Ciprofloxacin dry powder for inhalation in non-cystic fibrosis bronchiectasis: a phase II randomised study

Abstract

This phase II, randomised, double-blind, multicentre study (NCT00930982) investigated the safety and efficacy of ciprofloxacin dry powder for inhalation (DPI) in patients with non-cystic fibrosis bronchiectasis. Adults who were culture positive for pre-defined potential respiratory pathogens (including Pseudomonas aeruginosa and Haemophilus influenzae) were randomised to ciprofloxacin DPI 32.5 mg or placebo administered twice daily for 28 days (with 56 days of follow-up). Bacterial density in sputum (primary end-point), pulmonary function tests, health-related quality of life and safety were monitored throughout the study. 60 subjects received ciprofloxacin DPI 32.5 mg and 64 received placebo. Subjects on ciprofloxacin DPI had a significant reduction (p<0.001) in total sputum bacterial load at the end of treatment (-3.62 log10 CFU·g(-1) (range -9.78-5.02 log10 CFU·g(-1))) compared with placebo (-0.27 log10 CFU·g(-1) (range -7.96-5.25 log10 CFU·g(-1))); the counts increased thereafter. In the ciprofloxacin DPI group, 14 (35%) out of 40 subjects reported pathogen eradication at end of treatment versus four (8%) out of 49 in the placebo group (p=0.001). No abnormal safety results were reported and rates of bronchospasm were low. Ciprofloxacin DPI 32.5 mg twice daily for 28 days was well tolerated and achieved significant reductions in total bacterial load compared with placebo in subjects with non-cystic fibrosis bronchiectasis.

Keywords: Antibiotic; Pseudomonas aeruginosa; bacteria; chronic lung infection; exacerbation; inflammation.

Figure 1–

Study design and subject disposition. Protocol violations in screening failures included no positive culture (n=23), inadequate sputum (n=50), forced expiratory volume in 1 s outside range (n=6), exacerbations during screening (n=2), on antibacterials (n=6), no further information (n=25) and other (n=10). DPI: dry powder for inhalation.

Figure 2–

Mean bacterial load for the a) modified intent-to-treat population and b) per-protocol populations. Only results from valid cultures were considered. Cultures were excluded if subjects were administered concomitant antibacterials, if there were >25 squamous epithelial cells in the absence of Pseudomonas aeruginosa or if there were ≤25 leukocytes for P. aeruginosa-negative cultures pre-therapy. DPI: dry powder for inhalation. Shaded area indicates treatment period (days). ^#: number of patients with valid sputum cultures. ***: p<0.001.

Figure 3–

Mean colony count of selected pathogens at baseline and at end of treatment. Only results from valid cultures were considered. Cultures were excluded if subjects were administered concomitant antibacterials, if there were >25 squamous epithelial cells in absence of Pseudomonas aeruginosa or if there were ≤25 leukocytes for P. aeruginosa-negative cultures pre-therapy. DPI: dry powder for inhalation; EOT: end of treatment.

Figure 4–

Occurrence of exacerbations requiring antibacterial intervention throughout the study (modified intent-to-treat population). 22 subjects in the ciprofloxacin DPI group and 25 subjects in the placebo group experienced an exacerbation. Of these, 14 subjects in the ciprofloxacin DPI group and 18 subjects in the placebo group required antibacterial treatment. DPI: dry powder for inhalation. Shaded area indicates treatment period (days).