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Trial registered on ANZCTR


Registration number
ACTRN12615000718549
Ethics application status
Approved
Date submitted
29/06/2015
Date registered
10/07/2015
Date last updated
30/07/2019
Date data sharing statement initially provided
11/02/2019
Date results information initially provided
30/07/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
The COLDICE Trial: Cryobiopsy versus Open Lung biopsy in the Diagnosis of Interstitial lung disease allianCE
Scientific title
In patients with interstitial lung disease requiring histopathologic evaluation for diagnosis, are the transbronchial lung cryobiopsy (TBLC) and the gold-standard video-assisted thoracoscopic surgical (VATS) lung biopsy, similar in their diagnostic yield?
Secondary ID [1] 287007 0
Nil
Universal Trial Number (UTN)
U1111-1171-6880
Trial acronym
COLDICE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Interstitial Lung Disease 295474 0
Condition category
Condition code
Respiratory 295727 295727 0 0
Other respiratory disorders / diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Transbronchial lung cryobiopsy - a recently developed technique involving the bronchoscopic insertion of a frozen-tipped probe into peripheral airways for extraction of lung tissue specimens for diagnostic purposes.
This will take between 30-45 minutes in most cases.
Intervention code [1] 292215 0
Diagnosis / Prognosis
Comparator / control treatment
Video assisted thoracoscopic surgical lung biopsy - the current gold-standard for obtaining lung tissue for diagnosis of parenchymal lung disease. This involves general anaesthesia, and 2-3 small incisions of the chest wall, for insertion of a thoracoscope and trocars for instruments. Samples of lung (usually 2), are excised and the lung is stapled to prevent bleeding and air leak. The chest wall is sutured, and patients recover in the hospital ward.
This will take approximately 45-60minutes in most cases.
Control group
Active

Outcomes
Primary outcome [1] 295439 0
Diagnostic yield as measured by the proportion of cryobiopsy specimens where confident histopathological diagnosis can be made compared with VATS biopsy findings, as assessed by expert pathologists.
Timepoint [1] 295439 0
At trial completion, 3 years from 1st recruitment
Primary outcome [2] 295523 0
Diagnostic yield as assessed by proportion of patients with confident multi-disciplinary team consensus clinical diagnosis (including consideration of clinical, radiological and pathological information).
Timepoint [2] 295523 0
At trial completion (3 years from 1st recruitment)
Secondary outcome [1] 315589 0
Procedure-specific adverse events (e.g. TBLC: immediate pneumothorax on fluoroscopy, airway bleed; VATS: prolonged air leak, prolonged chest wall pain, wound infection, delayed bleed into chest cavity).
Timepoint [1] 315589 0
For individuals: at time of procedure, at day of discharge from hospital (estimated 3-7 days post-operatively), and at 6-month follow-up (phone call from study coordinators).
For study population: at trial completion (3 years).
Secondary outcome [2] 315590 0
Histopathologic features (eg site and size of specimens, presence of pleura, alveoli, airways and vessels, and pathologic features).
This is a composite secondary outcome of histopathologic quality (with specimens designated either 'adequate' or 'inadequate', based on the inclusion of the above features).
Timepoint [2] 315590 0
For individuals: at time of histopathologic analysis (1-6 weeks from biopsy procedure).
For study population: at trial completion (3 years).

Eligibility
Key inclusion criteria
Patients assessed as requiring histopathology for the diagnosis of their ILD (at specialist multidisciplinary team meetings), and considered suitable for VATS lung biopsy.
Minimum age
18 Years
Maximum age
80 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Age > 80
* Resting oxyhaemoglobin saturation under 90%
* Platelets less than 100
* INR > 1.5
* Advanced comorbidities (including poorly controlled systemic hypertension, congestive cardiac failure, unstable angina, significant stroke).
* History of of adverse reaction to general anaesthesia
* Inability to provide informed consent
* Systolic pulmonary artery pressure over 40mmHg on echocardiogram or evidence of right ventricular dysfunction
* Inability to withhold anti-platelet therapy (eg aspirin or clopidogrel)

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)
Subjects considered eligible for inclusion (as recommended by the referring site MDT discussion) will receive a trial participant information sheet. They will meet with both the cryobiopsy proceduralist and cardithoracic surgeon, and be given the opportunity to ask questions in regard to the research project, before signing informed consent in the presence of an independent witness.

All enrolled subjects will undergo both types of biopsy (TBLC and VATS biopsy) within the one procedure, under general anaesthesia. Following the procedure and local analysis, specimens will be sent to the reference centre for further evaluation.

Three centralised expert pathologists at the reference site will independently interpret biopsy specimens in blocks of 30 patients at a time. TBLC and VATS specimens will be assigned unique de-identifying code numbers, unrelated to the other specimen of the same patient, so as to preserve blinding.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Subjects will not be randomised, so not applicable
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



The people analysing the results/data
Intervention assignment
Single group
Other design features
Within the MDT discussion of every patient, panelists will review clinical details twice:
1) Background clinical information, then radiology, then cryobiopsy (or VATS), in random order
2) Background clinical information, then radiology, then the alternative biopsy to step 1. Panelists (with the exception of the pathologists) will be blinded to the nature of the specimen and the identity of the patient. Each patient's two samples will be randomly assigned a number, 1-132. Cases will be discussed in this order (n1--> 132), so that every specimen is considered at MDT, independently of the other specimen obtained from the patient.
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis
For primary endpoint assessment, histopathological findings will be categorised into 1 of 4 diagnostic groups: “UIP”, “probable UIP”, “indeterminate for UIP” or “alternative diagnosis”. Kappa statistic will be used to analyse agreement between the diagnoses yielded by the two procedures.

Secondary endpoint analysis:
1) Consensus diagnosis at MDD will also be recorded, with coding into nine categories: [IPF, idiopathic NSIP, desquamative interstitial pneumonia/ respiratory bronchiolitis interstitial lung disease (DIP/RB-ILD), connective-tissue disease associated ILD, hypersensitivity pneumonitis (HP), vasculitis, sarcoidosis, other, unclassifiable, consensus certainty levels of either “Low” or “High” or "Definite" will be recorded. Kappa statistics will be used to compare the agreement between diagnosis/ certainty of the two procedures during the MDD process, following the step-wise presentation of a) Clinical/ radiological information, the b) TBLC or VATS biopsy findings.
2) Kappa statistics will be calculated to measure interobserver agreement between pathologists for each of the TBLC specimens and VATS specimens.

Sample size:
A calculated sample size of 65 will enable estimation of a true kappa of at least 0.8 with a lower 95% confidence limit of at least 0.6, for histopathological agreement between cryobiopsy and VATS for the categories of “definite or probable for UIP pattern”, “indeterminate for UIP pattern”, or “alternative diagnosis”. This calculation follows the assumption that 55%, 15%, and 30% of cases in this population will be classified as definite/probable UIP, indeterminate for UIP, or an alternative diagnosis, respectively.

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,WA
Recruitment hospital [1] 3981 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [2] 3982 0
Liverpool Hospital - Liverpool
Recruitment hospital [3] 3983 0
Macquarie University Hospital - Macquarie Park
Recruitment hospital [4] 3984 0
Nepean Hospital - Kingswood
Recruitment hospital [5] 3985 0
Royal North Shore Hospital - St Leonards
Recruitment hospital [6] 3986 0
John Hunter Hospital Royal Newcastle Centre - New Lambton
Recruitment hospital [7] 3988 0
Sir Charles Gairdner Hospital - Nedlands
Recruitment hospital [8] 3989 0
Fiona Stanley Hospital - Murdoch
Recruitment hospital [9] 3990 0
Westmead Hospital - Westmead

Funding & Sponsors
Funding source category [1] 291561 0
Commercial sector/Industry
Name [1] 291561 0
Erbe
Address [1] 291561 0
Waldhornlestrasse 17, 72072 Tuebingen, Germany
Country [1] 291561 0
Germany
Funding source category [2] 293420 0
University
Name [2] 293420 0
University of Sydney
Address [2] 293420 0
The University of Sydney
NSW 2006
Country [2] 293420 0
Australia
Funding source category [3] 293421 0
Commercial sector/Industry
Name [3] 293421 0
Covidien
Address [3] 293421 0
97 Waterloo Road
North Ryde
NSW 2113
Country [3] 293421 0
Australia
Primary sponsor type
Individual
Name
Lauren Troy
Address
Respiratory Medicine
Royal Prince Alfred Hospital
Missenden Rd
Camperdown
NSW 2050
Country
Australia
Secondary sponsor category [1] 290236 0
Other Collaborative groups
Name [1] 290236 0
Australia New Zealand Interventional Pulmonology Group
Address [1] 290236 0
c/o Prof Martin Phillips (Chair)
Respiratory Medicine
Sir Charles Gairdner Hospital
Hospital Avenue, Nedlands WA 6009
Country [1] 290236 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 293103 0
Royal Prince Alfred Hospital Human Research Ethics Committee
Ethics committee address [1] 293103 0
Research Development Office
Royal Prince Alfred Hospital
Missenden Road
CAMPERDOWN NSW 2050
Ethics committee country [1] 293103 0
Australia
Date submitted for ethics approval [1] 293103 0
11/05/2015
Approval date [1] 293103 0
20/07/2015
Ethics approval number [1] 293103 0
X15-0180 and HREC/15/RPAH/240

Summary
Brief summary
The transbronchial lung cryobiopsy is a new, minimally invasive technique for obtaining lung tissue to diagnose ILD. In order to determine the place of cryobiopsy in ILD diagnostic algorithms and international guidelines, it is crucial that this procedure is validated against the current gold-standard practice, the VATS biopsy. This study brings together a team of leading proceduralists, ILD specialists and histopathologists from across Australia, with consultative input from international leaders in the field. The main objective of this project is to determine the role of cryobiopsy in the diagnosis of ILD.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 58474 0
Dr Lauren Troy
Address 58474 0
Respiratory Medicine
Royal Prince Alfred Hospital
Missenden Rd
Camperdown
NSW 2050
Country 58474 0
Australia
Phone 58474 0
(+612) 95158296
Fax 58474 0
Email 58474 0
ltroy@med.usyd.edu.au
Contact person for public queries
Name 58475 0
Ms Jessica Rhodes
Address 58475 0
Respiratory Medicine
Royal Prince Alfred Hospital
Missenden Rd
Camperdown
NSW 2050
Country 58475 0
Australia
Phone 58475 0
(+612) 95154188
Fax 58475 0
Email 58475 0
jessica.rhodes@sswahs.nsw.gov.au
Contact person for scientific queries
Name 58476 0
Dr Edmund Lau
Address 58476 0
Respiratory Medicine
Royal Prince Alfred Hospital
Missenden Rd
Camperdown
NSW 2050
Country 58476 0
Australia
Phone 58476 0
(+612) 95156111
Fax 58476 0
Email 58476 0
edmundmtlau@gmail.com

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
There is no plan to share individual patient data publicly
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