Clinical trial NCT00117208: Comparison of Inhaled Mannitol and rhDNase in Children With Cystic Fibrosis
Official title: A Cross-Over Comparative Study of Inhaled Mannitol, Alone and in Combination With Daily rhDNase, in Children With Cystic Fibrosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Cystic Fibrosis
Keywords: cystic fibrosis
Lead sponsor: Syntara
Sponsor class: INDUSTRY
First posted: 2005-07-04
Enrollment: 20
Sex: ALL
Minimum age (years): 8
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility 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

Primary outcomes:
measure: FEV1 after 12 weeks of each of the following treatment regimens: *mannitol only *rhDNase only *mannitol + rhDNase
timeFrame: 12 weeks
Secondary outcomes:
measure: to compare mannitol to rhDNase on FVC
timeFrame: 12 weeks
measure: to assess whether the effects of mannitol are additive to rhDNase
timeFrame: 12 weeks
measure: to demonstrate that mannitol does not cause deterioration in airway inflammation
timeFrame: 12 weeks
measure: to assess whether mannitol reduces the bacterial load in the lung
timeFrame: 12 weeks
measure: to assess whether the effects of mannitol are beneficial to quality of life
timeFrame: 12 weeks
measure: to assess whether mannitol, or mannitol + rhDNase are cost-effective compared to rhDNase alone
timeFrame: 12 weeks
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Great Ormond Hospital for Children
city: London
country: United Kingdom
facility: Royal Brompton Hospital
Study officials:
affiliation: Royal Brompton and Harefiled NHS Trust
name: Andrew Bush, FRCPCH
role: PRINCIPAL_INVESTIGATOR
affiliation: Great Ormond Street Hospital for Children NHS Foundation Trust
name: Colin Wallis, FRCPCH
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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. doi: 10.1016/S0140-6736(01)06412-1.
citation: 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. doi: 10.1034/j.1399-3003.1999.14c30.x.
citation: 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. doi: 10.1183/09031936.97.10112449.
citation: 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. doi: 10.1164/ajrccm.159.6.9809074.
citation: 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. doi: 10.1378/chest.119.2.414.
citation: 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. doi: 10.1111/j.1440-1843.2005.00659.x.
citation: Minasian C, Wallis C, Metcalfe C, Bush A. Comparison of inhaled mannitol, daily rhDNase and a combination of both in children with cystic fibrosis: a randomised trial. Thorax. 2010 Jan;65(1):51-6. doi: 10.1136/thx.2009.116970. Epub 2009 Dec 8.
citation: Minasian C, Wallis C, Metcalfe C, Bush A. Bronchial provocation testing with dry powder mannitol in children with cystic fibrosis. Pediatr Pulmonol. 2008 Nov;43(11):1078-1084. doi: 10.1002/ppul.20903.
citation: Yang C, Montgomery M. Dornase alfa for cystic fibrosis. Cochrane Database Syst Rev. 2021 Mar 18;3(3):CD001127. doi: 10.1002/14651858.CD001127.pub5.
citation: Enderby B, Doull I. Hypertonic saline inhalation in cystic fibrosis--salt in the wound, or sweet success? Arch Dis Child. 2007 Mar;92(3):195-6. doi: 10.1136/adc.2006.094979.