Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12621000166875
Ethics application status
Approved
Date submitted
17/11/2020
Date registered
18/02/2021
Date last updated
24/03/2024
Date data sharing statement initially provided
18/02/2021
Date results information initially provided
24/03/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
BlueCheck: a blue dye for detection of early-stage caries
Scientific title
Assessment of BlueCheck’s diagnostic performance for detection of active initial enamel caries in an orthodontic cohort
Secondary ID [1] 302784 0
Nil known
Universal Trial Number (UTN)
U1111-1240-8375
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Dental caries 319748 0
Tooth decay 319750 0
Condition category
Condition code
Oral and Gastrointestinal 317683 317683 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
After the subject's teeth are cleaned as part of routine procedure, a blue dye (BlueCheck) will be painted on the subject's teeth with a dental brush by a oral health professional (1-2 minutes). The subject will then rinse with water (<1 minute), and any residual colour on specific teeth will be noted in data records (2-3 minutes). The blue colour will then be washed off completely with tooth paste (<1 minute). In summary, BlueCheck may be on the teeth up to five minutes.

A second professional will observe the subject's teeth using standard tactile / visual methods, inspecting for white spot lesions (3-5 minutes) of which there may be more than one. These areas will be recorded on a separate chart (1-2 minutes). This procedure will be undertaken once. This procedure will be delivered in the clinic. All subjects will undergo the same procedure.
Intervention code [1] 319069 0
Diagnosis / Prognosis
Intervention code [2] 319070 0
Early detection / Screening
Intervention code [3] 319071 0
Prevention
Comparator / control treatment
The comparator or gold standard will be the visual / tactile inspection method using a dental probe to identify white spot lesions. Probing, identification and recording will require approximately 10 minutes.
Control group
Active

Outcomes
Primary outcome [1] 325727 0
Co-primary endpoints:
To evaluate the positive agreement between a BlueCheck response and active enamel caries
To evaluate the negative agreement between BlueCheck and visual inspection.
Timepoint [1] 325727 0
Negative and positive agreement will be determined by 1) comparison of the handwritten scoring sheets scored at the time of visual inspection (by two different clinicians) and 2) comparison of photographs of the visual inspection with photographs from the BlueCheck.
Interim analyses for both (1) and (2) will be made monthly, and a final review conducted at the end of the study. The data sets will be locked so that the timing of comparison is not critical to the outcome.
Secondary outcome [1] 388919 0
Comparison of active carious lesions identified using BlueCheck and visual inspection/photographic record,
Timepoint [1] 388919 0
From January 2023 when recruitment re-started, one interim analysis is planned after 15-20 participants have completed their (single) treatment visit to determine whether the formulation of BlueCheck needs to be amended. A second interim analysis is planned once 60 participants have completed their (single) treatment visit to facilitate a review of the sample size.
Secondary outcome [2] 391850 0
Comparison of arrested carious lessions identified by BlueCheck and visual inspection/photographic record,
Timepoint [2] 391850 0
From January 2023 when recruitment re-started, one interim analysis is planned after 15-20 participants have completed their (single) treatment visit to determine whether the formulation of BlueCheck needs to be amended. A second interim analysis is planned once 60 participants have completed their (single) treatment visit to facilitate a review of the sample size.

Eligibility
Key inclusion criteria
• Healthy participants > 12 years of age undergoing fixed-appliance orthodontic treatment
will be recruited.
• Able to read, understand and sign the Participant Information and Consent Form
• If under 18 years of age, must have a legal guardian sign the Participant Information
and Consent Form
Minimum age
12 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• Presence of oral ulcerations (chronic or acute)
• Presence of exposed dentine on the reference tooth surfaces
• Presence of carious lesions with cavitation on the reference tooth surfaces
• Presence of developmental defects of enamel on the reference tooth surfaces
• Allergic to meat or any of the components of BlueCheck or a history of alpha-gal
syndrome
• Unable or unwilling to participate in the required study procedures (e.g. due to religious,
moral, or ethical objection over exposure to cow-derived (non-Halal, non-Kosher)
material as is used in the manufacture of BlueCheck)
• Currently receiving intensive remineralisation therapy (e.g. fluoride varnish, tooth
mousse), or have received such therapy within the last 1 month.
• Pregnancy as disclosed by the participant

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
Crossover
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
The primary endpoint is the positive agreement between BlueCheck and visual inspection (an imperfect reference standard). The Diagnostic Unit of Assessment (DUOA) will be the individual carious lesion at a specific location on a tooth within an individual participant. Accordingly, this is a clustered study, with the teeth within a participant representing a cluster. It is assumed that positive agreement will be 80% and the lower 95% confidence limit needs to be > 70%.. If on average 1.5 active carious lesions are present per participant, then the study will require 80% power with 119 participants (sample size established through simulation). If greater than 2.0, then as few as 80 patients may be required.

After completion of 60 participants, the number of carious lesions will be assessed and the sample size may be reduced. If the average is >1.5 lesions/ participant and a simulation review of the sample size suggests fewer participants (i.e. <119) will suffice.

A detailed Statistical Analysis Plan (SAP) will be prepared prior to visual inspection of any data by the biostatistician and prior to database lock in which all aspects of data analysis will be defined in detail. The SAP will include details of the following:
• Definitions of analysis populations;
• Description of all data transformations and data derivations to be used together with
rationale and references (if applicable);
• Details of the statistical methods to be used;
• Methods of dealing with missing values;
• Specification of any subgroup or interaction analyses.

Recruitment
Recruitment status
Stopped early
Data analysis
Data collected is being analysed
Reason for early stopping/withdrawal
Participant recruitment difficulties
Date of first participant enrolment
Anticipated
15/03/2021
Actual
9/04/2021
Date of last participant enrolment
Anticipated
29/09/2023
Actual
7/12/2023
Date of last data collection
Anticipated
29/09/2023
Actual
15/12/2023
Sample size
Target
90
Accrual to date
Final
56
Recruitment in Australia
Recruitment state(s)
VIC

Funding & Sponsors
Funding source category [1] 307207 0
Commercial sector/Industry
Name [1] 307207 0
Incisive Technologies Pty Ltd
Country [1] 307207 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Incisive Technologies Pty Ltd
Address
Level 4
71 Collins St
Melbourne, VIC 3193
Country
Australia
Secondary sponsor category [1] 307823 0
None
Name [1] 307823 0
Address [1] 307823 0
Country [1] 307823 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 307309 0
Bellberry Human Research Ethics Committees
Ethics committee address [1] 307309 0
123 Glen Osmond Rd
Eastwood SA 5063
Ethics committee country [1] 307309 0
Australia
Date submitted for ethics approval [1] 307309 0
21/10/2020
Approval date [1] 307309 0
28/01/2021
Ethics approval number [1] 307309 0
2020-10-1048

Summary
Brief summary
This is a prospective trial designed to evaluate the diagnostic performance of the BlueCheck caries detection system in a cohort of adolescent and adult participants pursuing orthodontic treatment with fixed appliances. The study will recruit participants with at least one active carious lesion, identified by visual inspection. After recruitment, participants will undergo caries diagnosis using both visual inspection and BlueCheck detection (primary objective). Each inspection will be performed by separate assessors. Standardized photographs for orthodontic diagnostic purposes (intraoral
frontal and buccal views) will document the dentition before and after BlueCheck detection, and again after BlueCheck removal. Photographic records will subsequently be scored by blinded investigators. Data will be recorded as binary (yes/no) for visual inspection of: 1. initial caries, 2. activity status, and 3. BlueCheck detection.
All investigators will have training on caries inspection/assessment evaluations.

Lay description: This study will show if caries can be detected by BlueCheck. If so, BlueCheck may be a valuable tool allowing correction of early tooth decay using remineralisation products and obviate the need for more invasive procedures.
Trial website
Trial related presentations / publications
Public notes
The final study will not include patient data from 2022 because BlueCheck was slightly reformulated. The study will be conducted with the same BlueCheck formulation.. Therefore with the 2023 re-start, 14 data sets (patients) have since been collected. With the older formulation, 20 patient data sets were collected and reviewed, but will not be included in the final study.

Contacts
Principal investigator
Name 106778 0
Dr Paul Schneider
Address 106778 0
Melbourne Dental School, University of Melbourne
720 Swanston St,, Carlton, Victoria 3010
Country 106778 0
Australia
Phone 106778 0
+61 3 9653 3777
Fax 106778 0
Email 106778 0
[email protected]
Contact person for public queries
Name 106779 0
Dr Kerry Hegarty
Address 106779 0
Incisive Technologies Pty Ltd
Level 4
71 Collins St
Melbourne, VIC 3000
Country 106779 0
Australia
Phone 106779 0
+61 3 9653 3777
Fax 106779 0
Email 106779 0
[email protected]
Contact person for scientific queries
Name 106780 0
Dr Jonathan Mangum
Address 106780 0
Medical Building
Cnr Grattan Street & Royal Parade
University of Melbourne
Parkville, VIC 3010
Country 106780 0
Australia
Phone 106780 0
+61 3 9653 3777
Fax 106780 0
Email 106780 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.