Comparison of Inhaled Mannitol and rhDNase in Children With Cystic Fibrosis

Condition(s) targeted: Cystic Fibrosis

Intervention: mannitol (Drug); mannitol + pulmozyme (Drug); Dornase alpha (Drug)

Phase: Phase 2

Status: Completed

Sponsored by: Pharmaxis

Official(s) and/or principal investigator(s):
Andrew Bush, FRCPCH, Principal Investigator, Affiliation: Royal Brompton and Harefiled NHS Trust
Colin Wallis, FRCPCH, Principal Investigator, Affiliation: Great Ormond Street Hospital for Children

The purpose of this study is to determine the medium term efficacy and safety profile of inhaled mannitol, on its own and also as an additional therapy to rhDNase (pulmozyme). In particular, we will assess the impact on: lung function; airway inflammation; sputum microbiology; exacerbations; quality of life; adverse events; exercise tolerance; total costs of hospital and community care; and cost-effectiveness.

Official title: A Cross-Over Comparative Study of Inhaled Mannitol, Alone and in Combination With Daily rhDNase, in Children With Cystic Fibrosis

Study design: Treatment, Randomized, Open Label, Uncontrolled, Crossover Assignment, Safety/Efficacy Study

Primary outcome: FEV1 after 12 weeks of each of the following treatment regimens: *mannitol only *rhDNase only *mannitol + rhDNase

Secondary outcome:

to compare mannitol to rhDNase on FVC

to assess whether the effects of mannitol are additive to rhDNase

to demonstrate that mannitol does not cause deterioration in airway inflammation

to assess whether mannitol reduces the bacterial load in the lung

to assess whether the effects of mannitol are beneficial to quality of life

to assess whether mannitol, or mannitol + rhDNase are cost-effective compared to rhDNase alone

Minimum age: 8 Years. Maximum age: 18 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Known diagnosis of cystic fibrosis (sweat test or genotype)

- Of either gender

- Aged between 8 and 18 years

- Have a baseline FEV1 of <70% of the predicted normal value

- Currently taking rhDNase for at least 4 weeks

Exclusion Criteria:

- Currently active asthma, uncontrolled hypertension, colonised with Burkholderia

cepacia or MRSA

- Listed for transplantation

- Known intolerance to mannitol, rhDNase or bronchodilators

Royal Brompton Hospital, London, United Kingdom

Great Ormond Hospital for Children, London, United Kingdom

Pharmaxis homepage

Related publications:

Suri R, Metcalfe C, Lees B, Grieve R, Flather M, Normand C, Thompson S, Bush A, Wallis C. Comparison of hypertonic saline and alternate-day or daily recombinant human deoxyribonuclease in children with cystic fibrosis: a randomised trial. Lancet. 2001 Oct 20;358(9290):1316-21.

Robinson M, Daviskas E, Eberl S, Baker J, Chan HK, Anderson SD, Bye PT. The effect of inhaled mannitol on bronchial mucus clearance in cystic fibrosis patients: a pilot study. Eur Respir J. 1999 Sep;14(3):678-85.

Daviskas E, Anderson SD, Brannan JD, Chan HK, Eberl S, Bautovich G. Inhalation of dry-powder mannitol increases mucociliary clearance. Eur Respir J. 1997 Nov;10(11):2449-54.

Daviskas E, Anderson SD, Eberl S, Chan HK, Bautovich G. Inhalation of dry powder mannitol improves clearance of mucus in patients with bronchiectasis. Am J Respir Crit Care Med. 1999 Jun;159(6):1843-8.

Daviskas E, Anderson SD, Eberl S, Chan HK, Young IH. The 24-h effect of mannitol on the clearance of mucus in patients with bronchiectasis. Chest. 2001 Feb;119(2):414-21.

Daviskas E, Anderson SD, Gomes K, Briffa P, Cochrane B, Chan HK, Young IH, Rubin BK. Inhaled mannitol for the treatment of mucociliary dysfunction in patients with bronchiectasis: effect on lung function, health status and sputum. Respirology. 2005 Jan;10(1):46-56.

Starting date: November 2005
Ending date: February 2008
Last updated: February 27, 2008