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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]

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

Condition category

Condition code

Eye

Diseases / disorders of the eye

Metabolic and Endocrine

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]

Treatment: Drugs

Intervention code [2]

Diagnosis / Prognosis

Comparator / control treatment

No control group

Control group

Uncontrolled

Outcomes

Primary outcome [1]

Best-corrected visual acuity using the logMAR scale.

Timepoint [1]

7 months after the first treatment visit.

Primary outcome [2]

Optical Coherence Tomography (OCT) -derived measure of central retinal thickness

Timepoint [2]

7 months after the first treatment visit.

Secondary outcome [1]

Presence or absence of perifoveal capillary loss. This will be assessed by the Optical Coherence Tomography Angiography (OCTA) image.

Timepoint [1]

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?

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

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

Recruitment hospital [1]

Lions Eye Institute Day Surgery Centre - Nedlands

Recruitment postcode(s) [1]

6009 - Nedlands

Funding & Sponsors

Funding source category [1]

Commercial sector/Industry

Name [1]

Bayer Australia Ltd

Address [1]

875 Pacific Hwy, PYMBLE NSW 2073

Country [1]

Australia

Primary sponsor type

Hospital

Name

Lions Eye Institute

Address

2 Verdun St,
NEDLANDS WA 6009

Country

Australia

Secondary sponsor category [1]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

University of Western Australia

Ethics committee address [1]

Human Ethics, Office of Research Enterprise
M459, 35 Stirling Hwy
Crawley  WA  6009

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

14/11/2018

Approval date [1]

07/01/2019

Ethics approval number [1]

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

A/Prof Chandra Balaratnasingam

Address

Lions Eye Institute
2 Verdun St, Nedlands WA 6009

Country

Australia

Phone

+61 8 9381 0751

Fax

[email protected]

Contact person for public queries

Name

Chandra Balaratnasingam

Address

Lions Eye Institute
2 Verdun St, Nedlands WA 6009

Country

Australia

Phone

+61 8 9381 0751

Fax

[email protected]

Contact person for scientific queries

Name

Chandra Balaratnasingam

Address

Lions Eye Institute
2 Verdun St, Nedlands WA 6009

Country

Australia

Phone

+61 8 9381 0751

Fax

[email protected]

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

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.	Type	Citation	Link	Email	Other Details	Attachment
9725	Clinical study report				pending completion of report
9726	Study 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.

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