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Trial registered on ANZCTR


Registration number
ACTRN12619000963123
Ethics application status
Approved
Date submitted
25/06/2019
Date registered
8/07/2019
Date last updated
8/07/2019
Date data sharing statement initially provided
8/07/2019
Type of registration
Retrospectively registered

Titles & IDs
Public title
Aflibercept for Diabetic Macular Oedema: Outcomes Using a Treat and Extend Protocol
Scientific title
Effect of Aflibercept on best corrected visual acuity in patients with Diabetic Macular Oedema: Outcomes Using a Treat and Extend Protocol
Secondary ID [1] 298591 0
none
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Diabetic Macular Oedema 313433 0
Condition category
Condition code
Eye 311871 311871 0 0
Diseases / disorders of the eye
Metabolic and Endocrine 311982 311982 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The study will take the form of a prospective interventional case series and involve the use of 2.0mg aflibercept in treatment naïve centre-involving diabetic macula oedema (DMO). The participants will receive treatment according to a treat and extend protocol.
The treat-and-extend protocol denotes the following:
There will be an initial loading phase of 3 injections given 4 weeks apart, follow up and reinjection will occur at 4-week intervals until the macula is at pre-threshold for inclusion in the study (that is, the visual acuity is better than 78 letters (6/9.5) and CST has reached less than300um) or there has been no improvement in BCVA by greater than or equal to 5 letters or no further improvement in CST by 10% or more for the last two visits. Achieving these outcomes will indicate stability.
Once the macula is stable, follow up and injection will be increased by 2 week intervals. If there is no loss of BCVA by greater than or equal to 5 letters and no increase in CST by 10% or more this 2 week extension with treatment will be continued out to 12 weeks.
Where a patient reaches a 12 week interval, and remains stable, this will be continued for two further 12 week intervals. If stability remains at the fourth 12 week review, the injection will be withheld and the participant will be reviewed four weekly with BCVA and OCT scanning. Should stability be preserved after three four weekly checks no further injection will be given and the participant will be monitored 3 monthly as they would routinely in quiescent DMO.
If there is a loss of BCVA by greater than or equal to 5 letters or an increase in CST by 10% or more the participant will be re-injected and returned for review and further treatment at four weeks and then re-extended as indicated.
If, at any time, there is a deterioration of 5 or more letters in BCVA or an increase in CST of 10% or more, then the interval is reduced by 2 weeks at a time until the macula is once again stable. The patient can then be re-extended.
With this regimen, the patient receives an injection at each follow up and the interval of each follow up after the initial loading phase is determined by the treat-and-extend re treatment criteria.
Injections will be administered to the patients as required by the Ophthalmology study doctor for the 24 month duration of the study.
After the study is completed patients will be reviewed as outpatients as per standard clinical practice.
Patients are reminded at the point of signing consent of the importance of attending all study visits. Staff contact details are provided should any issues arise.

Intervention code [1] 314851 0
Treatment: Drugs
Comparator / control treatment
no control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 320539 0
Primary outcome will be the mean change in best corrected visual acuity (BCVA) from baseline to month 12. This will be measured using ETDRS letters at each visit.
Timepoint [1] 320539 0
BCVA measurement comparison at 12 month point
Secondary outcome [1] 371953 0
Secondary outcome will be the mean change in best corrected visual acuity (BCVA) from baseline to month 24. This will be measured using ETDRS letters at each visit.
Timepoint [1] 371953 0
Month 24
Secondary outcome [2] 371954 0
Secondary outcome variable will be the HbA1c level at baseline and at month 24. This will be accessed via the GP or endocrinologist.
Timepoint [2] 371954 0
Baseline compared to Month 24
Secondary outcome [3] 371955 0
Secondary outcome variable will be the quantitative and qualitative optical coherence tomography (OCT) changes that are predictive of response – including change in central sub-field thickness. OCT scans will be taken at each visit
Timepoint [3] 371955 0
Baseline, Month 12 and Month 24
Secondary outcome [4] 371956 0
Secondary outcome measurement will be the total and mean number of injections required per patient for the duration of the study.
Timepoint [4] 371956 0
Month 24

Eligibility
Key inclusion criteria
1. Adult patients 18 years or over with a diagnosis of type 1 or 2 diabetes mellitus.
2. Treatment naïve eyes with evidence of centre involving DMO on FFA and OCT.
3. BCVA equal to between 73 (6/9.5) and 24 (6/95) ETDRS letters inclusive.
4. Definite retinal thickening on clinical examination due to DMO involving the central macula.
5. Media clarity, pupillary dilatation and individual cooperation to allow adequate fundus photographs.
6. Central subfield thickness on Heidelberg Spectralis of equal to or greater than 300um.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Previous treatment with an anti-VEGF agent or intravitreal triamcinolone acetate.
2. Active proliferative diabetic retinopathy in the study eye.
3. Neovascularisation of the iris or angle.
4. Previous macular laser or pan retinal photocoagulation treatment within the last 4 months.
5. Maculopathy due to another cause.
6. History of retinal detachment or surgery for retinal detachment.
7. Previous vitrectomy.
8. Any existing ocular disorder that would prevent improvement in visual acuity such as macular ischaemia, dense foveal lipid exudates, epiretinal membrane or macular hole, or any significant media opacities such as cataract, which, in an otherwise healthy eye would reduce the vision to less than 6/12.
9. Aphakia
10. YAG laser use in the 2 months prior to treatment.
11. Any active periocular or intraocular infection or severe blepharitis.
12. Any active intraocular inflammation or uncontrolled intraocular pressure.
13. Any known hypersensitivity to aflibercept or any of the excipients in aflibercept.
14. Any arterial thromboembolic event including stoke, myocardial infarction or vascular embolism in the last 3 months.
15. Any positive pregnancy or current breast feeding or patients who are planning for a pregnancy or likely to be breast feeding over the next 24 months.
16. Chronic renal failure requiring dialysis or transplant.
17. Unstable blood pressure >180/110, cardiovascular disease or glycaemic control (BSL more often than not over 20mmol/L).
18. Participation within another trial of an unapproved drug within 30 days of entry into this trial.
19. Myocardial infarct, other acute cardiovascular event requiring hospitalisation, stroke, transient ischaemic attack, or treatment for acute congestive heart failure within 4 months prior to entry into the study.
20. Systemic anti-VEGF or pro-VEGF treatment within four months prior to study entry or anticipated use of the drug during the study period.

Study design
Purpose of the study
Treatment
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
Phase 4
Type of endpoint(s)
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 14090 0
The Royal Adelaide Hospital - Adelaide
Recruitment hospital [2] 14091 0
The Queen Elizabeth Hospital - Woodville
Recruitment postcode(s) [1] 26880 0
5000 - Adelaide
Recruitment postcode(s) [2] 26881 0
5011 - Woodville

Funding & Sponsors
Funding source category [1] 303134 0
Commercial sector/Industry
Name [1] 303134 0
Bayer Australia Limited
Address [1] 303134 0
Medical, Pharmaceuticals
Medical Affairs
875 Pacific Hwy, Pymble, NSW, 2073, Australia
Country [1] 303134 0
Australia
Primary sponsor type
Hospital
Name
The Royal Adelaide Hospital
Address
Port Road,
Adelaide,
South Australia, 5000
Country
Australia
Secondary sponsor category [1] 303134 0
None
Name [1] 303134 0
Address [1] 303134 0
Country [1] 303134 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 303683 0
Royal Adelaide Hospital Research Ethics Committee
Ethics committee address [1] 303683 0
Level 3, Roma Mitchell House,
136 North Terrace,
Adelaide
SA
5000
Ethics committee country [1] 303683 0
Australia
Date submitted for ethics approval [1] 303683 0
08/11/2018
Approval date [1] 303683 0
13/11/2018
Ethics approval number [1] 303683 0
HREC/15/RAH/485

Summary
Brief summary
Injecting medicine into the eye is an effective treatment for swelling of the macular in diabetes. Aflibercept is one of two medicines approved to treat this swelling.

While effective, treatment can be prolonged. After three initial monthly injections, the duration between subsequent injections varies. It can be fixed, given when the condition worsens or timed according to response.

The effectiveness of injections when timed according to a person’s response is being investigated. This is known as a ‘treat and extend’ protocol. This protocol reflects real world treatment in Australia.

This study will help look at the effectiveness of this approach. It will also allow us to identify the best interval between injections.

Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 94478 0
Dr Shane Durkin
Address 94478 0
Ophthalmology Network,
Room 6G-462,
Royal Adelaide Hospital,
Port Rd,
Adelaide,
SA,
5000
Country 94478 0
Australia
Phone 94478 0
+61 8 70742257
Fax 94478 0
Email 94478 0
shane.durkin@adelaide.edu.au
Contact person for public queries
Name 94479 0
Mrs Mel Willoughby
Address 94479 0
Ophthalmology Network,
Room 6G-462,
Royal Adelaide Hospital,
Port Rd,
Adelaide,
SA,
5000
Country 94479 0
Australia
Phone 94479 0
+61 08 7074 2257
Fax 94479 0
Email 94479 0
melanie.willoughby@sa.gov.au
Contact person for scientific queries
Name 94480 0
Dr Shane Durkin
Address 94480 0
Ophthalmology Network,
Room 6G-462,
Royal Adelaide Hospital,
Port Rd,
Adelaide,
SA,
5000
Country 94480 0
Australia
Phone 94480 0
+61 08 70742257
Fax 94480 0
Email 94480 0
shane.durkin@adelaide.edu.au

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 other documents available
Summary results
No Results