Trial from ClinicalTrials.gov

For full trial details, please see the original record at



Trial ID
NCT02432547
Ethics application status
Date submitted
23/04/2015
Date registered
23/04/2015
Date last updated
2/06/2015

Titles & IDs
Public title
Laser Therapy Combined With Intravitreal Aflibercept vs Intravitreal Aflibercept Monotherapy (LADAMO)
Scientific title
A Phase IV Randomised Clinical Trial of Laser Therapy for Peripheral Retinal Ischaemia Combined With Intravitreal Aflibercept (Eylea®) Versus Intravitreal Aflibercept Monotherapy for Diabetic Macular Oedema
Secondary ID [1] 0 0
X14-0157
Universal Trial Number (UTN)
Trial acronym
LADAMO
Linked study record

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

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: drugs - Aflibercept
Treatment: surgery - Targeted laser therapy

Active Comparator: Aflibercept Monotherapy - Intravitreal aflibercept injections according to a treat and extend regimen.

Experimental: Targeted laser therapy with Aflibercept - Targeted laser photocoagulation therapy to areas of peripheral retinal ischaemia and intravitreal aflibercept injections using a treat and extend regimen.


Treatment: drugs: Aflibercept
Aflibercept is a soluble decoy receptor and is produced by fusing all-human DNA sequences of the second immunoglobulin (Ig) domain of human VEGF receptor (VEGFR) 1 to the third Ig domain of human VEGFR-2, which are then fused to the Fc region of human IgG-1. By binding to VEGF-A, aflibercept prevents activation of the native VEGF receptors, VEGFR-1 and VEGFR-2. The study sites will be supplied by Bayer with aflibercept. Intravitreal injection of 2mg in 0.05 ml aflibercept will be administered to the study eye, according to a pre-defined treat and extend regimen.

Treatment: surgery: Targeted laser therapy
In the experimental group, targeted laser photocoagulation will be applied to areas of peripheral retinal ischaemia 1 month after the initial intravitreal aflibercept. The trial design allows another session of targeted laser photocoagulation 1 month later to complete the treatment if required. Wide-field photography is planned at 3 months to determine if further targeted laser photocoagulation is required, and if so a third session can be applied. The laser settings are based on those used in current clinical practice and have been prospectively defined in the protocol.

Intervention code [1] 0 0
Treatment: drugs
Intervention code [2] 0 0
Treatment: surgery
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of intravitreal aflibercept injections over 24 months - Number of intravitreal aflibercept injections in each of the 2 groups required over 24 months
Timepoint [1] 0 0
24 months
Secondary outcome [1] 0 0
Number of intravitreal aflibercept injections over 12 months - Number of intravitreal aflibercept injections in each of the 2 groups required over 12 months
Timepoint [1] 0 0
12 months
Secondary outcome [2] 0 0
Central macular thickness at 12 months - Proportion of eyes that have central macular thickness <300 microns at 12 months
Timepoint [2] 0 0
12 months
Secondary outcome [3] 0 0
Central macular thickness at 12 months - Mean change in central macular thickness (CMT) as measured by OCT at 12 months
Timepoint [3] 0 0
12 months
Secondary outcome [4] 0 0
Mean change in best corrected visual acuity - Mean change in best corrected visual acuity at 12 months
Timepoint [4] 0 0
12 months
Secondary outcome [5] 0 0
Any change in best corrected visual acuity at 12 months - Any change in best corrected visual acuity at 12 months
Timepoint [5] 0 0
12 months
Secondary outcome [6] 0 0
Effect of peripheral retinal ischaemia on number of aflibercept injections - Correlation between area of peripheral retinal ischaemia and number of intravitreal injections required at 12 months
Timepoint [6] 0 0
12 months
Secondary outcome [7] 0 0
Disc vessel measurement - Change in disc vessel diameter at 12 months
Timepoint [7] 0 0
12 months
Secondary outcome [8] 0 0
Number of intravitreal aflibercept injections over 24 months - Number of intravitreal aflibercept injections in each of the 2 groups required over 24 months
Timepoint [8] 0 0
24 months
Secondary outcome [9] 0 0
Central macular thickness at 24 months - Proportion of eyes that have central macular thickness <300 microns at 24 months
Timepoint [9] 0 0
24 months
Secondary outcome [10] 0 0
Central macular thickness at 24 months - Mean change in central macular thickness (CMT) as measured by OCT at 24 months
Timepoint [10] 0 0
24 months
Secondary outcome [11] 0 0
Mean change in best corrected visual acuity - Mean change in best corrected visual acuity at 24 months
Timepoint [11] 0 0
24 months
Secondary outcome [12] 0 0
Any change in best corrected visual acuity at 24 months - Any change in best corrected visual acuity at 24 months
Timepoint [12] 0 0
24 months
Secondary outcome [13] 0 0
Effect of peripheral retinal ischaemia on number of aflibercept injections - Correlation between area of peripheral retinal ischaemia and number of intravitreal injections required at 24 months
Timepoint [13] 0 0
24 months
Secondary outcome [14] 0 0
Disc vessel measurement - Change in disc vessel diameter at 24 months
Timepoint [14] 0 0
24 months
Secondary outcome [15] 0 0
Time until vision stabilisation - Length of time from baseline to vision stabilisation
Timepoint [15] 0 0
24 months
Secondary outcome [16] 0 0
Quality of life assessment - Quality of life assessment using IVI and NEI VFQ-25 forms at 24 months
Timepoint [16] 0 0
24 months

Eligibility
Key inclusion criteria
- At screening, the study eye must have DMO with retinal thickness > 300 microns in
central 1mm subfield on Spectral domain OCT

- Age >= 18 years

- Diagnosis of diabetes mellitus

- Best corrected visual acuity of 35-79 LogMAR letters at 4 meters (approximately
6/7.5-6/60) in the study eye

- Women of childbearing potential must have a negative urine pregnancy test at the
screening visit and prior to treatment. A woman is considered of childbearing
potential unless she is postmenopausal and without menses for 12 months or is
surgically sterilised

- Peripheral retinal ischaemia affecting an area greater than 10 disc diameters of the
wide-field fundus fluorescein angiogram (as per the Central Vein Occlusion Study)

- Centre involving DMO, which in the opinion of the investigator, would not benefit from
focal macular laser treatment (e.g. diffuse leak from the capillary bed, disruption of
the foveal avascular zone or perifoveal capillary dropout, complete macular grid
laser).

- Written informed consent has been obtained
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Known allergy to aflibercept or agents used in the study

- Women who are pregnant, nursing, or planning a pregnancy, or who are of childbearing
potential and not using reliable means of contraception

- Loss of vision due to other causes (e.g. age related macular degeneration, myopic
macular degeneration, retinal vein occlusion) in the study eye.

- Macular oedema due to other causes in the study eye.

- Macula hole, vitreo-macular traction or significant epiretinal membrane in the study
eye.

- An ocular condition that would prevent visual acuity improvement despite resolution of
oedema (such as foveal atrophy or substantial premacular fibrosis)

- Treatment with intravitreal triamcinolone acetonide (IVTA) within the last 6 months or
peribulbar triamcinolone within the last 3 months, or anti-VEGF drugs (bevacizumab,
ranibizumab or aflibercept) within the last 2 months in the study eye.

- Cataract surgery within the last 3 months in the study eye

- Previous PRP laser treatment in the study eye

- Previous vitrectomy in study eye

- Media opacity including cataract that already precludes adequate macular photography
or cataract that is likely to require surgery within 12 months

- Intercurrent severe disease such as septicaemia, any condition which would affect
follow-up or photographic documentation (e.g. geographical, psycho-social)

- History of chronic renal failure requiring dialysis or renal transplant

- Blood pressure >180/110

- Patient has a condition or is in a situation that in the investigator's opinion may
put the patient at significant risk, may confound the study results, or may interfere
significantly with the patient's participation in the study

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled 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
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Current
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
Save Sight Institute - Sydney
Recruitment hospital [2] 0 0
Centre for Eye Research Australia - Melbourne
Recruitment postcode(s) [1] 0 0
2001 - Sydney
Recruitment postcode(s) [2] 0 0
3002 - Melbourne

Funding & Sponsors
Primary sponsor type
Other
Name
University of Sydney
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Center for Eye Research Australia
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
This will be a 24 month phase IV, randomised, prospective, multicentre, clinical trial of
laser therapy to areas of peripheral retinal ischaemia combined with intravitreal aflibercept
versus intravitreal aflibercept monotherapy. Both arms will have 2mg intravitreal aflibercept
according to a treat and extend protocol.

The specific aim of the study is to test whether laser therapy of peripheral retinal
ischaemia reduces the overall number of intravitreal aflibercept injections required to
control DMO over a 24 month period.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Samantha Fraser-Bell, PhD FRANZCO
Address 0 0
Save Sight Institute
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Samantha Fraser-Bell, PhD FRANZCO
Address 0 0
Country 0 0
Phone 0 0
61 2 9382 7309
Fax 0 0
Email 0 0
sfraserbell@gmail.com
Contact person for scientific queries
Contact person responsible for updating information