EFFECTS OF 12-WEEK ADMINISTRATION OF DORNASE ALFA IN PATIENTS WITH ADVANCED CYSTIC-FIBROSIS LUNG-DISEASE

Study objective: The 12-week efficacy and safety of aerosolized recomb inant human DNase (dornase alfa) were evaluated in previously untreate d patients with cystic fibrosis (CF) with advanced lung disease. Desig n: In this multicenter, double-blind, placebo-controlled study, CF pat ients with advanced lung disease were randomized to receive either dor nase alfa or placebo once a day for 12 weeks. Patients: A total of 320 patients in clinically stable condition with documented CF and an FVC less than 40% of predicted were recruited from 65 CF Foundation care centers in the United States. The dornase alfa and placebo groups were comparable with respect to age (range, 7 to 57 years), height, and we ight, Male subjects outnumbered female subjects (55% vs 45%) and few s ubjects were younger than 17 years of age (15%), The percentages of pr edicted FEV(1) and FVC were significantly lower in the dornase alfa gr oup at baseline (p less than or equal to 0.05). Interventions: Patient s were randomly assigned to receive either 2.5 mg dornase alfa once da ily (n=158) or placebo once daily (n=162). All patients continued to r eceive standard medications and treatments administered for CF. Measur ements and results: Dornase alfa improved the mean percent change in F EV(1) from baseline by 9.4% compared with 2.1% for placebo (p<0.001). The actively treated group showed a 12.4% improvement in FVC compared with 7.3% for placebo (p<0.01). There were no differences between the treatment groups in dyspnea score, number of days receiving IV antibio tics, or length of hospital stay; the overall incidence of adverse eve nts was comparable between treatment groups, Fifteen patients died: 9 in the dornase alfa group and 6 in the placebo group; no differentiati ng clinical characteristics were demonstrated. Conclusions: Pulmonary function as measured by FEV(1) and FVC improved significantly in the d ornase alfa-treated patients, Dornase alfa was found to be safe and we ll tolerated over the 12-week study period.