Back to resultsStudy to Compare the Efficacy and Safety of Micafungin Versus Conventional Amphotericin B for the Treatment of Neonatal Candidiasis (MAGIC-2)
Primary Purpose
Candidiasis
Status
Terminated
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
micafungin
amphotericin B deoxycholate
Sponsored by
About this trial
This is an interventional treatment trial for Candidiasis focused on measuring candidiasis, candida, Neonate, candidemia, Micafungin, Mycamine, amphotericin B deoxycholate
Eligibility Criteria
Inclusion Criteria:
- Infant greater than 48 hours of life after birth up to day of life 120 at the time of culture acquisition
- Diagnosis of proven invasive candidiasis within 4 days prior to study start
- Subject's parent or legal guardian agrees not to allow subject to participate in another study with another investigational drug while on treatment.
Exclusion Criteria:
- Infant with any history of a hypersensitivity or severe vasomotor reaction to any echinocandin or systemic amphotericin B product
- Infant who has received more than 48 hours of systemic antifungal therapy prior to the first dose of study drug
- Infant who has a breakthrough systemic fungal infection while receiving amphotericin B product or an echinocandin as prophylaxis
- Infant who has failed prior systemic antifungal therapy for this episode of invasive candidiasis
- Infant who is co-infected with a non-Candida fungal organism
- Infant whose positive yeast cultures are solely from an indwelling bladder catheter (unless obtained at the time the indwelling catheter was placed) or sputum.
- Infant previously enrolled in this study
Sites / Locations
- Children's Hospital of Orange County
- UMDNJ/Robert Wood Johnson Medical School
- Duke University
- WakeMed Health and Hospitals
- Virginia Commonwealth University
- Irmandade da Santa Casa de Misericórdia de Belo Horizonte
- Hospital de Base da Faculdade de Medicina
- Spec Hospital for Active Treatment of Children Diseases
- McMaster Children's Hospital
- Hospital Pablo Tobon Uribe
- University Hospital of Patras
- Semmelweis Egyetem
- Hadassah University Hospital Ein Kerem
- Philippine General Hospital
- Emergency County Clinical Hospital
- Cukurova University Medical Faculty
- Municipal Institution "Odesa Regional Children's Hospital"
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Micafungin
Amphotericin B deoxycholate
Arm Description
Infants received micafungin at a dose of 10 mg/kg per day by intravenous infusion for a minimum of 21 days to a maximum of 28 days for infants without end-organ dissemination or for a maximum of 42 days for infants with end-organ dissemination.
Infants received amphotericin B deoxycholate (CAB) at a dose of 1.0 mg/kg per day by intravenous infusion for a minimum of 21 days to a maximum of 28 days for infants without end-organ dissemination or for a maximum of 42 days for infants with end-organ dissemination.
Outcomes
Primary Outcome Measures
Fungal-free Survival
Fungal-free survival was assessed by an independent data review panel (DRP). Fungal-free survival is defined as the percentage of participants alive at one week following the last dose of study drug with a mycological response of eradication and no requirement for alternative systemic antifungal therapy for continued treatment.
Eradication was defined as culture or histologically documented absence of the infecting Candida species from all positive normally sterile sites during therapy, documented by 2 negative samples, drawn at least 24 hours apart, or for Candida meningitis and/or candiduria, 1 negative culture.
Secondary Outcome Measures
Time to Mycological Clearance of Invasive Candidiasis
Time to mycological clearance of invasive candidiasis is defined as the time from first dose to the day of mycological eradication for baseline invasive candidiasis infection.
Eradication was defined as a culture or histologically documented absence of the infecting Candida species from all positive normally sterile sites during therapy, documented by 2 negative samples, drawn at least 24 hours apart, or for for Candida meningitis and/or candiduria, 1 negative culture.
Infants without eradication during the treatment period and who survived were censored at one day after the end of treatment. Infants without eradication who died before completing the treatment period or were lost to follow-up during the treatment were censored at their death or last contact day.
Fungal-free Survival at End of Study Drug Therapy in Infants With End-organ Dissemination
Fungal-free survival was assessed by an independent data review panel (DRP). Fungal-free survival is defined as the percentage of participants alive at the end of study drug therapy with a mycological response of eradication based upon the DRP assessment and no requirement for alternative systemic antifungal therapy for continued treatment.
Fungal-free Survival One Week After Last Dose of Study Drug in Infants With End-organ Dissemination
Fungal-free survival was assessed by an independent data review panel (DRP). Fungal-free survival is defined as the percentage of participants alive one week after last dose of study drug with a mycological response of eradication based upon the DRP assessment and no requirement for alternative systemic antifungal therapy for continued treatment.
Percentage of Participants With Emergent Fungal Infections
An emergent fungal infection is defined as
An invasive fungal infection which is detected at any time during the study that is a non-Candida organism, or
An invasive fungal infection which is detected during the treatment or post-treatment period with a Candida species identified other than those detected at Baseline. If this occurred within 96 hours of the first dose of study drug, the infection was considered part of the final diagnosis of enrolling infection and not an emergent infection.
Percentage of Participants With Recurrent Fungal Infections
A recurrent infection is defined as a systemic fungal infection in an infant with eradication at the end of study drug therapy, who developed positive blood cultures or a mycologically confirmed deep-seated Candida infection, with the same species as the enrolling infection.
Time to Positive Clinical Response
Time to a positive clinical response is defined as the time from the first dose to the day during the treatment period that a positive clinical response (defined as a complete response or partial response) is observed for the first time, assessed by the Investigator.
Complete Response is defined as the resolution of all attributable signs related to fungal infection, if present at baseline and Partial Response is defined as improvement in attributable signs related to the fungal infection, if present at baseline.
Infants without positive responses and who survived were censored at one day post the end of treatment. Infants without positive responses who died before completing the treatment period, or were lost to follow-up during the treatment were censored at their death or last contact day.
Clinical Response at the End of Study Drug Therapy
Clinical response assessments were based on the following definitions and assessed by the DRP:
Complete Response: Resolution of all attributable signs related to fungal infection, if present at baseline.
Partial Response: Improvement in attributable signs related to the fungal infection, if present at baseline.
Stabilization: Minor improvement or no change in attributable signs related to the fungal infection, if present at baseline, and infant continued on therapy without deterioration.
Progression: Deterioration in attributable signs related to the fungal infection, if present at baseline; or if death occurred presumably related to a fungal infection.
Clinical Response One Week After Last Dose of Study Drug
Clinical response assessments were based on the following definitions and assessed by the DRP:
Complete Response: Resolution of all attributable signs related to fungal infection, if present at baseline.
Partial Response: Improvement in attributable signs related to the fungal infection, if present at baseline.
Stabilization: Minor improvement or no change in attributable signs related to the fungal infection, if present at baseline, and infant continued on therapy without deterioration.
Progression: Deterioration in attributable signs related to the fungal infection, if present at baseline; or if death occurred presumably related to a fungal infection.
Mycological Response at End of Study Drug Therapy
Mycological response assessments were based on the following definitions and assessed by the DRP:
Eradication: Culture or histologically documented absence of the infecting Candida species from all positive normally sterile sites during therapy, documented by 2 negative samples, drawn at least 24 h apart; for Candida meningitis and/or candiduria, 1 negative culture.
Persistence: Continued isolation or histological documentation from a normally sterile site.
Mycological Response One Week After Last Dose of Study Drug
Mycological response assessments were based on the following definitions and assessed by the DRP:
Eradication: Culture or histologically documented absence of the infecting Candida species from all positive normally sterile sites during therapy, documented by 2 negative samples, drawn at least 24 h apart; for Candida meningitis and/or candiduria, 1 negative culture.
Persistence: Continued isolation or histological documentation from a normally sterile site.
Follow-up Status for Infants With End-organ Assessments
End-organ dissemination was assessed through abdominal ultrasound and/or computed tomography (CT), echocardiogram, head imaging and retinal exam. Each specific finding, documented by 1 of these techniques, was evaluated as follows:
Improvement: Improvement in size, number or density of identified lesions. Complete response was not expected but may have been documented.
Stabilization: Minor improvement or no change in size, number or density of identified lesions.
Worsening: Increase in size or number of identified lesions.
Plasma Micafungin Concentration
Full Information
NCT ID
NCT00815516
First Posted
December 27, 2008
Last Updated
October 12, 2015
Sponsor
Astellas Pharma Global Development, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT00815516
Brief Title
Study to Compare the Efficacy and Safety of Micafungin Versus Conventional Amphotericin B for the Treatment of Neonatal Candidiasis
Acronym
MAGIC-2
Official Title
A Phase 3, Randomized, Double-Blind, Multi-Center Study to Compare the Efficacy and Safety of Micafungin Versus Amphotericin B Deoxycholate for the Treatment of Neonatal Candidiasis
Study Type
Interventional
2. Study Status
Record Verification Date
October 2015
Overall Recruitment Status
Terminated
Why Stopped
It was decided to discontinue the study due to insufficient recruitment.
Study Start Date
February 2013 (undefined)
Primary Completion Date
December 2014 (Actual)
Study Completion Date
December 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Astellas Pharma Global Development, Inc.
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The study will evaluate how effective and how safe the drug micafungin is when compared to the drug amphotericin B deoxycholate in treating neonates and young infants with certain fungal infections.
Detailed Description
Neonates and young infants will be stratified by estimated gestational age and by world region
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Candidiasis
Keywords
candidiasis, candida, Neonate, candidemia, Micafungin, Mycamine, amphotericin B deoxycholate
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
30 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Micafungin
Arm Type
Experimental
Arm Description
Infants received micafungin at a dose of 10 mg/kg per day by intravenous infusion for a minimum of 21 days to a maximum of 28 days for infants without end-organ dissemination or for a maximum of 42 days for infants with end-organ dissemination.
Arm Title
Amphotericin B deoxycholate
Arm Type
Active Comparator
Arm Description
Infants received amphotericin B deoxycholate (CAB) at a dose of 1.0 mg/kg per day by intravenous infusion for a minimum of 21 days to a maximum of 28 days for infants without end-organ dissemination or for a maximum of 42 days for infants with end-organ dissemination.
Intervention Type
Drug
Intervention Name(s)
micafungin
Other Intervention Name(s)
Mycamine, FK463
Intervention Description
Administered by intravenous infusion
Intervention Type
Drug
Intervention Name(s)
amphotericin B deoxycholate
Other Intervention Name(s)
Fungizone, Conventional amphotericin B (CAB), Amphotericin B for injection
Intervention Description
Administered by intravenous infusion
Primary Outcome Measure Information:
Title
Fungal-free Survival
Description
Fungal-free survival was assessed by an independent data review panel (DRP). Fungal-free survival is defined as the percentage of participants alive at one week following the last dose of study drug with a mycological response of eradication and no requirement for alternative systemic antifungal therapy for continued treatment.
Eradication was defined as culture or histologically documented absence of the infecting Candida species from all positive normally sterile sites during therapy, documented by 2 negative samples, drawn at least 24 hours apart, or for Candida meningitis and/or candiduria, 1 negative culture.
Time Frame
One week after the last dose of study drug (maximum of 49 days)
Secondary Outcome Measure Information:
Title
Time to Mycological Clearance of Invasive Candidiasis
Description
Time to mycological clearance of invasive candidiasis is defined as the time from first dose to the day of mycological eradication for baseline invasive candidiasis infection.
Eradication was defined as a culture or histologically documented absence of the infecting Candida species from all positive normally sterile sites during therapy, documented by 2 negative samples, drawn at least 24 hours apart, or for for Candida meningitis and/or candiduria, 1 negative culture.
Infants without eradication during the treatment period and who survived were censored at one day after the end of treatment. Infants without eradication who died before completing the treatment period or were lost to follow-up during the treatment were censored at their death or last contact day.
Time Frame
From first dose up to 30 days after the last dose of study drug (maximum of 72 days)
Title
Fungal-free Survival at End of Study Drug Therapy in Infants With End-organ Dissemination
Description
Fungal-free survival was assessed by an independent data review panel (DRP). Fungal-free survival is defined as the percentage of participants alive at the end of study drug therapy with a mycological response of eradication based upon the DRP assessment and no requirement for alternative systemic antifungal therapy for continued treatment.
Time Frame
The end of study drug therapy; maximum of 42 days
Title
Fungal-free Survival One Week After Last Dose of Study Drug in Infants With End-organ Dissemination
Description
Fungal-free survival was assessed by an independent data review panel (DRP). Fungal-free survival is defined as the percentage of participants alive one week after last dose of study drug with a mycological response of eradication based upon the DRP assessment and no requirement for alternative systemic antifungal therapy for continued treatment.
Time Frame
One week after the last dose of study drug (maximum of 49 days)
Title
Percentage of Participants With Emergent Fungal Infections
Description
An emergent fungal infection is defined as
An invasive fungal infection which is detected at any time during the study that is a non-Candida organism, or
An invasive fungal infection which is detected during the treatment or post-treatment period with a Candida species identified other than those detected at Baseline. If this occurred within 96 hours of the first dose of study drug, the infection was considered part of the final diagnosis of enrolling infection and not an emergent infection.
Time Frame
Up to 30 days after the last dose of study drug (maximum of 72 days)
Title
Percentage of Participants With Recurrent Fungal Infections
Description
A recurrent infection is defined as a systemic fungal infection in an infant with eradication at the end of study drug therapy, who developed positive blood cultures or a mycologically confirmed deep-seated Candida infection, with the same species as the enrolling infection.
Time Frame
Up to 30 days after the last dose of study drug (maximum of 72 days)
Title
Time to Positive Clinical Response
Description
Time to a positive clinical response is defined as the time from the first dose to the day during the treatment period that a positive clinical response (defined as a complete response or partial response) is observed for the first time, assessed by the Investigator.
Complete Response is defined as the resolution of all attributable signs related to fungal infection, if present at baseline and Partial Response is defined as improvement in attributable signs related to the fungal infection, if present at baseline.
Infants without positive responses and who survived were censored at one day post the end of treatment. Infants without positive responses who died before completing the treatment period, or were lost to follow-up during the treatment were censored at their death or last contact day.
Time Frame
From first dose up to 30 days after the last dose of study drug (maximum of 72 days)
Title
Clinical Response at the End of Study Drug Therapy
Description
Clinical response assessments were based on the following definitions and assessed by the DRP:
Complete Response: Resolution of all attributable signs related to fungal infection, if present at baseline.
Partial Response: Improvement in attributable signs related to the fungal infection, if present at baseline.
Stabilization: Minor improvement or no change in attributable signs related to the fungal infection, if present at baseline, and infant continued on therapy without deterioration.
Progression: Deterioration in attributable signs related to the fungal infection, if present at baseline; or if death occurred presumably related to a fungal infection.
Time Frame
Baseline and end of study drug therapy; maximum of 42 days
Title
Clinical Response One Week After Last Dose of Study Drug
Description
Clinical response assessments were based on the following definitions and assessed by the DRP:
Complete Response: Resolution of all attributable signs related to fungal infection, if present at baseline.
Partial Response: Improvement in attributable signs related to the fungal infection, if present at baseline.
Stabilization: Minor improvement or no change in attributable signs related to the fungal infection, if present at baseline, and infant continued on therapy without deterioration.
Progression: Deterioration in attributable signs related to the fungal infection, if present at baseline; or if death occurred presumably related to a fungal infection.
Time Frame
Baseline and one week after the last dose of study drug (maximum of 49 days)
Title
Mycological Response at End of Study Drug Therapy
Description
Mycological response assessments were based on the following definitions and assessed by the DRP:
Eradication: Culture or histologically documented absence of the infecting Candida species from all positive normally sterile sites during therapy, documented by 2 negative samples, drawn at least 24 h apart; for Candida meningitis and/or candiduria, 1 negative culture.
Persistence: Continued isolation or histological documentation from a normally sterile site.
Time Frame
End of study drug therapy; maximum of 42 days
Title
Mycological Response One Week After Last Dose of Study Drug
Description
Mycological response assessments were based on the following definitions and assessed by the DRP:
Eradication: Culture or histologically documented absence of the infecting Candida species from all positive normally sterile sites during therapy, documented by 2 negative samples, drawn at least 24 h apart; for Candida meningitis and/or candiduria, 1 negative culture.
Persistence: Continued isolation or histological documentation from a normally sterile site.
Time Frame
One week after the last dose of study drug (maximum of 49 days)
Title
Follow-up Status for Infants With End-organ Assessments
Description
End-organ dissemination was assessed through abdominal ultrasound and/or computed tomography (CT), echocardiogram, head imaging and retinal exam. Each specific finding, documented by 1 of these techniques, was evaluated as follows:
Improvement: Improvement in size, number or density of identified lesions. Complete response was not expected but may have been documented.
Stabilization: Minor improvement or no change in size, number or density of identified lesions.
Worsening: Increase in size or number of identified lesions.
Time Frame
Baseline and 30 days after the last dose of study drug (maximum of 72 days)
Title
Plasma Micafungin Concentration
Time Frame
15 minutes post intravenous infusion (IV), 4-8 hours post IV and 15-24 hours post IV
10. Eligibility
Sex
All
Minimum Age & Unit of Time
48 Hours
Maximum Age & Unit of Time
120 Days
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Infant greater than 48 hours of life after birth up to day of life 120 at the time of culture acquisition
Diagnosis of proven invasive candidiasis within 4 days prior to study start
Subject's parent or legal guardian agrees not to allow subject to participate in another study with another investigational drug while on treatment.
Exclusion Criteria:
Infant with any history of a hypersensitivity or severe vasomotor reaction to any echinocandin or systemic amphotericin B product
Infant who has received more than 48 hours of systemic antifungal therapy prior to the first dose of study drug
Infant who has a breakthrough systemic fungal infection while receiving amphotericin B product or an echinocandin as prophylaxis
Infant who has failed prior systemic antifungal therapy for this episode of invasive candidiasis
Infant who is co-infected with a non-Candida fungal organism
Infant whose positive yeast cultures are solely from an indwelling bladder catheter (unless obtained at the time the indwelling catheter was placed) or sputum.
Infant previously enrolled in this study
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Senior Medical Director
Organizational Affiliation
Astellas Pharma Global Development
Official's Role
Study Director
Facility Information:
Facility Name
Children's Hospital of Orange County
City
Orange
State/Province
California
ZIP/Postal Code
92868
Country
United States
Facility Name
UMDNJ/Robert Wood Johnson Medical School
City
New Brunswick
State/Province
New Jersey
ZIP/Postal Code
08901
Country
United States
Facility Name
Duke University
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
WakeMed Health and Hospitals
City
Raleigh
State/Province
North Carolina
ZIP/Postal Code
27610
Country
United States
Facility Name
Virginia Commonwealth University
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23298
Country
United States
Facility Name
Irmandade da Santa Casa de Misericórdia de Belo Horizonte
City
Belo Horizonte
State/Province
Minas Gerais
ZIP/Postal Code
30150-221
Country
Brazil
Facility Name
Hospital de Base da Faculdade de Medicina
City
São José do Rio Preto
State/Province
Sao Paulo
ZIP/Postal Code
15090-000
Country
Brazil
Facility Name
Spec Hospital for Active Treatment of Children Diseases
City
Sofia
ZIP/Postal Code
1606
Country
Bulgaria
Facility Name
McMaster Children's Hospital
City
Hamilton
State/Province
Ontario
ZIP/Postal Code
L8N 3Z5
Country
Canada
Facility Name
Hospital Pablo Tobon Uribe
City
Medellin
State/Province
Antioque
ZIP/Postal Code
574
Country
Colombia
Facility Name
University Hospital of Patras
City
Patras
ZIP/Postal Code
26504
Country
Greece
Facility Name
Semmelweis Egyetem
City
Budapest
ZIP/Postal Code
8200
Country
Hungary
Facility Name
Hadassah University Hospital Ein Kerem
City
Jerusalem
ZIP/Postal Code
91120
Country
Israel
Facility Name
Philippine General Hospital
City
Manila
Country
Philippines
Facility Name
Emergency County Clinical Hospital
City
Cluj-Napoca
ZIP/Postal Code
400006
Country
Romania
Facility Name
Cukurova University Medical Faculty
City
Adana
ZIP/Postal Code
1330
Country
Turkey
Facility Name
Municipal Institution "Odesa Regional Children's Hospital"
City
Odesa
ZIP/Postal Code
65031
Country
Ukraine
12. IPD Sharing Statement
Citations:
PubMed Identifier
29596222
Citation
Benjamin DK Jr, Kaufman DA, Hope WW, Smith PB, Arrieta A, Manzoni P, Kovanda LL, Lademacher C, Isaacson B, Jednachowski D, Wu C, Kaibara A, Walsh TJ. A Phase 3 Study of Micafungin Versus Amphotericin B Deoxycholate in Infants With Invasive Candidiasis. Pediatr Infect Dis J. 2018 Oct;37(10):992-998. doi: 10.1097/INF.0000000000001996. Erratum In: Pediatr Infect Dis J. 2018 Nov;37(11):1198.
Results Reference
derived
Links:
URL
https://www.astellasclinicalstudyresults.com/study.aspx?ID=9463-CL-2303
Description
Link to results on Astellas Clinical Study Results Web site
Learn more about this trial
Study to Compare the Efficacy and Safety of Micafungin Versus Conventional Amphotericin B for the Treatment of Neonatal Candidiasis
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