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Trial registered on ANZCTR


Registration number
ACTRN12621001371886
Ethics application status
Approved
Date submitted
11/08/2021
Date registered
11/10/2021
Date last updated
11/10/2021
Date data sharing statement initially provided
11/10/2021
Type of registration
Retrospectively registered

Titles & IDs
Public title
Optical Coherence Tomography Angiography Biomarkers that Predict Early Response to Anti-VEGF Therapy in Diabetic Macular Oedema.
Scientific title
Optical Coherence Tomography Angiography Biomarkers that Predict Early Response to Anti-VEGF Therapy in Diabetic Macular Oedema.
Secondary ID [1] 291746 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Nil known
Linked study record
Nil known

Health condition
Health condition(s) or problem(s) studied:
Diabetic Macular Oedema 319727 0
Condition category
Condition code
Eye 317661 317661 0 0
Diseases / disorders of the eye
Metabolic and Endocrine 321104 321104 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
All patients included in this study will be treated with intravitreal aflibercept therapy in the study eye. Six treatments will be given to each patient. Each treatment will be separated by an interval of 4 weeks with the exception of the 6th treatment that will be given 8 weeks after the 5th treatment. Aflibercept will be administered under sterile conditions in a dedicated treatment room using conventional intravitreal injection protocols.
The intervention is intravitreal aflibercept.

If eligible both eyes will be included.
Eligibility will be confirmed by the presence of centre-involved diabetic macular oedema.
Only the ophthalmologist will be administering the intravitreal aflibercept.
The treatment administration will take approximately 20-30 minutes.
The dose of aflibercept is 0.05mL
The treatment schedule will be six treatments every four weeks over six to eight month period.
The experienced study staff (orthoptist, ophthalmic imagers, clinical trial coordinators) are delegated and training is confirmed by the PI.
Fluorescein angiography (FA): This test will help the PI to see the blood vessels in the patients eye so that they can be photographed. To do this test, fluorescein will be injected into a vein in the patients arm. With a special camera and flash, a series of photographs of the back of the patients eye are taken as the dye passes through it. The FA assessment will be performed by the orthoptist and PI at Visit 1 and the final visit, and will take approx. 20 minutes to complete.
The Optical Coherence Tomography (OCT) and Optical Coherence Tomography Angiography (OCTA): The orthoptist/photographer will use an OCT instrument to look at the back of the patients eye in great detail and to take some pictures. This will help the PI to determine if there are any changes in the patients retina or macula, including if there are any changes in the thickness of the retina. The patient will have dilating drops administered in their eyes to make the pupil bigger and to make it easier to see the back of the eye. This assessment will occur at every visit and take approx. 45 minutes to complete.
Intervention code [1] 319060 0
Treatment: Drugs
Intervention code [2] 321658 0
Diagnosis / Prognosis
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 325711 0
Best-corrected visual acuity using the logMAR scale.
Timepoint [1] 325711 0
7 months after the first treatment visit.
Primary outcome [2] 325712 0
Optical Coherence Tomography (OCT) -derived measure of central retinal thickness
Timepoint [2] 325712 0
7 months after the first treatment visit.
Secondary outcome [1] 388875 0
Presence or absence of perifoveal capillary loss. This will be assessed by the Optical Coherence Tomography Angiography (OCTA) image.
Timepoint [1] 388875 0
7 months after the first treatment visit.

Eligibility
Key inclusion criteria
Age greater or equal to 18 years
Type 1 or 2 diabetes mellitus
Diabetic macular oedema (both treatment naive and previously treated) causing vision loss, with study eye BCVA measuring 0.3 to 1.0 logarithm of the minimum angle of resolution; macular oedema defined clinically and by retinal thickness of <250um in the central subfield; and intraretinal or subretinal fluid seen on SD-OCT.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Another concomitant ocular disease that causes macular oedema such as age-related macular degeneration or retinal vein occlusion.
Another ocular condition that compromises visual acuity, except for the presence of cataract.
Previous treatment with intraocular corticosteroids within the 6 months of the baseline visit.

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
Statistical methods / analysis
Data will be summarized with descriptive statistics. Univariate regression models estimated using generalized estimating equations (GEE) will be fit using the data acquired at baseline, each as a single predictor, and BCVA at the final visit as the outcome.
A separate analysis will be performed using the same predictors and central retinal thickness at the final visit as the outcome. Results from univariate regression models will be used to create a final multivariate model in which VA and central retinal thickness measurement from the final visit will be the outcomes.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
5/03/2019
Date of last participant enrolment
Anticipated
Actual
16/02/2021
Date of last data collection
Anticipated
Actual
30/09/2021
Sample size
Target
50
Accrual to date
Final
48
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 18021 0
Lions Eye Institute Day Surgery Centre - Nedlands
Recruitment postcode(s) [1] 31990 0
6009 - Nedlands

Funding & Sponsors
Funding source category [1] 296240 0
Commercial sector/Industry
Name [1] 296240 0
Bayer Australia Ltd
Country [1] 296240 0
Australia
Primary sponsor type
Hospital
Name
Lions Eye Institute
Address
2 Verdun St,
NEDLANDS WA 6009
Country
Australia
Secondary sponsor category [1] 295159 0
None
Name [1] 295159 0
Address [1] 295159 0
Country [1] 295159 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 297481 0
University of Western Australia
Ethics committee address [1] 297481 0
Human Ethics, Office of Research Enterprise
M459, 35 Stirling Hwy
Crawley WA 6009
Ethics committee country [1] 297481 0
Australia
Date submitted for ethics approval [1] 297481 0
14/11/2018
Approval date [1] 297481 0
07/01/2019
Ethics approval number [1] 297481 0
RA/4/20/4812

Summary
Brief summary
This proposal aims to answer a critical question in the Diabetic Macular Oedema management, and by testing regularly with conventional and novel ophthalmic imaging to predict early response to anti-vascular endothelial growth factor (VEGF) therapy. This anti-vascular endothelial growth factor (VEGF) therapy, is standard of care approved by the Therapeutic Goods Administration for Diabetic Macular Oedema treatment.
Diabetes is a common condition that can result in severe vision loss. The structure of the eye can be considered very similar to a camera and diabetes causes damage to the retina which is analogous to the film in the camera. More specifically, diabetes causes injury to blood vessels in the retina causing them to bleed and leak fluid. A spectrum of these retinal changes can occur in diabetes and is referred to as diabetic retinopathy.
Currently, fluorescein angiography (FA) is considered the gold-standard technique for visualising the blood vessels in the retina. It is a more precise technique for detecting retinal vascular changes than clinical examination. FA is a technique that was described over 50 years ago and is still widely used. FA is an invasive technique that involves the injection of fluorescein dye into the human vein with images captured by a camera as the dye circulates through the retina. FA is associated with adverse effects including nausea, dizziness and rarely, death due to anaphylaxis. FA is also an expensive procedure and cannot be repeated frequently.
Over the past 3 years, a new technique known as optical coherence tomography angiography (OCTA), has come into widespread use for the clinical management of diabetic retinopathy. OCTA is a non-invasive technique that allows rapid image acquisition (3-5 seconds) of the retinal circulation. It is a commercial technique that is widely used by ophthalmologists today. Most importantly, our own research has shown that OCTA provides greater detail of the order and organisation of retinal capillaries and large vessels than FA.
The intervention to be administered is intravitreal aflibercept.

This study will help develop ways to detect diabetic changes in the eye at an earlier stage than what is possible with current technology. OCTA data acquired from this study may aid the evaluation and treatment of diabetic retinopathy for the individual diabetic participants.
Trial website
Nil
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 74182 0
A/Prof Chandra Balaratnasingam
Address 74182 0
Lions Eye Institute
2 Verdun St, Nedlands WA 6009
Country 74182 0
Australia
Phone 74182 0
+61 8 9381 0751
Fax 74182 0
Email 74182 0
[email protected]
Contact person for public queries
Name 74183 0
Chandra Balaratnasingam
Address 74183 0
Lions Eye Institute
2 Verdun St, Nedlands WA 6009
Country 74183 0
Australia
Phone 74183 0
+61 8 9381 0751
Fax 74183 0
Email 74183 0
[email protected]
Contact person for scientific queries
Name 74184 0
Chandra Balaratnasingam
Address 74184 0
Lions Eye Institute
2 Verdun St, Nedlands WA 6009
Country 74184 0
Australia
Phone 74184 0
+61 8 9381 0751
Fax 74184 0
Email 74184 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
The IPD will not be available outside of the investigation site. The IPD will only be available to the principle and the research team.


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
9725Clinical study report    pending completion of report
9726Study protocol    372781-(Uploaded-11-08-2021-11-29-38)-Study-related document.pdf



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.