Effects of 12-week administration of dornase alfa in patients with advanced cystic fibrosis lung disease. Pulmozyme Study Group.
OBJECTIVE
The 12-week efficacy and safety of aerosolized recombinant human DNase (dornase alfa) were evaluated in previously untreated patients with cystic fibrosis (CF) with advanced lung disease.


METHODS
In this multicenter, double-blind, placebo-controlled study, CF patients with advanced lung disease were randomized to receive either dornase alfa or placebo once a day for 12 weeks.


METHODS
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 weight. Male subjects outnumbered female subjects (55% vs 45%) and few subjects were younger than 17 years of age (15%). The percentages of predicted FEV1 and FVC were significantly lower in the dornase alfa group at baseline (p < or = 0.05).


METHODS
Patients were randomly assigned to receive either 2.5 mg dornase alfa once daily (n = 158) or placebo once daily (n = 162). All patients continued to receive standard medications and treatments administered for CF.


RESULTS
Dornase alfa improved the mean percent change in FEV1 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 i.v. antibiotics, or length of hospital stay; the overall incidence of adverse events was comparable between treatment groups. Fifteen patients died: 9 in the dornase alfa group and 6 in the placebo group; no differentiating clinical characteristics were demonstrated.


CONCLUSIONS
Pulmonary function as measured by FEV1 and FVC improved significantly in the dornase alfa-treated patients. Dornase alfa was found to be safe and well tolerated over the 12-week study period.
McCoy
K
K
Division of Pulmonary Medicine, Children's Hospital, Columbus, Ohio, USA.
Hamilton
S
S
Johnson
C
C
D000293:Adolescent; D000328:Adult; D002648:Child; D003550:Cystic Fibrosis / Q000188:drug therapy* / Q000503:physiopathology; D003850:Deoxyribonuclease I / Q000008:administration & dosage / Q000627:therapeutic use*; D004311:Double-Blind Method; D005100:Expectorants / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D016896:Treatment Outcome; D014797:Vital Capacity
D005100:Expectorants; D011994:Recombinant Proteins; C085693:DNASE1 protein, human; D003850:Deoxyribonuclease I