Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12624000146594p
Ethics application status
Submitted, not yet approved
Date submitted
24/10/2023
Date registered
15/02/2024
Date last updated
15/02/2024
Date data sharing statement initially provided
15/02/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
Assessment of regional lung ventilation following the commencement of ETI
(elexacaftor/tezacaftor/ivacaftor) treatment in children with cystic fibrosis
Scientific title
Assessment of regional lung ventilation via X-ray velocimetry (XV) imaging following the
commencement of ETI (elexacaftor/tezacaftor/ivacaftor) treatment in children with cystic fibrosis
Secondary ID [1] 310764 0
WCH_XV_003
Universal Trial Number (UTN)
U1111-1298-8130
Trial acronym
Linked study record
ACTRN12623000109606 - Parent study, data collection will be synchronised to allow pooled baseline data to be analysed
ACTRN12623000930684p - Participants will be eligible to be invited to participate in this interview study asking about XV scan experiences of CF patients.

Health condition
Health condition(s) or problem(s) studied:
cystic fibrosis 331723 0
Condition category
Condition code
Respiratory 328470 328470 0 0
Other respiratory disorders / diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Patients will be asked to have an x-ray velocimetry (XV) scan, physical exam, questionnaire (cystic fibrosis questionnaire - revised (CFQ-R)) and lung function measures (multiple breath washout, spirometry, lung volumes, diffusing capacity) in addition to their standard care. This will be conducted at Baseline (approximately 1 month pre-ETI commencement) and at 2 months post-ETI).

The intervention for this study is the x-ray velocimetry (XV) scan which is a fluoroscopic chest x-ray of tidal breathing at 5 different angles to create a 3D moving image. The patient needs to lie still for approximately 5 minutes while breathing normally. Participants need a clinically-indicated CT scan to be eligible as this is used to analyse the XV scan to produce the XV LVAS (x-ray velocimetry lung ventilation analysis software) report.

The medication ETI (elexacaftor/tezacaftor/ivacaftor) is newly listed on the PBS in Australia for cystic fibrosis patients 6 years and over. ETI dosing is age and weight dependant, with 2 morning and one night tablet taken with a high fat food. Children 6 to 11 years old and less than 30kg: morning tablet (elexacaftor 50 mg/tezacaftor 25 mg/ivacaftor 37.5 mg); night tablet (ivacaftor 75 mg). Children over 30kg or over 12 years to adult: morning tablet (elexacaftor 100 mg/tezacaftor 50 mg/ivacaftor 75 mg); night tablet (ivacaftor 150 mg). Children that take at least one tablet will be recorded as taking ETI, with compliance estimated at follow-up visit by parents (tablets left in weekly blister packs) and medication supplied by the patients as per usual clinical care.
Intervention code [1] 327169 0
Diagnosis / Prognosis
Intervention code [2] 327170 0
Treatment: Drugs
Comparator / control treatment
The reference comparator to x-ray velocimetry (XV) is lung function testing, with the children acting as their own control for changes in lung function measured by both methods after starting the ETI treatment.

Lung function testing takes 1.5-2 hours to attempt Spirometry, Multiple Breath Washout, Lung Volumes and Diffusing Capacity will be attempted by all participants. Spirometry is the gold standard test but is only introduced clinically at 5 to 6 years old as children need to be coached and the results are effort dependant. Multiple breath washout can be completed by children as young as 3 as this requires passive breathing only. Lung function testing will be carried out by the WCH's Lung Function Laboratory staff.
Control group
Active

Outcomes
Primary outcome [1] 336290 0
Changes in lung ventilation heterogeneity (VH) as measured by x-ray velocimetry lung ventilation analysis software (XV-LVAS) following commencement of ETI (elexacaftor/tezacaftor/ivacaftor) in children with cystic fibrosis
Timepoint [1] 336290 0
Baseline (1-month pre-ETI commencement) to Follow-up (2 months post-ETI commencement)
Primary outcome [2] 336677 0
Changes in regional lung ventilation (RLV) as measured by x-ray velocimetry lung ventilation analysis software (XV-LVAS) following commencement of ETI (elexacaftor/tezacaftor/ivacaftor) in children with cystic fibrosis
Timepoint [2] 336677 0
Baseline (1-month pre-ETI commencement) to Follow-up (2 months post-ETI commencement)
Secondary outcome [1] 427695 0
Determine whether XV provides an accurate clinical assessment of lung function compared to traditional lung function testing by assessing correlations between lung function and XV LVAS measures (Composite outcome).
Timepoint [1] 427695 0
Baseline (1-month pre-ETI commencement)
Follow-up (2 months post-ETI commencement)
Secondary outcome [2] 431335 0
Change in Quality of Life measurements
Timepoint [2] 431335 0
Baseline (1-month pre-ETI commencement)
Follow-up (2 months post-ETI commencement)

Eligibility
Key inclusion criteria
- Children with cystic fibrosis aged 5-18 years planning to start ETI (elexacaftor/tezacaftor/ivacaftor) treatment in the next 3 months
- must have a clinically indicated CT chest completed prior to screening or scheduled within the next 4 weeks
- must be willing to attempt all lung function testing and complete one of: spirometry, lung volumes, diffusing capacity, multiple breath washout
Minimum age
5 Years
Maximum age
18 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- pulmonary exacerbation within 4 weeks of planned screening visit
- currently receiving mechanical ventilation, intensive or other critical care
- contraindication to ionising radiation
- inability to remain still for periods of 30 seconds for each of the 5 XV image acquisitions during an XV scan
- use of ETI (elexacaftor/tezacaftor/ivacaftor) before Screening procedures are complete

Study design
Purpose of the study
Diagnosis
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Not Applicable
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
The XV and Lung Function Test outcome data obtained from this study will be described by timepoint (Baseline, Follow-up) using descriptive statistics. Continuous variables will be described using mean and standard deviation, or median and interquartile range (IQR) if the distribution is asymmetric. Categorical variables will be presented as numbers and percentages. Demographic variables age, sex, height and weight will also be described by group. Association between outcome measures (change within a participant’s lung function, XV results and CFQ-R responses) will be assessed graphically and described using correlation coefficients.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/03/2024
Actual
Date of last participant enrolment
Anticipated
31/12/2024
Actual
Date of last data collection
Anticipated
31/03/2025
Actual
Sample size
Target
20
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 25769 0
Womens and Childrens Hospital - North Adelaide
Recruitment postcode(s) [1] 41594 0
5006 - North Adelaide

Funding & Sponsors
Funding source category [1] 314994 0
Hospital
Name [1] 314994 0
Women's and Children's Hospital
Country [1] 314994 0
Australia
Primary sponsor type
Hospital
Name
Women's and Children's Hospital
Address
Women's and Children's Hospital, 72 King William Road, North Adelaide, SA 5006
Country
Australia
Secondary sponsor category [1] 317010 0
Commercial sector/Industry
Name [1] 317010 0
4DMedical
Address [1] 317010 0
Level 7, 700 Swanston Street, Carlton, VIC, 3053
Country [1] 317010 0
Australia

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 313967 0
Women's and Children's Health Network Human Research Ethics Committee
Ethics committee address [1] 313967 0
72 King William Street, North Adelaide, SA 5006
Ethics committee country [1] 313967 0
Australia
Date submitted for ethics approval [1] 313967 0
31/10/2023
Approval date [1] 313967 0
Ethics approval number [1] 313967 0
2023/HRE00276

Summary
Brief summary
This trial is evaluating a new imaging method, XV LVAS, which generates a 4D report of lung structure and function. This will be used to evaluate the increase in lung function reported in children with cystic fibrosis when starting the modulator therapy ETI (elexacaftor/tezacaftor/ivacaftor). Standard lung function tests will be compared to XV LVAS scan before and after commencement of ETI treatment. This will demonstrate the safety and clinical utility of XV LVAS scans in children and further characterise the improvement of lung function on commencement of ETI therapy.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 129954 0
Dr Andrew Tai
Address 129954 0
Women's and Children's Hospital, 72 King William St, North Adelaide, SA 5006
Country 129954 0
Australia
Phone 129954 0
+61 8 8161 7234
Fax 129954 0
Email 129954 0
andrew.tai@sa.gov.au
Contact person for public queries
Name 129955 0
Dr Jessica Phillips
Address 129955 0
Women's and Children's Hospital, 72 King William St, North Adelaide, SA 5006
Country 129955 0
Australia
Phone 129955 0
+61 8 8161 9179
Fax 129955 0
Email 129955 0
jessica.phillips2@sa.gov.au
Contact person for scientific queries
Name 129956 0
Dr Andrew Tai
Address 129956 0
Women's and Children's Hospital, 72 King William St, North Adelaide, SA 5006
Country 129956 0
Australia
Phone 129956 0
+61 8 8161 7234
Fax 129956 0
Email 129956 0
andrew.tai@sa.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
This is a small study in one hospital, so sharing a limited data set would make re-identification more possible. This study is one of a series, so composite data may be able to be disseminated after the series of studies have been completed.


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.