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Trial registered on ANZCTR


Registration number
ACTRN12619000411145
Ethics application status
Approved
Date submitted
29/11/2018
Date registered
13/03/2019
Date last updated
13/03/2019
Date data sharing statement initially provided
13/03/2019
Type of registration
Retrospectively registered

Titles & IDs
Public title
The OBSERVE Cystic Fibrosis (CF) Study, to assess the effect of orkambi on people with CF in Australia
Scientific title
A multicentre, OBSERVational, case control study to determine the efficacy and safety of Lumacaftor/Ivacaftor in patients with severe lung disease and Cystic Fibrosis
Secondary ID [1] 296957 0
nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cystic fibrosis
 309355 0
Condition category
Condition code
Human Genetics and Inherited Disorders 308221 308221 0 0
Cystic fibrosis

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
Patients with CF, homozygous Phedel508, prescribed Ivacaftor/lumacaftor 100/125mg taken orally twice daily, under the Vertex compassionate access scheme in Australia.
Participants must have taken Ivacaftor/Lumacaftor for at least 12 months under this scheme.
LUM/IVA intervention arm, with be homozygous for Phe508del and have commenced treatment with LUM/IVA on the compassionate access programme. Participants will need to have commenced treatment prior to March 2017 to potentially have at least 12 months of data available. To take part they need to consent for anonymysed data to be avaialble for researchers to access. The patient is not required to do anything. Only data that has already been recorded will be used.
Intervention code [1] 312218 0
Not applicable
Comparator / control treatment
The Control arm will be age and sex matched by the sites. Subjects will only be eligible if they have never received LUM/IVA or Ivacaftor alone or Tezecaftor/Ivacaftor. Subjects must have mutations in CFTR that will result in Class I or Class II dysfunction.
Control group
Active

Outcomes
Primary outcome [1] 307189 0
Number of exacerbations of CF lung disease requiring the use of intravenous antibiotics during a 12 month observation period. This will include all exacerbations treated with IV antibiotics, including hospitalisation and hospital in the home treatment. data is obtained from electronic medical records by site.
Timepoint [1] 307189 0
Compared after 12 months of treatment or follow-up.
Secondary outcome [1] 351057 0
• Mean rate of change in FEV1 percent predicted. Data in regard FEV1 will be obtained from sites. FEV1 at the time of commencement will be compared to FEV1 over the time of the trial. All data will be anonymous.
Timepoint [1] 351057 0
After 12 months
Secondary outcome [2] 351058 0
• Mean rate of change in BMI and/or Z score, as recorded in the medical record of CF centre.
Timepoint [2] 351058 0
after 12 months
Secondary outcome [3] 351059 0
• Time to first exacerbation relative to treatment initiation. Exacerbation will be an event rrecorded as a chest exacerbation requiring the use of IV antibiotics in the medical record of the site.
Timepoint [3] 351059 0
12 months
Secondary outcome [4] 351060 0
• Number of hospitalisation with a pulmonary exacerbation. Admissions to hospital due to chest infection or pulmonary exacerbation. Recorded by hospital medical record.
Timepoint [4] 351060 0
after 12 months treatment
Secondary outcome [5] 351061 0
• Number of IV antibiotic episodes delivered by hospital in the home service. Number of HITH events with a pulmonary exacerbation. HITH events due to chest infection or pulmonary exacerbation. Recorded by hospital medical record
Timepoint [5] 351061 0
After 12 months
Secondary outcome [6] 351062 0
Death. Recorded in the medical record by the CF centre.
Timepoint [6] 351062 0
after 12 months
Secondary outcome [7] 351063 0
• Lung transplantation. As recorded in the medical record by the CF centre.
Timepoint [7] 351063 0
after 12 months
Secondary outcome [8] 351064 0
Adverse events; chest tightness, breathlessness, cough, headache, anusea, abnormal liver function tests. Any reporterd by the CF centre as being possibly or deficitely related to the medication.
Timepoint [8] 351064 0
after 12 months

Eligibility
Key inclusion criteria
• Cystic Fibrosis; defined by the presence of two mutations known to cause dysfunction in CFTR, aged greater than or equal to 12 years.
• LUM/IVA intervention arm, with be homozygous for Phe508del and have commenced treatment with LUM/IVA on the compassionate access programme. Participants will need to have commenced treatment prior to March 2017 to potentially have at least 12 months of data available.
Minimum age
6 Years
Maximum age
85 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Insufficient data available to make a comparison over 12 months.
Data confirming CF genotype not available.

Study design
Purpose
Natural history
Duration
Longitudinal
Selection
Case control
Timing
Retrospective
Statistical methods / analysis
Clinical characteristics at baseline will be reported as means and standard deviations or frequencies and percentages as appropriate. The primary outcome measure will be analysed using Poisson regression and the effect of LUM/IVA will be estimated using treatment as a covariate in the model. To adjust for the effect of the matching, a fixed effect for the pairs will also be included in the model

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
16/01/2018
Date of last participant enrolment
Anticipated
8/07/2019
Actual
Date of last data collection
Anticipated
15/07/2019
Actual
Sample size
Target
144
Accrual to date
62
Final
Recruitment in Australia
Recruitment state(s)
ACT,NSW,QLD,SA,TAS,WA,VIC

Funding & Sponsors
Funding source category [1] 300482 0
Commercial sector/Industry
Name [1] 300482 0
Vertex
Country [1] 300482 0
United States of America
Primary sponsor type
University
Name
University of Newcastle
Address
C/Prof Peter Wark
University of Newcastle
Centre for Healthy Lungs Hunter Medical Research Institute
Lookout Rd
New Lambton NSW Australia
Country
Australia
Secondary sponsor category [1] 299956 0
None
Name [1] 299956 0
None
Address [1] 299956 0
Country [1] 299956 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 301283 0
Hunter New England Human Research Ethics Committee [EC00403],
Ethics committee address [1] 301283 0
Lookout Rd
New Lambton NSW 2305
Ethics committee country [1] 301283 0
Australia
Date submitted for ethics approval [1] 301283 0
11/06/2018
Approval date [1] 301283 0
31/08/2018
Ethics approval number [1] 301283 0
HNEHREC Reference No: 17/09/20/5.09 NSW HREC Reference No: LNR/17/HNE/401

Summary
Brief summary
Aim
To determine the safety and efficacy of LUM/IVA in subjects >12 years of age with CF, homozygous for F508del mutation of CFTR and an FEV1<40% of predicted normal, by comparing those patients treated with LUM/IVA with a cohort of age and sex matched CF controls with another set of mutations that lead to severe CFTR dysfunction (belonging to Class I, II or III), with an FEV1<40%5.
Trial website
Trial related presentations / publications
Public notes
Please note the trial is a retrospective review of data that was collected at the time subjects initiated a compassionate access programme. The programme ran independently of the trial and the data collected was determined independently. The trial seeks to utilise this data that was captured.

Contacts
Principal investigator
Name 86482 0
Prof Peter Wark
Address 86482 0
Centre for Healthy Lungs, HMRI level 2, Lookout Red New Lambton NSW 2305
Country 86482 0
Australia
Phone 86482 0
61249537527
Fax 86482 0
+61249213469
Email 86482 0
[email protected]
Contact person for public queries
Name 86483 0
Peter Wark
Address 86483 0
Centre for Healthy Lungs, HMRI level 2, Lookout Red New Lambton NSW 2305
Country 86483 0
Australia
Phone 86483 0
61249537527
Fax 86483 0
+61249213469
Email 86483 0
[email protected]
Contact person for scientific queries
Name 86484 0
Peter Wark
Address 86484 0
Centre for Healthy Lungs, HMRI level 2, Lookout Red New Lambton NSW 2305
Country 86484 0
Australia
Phone 86484 0
61249537527
Fax 86484 0
+61249213469
Email 86484 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
All anonymised data
When will data be available (start and end dates)?
At the conclusion of the trial, available for 5 years.
Available to whom?
Any researchers with HREA approval
Available for what types of analyses?
Any appropriate use of anonymised data
How or where can data be obtained?
Contact with the PI and written request.


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
569Study protocol    375856-(Uploaded-29-11-2018-13-34-48)-Study-related document.docx
570Informed consent form    375856-(Uploaded-07-12-2018-17-24-36)-Study-related document.docx



Results publications and other study-related documents

Documents added manually
TypeIs Peer Reviewed?DOICitations or Other DetailsAttachment
Basic resultsNo 375856-(Uploaded-25-11-2020-12-49-33)-Basic results summary.docx
Plain language summaryNo What was your research question? [50 words maximum... [More Details]
Study results articleYes Tong K, Barker D, France M, Burr L, Greville H, Vi... [More Details]

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseLumacaftor/ivacaftor reduces exacerbations in adults homozygous for Phe508del mutation with severe lung disease.2020https://dx.doi.org/10.1016/j.jcf.2019.12.006
N.B. These documents automatically identified may not have been verified by the study sponsor.