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Trial registered on ANZCTR


Registration number
ACTRN12619000708156
Ethics application status
Approved
Date submitted
19/04/2019
Date registered
13/05/2019
Date last updated
13/05/2019
Date data sharing statement initially provided
13/05/2019
Date results information initially provided
13/05/2019
Type of registration
Retrospectively registered

Titles & IDs
Public title
Observation effect of Ivacaftor/lumacaftor on lung function and exercise tolerance in subjects with Cystic Fibrosis and severe lung disease
Scientific title
Observation effect of Ivacaftor/lumacaftor on lung function and exercise tolerance in subjects with Cystic Fibrosis and severe lung disease, homozygous for phe508del
Secondary ID [1] 298112 0
nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cystic Fibrosis 312475 0
Condition category
Condition code
Human Genetics and Inherited Disorders 311021 311021 0 0
Cystic fibrosis

Intervention/exposure
Study type
Observational
Patient registry
True
Target follow-up duration
12
Target follow-up type
Months
Description of intervention(s) / exposure
Participants received Lumacaftor 400mg and Ivacaftor 250mg twice daily for 12 months. They received these as part of treatment, not for the study.Participation did not require any additional investigations or review. The data from the medical record was reviewed. All investigations were done as part of usual care.
Intervention code [1] 314253 0
Not applicable
Comparator / control treatment
10 adult historical controls, who attended the same centre from 2012 to 2015, aged at least 18years, homozygous for the Phe508del mutation, who also would have been eligible for access to LUM/IVA as above, who either had ppFEV1 of 40% or less when clinically stable at their annual review and or were judged to require referral for transplant at this time.
Control group
Historical

Outcomes
Primary outcome [1] 319817 0
Six minute walk test distance, measured in metres.
Timepoint [1] 319817 0
52 weeks post treatment.
Secondary outcome [1] 369597 0
FEV1 percent predicted, percentage change from baseline. Measured by spirometry. Standards used Global Lung Initiative.(GLI)
Timepoint [1] 369597 0
52 weeks post treatment.

Eligibility
Key inclusion criteria
Diagnosis of Cystic fibrosis, aged 18years, and homozygous for Phe508del mutation, eligible for access to LUM/IVA through a compassionate access programme provided by Vertex. To be eligible they had to have an FEV1? 40% when clinically stable, or experienced a 20% or more fall in FEV1, or had been referred for lung transplantation assessment.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Unable to participate in the measures required.

Study design
Purpose
Natural history
Duration
Longitudinal
Selection
Convenience sample
Timing
Retrospective
Statistical methods / analysis
Analysis of continuous variables was performed using parametric techniques to compare differences as these were normally distributed. This was done using a one-way ANOVA with Dunnett’s multiple comparisons test. Categorical comparisons were assessed using Fisher’s exact test. Analysis was carried out using Graphpad Prism version 7.

Recruitment
Recruitment status
Completed
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
Recruitment hospital [1] 13644 0
John Hunter Hospital - New Lambton
Recruitment postcode(s) [1] 26316 0
2305 - New Lambton

Funding & Sponsors
Funding source category [1] 302550 0
Hospital
Name [1] 302550 0
John Hunter Hospital
Address [1] 302550 0
John Hunter Hospital Lookout Rd NSW 2305.
Country [1] 302550 0
Australia
Primary sponsor type
Hospital
Name
John Hunter Hospital
Address
John Hunter Hospital Lookout Rd NSW 2305.
Country
Australia
Secondary sponsor category [1] 302457 0
None
Name [1] 302457 0
Address [1] 302457 0
Country [1] 302457 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 303194 0
Hunter New England LHD
Ethics committee address [1] 303194 0
AREA HQ LOOKOUT RD New Lambton NSW 2305
Ethics committee country [1] 303194 0
Australia
Date submitted for ethics approval [1] 303194 0
13/01/2015
Approval date [1] 303194 0
27/02/2015
Ethics approval number [1] 303194 0
Low risk application

Summary
Brief summary
Our aim was to determine a sensitive clinical measure of change, in patients with CF and severe airways disease as measured by an FEV1<40% when stable, following treatment with Lumacaftor/Ivacaftor. We assessed response with spirometry and compared this to changes seen in exercise capacity as measured by the six minute walk test (6MWT), the nitrogen multi-breath washout test, the carbon monoxide gas transfer factor and lung volumes measured by plethysmography.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 92810 0
Prof Peter Alexander Blanch Wark
Address 92810 0
Centre for Healthy Lungs HMRI, Lookout Rd New Lambton NSW 2305.
Country 92810 0
Australia
Phone 92810 0
+61249213470
Fax 92810 0
Email 92810 0
peter.wark@hnehealth.nsw.gov.au
Contact person for public queries
Name 92811 0
Prof Peter Alexander Blanch Wark
Address 92811 0
Centre for Healthy Lungs HMRI, Lookout Rd New Lambton NSW 2305.
Country 92811 0
Australia
Phone 92811 0
+61249213470
Fax 92811 0
Email 92811 0
peter.wark@hnehealth.nsw.gov.au
Contact person for scientific queries
Name 92812 0
Prof Peter Alexander Blanch Wark
Address 92812 0
Centre for Healthy Lungs HMRI, Lookout Rd New Lambton NSW 2305.
Country 92812 0
Australia
Phone 92812 0
+61249213470
Fax 92812 0
Email 92812 0
peter.wark@hnehealth.nsw.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
Clinical data recorded as for patient care, anonymised forms not possible.
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?
No
Results – basic reporting
Results – plain English summary
Treatment of people living with CF and 2 copies of the delta F 508 gene with Orkambi (lumacaftor/Ivacaftor) has been shown to improve outcomes in those with milder forms of lung disease. In those excluded from the trials with severe disease, this is not known.
We carefully assessed the effect of treatment on 10 individuals with severe lung disease and CF. WE showed improvments in exercise tolerance (6 minute walk test) and some effects on lung function, though this took up to 24 weeks to be demonstrated.