Study to Compare the Efficacy and Safety of Micafungin Versus Conventional Amphotericin B for the Treatment of Neonatal Candidiasis

Phase 3TerminatedNCT00815516

Astellas Pharma Global Development, Inc.30 enrolled

Overview

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.

Neonates and young infants will be stratified by estimated gestational age and by world region

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Candidiasis

Interventions

micafunginDRUG

Administered by intravenous infusion

amphotericin B deoxycholateDRUG

Administered by intravenous infusion

Eligibility

Sex: ALLMin age: 48 HoursMax age: 120 Days

Medical Language ↔ Plain English

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

Locations (17)

Children's Hospital of Orange County

Orange, California, United States

UMDNJ/Robert Wood Johnson Medical School

New Brunswick, New Jersey, United States

Outcomes

Primary Outcomes

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.

Time frame: One week after the last dose of study drug (maximum of 49 days)

Secondary Outcomes

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.

Time frame: From first dose up to 30 days after the last dose of study drug (maximum of 72 days)

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.

Time frame: The end of study drug therapy; maximum of 42 days

Data from ClinicalTrials.gov

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Duke University

Durham, North Carolina, United States

WakeMed Health and Hospitals

Raleigh, North Carolina, United States

Virginia Commonwealth University

Richmond, Virginia, United States

Irmandade da Santa Casa de Misericórdia de Belo Horizonte

Belo Horizonte, Minas Gerais, Brazil

Hospital de Base da Faculdade de Medicina

São José do Rio Preto, São Paulo, Brazil

Spec Hospital for Active Treatment of Children Diseases

Sofia, Bulgaria

McMaster Children's Hospital

Hamilton, Ontario, Canada

Hospital Pablo Tobon Uribe

Medellín, Antioque, Colombia

...and 7 more locations

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.

Time frame: One week after the last dose of study drug (maximum of 49 days)

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.

Time frame: Up to 30 days after the last dose of study drug (maximum of 72 days)

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 frame: Up to 30 days after the last dose of study drug (maximum of 72 days)

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.

Time frame: From first dose up to 30 days after the last dose of study drug (maximum of 72 days)

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.

Time frame: Baseline and end of study drug therapy; maximum of 42 days

Clinical Response One Week After Last Dose of Study Drug

Time frame: Baseline and one week after the last dose of study drug (maximum of 49 days)

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.

Time frame: End of study drug therapy; maximum of 42 days

Mycological Response One Week After Last Dose of Study Drug

Time frame: One week after the last dose of study drug (maximum of 49 days)

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.

Time frame: Baseline and 30 days after the last dose of study drug (maximum of 72 days)

Plasma Micafungin Concentration

Time frame: 15 minutes post intravenous infusion (IV), 4-8 hours post IV and 15-24 hours post IV