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Trial registered on ANZCTR


Registration number
ACTRN12615001067561
Ethics application status
Approved
Date submitted
24/08/2015
Date registered
13/10/2015
Date last updated
17/02/2020
Date data sharing statement initially provided
1/02/2019
Date results information initially provided
17/02/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
Saline Hypertonic in Preschoolers with Cystic Fibrosis and lung structure as measured by computed tomography (CT). SHIP-CT study.
Scientific title
A Phase 3 randomised, double-blind, controlled trial of inhaled 7% hypertonic saline versus 0.9% isotonic saline for 48 weeks on lung structure in patients with Cystic Fibrosis at 3-6 years of age, in parallel with the North American SHIP clinical trial, as measured by computed tomography (CT).
Secondary ID [1] 287189 0
NIL to date
Universal Trial Number (UTN)
U1111-1172-7860
Trial acronym
SHIP-CT
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cystic Fibrosis 295763 0
Condition category
Condition code
Human Genetics and Inherited Disorders 296044 296044 0 0
Cystic fibrosis

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Experimental: Active Treatment Group
7% Hypertonic Saline administered via inhalation twice daily for 48 weeks.

Drug - 7% Hypertonic Saline (HS)
Administered via inhalation of 4mL twice daily for 48 weeks. The delivery system is a PARI Sprint Junior nebulizer with a PARI Baby face mask or mouthpiece driven by a PARI compressor.
Intervention code [1] 292470 0
Treatment: Other
Comparator / control treatment
Active Comparator: Control Group
0.9% Isotonic Saline administered via inhalation twice daily for 48 weeks.

Drug - 0.9% Isotonic Saline (IS)
Administered via inhalation of 4mL twice daily for 48 weeks. The delivery system is a PARI Sprint Junior nebulizer with a PARI Baby face mask or mouthpiece driven by a PARI compressor.
Control group
Active

Outcomes
Primary outcome [1] 295713 0
Difference in the PRAGMA-CF score: the volume proportion of the lung with structural airways disease (%Dis), measured from chest CT images at 48 weeks between treatment arms
Timepoint [1] 295713 0
48 weeks after commencement of intervention
Secondary outcome [1] 316287 0
Composite outcome of longitudinal change in airway disease, bronchiectasis and trapped air, from baseline to end of study as established by PRAGMA-CF on CT scans
Timepoint [1] 316287 0
at baseline and 48 weeks after commencement of intervention.
Secondary outcome [2] 316288 0
Proportion of patients with bronchiectasis as established by PRAGMA-CF on CT scans
Timepoint [2] 316288 0
48 weeks after commencement of intervention
Secondary outcome [3] 316289 0
Longitudinal change in LCI from baseline to 48 weeks measured by N2 MBW
Timepoint [3] 316289 0
48 weeks after commencement of intervention
Secondary outcome [4] 316290 0
Protocol defined pulmonary exacerbation rate, by SAE review where a patient has ben admitted to hospital following a pulmonary exacerbation
Timepoint [4] 316290 0
48 weeks after commencement of intervention
Secondary outcome [5] 316291 0
Health-related quality of life as measured by the modified parent-reported CFQ-R for preschoolers
Timepoint [5] 316291 0
48 weeks after commencement of intervention

Eligibility
Key inclusion criteria
1. Diagnosis of CF as evidenced by one or more clinical feature consistent with the CF phenotype or positive CF newborn screen AND one or more of the following criteria:
a) A documented sweat chloride greater than or equal to 60 mEq/L by quantitative pilocarpineiontophoresis (QPIT)
b) A documented genotype with two disease-causing mutations in the CFTR gene
2. Informed consent by parent or legal guardian
3. Age greater than or equal to 36 months and less than or equal to 72 months at screening visit
4. Ability to comply with medication use, study visits and study procedures as judged by the site investigator
5. Ability to perform a chest CT at the enrolment visit
Minimum age
36 Months
Maximum age
72 Months
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Chest CT within 8 months prior to the Screening visit
2. Acute intercurrent respiratory infection, defined as an increase in cough, wheezing, or respiratory rate with onset within 3 weeks preceding screening or enrolment visit
3. Acute wheezing at screening or enrolment visit
4. Oxygen saturation < 95% (<90% in centres located above 4000 feet elevation) at screening or enrolment visit
5. Other major organ dysfunction, excluding pancreatic dysfunction
6. Physical findings that would compromise the safety of the participant or the quality of the study data as determined by site investigator
7. Investigational drug use within 30 days prior to screening or enrolment visit
8. Treatment with inhaled HS at any concentration within 30 days prior to screening or enrolment visit
9. Start of any additional inhaled saline solution at any concentration, or other hydrating agent such as mannitol or mucolytic drug such as dornase alpha within 30 days prior or following the Screening or Enrolment visit
10. Chronic lung disease not related to CF
11. Inability to tolerate first dose of study treatment at the enrolment visit

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)
A central Coordinating Centre in The USA will design and maintain a secure website system for enrolment and randomisation assignments. Only authorized site personnel are given access to the randomisation pages. On the website, authorized site personnel will enter participant eligibility information and verify that the parent/guardian signed informed consent. The system will verify that the participant is eligible and then provide the authorized site personnel with a unique randomisation assignment number that matches a number on the treatment (HS or IS) package stored at the site . Randomisation to HS or IS will be stratified by age (36 to 54 months, 55 to 72 months).
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The randomisation list will be created based on random permuted blocks stratified on age. Electronic copies of the randomisation lists will be archived in a secure off-site location for the duration of the trial and for three years thereafter.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Efficacy
Statistical methods / analysis
120 patients (approximately 55 subjects from Australia, 55 from Europe, and 10 from two US centres) will be recruited to the study. Multiple linear regression will be used to determine the cross-sectional (values at end of study) and longitudinal (change in outcomes between beginning and end of study) relationships between LCI, the volume proportion of the lung with structural airways disease assessed by PRAGMA-CF and secondary PRAGMA-CF outcomes percentage bronchiectasis and trapped air), and airway dimensions relative to adjacent arteries outcomes, with exposure variables included as appropriate. The relative ability of PRAGMA-CF and LCI to discriminate between treatment and active comparator arms will be determined by using linear regression against percentage disease and LCI in separate analyses, in the subset of patients with matched LCI and CT data.

For the power calculation, we used the mean (standard deviation) %Dis as measured on TLC CTs in fifty 4-6 year old children in the Perth CF cohort: 5.18 (2.54)%, with a range of 1.05 – 14.13%. A sample size of 50 in equal size groups with alpha=0.05 and beta=0.80 will be able to detect a difference of 1.44% (i.e. relative difference between the two treatment arms of 28% given the anticipated level of 5.18%). We estimate that we will fail to acquire a scan, or scan of sufficient quality at the end of study in around 20% of children. Hence we aim to enrol approximately 60 patients per group to end up with 50 patients per group with a chest CT scan.

Recruitment
Recruitment status
Active, not 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)
NSW,QLD,SA,WA,VIC
Recruitment hospital [1] 7749 0
The Children's Hospital at Westmead - Westmead
Recruitment hospital [2] 7750 0
Sydney Children's Hospital - Randwick
Recruitment hospital [3] 7751 0
The Royal Childrens Hospital - Parkville
Recruitment hospital [4] 7752 0
Lady Cilento Children's Hospital - South Brisbane
Recruitment hospital [5] 7753 0
John Hunter Children's Hospital - New Lambton
Recruitment hospital [6] 7754 0
Womens and Childrens Hospital - North Adelaide
Recruitment hospital [7] 13026 0
Perth Children's Hospital - Nedlands
Recruitment postcode(s) [1] 15683 0
2145 - Westmead
Recruitment postcode(s) [2] 15684 0
2031 - Randwick
Recruitment postcode(s) [3] 15685 0
3052 - Parkville
Recruitment postcode(s) [4] 15686 0
4101 - South Brisbane
Recruitment postcode(s) [5] 15687 0
2305 - New Lambton
Recruitment postcode(s) [6] 15688 0
5006 - North Adelaide
Recruitment postcode(s) [7] 25512 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 7114 0
Netherlands
State/province [1] 7114 0
Country [2] 7115 0
Belgium
State/province [2] 7115 0
Country [3] 7116 0
Spain
State/province [3] 7116 0
Country [4] 7117 0
France
State/province [4] 7117 0
Country [5] 7118 0
United Kingdom
State/province [5] 7118 0
Country [6] 7197 0
United States of America
State/province [6] 7197 0

Funding & Sponsors
Funding source category [1] 291898 0
Charities/Societies/Foundations
Name [1] 291898 0
Cystic Fibrosis Foundation Therapeutics
Address [1] 291898 0
6931 Arlington Road, Bethesda, Maryland 20814
Country [1] 291898 0
United States of America
Primary sponsor type
Other Collaborative groups
Name
Telethon Kids Institute
Address
PO Box 855, West Perth, Western Australia, 6872
Country
Australia
Secondary sponsor category [1] 290565 0
Charities/Societies/Foundations
Name [1] 290565 0
Cystic Fibrosis Foundation Therapeutics
Address [1] 290565 0
6931 Arlington Road, Bethesda, Maryland 20814
Country [1] 290565 0
United States of America
Secondary sponsor category [2] 290566 0
Other Collaborative groups
Name [2] 290566 0
Erasmus Medical Centre
Address [2] 290566 0
Erasmus Medical Centre, P.O. Box 2060, 3000 CB Rotterdam
Netherlands

Country [2] 290566 0
Netherlands
Other collaborator category [1] 278590 0
Other Collaborative groups
Name [1] 278590 0
Collaborative Health Studies Coordinating Center
Address [1] 278590 0
University of Washington, Collaborative Health Studies Coordinating Center, Building 29, Suite 310, 6200 NE 74th Street, Seattle, WA 98115-8160

Country [1] 278590 0
United States of America
Other collaborator category [2] 278591 0
Hospital
Name [2] 278591 0
University of Washington School of Medicine, Division of Pulmonary Medicine, Seattle Children’s Hospital

Address [2] 278591 0
Seattle Children’s Hospital, P.O. Box 537, Seattle, WA 98145-5005
Country [2] 278591 0
United States of America

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 293407 0
Princess Margaret Hospital for Children Ethics Committee
Ethics committee address [1] 293407 0
Level 1, Children's Clinical Research Facility
Princess Margaret Hospital
Roberts Road, Subiaco WA 6008
GPO Box D184
Perth WA 6840
Ethics committee country [1] 293407 0
Australia
Date submitted for ethics approval [1] 293407 0
13/10/2015
Approval date [1] 293407 0
28/07/2016
Ethics approval number [1] 293407 0

Summary
Brief summary
People with cystic fibrosis (CF) often have thick mucus in the airways of the lungs that is hard to cough up. The mucus builds up and eventually leads to chronic cough and lung infections. Research has shown that even young children with CF may have thickened mucus in the lungs.
Inhaling a concentrated salt solution, called hypertonic saline (HS), may help thin the mucus in the lungs. Thinning the mucus can make it easier to cough up. This helps to clear the lungs and improve lung health. Research studies about the safety and effectiveness of inhaled HS have been done in adults and children with CF 6 years of age and older. Patients in these studies took HS for up to a year. HS appears to be a safe treatment in these age groups. The main side effects were cough, throat irritation, and wheezing. The use of HS in older children and adults decreased the need for antibiotics for acute respiratory infections. It also improved lung function and quality of life. HS is now routinely used by many CF patients over 6 years of age. Because HS treats a very early step in the chain of events that leads to chronic lung problems in people with CF, it may be particularly helpful when started early in life.
Based on several studies, HS appears to be safe in children less than 6 years of age, but its effectiveness has been difficult to measure. In a previous study, children less than 6 year-old receiving HS had the same number of lung infections as children receiving normal saline. However, we think that children this young need a more sensitive test to see if HS works in preventing lung damage. In this study Computed Tomography (CT) scans will be used to get an image of the lung. In addition a new type of breathing test, called Multiple Breath Washout (MBW), will be used. This is relatively easy for preschool children to perform, and may allow us to measure the effectiveness of HS in preschool children with CF. The MBW tests measures lung function. This study will be conducted in parallel with the North American SHIP001 clinical study, registered on Clinicaltrials.gov NCT02378467.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 59214 0
Prof Stephen Stick
Address 59214 0
The Telethon Kids Institute,
PO BOX 855, West Perth, Western Australia, 6872

Country 59214 0
Australia
Phone 59214 0
+61 (0)8 9340 8830
Fax 59214 0
Email 59214 0
Stephen.Stick@health.wa.gov.au
Contact person for public queries
Name 59215 0
Ms Nat Eiffler
Address 59215 0
The Telethon Kids Institute,
PO BOX 855, West Perth, Western Australia, 6872
Country 59215 0
Australia
Phone 59215 0
+61 (0)8 9489 7814
Fax 59215 0
Email 59215 0
nat.eiffler@telethonkids.org.au
Contact person for scientific queries
Name 59216 0
Prof Stephen Stick
Address 59216 0
The Telethon Kids Institute,
PO BOX 855, West Perth, Western Australia, 6872
Country 59216 0
Australia
Phone 59216 0
+61 (0)8 9340 8830
Fax 59216 0
Email 59216 0
Stephen.Stick@health.wa.gov.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
What supporting documents are/will be available?
No other documents available
Summary results
Have study results been published in a peer-reviewed journal?
No
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary