Is Dornase alfa (Pulmozyme ) effective if administered at night, in relation to airways clearance techniques? A multi centre, crossover, randomised controlled trial for people with cystic fibrosis.

Following randomisation to determine morning or evening Dornase alfa (rhDNase, [Pulmozyme]) administration as commencement intervention, paediatric and adult CF outpatients were studied over a six week period: 14 day regimes of morning or evening rhDNase administration, with 14 days washout between the two regimes. These regimes resulted in alteration of the interval time between rhDNase nebulisation and chest physiotherapy. The subject’s usual routine for chest physiotherapy and exercise were unaltered. Outcomes were measured at start and end of each regime when participants attended four study visits (each approximately 30-60 minutes’ duration). The subjects were all current users of nebulised rhDNase (2.5mg unit dose ampoule nebulised once daily via Pari LC+ nebuliser; duration approximately 10 minutes); the study protocol required alteration of the time of day or night at which rhDNase was administered to alter the in-situ dwell time of rhDNase in relation to chest physiotherapy. Usual timing of rhDNase administration in relation to chest physiotherapy is highly variable, with "short" intervals in some users (eg 15 minutes prior to physiotherapy) and others having a "long" interval (eg 8-10 hours if rhDNase is taken at night). Patients acted as their own control, using their "usual" timing during the washout period of 14 days, and data was analysed with consideration of "usual" in-situ dwell time of rhDNase compared to longer or shorter intervals caused by the study protocol.