Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT05093348 |
| Other study ID # |
SAGM1006 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
November 25, 2021 |
| Est. completion date |
July 16, 2023 |
Study information
| Verified date |
November 2023 |
| Source |
Moorfields Eye Hospital NHS Foundation Trust |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
To undertake a randomised crossover trial in human subjects the Click2Print ocular prosthesis
versus an analogue ocular prosthesis demonstrating non-inferiority in the assessment of
ocular prosthesis motility, cosmesis, fit and function, comfort, mucous discharge and
benefits of use in daily life in 40 data subjects (Crossover Trial).
Description:
For this project, the investigators will conduct a randomised controlled crossover trial
comparing the efficacy, safety and performance of the Click2Print ocular prosthesis versus
the handmade analogue ocular prosthesis.
A non-invasive image is taken on an anterior segment optical coherence tomography device
(AS-OCT), which captures data subject data of the anophthalmic socket so that the anatomy of
the anterior orbit can be outlined. At the same sitting the data of the fellow eye is
captured by taking an AS-OCT of the volume of the cornea and iris.
Simultaneously a colour calibrated image of the fellow eye is captured. This unique data will
serve as a template for the design of the bespoke Click2Print ocular prosthesis. The
investigators anticipate that the Click2Print ocular prosthesis will not be inferior in fit
and function to the handmade analogue ocular prosthesis. The Click2Print ocular prosthesis is
also expected to match the analogue ocular prosthesis in the objective measures of prosthesis
motility and cosmesis and that there will be no adverse events in terms of the socket and
general health.
Statistical methodology and analysis:
The study design is a randomised, crossover trial of Click2Print ocular prosthesis versus
analogue ocular prosthesis. The methods will include a non-inferiority comparison of ocular
motility between the two prosthesis types, and a standard comparison of subjective outcomes
including: cosmesis, comfort, and durability of colour and structure. The analysis will
include the development of a non-inferiority margin for the comparison of motility,
non-parametric significance tests for questionnaire data, and parametric significance tests
for volume data. The alpha level is 0.05 and superiority significance tests will be
two-tailed.
Evaluation of clinical data that are relevant to the proposed clinical investigation.
The data will be statistically analysed to determine if a Click2Print ocular prosthesis is
non inferior in motility and in comparison, to an analogue ocular prosthesis. Cosmesis will
be assessed by standard comparison of subjective outcomes.
Data subjects will be requested to complete a general ocular prosthesis questionnaire. The
questionnaire will help to evaluate how a Click2Print ocular prosthesis compares to the
current analogue ocular prosthesis. Topics covered in the questionnaire will be:
- Cosmesis
- Fit and function
- Comfort
- Motility
- Mucoid discharge
- Benefits
Risk to benefit rationale.
The result of the risk management process is that the residual risks, as identified in the
risk analysis, as well as risk(s) to the subject associated with the clinical procedure are
outweighed by the anticipated benefits to the subjects.
Procedures to be taken in case of adverse events:
All adverse events and serious adverse events will be recorded in the medical records and
case report form. All serious adverse events will be reported to the sponsor.
Description of the measures taken to minimize or avoid bias, including randomization and
blinding/masking.
Data subjects enrolled in the clinical investigation will be allocated a study number.
Randomisation allocation of first ocular prosthesis wear by patient will be assigned, using
allocation concealment, against consecutive Study IDs. After 4 months, patient will crossover
to receive the alternative prosthesis. The randomisation list will be generated centrally
using random permutated blocks of varying sizes in STATA statistical software. Seed number
will be recorded for future reference in the original randomisation list.
Demographics will be such that the data subject cannot be identified. Every effort will be
made to mask the patient and investigators from knowing which type of prosthesis is being
worn during the trial.
The trial statistician who is analysing trial data will be masked until primary analysis is
completed.
Methods and timing for assessing, recording, and analysing variables.
- General Ocular Prosthesis Questionnaire visits 3,4,5 and 6
- Cosmesis assessment visit 2 and visit 4
- Motility assessments visits 2, 3, 4 and 5
Monitoring plan
Case Report Forms will be completed by the investigator and/or delegates within 2 working
days of the study visit. All data from the examinations and investigations will be
transferred to media provided by the sponsor and collected at the time of collection.
Moorfields Eye Hospital NHS Foundation Trust, the sponsor, will perform interim monitoring
visits. These will be undertaken by an independent monitor contracted with Moorfields.
Trial Management Group(TMG)
The TMG will monitor all aspects of the conduct and progress of the trial, ensure that
protocol is adhered to and take appropriate action to safeguard participants and the quality
of the trial itself. The group will meet to discuss any issues with data quality and any
concerns will be discussed at the trial steering committee
Independent Data Monitoring Committee (IDMC)
An IDMC will monitor the trial progress and patient safety data, at intervals, while the
clinical trial is ongoing. The IDMC will make recommendations to the TSC regarding
continuation, stopping or any modification to the trial.
Trial Steering Committee (TSC)
A TSC will be set up to provide the overall supervision of the trial and ensure that it is
being conducted in accordance with the principles of good clinical practice and the relevant
regulations. The TSC will have an independent chair and include members (including one lay
member) who are independent of the investigators, their employing organisations, funders and
sponsors. The TSC will agree the trial protocol and any protocol amendments, monitor trial
progress, monitor trial conduct and advise on scientific credibility. The TSC will consider
and act, as appropriate, upon the recommendations of the IDMC or equivalent and ultimately
carries the responsibility for deciding whether a trial needs to be stopped on grounds of
safety or efficacy.
Confidentiality All data will be handled in accordance with the General Data Protection
Regulation (GDPR) and United Kingdom Data Protection Act 2018. The case report forms will not
bear the subject's name or other personal identifiable data. The trial identification number
will be used for identification. Subjects will be assigned a trial identification number by
the study site sequentially starting with {01} upon enrolment into the study. The study site
will maintain a master Subject Identification Log.
Record keeping and archiving Archiving will be authorised by the Sponsor following submission
of the end of study report. Chief Investigators are responsible for the secure archiving of
essential trial documents as per trust policy. All essential documents will be archived in
line with the sponsor archiving procedure after completion of trial. Destruction of essential
documents will require authorisation from the Sponsor.
Statistical Analysis Plan:
The statistical analysis will be completed by Dr. Andrew W. Stacey. The analysis will be
completed using the R Statistical Environment software. The following analyses will be
completed:
- Demographic data will be listed as descriptive data only, there is no concern for
difference between groups in this cross-over design, and therefore no comparison between
groups is necessary.
- Design: The comparison of ocular prosthesis motility is designed as a non-inferiority
study. Therefore, the null hypothesis is taken to be that the new Click2Print ocular
prosthesis is inferior to the standard analogue prosthesis. If the null hypothesis is
rejected, the trial demonstrates non-inferiority of the Click2Print ocular prosthesis
device (Device 1) compared to the analogue ocular prosthesis.
- Ocular Motility: Ocular motility measurements will be calculated in four directions of
gaze in each eye (upgaze, downgaze, adduction and abduction). For each direction of
excursion, a ratio will be calculated as follows: excursion of the analogue ocular
prosthesis divided by excursion of the Click2Print ocular prosthesis. When the ratio
equal "1", the two measurements are equal. A number greater than 1 indicates better
excursion in the analogue ocular prosthesis. A number less than 1 indicates better
excursion in the Click2Print ocular prosthesis. A 95% confidence interval will be
calculated around this ratio using data from all subjects in the trial. The confidence
interval will be compared to the non-inferiority margin.
- Non-inferiority margin for excursion: There is little published research or a priori
data for comparison of different ocular prosthesis options. Pilot data from this study
demonstrated mean excursions of the analogue implant to be: adduction: 1.6mm, abduction:
1.5mm, upgaze: 4.0mm, downgaze: 2.1mm. It was determined that a difference of greater
than 25% motility would be necessary to see a clinically appreciable decrease between
the Click2Print ocular prosthesis and the analogue ocular prosthesis. The
non-inferiority margin for excursion was set at 25% of the excursion of the analogue
implant. If the upper limit of the 95% confidence interval of the ratio of excursions is
less than 1.25, the null hypothesis will be rejected and the Click2Print ocular
prosthesis prothesis will be demonstrated to be non-inferior.
- A Total Motility Score (TMS)will be calculated by adding all four directions of gaze
together. This will be compared in similar fashion with a 95% confidence interval as
described above and with a similar non-inferiority margin.
- Cosmesis Assessment: Data from the cosmesis assessment represent ordinal data. Due to
the subjective nature of these data, the results will be analysed with standard
statistical tests of superiority. These data will be analysed using non-parametric
tests, specifically Mann-Whitney. Data subject subjective responses will be compared
between groups.
- Each ocular prosthesis will undergo volumetric analysis as described previously. The
volume will be calculated for the analogue ocular prosthesis and the Click2Print ocular
prosthesis at the beginning and end of the trial period. The before and after volume
data will be compared to determine if any change in volume occurred while the device was
being worn by the data subject. These continuous data will be compared with Student
T-tests.
- Each ocular prosthesis will undergo a colorimetric analysis after the trial period. A
photograph will be taken, as previously described, at the beginning and end of each
trial period. The "before" and "after" photos will be graded by two separate,
independent graders. The graders will be asked to compare the colour of the "before"
photo to the colour of the "after" photo. The graders will be given two options for each
data subject and each ocular prosthesis type: "equal" or "not equal". Interrater
reliability will be calculated to verify reliability. The rate of "equal" and "not
equal" results for both prostheses will be compared using Fisher-exact tests.
- General Ocular Prosthesis Questionnaire: This is a 5-point Likert-type scale. The
analysis will be similar to the cosmesis assessment with direct comparison of groups
using non-parametric statistical tests (Mann-Whitney).
- Data subject Diary: Data from the data subject diary will be qualitative, these data
will be analysed only with prose and descriptive statistics.
