Study objective: To determine the effect of long-term
suppression of Pseudomonas aeruginosa on lung function
and other clinical end points in adolescent patients with cystic
Design: Two identical, randomized,
placebo-controlled trials followed by three open-label follow-on
Setting: Sixty-nine CF study centers in the
Interventions: Active drug consisting
of a 300-mg tobramycin solution for inhalation (TSI).
Patients: One hundred twenty-eight adolescent CF patients
(aged 13 to 17 years) with P aeruginosa and
mild-to-moderate lung disease (FEV1 percent predicted≥
25% and ≤ 75%).
function, P aeruginosa colony forming unit density,
incidence of hospitalization and IV antibiotic use, weight gain, and
aminoglycoside toxicity were monitored.
the end of the first three 28-day cycles of TSI treatment, patients
originally randomized to TSI and placebo treatments exhibited
improvements in FEV1 percent predicted of 13.5% and 9.4%,
respectively. FEV1 percent predicted was maintained above
the value at initiation of TSI treatment in both groups. At the end of
the last “on-drug” period (92 weeks), patients originally
randomized to TSI and placebo treatments showed improvements of 14.3%
and 1.8%, respectively. Improvement in pulmonary function was
significantly correlated with reduction in P aeruginosa
colony forming unit density (p = 0.0001). The average number of
hospitalizations and IV antibiotic courses did not increase over time.
TSI treatment was associated with increased weight gain and body mass
index. P aeruginosa susceptibility to tobramycin
decreased slightly over time, but this was not correlated with clinical
Conclusions: TSI treatment improved
pulmonary function and weight gain in adolescent patients with CF over
a 2-year period of long-term, intermittent use.