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Oral Lipid Nanocrystal Amphotericin B for Cryptococcal Meningitis: A Randomized Clinical Trial.
- Source :
-
Clinical Infectious Diseases . 12/15/2023, Vol. 77 Issue 12, p1659-1667. 9p. - Publication Year :
- 2023
-
Abstract
- Background Amphotericin B is the gold standard treatment for severe mycoses. A new orally delivered, less-toxic formulation of amphotericin has been developed. Methods In our randomized clinical trial, we tested oral lipid nanocrystal (LNC) amphotericin B (MAT2203, Matinas Biopharma) vs intravenous (IV) amphotericin for human immunodeficiency virus–associated cryptococcal meningitis in 4 sequential cohorts. Two pilot cohorts assessed safety and tolerability (n = 10 each), and 2 cohorts assessed efficacy with/without 2 IV loading doses (n = 40 each). The experimental arm received 1.8 g/d oral LNC amphotericin through 2 weeks with 100 mg/kg/d flucytosine, then 1.2 g/d LNC amphotericin through 6 weeks. The randomized control arm (n = 41) received 7 days of IV amphotericin with flucytosine, then 7 days of fluconazole 1200 mg/d. The primary end point was cerebrospinal fluid (CSF) early fungicidal activity (EFA). Results We randomized 80 participants to oral LNC amphotericin + flucytosine with (n = 40) and without (n = 40) 2 IV loading doses and 41 control participants to IV amphotericin + flucytosine. Mean EFA was 0.40 log10 colony-forming units (CFU)/mL/d for all-oral LNC amphotericin, 0.42 log10   Cryptococcus CFU/mL/d for oral LNC amphotericin with IV loading doses, and 0.46 log10 CFU/mL/d for IV amphotericin controls. LNC amphotericin groups achieved 2-week CSF sterility in 63% (44 of 70) vs 68% (23 of 34) of controls. The 18-week survival was 85% (34 of 40) with all-oral LNC amphotericin, 90% (36 of 40) with oral LNC amphotericin given IV loading doses, and 85% (35 of 41) with IV amphotericin. Grade 3–4 laboratory adverse events occurred less frequently in LNC amphotericin groups (41%) than the IV amphotericin group (61%, P =.05), particularly for anemia (21% vs 44%; P =.01) and potassium (5% vs 17%; P =.04). Conclusions This new oral amphotericin B LNC formulation appears promising for cryptococcal meningitis with antifungal activity, similar survival, and less toxicity than IV amphotericin. Clinical Trials Registration NCT04031833. [ABSTRACT FROM AUTHOR]
- Subjects :
- *DRUG delivery systems
*DRUG efficacy
*AMPHOTERICIN B
*ORAL drug administration
*HETEROCYCLIC compounds
*RANDOMIZED controlled trials
*COMPARATIVE studies
*CRYPTOCOCCUS neoformans
*DESCRIPTIVE statistics
*BACTERIAL growth
*MICROBIOLOGICAL techniques
*RESEARCH funding
*AIDS-related opportunistic infections
*MENINGITIS
*STATISTICAL sampling
*FLUCONAZOLE
*LIPIDS
*NANOPARTICLES
*PATIENT safety
*LONGITUDINAL method
*EVALUATION
Subjects
Details
- Language :
- English
- ISSN :
- 10584838
- Volume :
- 77
- Issue :
- 12
- Database :
- Academic Search Index
- Journal :
- Clinical Infectious Diseases
- Publication Type :
- Academic Journal
- Accession number :
- 174274753
- Full Text :
- https://doi.org/10.1093/cid/ciad440