Study design (if review, criteria of inclusion for studies)
double-blind, randomized, placebo-controlled Phase 2 study
Participants
Patients were 13 years and older with FEV1>or=40% predicted, chronic P. aeruginosa infection, and had used no anti-pseudomonal antibiotics for 56 days. Of 131 patients screened, 105 received AZLI or placebo. Mean age was 26 years and mean FEV1 percent predicted was 77% at baseline.
Interventions
75 and 225 mg AZLI administered BID for 14 days using the eFlow Electronic Nebulizer (Pari Innovative Manufacturers, Inc., Midlothian, VA)
Outcome measures
P. aeruginosa CFU density, FEV1, plasma aztreonam concentrations, Adverse events
Main results
There was a statistically significant reduction, compared to placebo, in P. aeruginosa CFU density in each AZLI group at Days 7 and 14 (P<0.001). The planned primary analysis, percent change in FEV1 at Day 14, demonstrated no statistically significant difference. Post hoc analysis demonstrated significant increase in FEV1 at Day 7 for the subset of patients with baseline FEV1<75% predicted in the 225 mg AZLI group. Bronchodilator use was associated with greater improvement in FEV1, as well as greater reduction in P. aeruginosa bacterial density and higher plasma aztreonam concentrations in the 225 mg AZLI group. Adverse events were similar between placebo and AZLI although there was a trend toward increased respiratory symptoms in the 225 mg AZLI group.
Authors' conclusions
These data support the further development of AZLI and provide information for the design of subsequent studies.