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Trial registered on ANZCTR


Registration number
ACTRN12610000754044
Ethics application status
Approved
Date submitted
23/08/2010
Date registered
13/09/2010
Date last updated
22/09/2010
Type of registration
Retrospectively registered

Titles & IDs
Public title
Trial of different concentrations of nebulised saline for cystic fibrosis
Scientific title
The effect of nebulised 0.9% vs 3% vs 6% saline on lung function and quality of life in people with cystic fibrosis
Secondary ID [1] 252549 0
There are no other identifying numbers for this trial
Universal Trial Number (UTN)
Trial acronym
Saline at lower tonicity in cystic fibrosis (SALTI-CF) trial
Linked study record

Health condition
Health condition(s) or problem(s) studied:
cystic fibrosis 256932 0
Condition category
Condition code
Human Genetics and Inherited Disorders 257076 257076 0 0
Cystic fibrosis

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Group A: Twice daily inhalation of 4mL of nebulised 6% hypertonic saline + 0.25mg/mL quinine sulphate for 16 weeks
Group B: Twice daily inhalation of 4mL of nebulised 3% hypertonic saline + 0.25mg/mL quinine sulphate for 16 weeks
Intervention code [1] 256122 0
Treatment: Drugs
Comparator / control treatment
Group C: Twice daily inhalation of 4mL of nebulised 0.9% isotonic saline + 0.25mg/mL quinine sulphate for 16 weeks
Control group
Placebo

Outcomes
Primary outcome [1] 257982 0
Lung function as measured by spirometry as the change in Forced Expiratory Volume in 1 second (FEV1) in units of percent predicted
Timepoint [1] 257982 0
Week 0 (baseline)
Week 1
Week 4
Week 8
Week 16 (end of trial)
Secondary outcome [1] 263522 0
Lung function as measured by spirometry in the change in Forced Vital Capacity (FVC) in units of percent predicted
Timepoint [1] 263522 0
Week 0
Week 1
Week 4
Week 8
Week 16
Secondary outcome [2] 263523 0
Lung function as measured by spirometry in the change in Forced Expiratory Volume 25-75 (FEF25-75) in units of percent predicted
Timepoint [2] 263523 0
Week 0
Week 1
Week 4
Week 8
Week 16
Secondary outcome [3] 263524 0
Quality of life as measured by the Cystic Fibrosis Questionnaire-Revised (CFQ-R)
Timepoint [3] 263524 0
Week 0
Week 1
Week 4
Week 8
Week 16
Secondary outcome [4] 263525 0
Quality of lfe as measured by the Medical Outcomes Survey Short Form-36 (SF-36)
Timepoint [4] 263525 0
Week 0
Week 1
Week 4
Week 8
Week 16
Secondary outcome [5] 263526 0
Exercise capacity as measured by the total distance covered in the Modified Shuttle Test-25 (MST-25)
Timepoint [5] 263526 0
Week 0
Week 4
Week 16
Secondary outcome [6] 263527 0
Exercise capacity as measured by the total exercise time in the Endurance Shuttle Test-25 (EST-25)
Timepoint [6] 263527 0
Week 0
Week 4
Week 16
Secondary outcome [7] 263528 0
Sputum bacterial diversity as measured by the acquisition or loss of bacterial organisms in expectorated sputum as measured by routine microscopy culture and sensitivity (M/C/S).
Timepoint [7] 263528 0
Week 0
Week 16
Secondary outcome [8] 263529 0
Tolerability of nebulised trial solution as measured by participant on a 10-point visual analogue scale
Timepoint [8] 263529 0
Week 0
Week 1
Week 4
Week 8
Week 16
Secondary outcome [9] 263530 0
Medication use as measured by number of doses of each prescribed medication
Timepoint [9] 263530 0
Week 0
Weekly during trial (Week 1-week 16)
Secondary outcome [10] 263531 0
Pulmonary exacerbations as measured by the Fuchs exacerbation criteria (presence of at least four of the following symptoms: change in sputum; new/increased haemoptysis; increased cough; increased dyspnoea; malaise/fatigue/lethargy; temperature>38C; anorexia/weight loss; sinus pain/tenderness; change in sinus discharge; change in auscultation; drop in FEV1>10% from best in last 6 months; change in xray/magnetic resonance imaging (MRI))
Timepoint [10] 263531 0
Weekly during trial (Week 1-week 16)
Secondary outcome [11] 263532 0
Adverse events (such as intolerable cough, sore throat, bronchospasm, haemoptysis, nausea, pulmonary exacerbation) as measured by presence of new symptoms, likelihood of being related to trial solution, severity of symptoms and time to resolution of symptoms.
Timepoint [11] 263532 0
Weekly during trial (Week 1-week 16)
Secondary outcome [12] 263533 0
Adherence to nebulisation of trial solution as measured weekly by self-report in patient diary and count of returned unused ampoules of trial solution at the end of the trial (week 16).
Timepoint [12] 263533 0
Weekly during trial (Week 1-week 16)
Secondary outcome [13] 264759 0
Administration time of nebulised trial solution as measured by stop watch from start to completion of one dose of trial inhalation solution
Timepoint [13] 264759 0
Week 0
Week 1
Week 4
Week 8
Week 16

Eligibility
Key inclusion criteria
Provides informed consent Diagnosis of cystic fibrosis (positive sweat test or genotyping) Best FEV1 in the previous six months >20% of predicted normal value FEV1 >85% of best in the previous six months No non-routine antibiotics in the last 14 days
Minimum age
6 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Colonisation with Burkholderia cepacia
Major haemoptysis within the last 12 months
Pregnant or lactating females
Investigational drugs within the last 30 days
Previous lung transplant
Hypertonic saline within the last 14 days
Inhaled mannitol within the last 14 days

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Participants will be randomly allocated to one of three groups. The allocation will be performed by the Trial Pharmacist at the trial co-ordinating centre. The treatment allocation is recorded at the Trial Pharmacy and the random allocation lists, randomisation procedure and the unblinded treatment allocation is to be concealed from all other trial staff and the participant.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Random number generation with block allocation. Treatment allocation is stratified for: age, gender, FEV1
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)

Funding & Sponsors
Funding source category [1] 256630 0
Charities/Societies/Foundations
Name [1] 256630 0
Australian Cystic Fibrosis Research Trust
Address [1] 256630 0
PO Box 254
North Ryde NSW 1670
Country [1] 256630 0
Australia
Primary sponsor type
Hospital
Name
Royal Prince Alfred Hospital
Address
Missenden Road
Camperdown NSW 2050
Country
Australia
Secondary sponsor category [1] 255918 0
None
Name [1] 255918 0
Address [1] 255918 0
Country [1] 255918 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 258657 0
Royal Prince Alfred Hospital
Ethics committee address [1] 258657 0
Research Development Office
Level 3, Building 92
Royal Prince Alfred Hospital
Camperdown NSW 2050
Ethics committee country [1] 258657 0
Australia
Date submitted for ethics approval [1] 258657 0
Approval date [1] 258657 0
08/12/2009
Ethics approval number [1] 258657 0
HREC/09/RPAH/406

Summary
Brief summary
Background People with Cystic Fibrosis (CF) have abnormally slow clearance of mucus from their airways. This causes chronic lung infection with obstruction of the airways by mucus. The chronic lung infection is characterised by (A) periods of acute worsening of the infection known as exacerbations, (B) progressive deterioration in lung function outside periods of exacerbation, (C) reduced quality of life, and (D) reduced ability to exercise. A strong, sterile, salt-water solution known as hypertonic saline is commonly used to assist clearance of mucus from the airways of people with CF. We know that long-term use of hypertonic saline where the concentration of salt is 7% produces significant benefits for people with CF in terms of (A) exacerbations, (B) lung function, and (C) quality of life. Some patients find 7% hypertonic saline difficult or impossible to tolerate. Some of these patients use lower concentrations of saline, although it is not known whether these are as effective, nor even whether they are more effective than doing nothing. Some patients often skip doses of hypertonic saline because the delivery is time consuming. Faster nebulisers are now available. The efficacy and tolerability of hypertonic saline delivered through these new nebulisers have not been formally assessed. Also, hypertonic saline has not been tested in patients with very badly affected lungs.
Aim One aim of the study is to determine the benefits of 6% and 3% hypertonic saline when delivered via a new, fast nebuliser, in people with CF. Another important aim is to determine whether hypertonic saline is tolerable when delivered via a fast nebuliser. A final aim is to compare the response to hypertonic saline among those with very badly affected lungs with the response to those with mildly and moderately affected lungs.
Method 140 people with CF will be enrolled in the study. For the first time, patients with very badly affected lungs will be eligible to enrol. All will be required to be in a stable clinical condition. At enrolment, lung function, quality of life, and some other relevant measures will be assessed. Participants will then be randomised to inhale either 6%, 3% or 0.9% saline. All other standard care will continue in all groups. Participants will be regularly assessed during the 16-week period over which they will inhale their allocated saline solution, twice a day, via a fast nebuliser. The progress of the groups inhaling the different concentrations of saline will be compared in terms of (A) exacerbations, (B) lung function, (C) quality of life and (D) exercise capacity. The tolerability of the solutions will also be recorded. We will also compare the response to the saline among those with very badly affected lungs to those with milder disease.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 30913 0
Address 30913 0
Country 30913 0
Phone 30913 0
Fax 30913 0
Email 30913 0
Contact person for public queries
Name 14160 0
Professor Peter Bye
Address 14160 0
Department of Respiratory Medicine
Level 11 West
Royal Prince Alfred Hospital
Missenden Road
Camperdown NSW 2050
Country 14160 0
Australia
Phone 14160 0
+61 2 9515 7427
Fax 14160 0
+61 2 9515 8196
Email 14160 0
peterb@med.usyd.edu.au
Contact person for scientific queries
Name 5088 0
Professor Peter Bye
Address 5088 0
Department of Respiratory Medicine
Level 11 West
Royal Prince Alfred Hospital
Missenden Road
Camperdown NSW 2050
Country 5088 0
Australia
Phone 5088 0
+61 2 9515 7427
Fax 5088 0
+61 2 9515 8196
Email 5088 0
peter.bye@sswahs.nsw.gov.au

No information has been provided regarding IPD availability
Summary results
No Results