitis
- Being tested
- Micafungin
- Keywords
- candida meningitis, Mycamine, candidiasis, systemic, micafungin
- Medical subject headings
- Candidiasis, Invasive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MicafunginDrug
Also called Mycamine
Participants will receive micafungin 8 mg/kg per day via intravenous infusion for approximately 1 hour.
| Study group | Role | What they receive |
|---|---|---|
| Micafungin | Experimental | 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. Receives: Drug: Micafungin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Concentration of Micafungin in Blood
Concentration will be determined from the pharmacokinetic (PK) blood samples collected via capillary micro-method (draws from the heel).
Measured: Predose and after 1, 3, and 8 hours post-dose on one of treatment days from Day 3 to Day 10
Concentration of Micafungin in Cerebral Spinal Fluid (CSF)
Concentration will be determined from the from the CSF samples collected.
Measured: Predose and after 1, 3, and 8 hours post-dose on one of treatment days from Day 3 to Day 10
Secondary outcomes (4)
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.
Measured: Up to day 14
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.
Measured: Up to day 14
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.
Measured: From the first dose of study drug administration up 72 hours after the last dose, up to 17 days
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.
Measured: Predose and after 1, 3, and 8 hours post-dose on one of treatment days from Day 3 to Day 10
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Feb 2018
- Study start30 May 2015
- Primary completion10 Apr 2018
- Study completion10 Apr 2018
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 Candidiasis, SystemicStudies of the same condition, open and under way.
- More trials run by Astellas Pharma Global Development, Inc.The 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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 35 participants (actual)
Sponsor and investigators
- Lead sponsor
- Astellas Pharma Global Development, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- IRCCS, Ospedale Pediatrico Bambino Gesu
- Responsible party
- Sponsor
- Investigators
- Executive Medical Director, Study director, Astellas Pharma Global Development, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03421002
- Sponsor's protocol ID
- 9463-CL-6001
- Other IDs
- 2014-003087-20, 800_OPBG_2014, 2014
- Status last verified
- Nov 2024
- First submitted
- 9 Jan 2018
- Last updated
- 18 Nov 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Access to anonymized individual participant level data will not be provided for this trial. Further details on Astellas' data sharing policy can be found at https://www.clinicaltrials.astellas.com/transparency/.
Publications
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.
PubMed 33558294
Study at a glance
From the registry record, last updated by the sponsor on 18 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Determination of Plasmatic and CSF Levels of High Doses of Micafungin in Neonates Suffering From Systemic Candidiasis and/or Candida Meningitis
- ClinicalTrials.gov ID
- NCT03421002
- Acronym / sponsor ID
- 9463-CL-6001
- Conditions
- Candidiasis, Systemic, Candida Meningitis
- Keywords
- candida meningitis, Mycamine, candidiasis, systemic, micafungin
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 35 participants (actual)
- Lead sponsor
- Astellas Pharma Global Development, Inc.Industry (pharma, biotech, devices)
- Collaborators
- IRCCS, Ospedale Pediatrico Bambino Gesu
- Study start
- 30 May 2015 (actual)
- Primary completion
- 10 Apr 2018 (actual)
- Study completion
- 10 Apr 2018 (actual)
- First posted
- 5 Feb 2018 (actual)
- 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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Micafungin | Experimental | Drug: MicafunginParticipants 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. |
Who may qualify
- Ages
- 1 day to 180 days
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (2 listed)
- 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.
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 |
|---|---|---|
| MicafunginAlso: MycamineParticipants will receive micafungin 8 mg/kg per day via intravenous infusion for approximately 1 hour. | Drug | Micafungin |
Primary outcome
Concentration of Micafungin in Blood
Time frame: Predose and after 1, 3, and 8 hours post-dose on one of treatment days from Day 3 to Day 10
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)
Time frame: Predose and after 1, 3, and 8 hours post-dose on one of treatment days from Day 3 to Day 10
Concentration will be determined from the from the CSF samples collected.
4 secondary outcomes
Percentage of Participants with a Response at End of Treatment (EOT) - Success of Therapy (SOT)
Time frame: Up to day 14
Percentage of Participants with A Response at EOT - Failure of Therapy (FOT)
Time frame: Up to day 14
Number of Participants with Adverse Events (AEs)
Time frame: From the first dose of study drug administration up 72 hours after the last dose, up to 17 days
Comparison of Capillary and Venous Plasma Concentrations of Micafungin
Time frame: Predose and after 1, 3, and 8 hours post-dose on one of treatment days from Day 3 to Day 10
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 18 Nov 2024.
- Derived from this study: PubMed 33558294Auriti 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.
- Individual participant dataSharing planned: No. Access to anonymized individual participant level data will not be provided for this trial. Further details on Astellas' data sharing policy can be found at https://www.clinicaltrials.astellas.com/transparency/.
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.
Executive Medical Director study director
Astellas Pharma Global Development, Inc.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Micafungin in people with Candidiasis, Systemic and Candida Meningitis, run by Astellas Pharma Global Development, Inc. at 2 sites in Italy.
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 4 inclusion and 2 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 18 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Italy. 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 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.
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?
Concentration of Micafungin in Blood (time frame: Predose and after 1, 3, and 8 hours post-dose on one of treatment days from Day 3 to Day 10). The study lists 2 primary outcomes in all. 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 NCT03421002, 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 18 Nov 2024; AzTrials last refreshed its copy on 8 Nov 2026.