Clinical trial NCT00446680: Long Term Administration of Inhaled Dry Powder Mannitol In Cystic Fibrosis - A Safety and Efficacy Study
Official title: Long Term Administration of Inhaled Dry Powder Mannitol In Cystic Fibrosis - A Safety and Efficacy Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Cystic Fibrosis
Keywords: Mannitol
Cystic Fibrosis
Mucolytic
Exacerbation
FEV1
Quality of Life
Lead sponsor: Syntara
Sponsor class: INDUSTRY
First posted: 2007-03-13
Enrollment: 340
Sex: ALL
Minimum age (years): 6
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine the efficacy and safety of chronic treatment with inhaled dry powder mannitol in subjects with cystic fibrosis. Previous studies have demonstrated an improvement in lung function related to small airways obstruction and a significant improvement in respiratory symptoms and quality of life after a 2 week treatment with mannitol. This current study seeks to support these early findings and to extend the evidence to support its use as a mucoactive therapy in cystic fibrosis. In particular, the hypothesis that enhanced mucus clearance will improve the lung function and clinical presentation in this population, will be investigated. We also hypothesize that enhanced mucociliary clearance will result in a sustained reduction in mucus load, thus providing less opportunity for bacteria to proliferate, affording a reduction in antibiotic use and hospitalizations. The initial 6 month blinded phase will be followed with an additional 6 months of open label treatment.


Eligibility criteria: Main Inclusion Criteria:

* Written informed consent
* Confirmed diagnosis of cystic fibrosis
* Aged \> 6 years
* FEV1 \>30 % and \< 90% predicted
* Able to perform all the techniques necessary to measure lung function

Main Exclusion Criteria:

* "Terminally ill" or listed for lung transplantation
* Had a lung transplant
* Using nebulised hypertonic saline
* Significant episode of haemoptysis (\>60 mL) in the three months prior to enrolment
* Recent myocardial infarction or cerebral vascular accident
* Breast feeding or pregnant, or plan to become pregnant while in the study participating in another investigative drug study, parallel to, or within 4 weeks of study entry
* Allergy or intolerance to mannitol
* Using beta blockers
* Have a condition or be in a situation which in the Investigator's opinion may put the subject at significant risk, may confound results or may interfere significantly with the patient's participation in the study

Primary outcomes:
measure: To determine the effects of 400 mg twice-daily administration of IDPM on FEV1 in patients with CF compared to control
timeFrame: 6 months
Secondary outcomes:
measure: To determine the effects of 400 mg twice-daily administration of IDPM on FEV1 in patients with CF on existing RhDNase treatment compared to control. (key objective)
timeFrame: 6 months
measure: Reduces pulmonary exacerbations in those taking RhDNase as a sub-group and in the total cohort (key objective)
timeFrame: 6 months / 12 months
measure: Improves quality of life (key objective)
timeFrame: 6 months
measure: Reduces days on IV antibiotics, rescue oral or inhaled antibiotics
timeFrame: 6 months / 12 months
measure: Reduces days in hospital due to pulmonary exacerbations
timeFrame: 6 months / 12 months
measure: Improves other measures of lung function
timeFrame: 6 months
measure: Demonstrates an appropriate safety profile (adverse events, haematology, biochemistry, change in bronchodilator response, sputum microbiology, physical examination)
timeFrame: 6 months / 12 months
measure: Reduces hospital and community care costs
timeFrame: 6 months / 12 months
Other outcomes:
Locations:
city: Sydney
country: Australia
facility: Childrens Hospital at Westmead
state: New South Wales
city: Sydney
country: Australia
facility: Sydney Childrens Hospital
state: New South Wales
city: Brisbane
country: Australia
facility: Royal Brisbane Children's Hospital
state: Queensland
city: Brisbane
country: Australia
facility: The Prince Charles Hospital
state: Queensland
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: Melbourne
country: Australia
facility: Royal Childrens Hospital
state: Victoria
city: Dublin
country: Ireland
facility: Beaumont Hospital
city: Dublin
country: Ireland
facility: National Children's Hospital
city: Dublin
country: Ireland
facility: Our Lady's Hospital for Sick Children
city: Dublin
country: Ireland
facility: St Vincent's University Hospital
city: West Derby
country: United Kingdom
facility: Alder Hey Children's Hospital
state: Liverpool
city: Belfast
country: United Kingdom
facility: Belfast City Hospital
state: Northern Ireland
city: Cardiff
country: United Kingdom
facility: Children's Hospital for Wales
state: Wales
city: Cardiff
country: United Kingdom
facility: Llandough Hospital
state: Wales
city: Birmingham
country: United Kingdom
facility: Birmingham Children's Hospital
city: Birmingham
country: United Kingdom
facility: Birmingham Heartlands Hospital
city: Bristol
country: United Kingdom
facility: Bristol Royal Hospital for Children
city: Bristol
country: United Kingdom
facility: Bristol Royal Infirmary
city: Cambridge
country: United Kingdom
facility: Addenbrooke's Hospital
city: Cambridge
country: United Kingdom
facility: Papworth Hospital
city: Leeds
country: United Kingdom
facility: Seacroft Hospital
city: Liverpool
country: United Kingdom
facility: Cardiothoracic Centre
city: London
country: United Kingdom
facility: The London Chest Hospital
city: Newcastle
country: United Kingdom
facility: Freeman Hospital
city: Norwich
country: United Kingdom
facility: Norfolk and Norwich University Hospital
city: Nottingham
country: United Kingdom
facility: Nottingham City Hospital
city: Sheffield
country: United Kingdom
facility: Northern General Hospital
city: Sheffield
country: United Kingdom
facility: Sheffield Children's Hospital
city: Southampton
country: United Kingdom
facility: Southampton General Hospital
Study officials:
affiliation: Pharmaxis Ltd Australia
name: Brett Charlton, MBBS
role: STUDY_DIRECTOR
affiliation: Papworth Hospital NHS Foundation Trust
name: Dr Diana Bilton
role: PRINCIPAL_INVESTIGATOR
affiliation: Royal Children's Hospital
name: Dr Philip Robinson
role: PRINCIPAL_INVESTIGATOR
References:
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: Nevitt SJ, Thornton J, Murray CS, Dwyer T. Inhaled mannitol for cystic fibrosis. Cochrane Database Syst Rev. 2020 May 1;5(5):CD008649. doi: 10.1002/14651858.CD008649.pub4.
citation: Bilton D, Robinson P, Cooper P, Gallagher CG, Kolbe J, Fox H, Jaques A, Charlton B; CF301 Study Investigators. Inhaled dry powder mannitol in cystic fibrosis: an efficacy and safety study. Eur Respir J. 2011 Nov;38(5):1071-80. doi: 10.1183/09031936.00187510. Epub 2011 Apr 8.