A two-year randomized, placebo-controlled trial of dornase alfa in young patients with cystic fibrosis with mild lung function abnormalities

J Pediatr. 2001 Dec;139(6):813-20. doi: 10.1067/mpd.2001.118570.

Abstract

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.

Study design: 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.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Body Weight / drug effects
  • Body Weight / physiology
  • Child
  • Cystic Fibrosis / complications
  • Cystic Fibrosis / drug therapy*
  • Cystic Fibrosis / physiopathology
  • Deoxyribonuclease I / administration & dosage
  • Deoxyribonuclease I / therapeutic use*
  • Double-Blind Method
  • Expectorants / administration & dosage
  • Expectorants / therapeutic use*
  • Female
  • Humans
  • Lung / abnormalities*
  • Lung / drug effects
  • Lung / physiopathology
  • Lung Diseases / congenital*
  • Lung Diseases / drug therapy*
  • Lung Diseases / etiology
  • Male
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / therapeutic use*
  • Respiratory Function Tests
  • Respiratory System / drug effects
  • Respiratory System / physiopathology
  • Time Factors
  • Treatment Outcome

Substances

  • Expectorants
  • Recombinant Proteins
  • DNASE1 protein, human
  • Deoxyribonuclease I