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Trial registered on ANZCTR


Registration number
ACTRN12615000417583
Ethics application status
Approved
Date submitted
16/04/2015
Date registered
1/05/2015
Date last updated
19/11/2019
Date data sharing statement initially provided
8/11/2018
Date results information initially provided
8/11/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
The efficacy of intravitreal aflibercept given in a ‘treat and extend’ regime in the treatment of cystoid macular oedema secondary to central retinal vein occlusion.
Scientific title
The efficacy of intravitreal aflibercept given in a ‘treat and extend’ regime in the treatment of cystoid macular oedema secondary to central retinal vein occlusion
Secondary ID [1] 286540 0
NONE
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
central retinal vein occlusion (CRVO). 294775 0
cystoid macular oedema 294826 0
Condition category
Condition code
Eye 295059 295059 0 0
Diseases / disorders of the eye

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
All patients entered into the study will receive intravitreal injections of Aflibercept (Eylea) 2 mg/ 0.05mls. All patient's will be required to have an injection every month for a minimum of 3 months. After the mandatory 3 injections (week 8) BCVA, fundal examination and OCT assessment of the patient is used to determine the presence of residual CME.
- If there is continued BCVA improvement of greater than or equal to 5 letters from the previous visit further injections will be given at a 4 weekly until there is no further improvement. Once BCVA is stable (within 5 letters of best recorded acuity), the OCT is free of either SRF or IRF and CMT is within 50 microns of previous best (minimum) recorded, an injection is given and the interval between the next visit is extended by two weeks up to a maximum of 12 weeks.


- During the period of extension, if there is a reduction in BCVA greater than or equal to 5 letters, evidence of recurrent SRF/ IRF or an increase of greater than or equal to 50 microns (from previous best recorded CMT), an aflibercept injection will be given and the follow up interval will be reduced by 2 weeks.


Following this protocol the time between injections will be extended by 2 weeks at each visit if the patient’s condition is stable, Using this treatment regimen, each patient receives at least seven injections in the first year.

In the second year treatment may continued as per the criteria in year one, in addition treatment be suspended based on BCVA, OCT and fundus examination. Rescue treatment of intravitreal steroid or scatter laser may be performed if required.
Intervention code [1] 291644 0
Treatment: Drugs
Comparator / control treatment
This is a proof of concept study to assess the utility of a treat and extend strategy in the treatment of macular oedema associated with CRVO.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 294826 0
Assess the mean change in best-corrected visual acuity from baseline to 24 months in patients with macular oedema associated with central retinal vein occlusion. BCVA will be performed at every visit by a qualified Orthoptist and Retroilluminated LOGMAR charts are used in this study. The illuminator box will be either wall-mounted or mounted on a stand manufactured. Charts 1, 2, and R are used for testing the right eye, left eye, and refraction, respectively.
Timepoint [1] 294826 0
24 months after baseline
Secondary outcome [1] 314154 0
Assess the number of aflibercept injections given by 6 months. All aflibercept injections administer to patients whilst on the study will be properly recorded in the patient's medical history and Study Case Report Forms.
Timepoint [1] 314154 0
6 months after baseline visit
Secondary outcome [2] 314155 0
Assess the proportion of patients gaining greater than or equal to15 letters of best corrected visual acuity at 6 months. BCVA will be performed at every visit by a qualified Orthoptist and Retroilluminated LOGMAR charts are used in this study. The illuminator box will be either wall-mounted or mounted on a stand manufactured. Charts 1, 2, and R are used for testing the right eye, left eye, and refraction, respectively.
Timepoint [2] 314155 0
6 months after baseline visit
Secondary outcome [3] 314156 0
Assess the number of aflibercept injections given by 12 and 24 months. All aflibercept injections administer to patients whilst on the study will be properly recorded in the patient's medical history and Study Case Report Forms.
Timepoint [3] 314156 0
12 and 24 months after baseline visit.
Secondary outcome [4] 314162 0
Assess the proportion of patients gaining greater than or equal to15 letters of best corrected visual acuity at 12 and 24 months. BCVA will be performed at every visit by a qualified Orthoptist and Retroilluminated LOGMAR charts are used in this study. The illuminator box will be either wall-mounted or mounted on a stand manufactured. Charts 1, 2, and R are used for testing the right eye, left eye, and refraction, respectively.
Timepoint [4] 314162 0
12 and 24 months after baseline visit
Secondary outcome [5] 314163 0
Assess the mean best-corrected visual acuity at 12 and 24 months. BCVA will be performed at every visit by a qualified Orthoptist and Retroilluminated LOGMAR charts are used in this study. The illuminator box will be either wall-mounted or mounted on a stand manufactured. Charts 1, 2, and R are used for testing the right eye, left eye, and refraction, respectively.
Timepoint [5] 314163 0
12 and 24 months after baseline visit
Secondary outcome [6] 314164 0
Assess the mean change in macular thickness from baseline to 12 and 24 months. Change will be assessed using a Heidelberg Optical Coherence Tomography which is performed at every visit. The eye(s) should be maximally dilated to help insure optimal quality scans.
Both eyes will be scanned at each visit requiring spectralis OCT imaging. The scan parameters are as follows:
*Used scan mode is OCT
*High Speed
*20° *20°
*49 slices
*30 frames
Timepoint [6] 314164 0
12 and 24 months after baseline visit.
Secondary outcome [7] 329511 0
Assess the proportion of patients losing greater than or equal to 15 letters of best corrected visual acuity at 12 and 24 months. BCVA will be performed at every visit by a qualified Orthoptist and Retroilluminated LOGMAR charts are used in this study. The illuminator box will be either wall-mounted or mounted on a stand manufactured. Charts 1, 2, and R are used for testing the right eye, left eye, and refraction, respectively.
Timepoint [7] 329511 0
12 and 24 months after baseline visit
Secondary outcome [8] 329512 0
Assess the quality of life assessment (IVI and VFQ-25) at 12 and 24 months
Timepoint [8] 329512 0
12 and 24 months

Eligibility
Key inclusion criteria
1. Age greater than or equal to18 years
2. CRVO with cystoid macular as determined by fluorescein angiography and duration of onset less than 12 months
3. Best-corrected visual acuity (BCVA) of 17-70 letters (6/12 –6/120)
4. Central macular thickness of greater than or equal to 300 microns as measured by Heidelberg Optical coherence tomography.
5. Absent relative afferent pupillary defect
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Systemic
1. Uncontrolled blood pressure (greater than or equal to180 mmHg, systolic and 110 mmHg, diastolic)
2. Chronic renal failure
3. Major surgery within one month of study
4. Previous systemic anti-VEGF treatment
5. Women of childbearing potential not using adequate contraception and women who are breast feeding
6. Intercurrent severe disease such as septicaemia

Ocular
1. Glaucoma which is uncontrolled with intraocular pressure-lowering medications
2. Past history of severe steroid response with IOP greater than or equal to 35 mmHg following steroid treatment
3. Loss of vision due to other causes (e.g. age-related macular degeneration, myopic macular degeneration)
4. VA of <6/60 in the fellow eye
5. Argon laser photocoagulation within 3 months of study entry
6. Previous intraocular surgery (within 6 months)
7. Stroke or myocardial infarction less than 3 months prior to screening.
8. Any active periocular or ocular infection or inflammation at screening or baseline.
9. Subjects, who in the opinion of the Investigator, may not benefit from the Investigational Product due to pre-existing or current macular condition (eg, vitreomacular traction, epiretinal membrane, scar, foveal atrophy)

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)
not applicable
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
not applicable
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 3
Type of endpoint/s
Efficacy
Statistical methods / analysis
Sample size justification:

This is a proof of concept study to assess the utility of a treat and extend strategy in the treatment of macular oedema associated with CRVO. In the context of this pilot study, 20 patients are considered as sufficient to give estimates on study objectives , to allow further scientific planning.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
4/05/2015
Actual
4/05/2015
Date of last participant enrolment
Anticipated
28/02/2017
Actual
2/02/2017
Date of last data collection
Anticipated
2/02/2019
Actual
1/02/2019
Sample size
Target
20
Accrual to date
Final
20
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 3703 0
The Royal Victorian Eye and Ear Hospital - East Melbourne
Recruitment postcode(s) [1] 9536 0
3002 - East Melbourne

Funding & Sponsors
Funding source category [1] 291105 0
Commercial sector/Industry
Name [1] 291105 0
Bayer Healthcare
Country [1] 291105 0
Australia
Primary sponsor type
Other
Name
Centre for Eye Research Australia
Address
Royal Victorian Eye and Ear Hospital
Level 7, 32 Gisborne Street
East Melbourne, VIC, 3002
Country
Australia
Secondary sponsor category [1] 289782 0
None
Name [1] 289782 0
Address [1] 289782 0
Country [1] 289782 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 292684 0
Royal Victorian Eye and Hospital Human Research Ethics Committee
Ethics committee address [1] 292684 0
Royal Victorian Eye and Ear Hospital
32 Gisborne Street
East Melbourne, VIC, 3002
Ethics committee country [1] 292684 0
Australia
Date submitted for ethics approval [1] 292684 0
Approval date [1] 292684 0
24/11/2014
Ethics approval number [1] 292684 0
14/1201H

Summary
Brief summary
In this prospective case series participants with cystoid macula oedema secondary to Central Retinal Vein Occlusion (CRVO) who are treatment naive will receive treatment with Eylea using an ‘inject and extend’ treatment protocol. In this study we aim to assess whether a ‘treat and extend’ regimen is a useful option in the treatment of CME associated with CRVO. We hypothesise that visual acuity outcomes will be non-inferior to that achieved in the pivotal trials and that this will be achieved with fewer visits to the clinic. The study will run for approximately 36 months. The recruitment period will last approximately 12 months. Participant involvement will last approximately 24 months.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 56574 0
Dr Dr Sanj Wickremasinghe
Address 56574 0
Centre for Eye Research Australia
32 Gisborne St, East Melbourne,
Victoria 3002 Australia
Country 56574 0
Australia
Phone 56574 0
+61 434 497 215
Fax 56574 0
+61 3 9929 8030
Email 56574 0
Sanj.Wickremasinghe@eyeandear.org.au
Contact person for public queries
Name 56575 0
Mr Thuy Chau
Address 56575 0
Centre for Eye Research Australia
32 Gisborne St, East Melbourne,
Victoria 3002 Australia
Country 56575 0
Australia
Phone 56575 0
+61 3 9929 8076
Fax 56575 0
+61 3 9929 8030
Email 56575 0
thuy.chau@unimelb.edu.au
Contact person for scientific queries
Name 56576 0
Dr Dr Sanj Wickremasinghe
Address 56576 0
Centre for Eye Research Australia
32 Gisborne St, East Melbourne,
Victoria 3002 Australia
Country 56576 0
Australia
Phone 56576 0
+61 434 497 215
Fax 56576 0
+61 3 9929 8030
Email 56576 0
Sanj.Wickremasinghe@eyeandear.org.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 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.