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Trial registered on ANZCTR


Registration number
ACTRN12623000629639
Ethics application status
Approved
Date submitted
23/05/2023
Date registered
8/06/2023
Date last updated
12/07/2023
Date data sharing statement initially provided
8/06/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
Ex-vivo confocal microscopy: diagnostic accuracy, acceptability & feasibility for skin cancers and inflammatory dermatoses
Scientific title
Ex-vivo confocal microscopy: diagnostic accuracy, acceptability & feasibility for skin cancers and inflammatory dermatoses in adults
Secondary ID [1] 309716 0
None
Universal Trial Number (UTN)
U1111-1292-9526
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
skin cancer 330106 0
inflammatory dermatoses 330107 0
Condition category
Condition code
Cancer 326990 326990 0 0
Non melanoma skin cancer
Cancer 326991 326991 0 0
Malignant melanoma
Inflammatory and Immune System 326992 326992 0 0
Autoimmune diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This project aims to assess the performance of fusion ex-vivo confocal microscopy (fevCM) as a novel and cutting-edge imaging technology in the field of histological diagnosis. The instrument to be used in this study is the VivaScope® [MAVIG GmbH, Munich, Germany].

FevCM is a real-time technique that provides high-resolution digital images at the microscopic level of fresh tissue without causing any damage to the tissue. This allows for rapid diagnosis and/or margin assessment at the bedside or during a surgical procedure.

This pilot study will assess the correlation of digital microscopic images obtained by fevCM with conventional pathology sections in keratinocyte cancers, melanocytic lesions and inflammatory dermatoses, to determine diagnostic accuracy (sensitivity, specificity, and predictive values). We will assess feasibility and user friendliness including through implementation outcomes, such as measurement of time required for fevCM and user acceptability for the clinician and pathologist. We also aim to describe disease-specific morphological features under fevCM visualization and correlate them with histopathology (hematoxylin-eosin) routine sections (frozen and paraffin).
There may be one or more samples provided by each participant, depending on their number of lesions that are clinically suspicious for skin cancer and require biopsy or excision as part of their standard clinical care. Dermatologists with expertise in Mohs micrographic excision and/or confocal microscopy will analyse the specimens using fevCM; specialist histopathologists will then report on the specimens as per standard clinical care. FevCM examination of specimens for diagnostic confirmation can be done after participants have left the clinic; fevCM examination of specimens for margin control will take ~20 minutes per sample. Monitoring of adherence to the interventioncomprises the basis of this study (ie comparison of fevCM with standard histopathology).
Intervention code [1] 326157 0
Diagnosis / Prognosis
Comparator / control treatment
Control diagnostic procedure is standard histopathology (formalin fixed paraffin embedded haematoxylin and eosin stained for all specimens as per standard of care.
Control group
Active

Outcomes
Primary outcome [1] 334837 0
To determine the accuracy (ie composite sensitivity, specificity, positive predictive value and negative predictive value) of fusion ex vivo confocal microscopy (fevCM) in keratinocyte cancers, melanocytic lesions and inflammatory dermatoses compared to routine histological sections (frozen and paraffin sections).
Timepoint [1] 334837 0
Assessed post tissue excision
Secondary outcome [1] 422218 0
To determine fevCM processing time
Timepoint [1] 422218 0
Assessed at the time of fevCM processing post tissue excision

Eligibility
Key inclusion criteria
-Aged 18 years or older
-Have a clinician-identified lesion that is consistent with basal cell carcinoma ( BCC), squamous cell carcinoma (SCC), inflammatory dermatosis (including but not limited to dermatitis, psoriasis, rosacea, lichen planus, cutaneous lupus, etc.), or biopsy-proven lentigo maligna (LM) with a residual pigmented macule.
-Have a lesion needing biopsy or excision as per clinical evaluation, that is to be collected by punch biopsy, elliptical excision, excision with margin control or shave excision depending on the lesion itself
-Be willing and capable to provide informed consent and be willing to participate and comply with the study requirements.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
-Be unwilling or unable to provide informed consent or participate in the study
-Be deemed unsuitable by the treating clinician

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
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
Planned Sample Size
N=10 lesions for each of BCC and SCC proof of concept and acceptability pilot; n=20 lesions for inflammatory dermatoses proof of concept; and n= 52 for margin control assessment for each of BCC, SCC and LM). Hence total sample size is 196 specimens.
This achieves 90% power to detect a change in sensitivity from 0.99 to 0.9 using a two-sided binomial test and 3% power to detect a change in specificity from 0.99 to 0.95 using a two-sided binomial test. The tumour prevalence (i.e. BCC) amongst tissue that is eligible to be examined with fevCM is assumed to be 99%. The target significance level is 0.05. The actual significance level achieved by the sensitivity test is 0.0154 and achieved by the specificity test is 0.0015. The prevalence of the disease is 0.9.

Variables and outcomes:
1. Diagnostic accuracy of fevCM versus conventional histological sections (gold standard) will be evaluated by calculating:
a. Sensitivity, Specificity, Positive Predictive Value (PPV), Negative Predictive Value (NPV).
2. Correlation of morphologic features under fevCM and routine histopathology for each specific diagnosis.
3. Inter-observer and intra-observer analysis will be performed between confocal-trained dermatologists and pathologists using kappa-index (measure of inter-rater reliability).
4. All tests to be performed with a significance level of p = 0.05.
5. Implementation outcomes will be assessed with:
a. Quantitative assessment of time for tissue preparation and image acquisition.
b. Qualitative assessment of fevCM image quality for interpretation by users (dermatologists and pathologists).
c. Qualitative assessment of fevCM in terms of acceptability and feasibility by users (dermatologists and pathologists).

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
31/07/2023
Actual
Date of last participant enrolment
Anticipated
31/12/2027
Actual
Date of last data collection
Anticipated
31/12/2027
Actual
Sample size
Target
196
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 24783 0
Royal Prince Alfred Hospital - Camperdown
Recruitment postcode(s) [1] 40422 0
2050 - Camperdown

Funding & Sponsors
Funding source category [1] 313910 0
University
Name [1] 313910 0
University of Sydney
Country [1] 313910 0
Australia
Primary sponsor type
Hospital
Name
Royal Prince Alfred Hospital
Address
Royal Prince Alfred Hospital
Missenden Rd
Camperdown NSW 2050
Country
Australia
Secondary sponsor category [1] 315764 0
None
Name [1] 315764 0
Address [1] 315764 0
Country [1] 315764 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 313056 0
Sydney Local Health District Ethics Review Committee (RPAH Zone)
Ethics committee address [1] 313056 0
Royal Prince Alfred Hospital
Missenden Rd
Camperdown NSW 2050
Ethics committee country [1] 313056 0
Australia
Date submitted for ethics approval [1] 313056 0
Approval date [1] 313056 0
21/10/2022
Ethics approval number [1] 313056 0
2022/ETH01745

Summary
Brief summary
SUMMARY
Study title: Ex-vivo confocal microscopy: diagnostic accuracy, acceptability & feasibility

This study is investigating the accuracy of a new method of analysing skin biopsies using a high-powered microscope to determine the diagnosis (for example, skin cancer, inflammatory skin condition) and whether the lesion is clear of the surgical margins or not.

Who is it for?
You may be eligible for this study if you are an adult aged 18 years or older, you have one or more skin lesions that need to be investigated and you are willing to have a biopsy (tissue sample) taken, when a biopsy is recommended for you as standard care by your treating doctor..

Study details
All participants who choose to enrol in this study will not be asked to provide any extra skin samples that they would not already be providing as part of their standard clinical care. Participants who choose to enrol in this study would give permission for up to three of their skin biopsies to be examined with the new microscope. The skin biopsies will then undergo further preparation for scanning with the new fusion ex-vivo confocal microscope (fevCM) system and will also be assessed by the standard histology (staining of the tissue) analysis method. It is not anticipated that participation in this study will require additional time or travel commitments from patients.

It is hoped this research will determine whether the new microscope method of assessing skin tissue is comparable to the standard assessment methods in terms of accuracy and time needed to prepare and analyse tissue samples. If the new microscope system is found to be accurate and quicker than the current assessment methods, use of this technology may be expanded to a greater number of patients.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 126838 0
Prof Diona Damian
Address 126838 0
Dermatology, GH3, Royal Prince Alfred Hospital Camperdown, Missenden Rd NSW 2050
Country 126838 0
Australia
Phone 126838 0
+61 2 9515 8295
Fax 126838 0
+61 2 9515 3755
Email 126838 0
diona.damian@health.nsw.gov.au
Contact person for public queries
Name 126839 0
Prof Diona Damian
Address 126839 0
Dermatology, GH3, Royal Prince Alfred Hospital, Missenden Rd Camperdown NSW 2050
Country 126839 0
Australia
Phone 126839 0
+61 2 9515 8295
Fax 126839 0
+61 2 9515 3755
Email 126839 0
diona.damian@health.nsw.gov.au
Contact person for scientific queries
Name 126840 0
Prof Diona Damian
Address 126840 0
Dermatology, GH3, Royal Prince Alfred Hospital, Missenden Rd Camperdown NSW 2050
Country 126840 0
Australia
Phone 126840 0
+61 2 9515 8295
Fax 126840 0
+61 2 9515 3755
Email 126840 0
diona.damian@health.nsw.gov.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
after deidentification; all of the individual participant data collected during the trial
When will data be available (start and end dates)?
After trial publication, no end date determined
Available to whom?
Case by case basis at discretion of primary sponsor
Available for what types of analyses?
any purpose
How or where can data be obtained?
access subject to approval by PI as listed (diona.damian@health.nsw.gov.u)


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.