Inhaled mannitol in patients with cystic fibrosis: A randomised open-label dose response trial.
BACKGROUND
Cystic fibrosis (CF) is characterised by impaired mucociliary clearance (MCC), chronic inflammation and infection, and progressively deteriorating lung function. Inhaled mannitol (Bronchitol) has been shown to increase MCC and cough clearance and FEV(1) in CF patients, contributing to better lung hygiene and consequently a slower decline in lung function. This study was designed to determine the dose relationship of mannitol treatment and improvement in FEV(1) and FVC as well as safety.


METHODS
This was a randomised, open-label, crossover, dose response study. Following a 2-week treatment with mannitol 400mg b.i.d., 48 CF patients with a mean (SD) FEV(1) % predicted of 64 (13.2), received a further 3 treatments with 40mg, 120mg or 240mg b.i.d. for 2weeks each, in random order.


RESULTS
The study demonstrated a dose dependent increase in FEV(1) and FVC. The 400mg dose showed the greatest improvement and the 40mg dose had no discernible effect. The mean percent change in FEV(1) was -1.57%, 3.61%, 3.87% and 8.75% respectively for the 40mg, 120mg, 240mg and 400mg treatments. There was a statistically significant change in FEV(1) for 400mg compared to 40mg (p<0.0001) but the difference with 120mg and 240mg did not reach significance. The mean % change in FVC was -0.90, 1.74, 3.07 and 8.14, for the 40mg, 120mg, 240mg and 400mg treatment arms, with p=0.0001, p=0.0037 and p=0.0304 respectively when compared to 400mg. The highest tested dose of 400mg had a similar safety profile to the other doses tested. The change in FEV(1) and FVC by dose in the paediatric age group (<18years) was similar to the results in the adult population.


CONCLUSIONS
Based on these results the 400mg b.i.d. dose has been further studied in phase III trials.
Teper
Alejandro
A
Hospital de Niños "Dr Ricardo Gutierrez", Ciudad Autónoma de Buenos Aires, C1425EFD, Argentina.
Jaques
Anna
A
Charlton
Brett
B
D000280:Administration, Inhalation; D000293:Adolescent; D000328:Adult; D000368:Aged; D001986:Bronchial Spasm / Q000139:chemically induced; D002648:Child; D002908:Chronic Disease; D003550:Cystic Fibrosis / Q000150:complications / Q000175:diagnosis* / Q000188:drug therapy* / Q000503:physiopathology; D004234:Diuretics, Osmotic / Q000008:administration & dosage / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D016903:Drug Monitoring; D058492:Drug Repositioning; D058995:Dry Powder Inhalers / Q000009:adverse effects; D005260:Female; D006801:Humans; D008168:Lung / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008353:Mannitol / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D009079:Mucociliary Clearance / Q000187:drug effects*; D011014:Pneumonia / Q000209:etiology; D012129:Respiratory Function Tests; D016896:Treatment Outcome
D004234:Diuretics, Osmotic; D008353:Mannitol