A two-year randomized, placebo-controlled trial of dornase alfa in young patients with cystic fibrosis with mild lung function abnormalities.
OBJECTIVE
Our objective was to determine whether long-term treatment of young patients with cystic fibrosis (CF) with dornase alfa maintains lung function and reduces respiratory tract exacerbations.


METHODS
This was a 96-week, randomized, double-blind, placebo-controlled trial involving 49 CF centers. Inclusion criteria were age 6 to 10 years and forced vital capacity > or = 85% predicted. Patients were excluded for hospitalization for complications of CF within 2 months and use of dornase alfa within 6 months. Patients were treated with dornase alfa 2.5 mg or placebo once daily with a jet nebulizer and a compressor.


RESULTS
Patients were randomized, 239 to dornase alfa and 235 to placebo. At baseline the mean age was 8.4 years, the mean forced expiratory volume in 1 second 95% predicted, the mean forced expiratory flow, midexpiratory phase 85% predicted, and the mean forced vital capacity 102% predicted. At 96 weeks the treatment benefit for dornase alfa compared with placebo in percent predicted (mean +/- SE) was 3.2 +/- 1.2 for forced expiratory volume in 1 second (P =.006), 7.9 +/- 2.3 for forced expiratory flow between 25% and 75% of vital capacity (P =.0008), and 0.7 +/- 1.0 for forced vital capacity (P =.51). The risk of respiratory tract exacerbation was reduced by 34% in patients who received dornase alfa (relative risk 0.66, P =.048). There was no statistically significant difference between the groups in changes in weight-for-age percentile. Adverse event profiles for the treatment groups were similar.


CONCLUSIONS
Treatment of young patients with CF with dornase alfa maintains lung function and reduces the risk of exacerbations over a 96-week period.
Quan
J M
JM
Department of Medical Affairs, Genentech, Inc, South San Francisco, California 94080, USA.
Tiddens
H A
HA
Sy
J P
JP
McKenzie
S G
SG
Montgomery
M D
MD
Robinson
P J
PJ
Wohl
M E
ME
Konstan
M W
MW
D000367:Age Factors; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D002648:Child; D003550:Cystic Fibrosis / Q000150:complications / 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; D006801:Humans; D008168:Lung / Q000002:abnormalities* / Q000187:drug effects / Q000503:physiopathology; D008171:Lung Diseases / Q000151:congenital* / Q000188:drug therapy* / Q000209:etiology; D008297:Male; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use*; D012129:Respiratory Function Tests; D012137:Respiratory System / Q000187:drug effects / Q000503:physiopathology; D013997:Time Factors; D016896:Treatment Outcome
D005100:Expectorants; D011994:Recombinant Proteins; C085693:DNASE1 protein, human; D003850:Deoxyribonuclease I