title: Treatment of Aspergillus fumigatus in patients with cystic fibrosis: a randomized, placebo-controlled pilot study.
abstract: BACKGROUND
  Many patients with cystic fibrosis develop persistent airway infection/colonization with Aspergillus fumigatus, however the impact of A. fumigatus on clinical outcomes remains unclear. The objective of this study was to determine whether treatment directed against Aspergillus fumigatus improves pulmonary function and clinical outcomes in patients with cystic fibrosis (CF).
  
  
  METHODS
  We performed a double-blind randomized placebo-controlled pilot clinical trial involving 35 patients with CF whose sputum cultures were chronically positive for A. fumigatus. Participants were centrally randomized to receive either oral itraconazole 5 mg/kg/d (N = 18) or placebo (N = 17) for 24 weeks. The primary outcome was the proportion of patients who experienced a respiratory exacerbation requiring intravenous antibiotics over the 24 week treatment period. Secondary outcomes included changes in FEV(1) and quality of life.
  
  
  RESULTS
  Over the 24 week treatment period, 4 of 18 (22%) patients randomized to itraconazole experienced a respiratory exacerbation requiring intravenous antibiotics, compared to 5 of 16 (31%) placebo treated patients, P = 0.70. FEV(1) declined by 4.62% over 24 weeks in the patients randomized to itraconazole, compared to a 0.32% improvement in the placebo group (between group difference = -4.94%, 95% CI: -15.33 to 5.45, P = 0.34). Quality of life did not differ between the 2 treatment groups throughout the study. Therapeutic itraconazole blood levels were not achieved in 43% of patients randomized to itraconazole.
  
  
  CONCLUSIONS
  We did not identify clinical benefit from itraconazole treatment for CF patients whose sputum was chronically colonized with A. fumigatus. Limitations of this pilot study were its small sample size, and failure to achieve therapeutic levels of itraconazole in many patients.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT00528190.
authors.affiliation: The Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario, Canada. saaron@ohri.ca
authors.forename: Shawn D
authors.initials: SD
authors.lastname: Aaron
authors.forename: Katherine L
authors.initials: KL
authors.lastname: Vandemheen
authors.forename: Andreas
authors.initials: A
authors.lastname: Freitag
authors.forename: Linda
authors.initials: L
authors.lastname: Pedder
authors.forename: William
authors.initials: W
authors.lastname: Cameron
authors.forename: Annick
authors.initials: A
authors.lastname: Lavoie
authors.forename: Nigel
authors.initials: N
authors.lastname: Paterson
authors.forename: Pearce
authors.initials: P
authors.lastname: Wilcox
authors.forename: Harvey
authors.initials: H
authors.lastname: Rabin
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Tullis
authors.forename: Nancy
authors.initials: N
authors.lastname: Morrison
authors.forename: Felix
authors.initials: F
authors.lastname: Ratjen
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000935:Antifungal Agents / Q000627:therapeutic use; D001228:Aspergillosis / Q000150:complications / Q000188:drug therapy; D001232:Aspergillus fumigatus / Q000472:pathogenicity*; D002648:Child; D003550:Cystic Fibrosis / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D004311:Double-Blind Method; D005260:Female; D005541:Forced Expiratory Volume; D006760:Hospitalization; D006801:Humans; D007275:Injections, Intravenous; D017964:Itraconazole / Q000627:therapeutic use; D008168:Lung / Q000503:physiopathology; D008297:Male; D010865:Pilot Projects; D015990:Placebo Effect; D011788:Quality of Life; D012129:Respiratory Function Tests; D013183:Sputum / Q000382:microbiology; D013997:Time Factors; D055815:Young Adult
chemical_list: D000935:Antifungal Agents; D017964:Itraconazole