Chest
Volume 121, Issue 1, January 2002, Pages 55-63
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Clinical Investigations
Cystic Fibrosis
Long-term Benefits of Inhaled Tobramycin in Adolescent Patients With Cystic Fibrosis

https://doi.org/10.1378/chest.121.1.55Get rights and content

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 fibrosis (CF).

Design

Two identical, randomized, placebo-controlled trials followed by three open-label follow-on trials.

Setting

Sixty-nine CF study centers in the United States.

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%).

Measurements

Pulmonary function, P aeruginosa colony forming unit density, incidence of hospitalization and IV antibiotic use, weight gain, and aminoglycoside toxicity were monitored.

Results

At 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 response.

Conclusions

TSI treatment improved pulmonary function and weight gain in adolescent patients with CF over a 2-year period of long-term, intermittent use.

Section snippets

Materials and Methods

The data presented here were collected during a 96-week series of clinical trials that consisted of a 24-week, double-blind, randomized, pivotal phase and 72-week, open-label phase. Figure 1 , upper panel, illustrates the two phases. In the pivotal phase, patients were randomized to treatment with either 300 mg of TSI bid or taste-masked placebo bid. In the open-label phase, all patients received TSI. The overall design of the open-label trials is identical to that of the controlled trials as

Patient Population

Patients were assigned to age subgroups (children, 6 to 12 years; adolescent, 13 to 17 years; adult, ≥ 18 years) according to their age at the first visit of the controlled trials (visit 3, week 0). One hundred twenty-eight adolescent patients were enrolled in the controlled trials. Of these 128 patients, 120 patients completed 24 weeks of randomized treatment. Ninety-three adolescent patients entered the open-label phase of the study and 65 adolescent patients completed the 96-week series.

Of

Discussion

Pulmonary function is the single best predictor of morbidity and mortality in patients with CF.5 Adolescent CF patients are at a particularly vulnerable stage in their life cycle when they are susceptible to rapid decline in pulmonary function and high rates of death through early adulthood. The 2-year TSI results show long-term improvement in pulmonary function in adolescent CF patients. The substantial improvements in FEV1 percent predicted and the maintenance of lung function above baseline

References (18)

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The author has received speaking and consulting fees from Chiron Corporation.

Presented in part at the 1999 North American Cystic Fibrosis Conference, Seattle, WA, October 7–10, 1999.

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