Comparison of Inhaled Mannitol and rhDNase in Children With Cystic Fibrosis - Full Text View

Purpose

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.

Condition	Intervention	Phase
Cystic Fibrosis	Drug: mannitol Drug: mannitol + pulmozyme Drug: Dornase alpha	Phase 2

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Crossover Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	A Cross-Over Comparative Study of Inhaled Mannitol, Alone and in Combination With Daily rhDNase, in Children With Cystic Fibrosis

Resource links provided by NLM:

Genetics Home Reference related topics: cystic fibrosis

MedlinePlus related topics: Cystic Fibrosis

Drug Information available for: Mannitol Dornase alfa

U.S. FDA Resources

Further study details as provided by Pharmaxis:

Primary Outcome Measures:

FEV1 after 12 weeks of each of the following treatment regimens: *mannitol only *rhDNase only *mannitol + rhDNase [ Time Frame: 12 weeks ]

Secondary Outcome Measures:

to compare mannitol to rhDNase on FVC [ Time Frame: 12 weeks ]
to assess whether the effects of mannitol are additive to rhDNase [ Time Frame: 12 weeks ]
to demonstrate that mannitol does not cause deterioration in airway inflammation [ Time Frame: 12 weeks ]
to assess whether mannitol reduces the bacterial load in the lung [ Time Frame: 12 weeks ]
to assess whether the effects of mannitol are beneficial to quality of life [ Time Frame: 12 weeks ]
to assess whether mannitol, or mannitol + rhDNase are cost-effective compared to rhDNase alone [ Time Frame: 12 weeks ]

Enrollment:	20
Study Start Date:	November 2005
Study Completion Date:	February 2008
Primary Completion Date:	February 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1	Drug: mannitol 400mg BD for 12 weeks
Active Comparator: 2 DNase daily for 12 weeks	Drug: Dornase alpha 2.5mg daily for 2 weeks Other Name: rhDNase, pulmozyme
3 combination	Drug: mannitol + pulmozyme combination

Eligibility

Ages Eligible for Study:	8 Years to 18 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00117208

Locations

United Kingdom
Royal Brompton Hospital
London, United Kingdom
Great Ormond Hospital for Children
London, United Kingdom

Sponsors and Collaborators

Pharmaxis

Investigators

Principal Investigator:	Andrew Bush, FRCPCH	Royal Brompton and Harefiled NHS Trust
Principal Investigator:	Colin Wallis, FRCPCH	Great Ormond Street Hospital for Children NHS Foundation Trust

More Information

Additional Information:

Pharmaxis homepage This link exits the ClinicalTrials.gov site

Publications:

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. Epub 2009 Dec 8.

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):1078-84.

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.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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. No abstract available.

ClinicalTrials.gov Identifier:	NCT00117208 History of Changes
Other Study ID Numbers:	DPM-CF-203
Study First Received:	June 30, 2005
Last Updated:	January 31, 2010
Health Authority:	United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Pharmaxis:

cystic fibrosis

Additional relevant MeSH terms:

Cystic Fibrosis
Fibrosis
Pancreatic Diseases
Digestive System Diseases
Lung Diseases
Respiratory Tract Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases
Pathologic Processes

Mannitol
Diuretics, Osmotic
Diuretics
Natriuretic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Cardiovascular Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on May 19, 2013