Respiratory Trials·org

Cystic fibrosis · Mucolytic therapy

Fuchs 1994 randomised trial

Effect of aerosolized recombinant human DNase on exacerbations of respiratory symptoms in cystic fibrosis

Fuchs 1994 trial design and results
Design Randomised, double-blind, placebo-controlled trial
Treatment Aerosolised recombinant human DNase once or twice daily
Control Placebo
Population 968 patients with cystic fibrosis and mild to moderate lung disease
Follow-up 24 weeks
Primary endpoint Occurrence of respiratory exacerbations
Result One or more exacerbations occurred in 27% on placebo, 22% on once-daily rhDNase and 19% on twice-daily rhDNase — age-adjusted risk reductions of 28% (p=0.04) and 37% (p<0.01). FEV1 improved by a mean of about 5.8% with treatment.
Secondary endpoints FEV1, need for parenteral antibiotics, tolerability

In patients with cystic fibrosis, the administration of rhDNase reduced but did not eliminate exacerbations of respiratory symptoms, resulted in slight improvement in pulmonary function, and was well tolerated.

The trial authors, in the published abstract

How it has aged

The first drug shown to modify the course of cystic fibrosis lung disease, and a mainstay for thirty years. Its striking companion finding came later: the same drug is actively harmful in non-CF bronchiectasis (rhDNase in bronchiectasis). Same radiographic pattern, different sputum biology. In the modulator era, SIMPLIFY has shown many stable patients can now stop it.

Publications

Effect of aerosolized recombinant human DNase on exacerbations of respiratory symptoms and on pulmonary function in patients with cystic fibrosis. The Pulmozyme Study Group

Fuchs HJ, Borowitz DS, Christiansen DH, et al. Effect of aerosolized recombinant human DNase on exacerbations of respiratory symptoms and on pulmonary function in patients with cystic fibrosis. The Pulmozyme Study Group. N Engl J Med 1994 Sep 8;331(10):637-42.

  • 28% to 37% reduction in the risk of respiratory exacerbation
  • Small improvement in FEV1
  • Well tolerated over 24 weeks