Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12621001367831
Ethics application status
Approved
Date submitted
14/07/2021
Date registered
11/10/2021
Date last updated
11/10/2021
Date data sharing statement initially provided
11/10/2021
Type of registration
Retrospectively registered

Titles & IDs
Public title
Comparison of computed tomography scans (CT) and clinical risk tools to standard dual-energy X-ray absorptiometry scans (DXA) to detect osteoporosis and predict spinal fracture in lung cancer screening participants
Scientific title
Comparison of DXA to CT-based methods (CT Hounsfield unit attenuation value from the first lumbar vertebra [L1HU] and quantitative CT [QCT]) to detect osteoporosis and predict vertebral fracture in lung cancer screening participants
Secondary ID [1] 304462 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record
NCT02871856 (International Lung Screening Trial [ILST]) is the larger parent trial to this substudy. This study will recruit participants who are already enrolled into the above trial.
The investigators of this sub-study are also co-investigators in the ILST.

Health condition
Health condition(s) or problem(s) studied:
Osteoporosis 322283 0
Vertebral fracture 322284 0
Lung cancer screening 322285 0
Quantitative computed tomography 323775 0
Dual-energy x-ray absorptiometry 323776 0
Condition category
Condition code
Musculoskeletal 319964 319964 0 0
Osteoporosis
Musculoskeletal 320622 320622 0 0
Other muscular and skeletal disorders
Respiratory 320623 320623 0 0
Other respiratory disorders / diseases
Cancer 320624 320624 0 0
Lung - Non small cell
Cancer 320625 320625 0 0
Lung - Small cell

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Participants who consent will have a single dual energy X-ray absorptiometry (DXA) scan within 6 months of their ILST low dose chest CT scan.

DXA scans will measure the areal bone density from the femur and lumbar spine (L1-L4). T-scores will be calculated. Standard protocols for performing and reporting DXA scans will be followed. DXA scans will be performed by a trained Nuclear Medicine technologist and reported by a consultant Nuclear Medicine physician.

The DXA scan will take up to 20 minutes to perform.
Intervention code [1] 320805 0
Diagnosis / Prognosis
Intervention code [2] 320806 0
Early detection / Screening
Comparator / control treatment
This DXA study will utilise existing data collected as part of the International Lung Screening trial (ILST) (NCT02871856) and its Osteoporosis Sub-study (an approved observational sub-study of ILST which is not registered as a separate trial).

Bone density will be assessed from low-dose CT scans using:
1) Hounsfield unit attenuation value of lumbar/thoracic vertebrae (L1HU) and
2) Quantitative CT (QCT)

Under the ILST protocol, participants undergo non-contrast lung cancer screening chest CT scans using a low-dose protocol, at ILST study entry (T0) and at 2-years (T2).

Bone density will be assessed from each participants' T2 chest CT scan using:
1) L1HU - measurement of the mean vertebral attenuation from a single region-of interest in the 1st lumbar (L1) vertebral trabecular bone using DICOM viewer software (as per Pickhardt, 2013). Low thoracic vertebra (T12 or T11) will be measured if L1 is not imaged or is fractured.

2) QCT - measurement of average volumetric bone density from T11-L1 imaged vertebra using Mindways software, according to manufacturer guidelines. Quality control assessments and asynchronous calibration will be performed in accordance with manufacturer guidelines.

Bone density measurements from CT will be performed by a trained medical doctor who has undergone a training session with a consultant Radiologist and whose measurement method has been validated against a consultant and trainee Radiologist in an independent lung cancer screening CT dataset.
Control group
Active

Outcomes
Primary outcome [1] 327843 0
Sensitivity and specificity of L1HU (at a threshold of 110HU) in detection of osteoporosis compared to the reference-standard DXA (using World Health Organisation criteria).
Timepoint [1] 327843 0
At acquisition of DXA scan (T2)
Secondary outcome [1] 396740 0
Predictive accuracy (area under receiver-operating characteristic curve) of L1HU to classify participants with incident osteoporotic fractures (determined from verified participant self-report in study-specific annual questionnaires over 3 years).
Timepoint [1] 396740 0
At 3 years from acquisition of DXA scan
Secondary outcome [2] 401356 0
Predictive accuracy (area under receiver-operating characteristic curve) of clinical risk tools (including DXA T-Score) to classify participants with incident osteoporotic fractures (determined from verified participant self-report in study-specific annual questionnaires over 3 years).
Timepoint [2] 401356 0
At 3 years from acquisition of DXA scan
Secondary outcome [3] 401358 0
Discriminative accuracy (area under receiver-operating characteristic curve) of L1HU classify participants with prevalent vertebral fractures (objective blinded assessment of fractures from T2 CT scans using Genant semiquantitative method (Genant, 1993)).
Timepoint [3] 401358 0
At DXA scan acquisition (T2)
Secondary outcome [4] 401361 0
Discriminative accuracy (area under receiver-operating characteristic curve) of clinical risk tools (including DXA T-score) to classify participants with prevalent vertebral fractures (objective blinded assessment of fractures from T2 CT scans using Genant semiquantitative method (Genant, 1993)).
Timepoint [4] 401361 0
At DXA scan acquisition (T2)

Eligibility
Key inclusion criteria
-Participants enrolled in the ILST (men and women, aged 55-80 years, current or former smokers quit <15 years prior, >=30 pack-year smoking history and/or estimated lung cancer risk >=1.51% based on the PLCOm2012 risk prediction model, ECOG performance status 0 or 1) who are also volunteers in the ILST osteoporosis sub-study
-Participants who provide written consent.
Minimum age
55 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria per ILST:
• Clinical symptoms suspicious for lung cancer Exclusion criteria:
• Concurrent major medical illness (Any medical condition that, in the investigator’s opinion, may jeopardize the subject’s safety during participation in the study or mean that the subject is unlikely to benefit from screening due to shortened life expectancy)
• Previous lung cancer
• Other non-curatively treated non-pulmonary cancer or <5 years cancer-free if previous cancer
• Pneumonia/bronchitis requiring antibiotics within previous 12 weeks
• CT chest within the last 2 years
• Received chemotherapy/other cytotoxic drugs within the last 6 months
• Pregnancy
• Unwilling/unable to have chest CT

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
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
Intervention assignment
Single group
Other design features
Phase
Not Applicable
Type of endpoint/s
Statistical methods / analysis
Reporting will follow the STARD guidelines.
Correlation between methods will be assessed using a scatter plot and Pearson's correlation coefficient.
Discrimination will be assessed using area under receiver-operating characteristic curves.
Inter-method agreement will be assessed using intra-class correlation coefficient for continuous measurements and kappa coefficient for ordinal categories
Diagnostic accuracy will be assessed with specificity, sensitivity, positive predictive value, negative predictive value.
Optimal L1HU cut-off thresholds from receiver-operating curves will be determined using the Youden index method.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
3/09/2021
Date of last participant enrolment
Anticipated
3/01/2022
Actual
Date of last data collection
Anticipated
3/01/2022
Actual
Sample size
Target
94
Accrual to date
15
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 19730 0
The Prince Charles Hospital - Chermside
Recruitment postcode(s) [1] 34368 0
4032 - Chermside

Funding & Sponsors
Funding source category [1] 308822 0
Charities/Societies/Foundations
Name [1] 308822 0
The Prince Charles Hospital Foundation
Country [1] 308822 0
Australia
Primary sponsor type
University
Name
The University of Queensland
Address
The University of Queensland,
St Lucia 4072
QLD
Country
Australia
Secondary sponsor category [1] 310001 0
None
Name [1] 310001 0
Address [1] 310001 0
Country [1] 310001 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 308735 0
The Prince Charles Hospital Human Research Ethics Committee
Ethics committee address [1] 308735 0
Ethics committee country [1] 308735 0
Australia
Date submitted for ethics approval [1] 308735 0
10/06/2021
Approval date [1] 308735 0
09/07/2021
Ethics approval number [1] 308735 0
HREC/2021/QPCH/76621

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 111706 0
A/Prof Henry Marshall
Address 111706 0
The Prince Charles Hospital
Rode Road, Chermside 4032
QLD
Country 111706 0
Australia
Phone 111706 0
+61 7 3139 6805
Fax 111706 0
Email 111706 0
[email protected]
Contact person for public queries
Name 111707 0
Linda Passmore
Address 111707 0
The Prince Charles Hospital
Rode Road, Chermside 4032
QLD
Country 111707 0
Australia
Phone 111707 0
+61 7 3139 6632
Fax 111707 0
Email 111707 0
[email protected]
Contact person for scientific queries
Name 111708 0
Nikita Patel
Address 111708 0
The Prince Charles Hospital
Rode Road, Chermside 4032
QLD
Country 111708 0
Australia
Phone 111708 0
+64 21 434 114
Fax 111708 0
Email 111708 0
[email protected]

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 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.