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Trial registered on ANZCTR


Registration number
ACTRN12607000379415
Ethics application status
Approved
Date submitted
12/07/2007
Date registered
19/07/2007
Date last updated
3/02/2011
Type of registration
Prospectively registered

Titles & IDs
Public title
The prevention of airway narrowing following dry powder mannitol inhalation in susceptible bronchiectatic patients
Scientific title
In bronchiectatic patients susceptible to airway narrowing after inhaling dry powder mannitol is a single dose of sodium cromoglycate or eformoterol more effective than placebo in preventing airway narrowing
Secondary ID [1] 447 0
Royal Prince Alfred Hospital: Protocol Number X07-0128
Secondary ID [2] 457 0
CTN Trial Number 2007/483
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Prevention of airway narrowing in bronchiectatic patients following inhalation of dry powder mannitol 1961 0
Condition category
Condition code
Respiratory 2058 2058 0 0
Asthma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
At a screening visit subjects will be asked to perform a mannitol challenge test in order to determine if their airways narrow significantly in response to the inhalation of up to 635mg of dry powder mannitol. During the challenge test, subjects will be asked to inhale mannitol from a series of capsules using a simple, dry powder inhaler: the Osmohaler. The challenge begins with a 5mg dose of mannitol, and this dose is gradually increased over a series of steps. At each step lung function (spirometry) will be measured before moving on to the next dose. Mannitol will cause the airways to narrow if the subject has hyperresponsive airways. The challenge test will stop either when the breathing tests show that the subject’s airways function is 15% less than when the test started or after 635mg of mannitol has been inhaled. After the challenge test, if the subject’s airways have narrowed, they will be given bronchodilator (200ug salbutamol, i.e.Ventolin, inhaled from a metered dose inhaler via a large volume spacer, the Volumatic) and recovery will be monitored by spirometry. If recovery to within 5% of baseline has not occurred within 15 minutes further doses of Ventolin will be given every 15 minutes until recovery to within 5% of baseline. Upon satisfying all inclusion/exclusion criteria for the study subjects will be asked to return for a further 3 treatment visits, with a washout period of 3 or more days separating each visit. During these visits subjects will be pre-medicated with either placebo (used as a control), 20mg sodium cromoglycate or 12ug eformoterol fumarate dihydrate 15 minutes prior to performing a mannitol challenge test. The challenge test will proceed as described above. Please note that the sodium cromoglycate, eformoterol fumarate dihydrate, placebo and mannitol will all be inhaled in dry powder form using an Aerolizer dry powder inhaler.
Intervention code [1] 1887 0
Prevention
Comparator / control treatment
Placebo
Control group
Active

Outcomes
Primary outcome [1] 3141 0
The dose of mannitol required to induce a 15% fall in forced expired volume in one second (FEV1)
Timepoint [1] 3141 0
At Visit 1, and for Visits 2-4: 15 minutes after the administration of placebo, sodium cromoglycate or eformoterol
Primary outcome [2] 3142 0
The response dose ratio (final percentage fall in FEV1 divided by the dose of mannitol administered)
Timepoint [2] 3142 0
At Visit 1, and for Visits 2-4: 15 minutes after the administration of placebo, sodium cromoglycate or eformoterol
Secondary outcome [1] 4869 0
Arterial blood oxygen saturation as estimated by pulse oximetry
Timepoint [1] 4869 0
At Visits 1-4, measured pre- and post-mannitol challenge and following recovery after the administration of salbutamol, if required.
Secondary outcome [2] 4870 0
Evidence of atopy as determined by skin prick testing using common airborne allergens
Timepoint [2] 4870 0
At Visit 1

Eligibility
Key inclusion criteria
Subjects must: 1) Have given written informed consent to participate in this study, 2) Have symptomatic (i.e. daily production of sputum) non-cystic fibrosis (CF) bronchiectasis, confirmed by high resolution computed tomography (HRCT), 3) Be a non smoker, 5) Be able to perform reproducible spirometry, 4) Have an FEV1 1.2 Litres, 5) Be in a stable clinical condition at the time of, and for a period of 14 days prior to, recruitment into the study, 6) Have a positive response to inhaled mannitol, as measured by a fall in FEV1 of 15% after < 315mg of mannitol on Visit 1
Minimum age
18 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Subjects must not: 1) Have bronchiectasis as a consequence of cystic fibrosis or focal endobronchial lesion, 2) Be considered “terminally ill” or listed for lung transplantation, 3) Have had a significant episode of haemoptysis (>60 mL) in the previous six months, 4) Have had an exacerbation for which they have been prescribed intravenous antibiotics in the 4 weeks prior to study entry, 5) Have a smoking history of >20 pack years or have smoked more than one cigarette a week within the previous three months, 6) Have had a myocardial infarction in the three months prior to enrolment, 7) Have had a cerebral vascular accident in the three months prior to enrolment, 8) Have had major ocular surgery in the three months prior to enrolment, 9) Have had major abdominal, chest or brain surgery in the three months prior to enrolment, 10) Have a known cerebral, aortic or abdominal aneurysm, 11) Have active tuberculosis, 12) Have active malignancy including melanoma (other skin carcinomas and remissions exempted), 13) Be breast feeding or pregnant, or plan to become pregnant while in the study, 14) Be using an unreliable form of contraception (female subjects at risk of pregnancy only), 15) Be participating in another investigative drug study, parallel to, or within 4 weeks of study entry, 16) Have a known intolerance to mannitol or ß-agonists, 17) Have uncontrolled hypertension – systolic BP > 190 and/or diastolic BP > 100, 18) Have resting oximetry of less than 90%, 19) 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.

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Once a subject meets inclusion/exclusion criteria they will be enrolled in the trial. Each subject will act as their own control. A third party, located at a central administration site, will allocate each patient to a randomised treatment plan.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Permuted block randomisation
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
Both the people administering the treatments and the subjects will be blinded
Phase
Phase 4
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Date of first participant enrolment
Anticipated
20/08/2007
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
25
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)

Funding & Sponsors
Funding source category [1] 2202 0
Hospital
Name [1] 2202 0
Department of Respiratory and Sleep Medicine
Royal Prince Alfred Hospital
Country [1] 2202 0
Australia
Primary sponsor type
Government body
Name
Sydney South West Area Health Service
Address
Research Development Office
Level 8 Building 14
Royal Prince Alfred Hospital
Camperdown NSW 2050
Country
Australia
Secondary sponsor category [1] 1988 0
None
Name [1] 1988 0
Nil
Address [1] 1988 0
Country [1] 1988 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 4004 0
Sydney South West Area Health Service Ethics Review Committee & Clinical Trials Sub-committee
Ethics committee address [1] 4004 0
Research Development Office
Level 8 Building 14
Royal Prince Alfred Hospital
Camperdown NSW 2050
Ethics committee country [1] 4004 0
Australia
Date submitted for ethics approval [1] 4004 0
28/05/2007
Approval date [1] 4004 0
31/07/2007
Ethics approval number [1] 4004 0

Summary
Brief summary
Dry powder mannitol has the potential to be prescribed as a treatment for bronchiectasis because of its demonstrated ability to enhance mucociliary clearance. However, some bronchiectatic patients demonstrate airway narrowing after inhaling mannitol. If pre-medicating these patients with either sodium cromoglycate or eformoterol can be shown to protect them from developing significant airway narrowing after inhaling mannitol, this patient population may be able to access a potential new treatment for their disease.
Trial website
Trial related presentations / publications
Peter J. Briffa, Sandra D. Anderson, Deborah L. Burton and Iven H. Young, "Sodium cromoglycate and eformoterol attenuate sensitivity and
reactivity to inhaled mannitol in subjects with bronchiectasis", Respirology (2011) 16, 161–166
doi: 10.1111/j.1440-1843.2010.01894.x
Public notes

Contacts
Principal investigator
Name 27701 0
Address 27701 0
Country 27701 0
Phone 27701 0
Fax 27701 0
Email 27701 0
Contact person for public queries
Name 11076 0
Mr Peter J Briffa
Address 11076 0
Respiratory Investigation Unit
11 West Building 75
Royal Prince Alfred Hospital
Missenden Road
Camperdown NSW 2050
Country 11076 0
Australia
Phone 11076 0
+61 2 95156131
Fax 11076 0
+61 2 95158196
Email 11076 0
[email protected]
Contact person for scientific queries
Name 2004 0
Dr Sandra Anderson
Address 2004 0
Respiratory Investigation Unit
11 West Building 75
Royal Prince Alfred Hospital
Missenden Road
Camperdown NSW 2050
Country 2004 0
Australia
Phone 2004 0
+61 2 95156131
Fax 2004 0
+61 2 95158196
Email 2004 0
[email protected]

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