Journal of Fungi (Mar 2024)

A Phase I/IIa Prospective, Randomized, Open-Label Study on the Safety and Efficacy of Nebulized Liposomal Amphotericin for Invasive Pulmonary Aspergillosis

  • Jesús Fortún,
  • Elia Gómez-García de la Pedrosa,
  • Alberto Martínez-Lorca,
  • Patricia Paredes,
  • Pilar Martín-Dávila,
  • Alicia Gómez-López,
  • María José Buitrago,
  • Javier López-Jiménez,
  • Francesca Gioia,
  • Rosa Escudero,
  • Maria Elena Alvarez-Alvarez,
  • Cruz Soriano,
  • Javier Moreno-García,
  • Diana San Miguel,
  • Noelia Vicente,
  • Santiago Moreno

DOI
https://doi.org/10.3390/jof10030191
Journal volume & issue
Vol. 10, no. 3
p. 191

Abstract

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Although nebulized liposomal amphotericin B (NLAB) is being used in invasive pulmonary aspergillosis (IPA) prophylaxis, no clinical trial has shown its efficacy as a therapeutic strategy. NAIFI is the inaugural randomized, controlled clinical trial designed to examine the safety and effectiveness of NLAB (dosage: 25 mg in 6 mL, three times per week for 6 weeks) against a placebo, in the auxiliary treatment of IPA. Throughout the three-year clinical trial, thirteen patients (six NLAB, seven placebo) were included, with 61% being onco-hematological with less than 100 neutrophils/μL. There were no significant differences noted in their pre- and post-nebulization results of forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), and oxygen saturation between the groups. Neither bronchospasm nor serum amphotericin B levels were reported in any patients given NLAB. 18F-Fluorodeoxyglucose positron emission tomography (FDG-PET-TC) was carried out at the baseline and after 6 weeks. A notable decrease in median SUV (standardized uptake value) was observed in NLAB patients after 6 weeks (−3.6 vs. −0.95, p: 0.039, one tail). Furthermore, a reduction in serum substance galactomannan and beta-D-Glucan was identified within NLAB recipients. NLAB is well tolerated and safe for patients with IPA. Encouraging indirect efficacy data have been derived from image monitoring or biomarkers. However, further studies involving more patients are necessary.

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