Recombinant human DNase I in cystic fibrosis patients with severe pulmonary disease: A short-term, double-blind study followed by six months open-label treatment

P. I. Shah, A. Bush, G. J. Canny, Andrew Colin, H. J. Fuchs, D. M. Geddes, C. A C Johnson, M. C. Light, S. F. Scott, D. E. Tullis, A. De Vault, M. E. Wohl, M. E. Hodson

Research output: Contribution to journalArticle

60 Citations (Scopus)

Abstract

Chronic pulmonary infection is the major cause of morbidity and mortality in cystic fibrosis (CF). Recombinant human deoxyribonuclease (rhDNase) in vitro has been shown to dramatically reduce the viscoelasticity of the sputum from CF patients. Phase II and III clinical trials have shown the drug to be safe, and that patients with a forced vital capacity (EVC) of >40% predicted show an improvement in pulmonary function when receiving rhDNase. The current study evaluates the safety and efficacy of rhDNase in the most severely ill CF patients (FVC <40% predicted). A double-blind, randomized, placebo-controlled trial in which patients received either 2.5 mg rhDNase twice daily or placebo for a period of 14 days followed by a 6 month open extension period (OEP) is reported. Seventy patients were recruited for the double-blind study, and 64 entered the OEP of whom 38 completed. During the OEP, all patients received 2.5 mg rhDNase twice daily. In both the double-blind period and the OEP the drug appeared to be safe. During the double-blind study, forced expiratory volume in one second (FEV1) and FVC improved in both groups but there was no statistically significant difference between the groups. In the OEP, there was mean improvement in percentage predicted FEV1 and FVC, 9 and 18%, respectively, for all patients participating. In conclusion, DNase is safe when administered in conjunction with a rigorous regimen of chest physiotherapy to severely ill patients (FVC <40% predicted) with CF. The double-blind, 14 day study showed no significant improvement in pulmonary function but some patients may have improved after longer administration of rhDNase.

Original languageEnglish
Pages (from-to)954-958
Number of pages5
JournalEuropean Respiratory Journal
Volume8
Issue number6
StatePublished - Jul 13 1995
Externally publishedYes

Fingerprint

Deoxyribonuclease I
Double-Blind Method
Cystic Fibrosis
Lung Diseases
Deoxyribonucleases
Therapeutics
Lung
Placebos
dornase alfa
Phase III Clinical Trials
Phase II Clinical Trials
Vital Capacity
Forced Expiratory Volume
Sputum
Pharmaceutical Preparations
Thorax
Randomized Controlled Trials
Morbidity
Safety
Mortality

Keywords

  • Cystic fibrosis
  • Deoxyribonuclease
  • Sputum

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

Recombinant human DNase I in cystic fibrosis patients with severe pulmonary disease : A short-term, double-blind study followed by six months open-label treatment. / Shah, P. I.; Bush, A.; Canny, G. J.; Colin, Andrew; Fuchs, H. J.; Geddes, D. M.; Johnson, C. A C; Light, M. C.; Scott, S. F.; Tullis, D. E.; De Vault, A.; Wohl, M. E.; Hodson, M. E.

In: European Respiratory Journal, Vol. 8, No. 6, 13.07.1995, p. 954-958.

Research output: Contribution to journalArticle

Shah, PI, Bush, A, Canny, GJ, Colin, A, Fuchs, HJ, Geddes, DM, Johnson, CAC, Light, MC, Scott, SF, Tullis, DE, De Vault, A, Wohl, ME & Hodson, ME 1995, 'Recombinant human DNase I in cystic fibrosis patients with severe pulmonary disease: A short-term, double-blind study followed by six months open-label treatment', European Respiratory Journal, vol. 8, no. 6, pp. 954-958.
Shah, P. I. ; Bush, A. ; Canny, G. J. ; Colin, Andrew ; Fuchs, H. J. ; Geddes, D. M. ; Johnson, C. A C ; Light, M. C. ; Scott, S. F. ; Tullis, D. E. ; De Vault, A. ; Wohl, M. E. ; Hodson, M. E. / Recombinant human DNase I in cystic fibrosis patients with severe pulmonary disease : A short-term, double-blind study followed by six months open-label treatment. In: European Respiratory Journal. 1995 ; Vol. 8, No. 6. pp. 954-958.
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abstract = "Chronic pulmonary infection is the major cause of morbidity and mortality in cystic fibrosis (CF). Recombinant human deoxyribonuclease (rhDNase) in vitro has been shown to dramatically reduce the viscoelasticity of the sputum from CF patients. Phase II and III clinical trials have shown the drug to be safe, and that patients with a forced vital capacity (EVC) of >40{\%} predicted show an improvement in pulmonary function when receiving rhDNase. The current study evaluates the safety and efficacy of rhDNase in the most severely ill CF patients (FVC <40{\%} predicted). A double-blind, randomized, placebo-controlled trial in which patients received either 2.5 mg rhDNase twice daily or placebo for a period of 14 days followed by a 6 month open extension period (OEP) is reported. Seventy patients were recruited for the double-blind study, and 64 entered the OEP of whom 38 completed. During the OEP, all patients received 2.5 mg rhDNase twice daily. In both the double-blind period and the OEP the drug appeared to be safe. During the double-blind study, forced expiratory volume in one second (FEV1) and FVC improved in both groups but there was no statistically significant difference between the groups. In the OEP, there was mean improvement in percentage predicted FEV1 and FVC, 9 and 18{\%}, respectively, for all patients participating. In conclusion, DNase is safe when administered in conjunction with a rigorous regimen of chest physiotherapy to severely ill patients (FVC <40{\%} predicted) with CF. The double-blind, 14 day study showed no significant improvement in pulmonary function but some patients may have improved after longer administration of rhDNase.",
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