NCT00446680

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.

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
340

participants targeted

Target at P50-P75 for phase_3

Timeline
Completed

Started Mar 2007

Typical duration for phase_3

Geographic Reach
3 countries

29 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

March 1, 2007

Completed
11 days until next milestone

First Submitted

Initial submission to the registry

March 12, 2007

Completed
1 day until next milestone

First Posted

Study publicly available on registry

March 13, 2007

Completed
3.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 1, 2010

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

May 1, 2010

Completed
Last Updated

June 25, 2010

Status Verified

June 1, 2010

Enrollment Period

3.2 years

First QC Date

March 12, 2007

Last Update Submit

June 23, 2010

Conditions

Keywords

MannitolCystic FibrosisMucolyticExacerbationFEV1Quality of Life

Outcome Measures

Primary Outcomes (1)

  • To determine the effects of 400 mg twice-daily administration of IDPM on FEV1 in patients with CF compared to control

    6 months

Secondary Outcomes (8)

  • 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)

    6 months

  • Reduces pulmonary exacerbations in those taking RhDNase as a sub-group and in the total cohort (key objective)

    6 months / 12 months

  • Improves quality of life (key objective)

    6 months

  • Reduces days on IV antibiotics, rescue oral or inhaled antibiotics

    6 months / 12 months

  • Reduces days in hospital due to pulmonary exacerbations

    6 months / 12 months

  • +3 more secondary outcomes

Study Arms (2)

1

EXPERIMENTAL
Drug: Mannitol

2

PLACEBO COMPARATOR
Drug: placebo

Interventions

400mg BD for 6 months followed by a 6 month open label period

1

placebo BD for 6 months

2

Eligibility Criteria

Age6 Years+
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • "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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (29)

Childrens Hospital at Westmead

Sydney, New South Wales, 2145, Australia

Location

Sydney Childrens Hospital

Sydney, New South Wales, Australia

Location

Royal Brisbane Children's Hospital

Brisbane, Queensland, 4029, Australia

Location

The Prince Charles Hospital

Brisbane, Queensland, 4032, Australia

Location

Royal Adelaide Hospital

Adelaide, South Australia, Australia

Location

Royal Childrens Hospital

Melbourne, Victoria, 3052, Australia

Location

Beaumont Hospital

Dublin, Ireland

Location

National Children's Hospital

Dublin, Ireland

Location

Our Lady's Hospital for Sick Children

Dublin, Ireland

Location

St Vincent's University Hospital

Dublin, Ireland

Location

Alder Hey Children's Hospital

West Derby, Liverpool, United Kingdom

Location

Belfast City Hospital

Belfast, Northern Ireland, BT9 7AB, United Kingdom

Location

Children's Hospital for Wales

Cardiff, Wales, CF14 4XW, United Kingdom

Location

Llandough Hospital

Cardiff, Wales, CF64 2XX, United Kingdom

Location

Birmingham Children's Hospital

Birmingham, United Kingdom

Location

Birmingham Heartlands Hospital

Birmingham, United Kingdom

Location

Bristol Royal Hospital for Children

Bristol, United Kingdom

Location

Bristol Royal Infirmary

Bristol, United Kingdom

Location

Addenbrooke's Hospital

Cambridge, United Kingdom

Location

Papworth Hospital

Cambridge, United Kingdom

Location

Seacroft Hospital

Leeds, United Kingdom

Location

Cardiothoracic Centre

Liverpool, L14 3PE, United Kingdom

Location

The London Chest Hospital

London, E2 9JX, United Kingdom

Location

Freeman Hospital

Newcastle, NE7 7DN, United Kingdom

Location

Norfolk and Norwich University Hospital

Norwich, NR4 7UY, United Kingdom

Location

Nottingham City Hospital

Nottingham, United Kingdom

Location

Northern General Hospital

Sheffield, United Kingdom

Location

Sheffield Children's Hospital

Sheffield, United Kingdom

Location

Southampton General Hospital

Southampton, United Kingdom

Location

Related Publications (3)

  • 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.

  • 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.

  • 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.

MeSH Terms

Conditions

Cystic Fibrosis

Interventions

Mannitol

Condition Hierarchy (Ancestors)

Pancreatic DiseasesDigestive System DiseasesLung DiseasesRespiratory Tract DiseasesGenetic Diseases, InbornCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesInfant, Newborn, Diseases

Intervention Hierarchy (Ancestors)

Sugar AlcoholsAlcoholsOrganic ChemicalsCarbohydrates

Study Officials

  • Brett Charlton, MBBS

    Pharmaxis Ltd Australia

    STUDY DIRECTOR
  • Dr Diana Bilton

    Papworth Hospital NHS Foundation Trust

    PRINCIPAL INVESTIGATOR
  • Dr Philip Robinson

    Royal Children's Hospital

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY

Study Record Dates

First Submitted

March 12, 2007

First Posted

March 13, 2007

Study Start

March 1, 2007

Primary Completion

May 1, 2010

Study Completion

May 1, 2010

Last Updated

June 25, 2010

Record last verified: 2010-06

Locations