RECOMBINANT HUMAN DNASE-I IN CYSTIC-FIBROSIS PATIENTS WITH SEVERE PULMONARY-DISEASE - A SHORT-TERM, DOUBLE-BLIND-STUDY FOLLOWED BY 6 MONTHSOPEN-LABEL TREATMENT

Chronic pulmonary infection is the major cause of morbidity and mortal ity in cystic fibrosis (CF), Recombinant human deoxyribonuclease (rhDN ase) in vitro has been shown to dramatically reduce the viscoelasticit y of the sputum from CF patients, Phase II and III clinical trials hav e shown the drug to be safe, and that patients with a forced vital cap acity (FVC) of >40% predicted show an improvement in pulmonary functio n when receiving rhDNase. The current study evaluates the safety and e fficacy of rhDNase in the most severly ill CF patients (FVC <40% predi cted). A double-blind, randomized, placebo-controlled trial in which p atients received either 2.5 mg rhDNase twice daily or placebo for a pe riod of 14 days followed by a 6 month open extension period (OEP) is r eported, Seventy patients were recruited for the double-blind study, a nd 64 entered the OEP of whom 38 completed, During the OEP, all patien ts received 2.5 mg rhDNase twice daily. In both the double-blind perio d and the OEP the drug appeared to be safe, During the double-blind st udy, forced expiratory volume in one second (FEV1) and FVC improved in both groups but there was no statistically significant difference bet ween the groups, In the OEP, there was mean improvement in percentage predicted FEV1 and FVC, 9 and 18%, respectively, for all patients part icipating.In conclusion, DNase is safe when administered in conjunctio n with a rigorous regimen of chest physiotherapy to severely ill patie nts (FVC <40% predicted) with CF, The double-blind, 14 day study showe d no significant improvement in pulmonary function but some patients m ay have improved after longer administration of rhDNase.