Comparison of hypertonic saline and alternate-day or daily recombinant human deoxyribonuclease in children with cystic fibrosis: a randomised trial

Lancet. 2001 Oct 20;358(9290):1316-21. doi: 10.1016/S0140-6736(01)06412-1.

Abstract

Background: Daily recombinant human deoxyribonuclease (rhDNase) is an established but expensive treatment in cystic fibrosis. Alternate-day treatment, if equally effective, would reduce the drug cost. Hypertonic saline improved lung function to the same degree as rhDNase in short-term studies. We compared the effectiveness of daily rhDNase, hypertonic saline, and alternate-day rhDNase in children with cystic fibrosis.

Methods: In an open cross-over trial, 48 children were allocated in random order to 12 weeks of once-daily rhDNase (2.5 mg), alternate-day rhDNase (2.5 mg), and twice-daily 5 mL 7% hypertonic saline. The primary outcome was forced expiratory volume in 1 s (FEV(1)). Secondary outcomes were forced vital capacity, number of pulmonary exacerbations, weight gain, quality of life, exercise tolerance, and the total costs of hospital and community care.

Findings: Mean FEV(1) increased by 16% (SD 25%), 14% (22%), and 3% (21%) with daily rhDNase, alternate-day rhDNase, and hypertonic saline, respectively. There was no difference between daily and alternate-day rhDNase (2% [95% CI -4 to 9], p=0.55). However, daily rhDNase showed a significantly greater increase in FEV(1) than hypertonic saline (8% [2 to 14], p=0.01). The average difference in 12-week cost between daily and alternate-day rhDNase was pound513 (95% CI -546 to 1510) and that between daily rhDNase and hypertonic saline was pound1409 (440 to 2318). None of the secondary clinical outcomes showed significant differences between treatments.

Interpretation: Hypertonic saline, delivered by jet nebuliser, is not as effective as daily rhDNase, although there is variation in individual response. There is no evidence of a difference between daily and alternate-day rhDNase.

Publication types

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

MeSH terms

  • Adolescent
  • Child
  • Child, Preschool
  • Cross-Over Studies
  • Cystic Fibrosis / drug therapy*
  • Deoxyribonuclease I / therapeutic use*
  • Drug Administration Schedule
  • Exercise Tolerance / drug effects
  • Expectorants / therapeutic use*
  • Female
  • Humans
  • Male
  • Recombinant Proteins / therapeutic use*
  • Saline Solution, Hypertonic / therapeutic use*
  • Spirometry

Substances

  • Expectorants
  • Recombinant Proteins
  • Saline Solution, Hypertonic
  • DNASE1 protein, human
  • Deoxyribonuclease I