Treatment of Aspergillus fumigatus in patients with cystic fibrosis: a randomized, placebo-controlled pilot study

• Published in: PloS one 2012-04, Vol.7 (4), p.e36077-e36077
• Main Authors: Aaron, Shawn D, Vandemheen, Katherine L, Freitag, Andreas, Pedder, Linda, Cameron, William, Lavoie, Annick, Paterson, Nigel, Wilcox, Pearce, Rabin, Harvey, Tullis, Elizabeth, Morrison, Nancy, Ratjen, Felix
• Format: Article
• Language: English
• Subjects: Administration, Oral; Adolescent; Adult; Antibiotics; Antifungal Agents - therapeutic use; Aspergillosis - complications; Aspergillosis - drug therapy; Aspergillus; Aspergillus fumigatus; Aspergillus fumigatus - pathogenicity; Biology; Blood levels; Bronchitis; Care and treatment; Child; Clinical outcomes; Clinical trials; Colonization; Cultures; Cystic fibrosis; Cystic Fibrosis - complications; Cystic Fibrosis - drug therapy; Cystic Fibrosis - physiopathology; Development and progression; Double-Blind Method; Ethics; Female; Fibrosis; Forced Expiratory Volume; Health sciences; Hospitalization; Hospitals; Humans; Infections; Injections, Intravenous; Intravenous administration; Itraconazole; Itraconazole - therapeutic use; Lung - physiopathology; Male; Medical research; Medicine; Patients; Pediatrics; Pilot Projects; Placebo Effect; Pseudomonas aeruginosa; Pulmonary functions; Quality of Life; Randomization; Respiratory function; Respiratory Function Tests; Respiratory tract; Sputum; Sputum - microbiology; Studies; Time Factors; Young Adult
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0036077

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). 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. 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. 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. ClinicalTrials.gov NCT00528190.