A Phase 3 Study of Micafungin Versus Amphotericin B Deoxycholate in Infants With Invasive Candidiasis



Benjamin, Daniel K Jr, Kaufman, David A, Hope, William W ORCID: 0000-0001-6187-878X, Smith, P Brian, Arrieta, Antonio, Manzoni, Paolo, Kovanda, Laura L, Lademacher, Christopher, Isaacson, Brigit, Jednachowski, Deborah
et al (show 3 more authors) (2018) A Phase 3 Study of Micafungin Versus Amphotericin B Deoxycholate in Infants With Invasive Candidiasis. PEDIATRIC INFECTIOUS DISEASE JOURNAL, 37 (10). pp. 992-998.

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Abstract

<h4>Background</h4>Amphotericin B deoxycholate (AmB-D) is standard of care treatment for neonatal invasive candidiasis (IC). Micafungin (MCA) has broad-spectrum fungicidal activity against Candida spp. We compared the efficacy and safety of intravenous MCA with intravenous AmB-D and assessed the pharmacokinetics of MCA in infants >2-120 days of age with proven IC in a phase 3, randomized, double-blind, multicenter, parallel-group, noninferiority study (NCT00815516).<h4>Methods</h4>Infants were randomized 2:1 to MCA (10 mg/kg/d) or AmB-D (1 mg/kg/d) for ≥21 days. Primary efficacy endpoint was fungal-free survival (FFS) 1 week after last study drug dose. MCA population pharmacokinetics included simulated area under the curve (AUC) at steady state and maximum plasma concentration after 2-hour infusion. AUC pharmacodynamic target exposure was 170 µg·h/mL.<h4>Results</h4>Thirty infants received MCA (n = 20) or AmB-D (n = 10). The trial was terminated early because of slow recruitment. FFS was observed in 12 of 20 [60%; 95% confidence interval (CI): 36%-81%] MCA-group infants and in 7 of 10 (70%; 95% CI: 35%-93%) AmB-D-group infants. The most common treatment-emergent adverse events were anemia [MCA: n = 9 (45%); AmB-D: n = 3 (30%)] and thrombocytopenia [n = 2 (10%) and n = 3 (30%), respectively]. Model-derived mean AUC at steady state for MCA was 399.3 ± 163.9 µg·h/mL (95% prediction interval: 190.3-742.3 µg/mL); steady state and maximum plasma concentration after 2-hour infusion was 31.1 ± 10.5 µg/mL (95% prediction interval: 17.0-49.7 µg/mL). MCA exposures were above the AUC pharmacodynamic target exposure.<h4>Conclusions</h4>Within the study limitations, infants with IC treated with MCA achieved similar FFS compared with AmB-D. Both agents were safe and well tolerated.

Item Type: Article
Uncontrolled Keywords: amphotericin B deoxycholate, infants, invasive candidiasis, micafungin, neonates
Depositing User: Symplectic Admin
Date Deposited: 18 Apr 2018 09:42
Last Modified: 15 Mar 2024 02:57
DOI: 10.1097/INF.0000000000001996
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3020301