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Trial registered on ANZCTR


Registration number
ACTRN12621001169831
Ethics application status
Approved
Date submitted
15/07/2021
Date registered
30/08/2021
Date last updated
30/08/2021
Date data sharing statement initially provided
30/08/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Randomised controlled trial of diagnosis and safety in bronchoscopic versus computed tomography (CT) guided biopsy for peripheral lung nodules.
Scientific title
Randomized pragmatic trial of comprehensive tissue sampling enabled by ultraslim bronchoscopic radial probe endobronchial ultrasound via versus CT-guided transthoracic needle aspiration/biopsy for evaluation of peripheral pulmonary lesions.
Secondary ID [1] 304791 0
Nil known
Universal Trial Number (UTN)
U1111-1268-0811
Trial acronym
REBUTT
Linked study record
Follow-on study from pilot ACTRN12619000703101

Health condition
Health condition(s) or problem(s) studied:
peripheral lung nodule 322858 0
lung cancer 322859 0
Condition category
Condition code
Cancer 320435 320435 0 0
Lung - Non small cell
Respiratory 320436 320436 0 0
Other respiratory disorders / diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Bronchoscopic
Pre-procedural bronchial branch tracing mapping. To be performed by respiratory physician prior to randomisation. Approximately 5-10 minutes duration.
Bronchoscopy performed with ultrathin bronchoscope (Olympus MP190F) with radial probe endobronchial ultrasound (Olympus UM-S20-17S). To be performed by experienced respiratory physician. Sampling to include peripheral transbronchial needle aspiration (pTBNA) with Olympus Periview Flex needle, +/- forceps/brush/wash. Approximate duration 30-45 minutes. Procedure to be performed once only.
Intervention code [1] 321168 0
Diagnosis / Prognosis
Comparator / control treatment
CT guided biopsy
To be performed by experienced interventional radiologist. On table planning CT immediately prior to procedure. Subjects will have fine needle and core biopsies using a coaxial approach, meaning only one passage of the needle (such as Speedybell, Biopsybell, Mirandola, Italy or similar) through the pleura is made. Needle size is either 18G or 20G, and one to three passes with a 2-cm throw depending on the subjective visual assessment of the size and quality of the specimen and the CT image showing the needle within the target lesion. Approximate procedure duration 30 minutes.
Control group
Active

Outcomes
Primary outcome [1] 328275 0
Difference in diagnostic yield between bronchoscopic and CT guided sampling assessed by proportion of cases with definitive diagnosis on samples obtained by study procedure. Malignancy defined as a definite report of cancer. 'Suspicious' to be regarded as non-diagnostic unless pathologist interpretation altered with additional clinico-radiologic correlation at time of multi-disciplinary lung cancer meeting. Benign lesions defined as those in whom working diagnosis from procedural sampling in keeping with end diagnosis on subsequent biopsy or on progress interval imaging of at least 6 months duration.
Timepoint [1] 328275 0
6 months post procedure
Primary outcome [2] 328276 0
Difference in complication rate between bronchoscopic and CT guided sampling as assessed as binary outcome (yes/no), defined as any one of bleeding, pneumothorax, pneumonia, hospital admission, air-embolism, respiratory failure or death within 7 days of procedure. To be prospectively collected and confirmed with documentation from patient medical record.
Timepoint [2] 328276 0
1 week post procedure
Secondary outcome [1] 398319 0
Procedural time as assessed by stopwatch commenced at time of patient entering procedure room and stopped at time of patient leaving procedure room.
Timepoint [1] 398319 0
Post procedure
Secondary outcome [2] 398320 0
Human resource use, to be assessed as number and role of individuals present at each procedure. Collated prospectively at time of procedure.
Timepoint [2] 398320 0
Post procedure
Secondary outcome [3] 398321 0
Equipment cost, assessed by calculation of consumables utilised at each procedure, data to be collated at time of procedure.
Timepoint [3] 398321 0
Post procedure

Eligibility
Key inclusion criteria
Presence of peripheral (outer 1/3 of lung field) lung nodule (1-3cm) clinically requiring biopsy in whom both bronchoscopic and CT guided biopsy are considered feasible.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Lesion <1cm diameter
Evidence of central (endobronchially visible) lesion
Other clinical site of disease more amenable to tissue diagnosis
Unacceptably high risk for CT guided biopsy, anaesthetic, bronchoscopy or bleeding.
Significant peri-lesional emphysema.
Pregnancy

Study design
Purpose of the study
Diagnosis
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Central randomisation by computer
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
Hypothesis 1: The diagnostic yield obtained by radial endobronchial ultrasound (rEBUS) is non-inferior to Transthoracic needle aspiration (TTNA)
Based on a systematic review of 48 studies, it is anticipated that the diagnostic yield from CT- guided TTNA will be about 92%. Based on a meta-analysis of rEBUS, it is anticipated that the true diagnostic accuracy for the test procedure will be 81%. The non-inferiority margin was set at D0=-0.20 based on clinical reasoning. A sample size of 450 patients (225 in each group) would achieve 80% power to detect a difference of -0.11 when the non-inferiority difference is -0.20. The diagnostic accuracy in the TTNA group is assumed to be 0.92 and the rEBUS group proportion is 0.72 under the null hypothesis. The power was computed for the case when the actual rEBUS group proportion is 0.81. The difference between group proportions will be tested using a one-sided z-test (pooled) with a significance level of 0.025. It is assumed any centre effect will be minimal.
• Allowing for ~10% missing data, we will recruit a sample of 500 patients.
Hypothesis 2: The odds of complications following the rEBUS procedure is lower than that
experienced following TTNA
The binary primary outcome measure to evaluate safety will be procedural complication (yes/no) defined as any one of pneumothorax, bleeding, fever, infection, respiratory failure, admission, cardiac disease or death occurring within 7 days of the procedure. Based on a meta-analysis, the expected proportion of complications in the TTNA group will be 15-20% compared to 2-5% in the rEBUS group. Differences in complications between groups will be tested using a two-sided Wald test following binary logistic regression, with effect estimates expressed as odds ratios with 95% confidence intervals. A logistic regression of a binary response variable on a binary independent variable with a sample size of 450 observations (of which 50% are in each group) achieves 92% power at a 0.05 significance level to detect a difference in the proportion of procedural complications when the proportion is 0.15 in the TTNA group and to 0.05 in the rEBUS group. This difference corresponds to an odds ratio of 0.30.
• The sample size of 500 patients for hypothesis 1, exceeds the sample size required for hypothesis 2.
Sample size calculations were performed using the PASS software (v20.02).

Statistics will be performed using the IBM SPSS Version 23 package, with paired t-test and chi- squared test utilized to determine significance (p < 0.05) for normally distributed and no-parametric test for non-normal data.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
7/09/2021
Actual
Date of last participant enrolment
Anticipated
2/09/2024
Actual
Date of last data collection
Anticipated
3/03/2025
Actual
Sample size
Target
500
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,WA,VIC
Recruitment hospital [1] 19974 0
The Prince Charles Hospital - Chermside
Recruitment hospital [2] 19975 0
Royal Brisbane & Womens Hospital - Herston
Recruitment hospital [3] 19976 0
Sunshine Coast University Hospital - Birtinya
Recruitment hospital [4] 19977 0
Gold Coast University Hospital - Southport
Recruitment hospital [5] 19978 0
Macquarie University Hospital - Macquarie Park
Recruitment hospital [6] 19979 0
Royal North Shore Hospital - St Leonards
Recruitment hospital [7] 19980 0
Austin Health - Austin Hospital - Heidelberg
Recruitment hospital [8] 19981 0
Royal Melbourne Hospital - City campus - Parkville
Recruitment hospital [9] 19982 0
The Royal Adelaide Hospital - Adelaide
Recruitment hospital [10] 19983 0
Fiona Stanley Hospital - Murdoch
Recruitment postcode(s) [1] 34682 0
4032 - Chermside
Recruitment postcode(s) [2] 34683 0
4029 - Herston
Recruitment postcode(s) [3] 34684 0
4575 - Birtinya
Recruitment postcode(s) [4] 34685 0
4215 - Southport
Recruitment postcode(s) [5] 34686 0
2109 - Macquarie Park
Recruitment postcode(s) [6] 34687 0
2065 - St Leonards
Recruitment postcode(s) [7] 34688 0
3084 - Heidelberg
Recruitment postcode(s) [8] 34689 0
3050 - Parkville
Recruitment postcode(s) [9] 34690 0
5000 - Adelaide
Recruitment postcode(s) [10] 34691 0
6150 - Murdoch

Funding & Sponsors
Funding source category [1] 309165 0
Hospital
Name [1] 309165 0
The Prince Charles Hospital
Country [1] 309165 0
Australia
Primary sponsor type
University
Name
University of Queensland
Address
Research Contracts Officer
Faculty of Medicine
The University of Queensland
288 Herston Road
Herston Qld 4006
Country
Australia
Secondary sponsor category [1] 310122 0
None
Name [1] 310122 0
N/A
Address [1] 310122 0
N/A
Country [1] 310122 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 309027 0
The Prince Charles Hospital Human Research Ethics Committee
Ethics committee address [1] 309027 0
Ethics committee country [1] 309027 0
Australia
Date submitted for ethics approval [1] 309027 0
02/03/2021
Approval date [1] 309027 0
16/03/2021
Ethics approval number [1] 309027 0
HREC/2021/QPCH/69896

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

Contacts
Principal investigator
Name 112698 0
Prof Kwun Fong
Address 112698 0
The Prince Charles Hospital
Thoracic Department
627 Rode Road
Chermside QLD 4032
Country 112698 0
Australia
Phone 112698 0
+61 07 31394000
Fax 112698 0
Email 112698 0
Kwun.fong@health.qld.gov.au
Contact person for public queries
Name 112699 0
Gerard Olive
Address 112699 0
The Prince Charles Hospital
Thoracic Department
627 Rode Road
Chermside QLD 4032
Country 112699 0
Australia
Phone 112699 0
+61 07 31394000
Fax 112699 0
Email 112699 0
gerard.olive@health.qld.gov.au
Contact person for scientific queries
Name 112700 0
Gerard Olive
Address 112700 0
The Prince Charles Hospital
Thoracic Department
627 Rode Road
Chermside QLD 4032
Country 112700 0
Australia
Phone 112700 0
+61 07 31394000
Fax 112700 0
Email 112700 0
gerard.olive@health.qld.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
Not included in approved HREC application


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.