N Engl J Med. 1994 Sep 8;331(10):637-42.

Randomised, double-blind parallel trial with 3 arms over 24 weeks.

968 participants, diagnosed CF on genotype, sweat test or clinically, aged over five years with FVC > 40 % predicted and clinically stable. 25 people withdrew from the study, 8 in the placebo group and once-daily group and 9 in the twice-daily group.

Nebulized dornase alfa 2.5 mg od (n = 322) or bd (n = 321) compared to placebo (n = 325), over 24 weeks. QoL questionnaire

Outcomes included in this review: pulmonary-function tests, dyspnea, patients' general well-being and cystic fibrosis-related symptoms, number of days of school or work missed, number of days in the hospital, number of days patients received parenteral antibiotics, serum rhDNase antibodies and serum concentration of DNase

One or more exacerbations occurred in 27 percent of the patients given placebo, 22 percent of those treated with rhDNase once daily, and 19 percent of those treated with rhDNase twice daily. As compared with placebo, the administration of rhDNase once daily and twice daily reduced the age-adjusted risk of respiratory exacerbations by 28 percent (P = 0.04) and 37 percent (P < 0.01), respectively. The administration of rhDNase once daily and twice daily improved forced expiratory volume in one second during the study by a mean (+/- SD) of 5.8 +/- 0.7 and 5.6 +/- 0.7 percent, respectively. None of the patients had anaphylaxis. Voice alteration and laryngitis were more frequent in the rhDNase-treated patients than in those receiving placebo but were rarely severe and resolved within 21 days of onset.

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.