Clinical trial NCT02432547: Laser Therapy Combined With Intravitreal Aflibercept vs Intravitreal Aflibercept Monotherapy (LADAMO)
Official 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Diabetic Retinopathy
Keywords: Diabetic
Macular Oedema
Retinopathy
Lead sponsor: University of Sydney
Sponsor class: OTHER
Collaborators: name: Center for Eye Research Australia
First posted: 2015-05-04
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed description: Diabetic retinopathy is the most common cause of blindness in individuals between the ages of 20 and 65 years in developed countries. Swelling of the central retina, or "macular oedema", is the commonest cause of visual loss in diabetic retinopathy.

Recent studies have suggested peripheral retinal ischaemia contributes to macula oedema in diabetes and retinal vein occlusions. Intravitreal anti-Vascular Endothelial Growth Factor (VEGF) therapy, such as Aflibercept (Eylea) has shown encouraging results in managing Diabetic Macular Oedema (DMO). There is evidence that regular treatment with anti-VEGF drugs reduces DMO and improves vision on average.

Previous research at this institution has shown that an average of between 7 and 11 injections are required in the first year to stabilise the disease. However, there is a significant burden to patients in terms of frequent visits to the eye specialist, time off work and repeated injections into the eye. The purpose of this study is to see whether targeted peripheral retinal laser therapy to areas of the retina with impaired blood supply can reduce the number of intravitreal aflibercept injections required over 2 years to stabilise DMO.

Eligibility criteria: 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

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

Primary outcomes:
measure: Number of intravitreal aflibercept injections over 24 months
timeFrame: 24 months
Secondary outcomes:
measure: Number of intravitreal aflibercept injections over 12 months
timeFrame: 12 months
measure: Proportion of eyes that have central macular thickness <300 microns at 12 months
timeFrame: 12 months
measure: Mean change in central macular thickness (CMT) as measured by OCT at 12 months
timeFrame: 12 months
measure: Mean change in best corrected visual acuity
timeFrame: 12 months
measure: Any change in best corrected visual acuity at 12 months
timeFrame: 12 months
measure: Effect of peripheral retinal ischaemia on number of aflibercept injections
timeFrame: 12 months
measure: Disc vessel measurement
timeFrame: 12 months
measure: Number of intravitreal aflibercept injections in each of the 2 groups required over 24 months
timeFrame: 24 months
measure: Proportion of eyes that have central macular thickness <300 microns at 24 months
timeFrame: 24 months
measure: Mean change in central macular thickness (CMT) as measured by OCT at 24 months
timeFrame: 24 months
measure: Mean change in best corrected visual acuity
timeFrame: 24 months
measure: Any change in best corrected visual acuity at 24 months
timeFrame: 24 months
measure: Effect of peripheral retinal ischaemia on number of aflibercept injections
timeFrame: 24 months
measure: Disc vessel measurement
timeFrame: 24 months
measure: Time until vision stabilisation
timeFrame: 24 months
measure: Quality of life assessment
timeFrame: 24 months
measure: Change in area of macular hard exudates
timeFrame: 24 months
measure: Change in distance of closest hard exudate from the foveal centre
timeFrame: 24 months
measure: Mean change in treatment interval over time
timeFrame: 24 months
Other outcomes:
measure: Mean change in foveal avascular zone
timeFrame: 24 months
measure: Incidence of requirement for rescue macular laser treatment
timeFrame: 24 months
measure: Ocular adverse events
timeFrame: 24 months
measure: Non-ocular adverse events
timeFrame: 24 months
measure: Change in visual field from baseline
timeFrame: 24 months
measure: Development of new neovascular complexes on posterior pole OCT imaging
timeFrame: 24 months
measure: Development of new proliferative diabetic retinopathy on wide-field fluorescein angiography
timeFrame: 24 months
Locations:
city: Sydney
country: Australia
facility: Save Sight Institute
state: New South Wales
city: Melbourne
country: Australia
facility: Centre for Eye Research Australia
state: Victoria
Study officials:
affiliation: Save Sight Institute
name: Samantha Fraser-Bell, PhD FRANZCO
role: PRINCIPAL_INVESTIGATOR
References: