Trial to Compare the Efficacy and Safety of Micafungin versus Amphotericin B Deoxycholate to Treat Neonatal Candidiasis

Conditions: eonatal Candidiasis
Therapeutic area: Diseases [C] - Bacterial Infections and Mycoses [C01]

Registration Number: EUCTR2012-000780-24-GR

Lead Sponsor: Astellas Pharma Global Development, Inc.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 225

Inclusion Criteria

Subject is eligible for the study if all of the following apply:
1. Institutional Review Board (IRB)-/Independent Ethics Committee (IEC)-approved written Informed Consent and privacy language as per national regulations (e.g., HIPAA Authorization for U.S. sites) must be obtained from legally authorized representative prior to any study-related procedures (including withdrawal of prohibited medication, if applicable).
2. Infant greater than 48 hours of life up to DOL 120 at the time of culture acquisition.
3. Diagnosis of invasive candidiasis by one of the following (see Appendix 1 for Site-Specific Diagnostic Criteria):
a. Proven Candidemia: One positive blood culture collected within 4 days prior to the first dose of study drug.
b. Proven Candiduria: One positive urine fungal culture obtained within 4 days prior to the first dose of study drug by I/O catheterization or suprapubic aspiration. Positive fungal culture must show greater than or equal to 1000 CFU/mL in a single urine culture collected via I/O catheterization or greater than or equal to 100 CFU/mL in a single urine culture collected via suprapubic aspiration.
c. Proven Candida Meningitis: The presence of Candida species in CSF culture obtained within +/- 4 days from the first dose of study drug.
d. Candida – Other focus:
i. Positive tissue biopsy or positive culture from a normally sterile body fluid obtained within 4 days prior to the first dose of study drug, or
ii. Positive culture for Candida (or yeast) from a new drain placed within the last 7 days prior to the first dose of study drug in a normally sterile site. Culture must have been obtained at the time of drain placement or within 1 day after drain placement. NB: Culture results to confirm Candida species may be pending at the time of enrollment if the following criteria are met:
- For candidemia, staining/microscopy of the blood culture sample reveals preliminary evidence of yeast.
- For invasive candidiasis other than candidemia, histology/cytology reveals findings consistent with yeast.
Note: All Candida organisms must be speciated.
4. Infant must have sufficient venous access to permit administration of study medication and monitoring of safety variables.

Are the trial subjects under 18? yes
Number of subjects for this age range: 225
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

Subject will be excluded from participation if any of the following apply:
1. Infant with any history of a hypersensitivity or severe vasomotor reaction to any echinocandin or systemic amphotericin B product.
2. Infant who has received more than 48 hours of systemic antifungal therapy prior to the first dose of study drug for treatment of the current Candida infection. Cumulative doses must not exceed 2 mg/kg of CAB. For systemic antifungal therapy not specifically stated here,
infants with more than 2 therapeutic daily doses within the 48 hours prior to the first dose of study drug will not be eligible.
3. Infant who has a breakthrough systemic fungal infection while receiving an amphotericin B product or an echinocandin as prophylaxis.
NOTE: Infants with a breakthrough fungal infection while receiving azole prophylaxis will be eligible for enrollment.
4. Infant who has failed prior systemic antifungal therapy for this episode of invasive candidiasis, including recurrence of the same Candida infection within 2 weeks of completing systemic antifungal therapy.
5. Infant with a concomitant medical condition, whose participation, in the opinion of the Investigator and/or medical advisor, may create an unacceptable additional risk.
6. Infant previously enrolled in this study.
7. Infant who is co-infected with a non-Candida fungal organism.
8. Infant whose positive yeast cultures are solely from an indwelling bladder catheter or sputum.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate the efficacy and safety of Micafungin in comparison to amphotericin B deoxycholate (CAB) in the treatment of proven neonatal candidiasis<br><br>;Secondary Objective: To further evaluate the pharmacokinetics of micafungin as well as CAB in this patient population ;Primary end point(s): The primary endpoint for the study is fungal free survival at one week following the last dose of study drug.<br>Fungal free survival is defined as alive at one week following the last dose of study drug and eradication (fungal free) with no requirement for alternative systemic antifungal therapy for continued treatment.;Timepoint(s) of evaluation of this end point: One week following the last dose of study drug

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): - Time to mycological clearance of invasive candidiasis.<br>- Fungal free survival in infants with end-organ dissemination at end of<br>study drug therapy and one week after last dose of study drug.<br>- Overall incidence of emergent and recurrent fungal infections through the end of study.<br>- Time to positive clinical response (complete or partial).<br>- Clinical response (complete, partial, stabilization, progression) at the end of study drug therapy and one week after last dose of study drug.<br>- Mycological response at end of study drug therapy and one week after<br>last dose of study drug.<br>- Status of follow-up imaging and exams (improved, stable, worse) for<br>infants with end-organ assessments.<br>- Model parameters such as clearance and volume of distribution.;Timepoint(s) of evaluation of this end point: At end of study drug therapy and/or one week after last dose of study drug.