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

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.

• Authors: R Suri, C Metcalfe, B Lees, R Grieve, M Flather, C Normand, S Thompson, A Bush, C Wallis
• Journal: Lancet (London, England) (Lancet) Vol. 358 Issue 9290 Pg. 1316-21 (Oct 20 2001) ISSN: 0140-6736 [Print] England
• PMID: 11684212 (Publication Type: Clinical Trial, Comparative Study, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

• 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