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CompletedNCT02432547LADAMOUpdated May 31, 2022

Laser Therapy Combined With Intravitreal Aflibercept vs Intravitreal Aflibercept Monotherapy (LADAMO)

A Phase 4 interventional study of Aflibercept and Targeted laser therapy in Diabetic Retinopathy, sponsored by University of Sydney. Completed at 2 sites in Australia. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2022-05-31.

Sponsored by University of Sydney · Phase 4, Interventional, and Treatment

Phase
Phase 4
Study type
Interventional
Enrollment
48
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study 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.

Read the 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.

02

Conditions studied

  • Diabetic Retinopathy

Keywords

  • Diabetic
  • Macular Oedema
  • Retinopathy
03

In context

Diabetic Retinopathy

791 studies on the registry are indexed under Diabetic Retinopathy; 139 are open to participants now.

This study's enrollment of 48 is below the median of 80 across 491 interventional studies indexed under Diabetic Retinopathy.

Browse Diabetic Retinopathy studies →

Lead sponsor

University of Sydney is the lead sponsor of 94 studies on the registry; 26 are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

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

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
05

Study design

Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Triple (Participant, Care provider, Outcomes assessor)
Enrollment
48 participants (actual)

Study arms

  • Active comparator
    Aflibercept Monotherapy

    Intravitreal aflibercept injections according to a treat and extend regimen.

    Drug: Aflibercept

  • 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.

    Drug: Aflibercept · Procedure: Targeted laser therapy

Interventions

  • DrugAflibercept

    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.

    Also known as: Eylea

  • ProcedureTargeted 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.

    Also known as: Laser

06

What researchers measure

Primary outcomes

  1. Number of intravitreal aflibercept injections over 24 months

    Number of intravitreal aflibercept injections in each of the 2 groups required over 24 months

    Time frame: 24 months

Secondary outcomes

  1. Number of intravitreal aflibercept injections over 12 months

    Number of intravitreal aflibercept injections in each of the 2 groups required over 12 months

    Time frame: 12 months

  2. Proportion of eyes that have central macular thickness <300 microns at 12 months

    Time frame: 12 months

  3. Mean change in central macular thickness (CMT) as measured by OCT at 12 months

    Time frame: 12 months

  4. Mean change in best corrected visual acuity

    Mean change in best corrected visual acuity at 12 months

    Time frame: 12 months

  5. Any change in best corrected visual acuity at 12 months

    Any change in best corrected visual acuity at 12 months

    Time frame: 12 months

  6. 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

    Time frame: 12 months

  7. Disc vessel measurement

    Change in disc vessel diameter at 12 months

    Time frame: 12 months

  8. Number of intravitreal aflibercept injections in each of the 2 groups required over 24 months

    Time frame: 24 months

  9. Proportion of eyes that have central macular thickness <300 microns at 24 months

    Time frame: 24 months

  10. Mean change in central macular thickness (CMT) as measured by OCT at 24 months

    Time frame: 24 months

  11. Mean change in best corrected visual acuity

    Mean change in best corrected visual acuity at 24 months

    Time frame: 24 months

  12. Any change in best corrected visual acuity at 24 months

    Any change in best corrected visual acuity at 24 months

    Time frame: 24 months

  13. 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

    Time frame: 24 months

  14. Disc vessel measurement

    Change in disc vessel diameter at 24 months

    Time frame: 24 months

  15. Time until vision stabilisation

    Length of time from baseline to vision stabilisation

    Time frame: 24 months

  16. Quality of life assessment

    Quality of life assessment using IVI and NEI VFQ-25 forms at 24 months

    Time frame: 24 months

  17. Change in area of macular hard exudates

    Change in area of macular hard exudates from baseline to 24 months

    Time frame: 24 months

  18. Change in distance of closest hard exudate from the foveal centre

    Change in distance of closest hard exudate from the foveal centre between baseline and 24 months

    Time frame: 24 months

  19. Mean change in treatment interval over time

    Mean change in treatment interval between intravitreal aflibercept injections over time

    Time frame: 24 months

Other outcomes

  1. Mean change in foveal avascular zone

    Mean change in maximum diameter of foveal avascular zone at 24 months

    Time frame: 24 months

  2. Incidence of requirement for rescue macular laser treatment

    Incidence of requirement for rescue macular laser treatment

    Time frame: 24 months

  3. Ocular adverse events

    Incidence and severity of ocular adverse events including severe (\>15 letter) loss of vision

    Time frame: 24 months

  4. Non-ocular adverse events

    Incidence and severity of non-ocular adverse events

    Time frame: 24 months

  5. Change in visual field from baseline

    Incidence of new visual field defect that would fail to meet driving standard at 24 months. (Selected study sites only).

    Time frame: 24 months

  6. Development of new neovascular complexes on posterior pole OCT imaging

    Incidence of new neovascular complexes at 24 months

    Time frame: 24 months

  7. Development of new proliferative diabetic retinopathy on wide-field fluorescein angiography

    Incidence of new proliferative diabetic retinopathy at 24 months

    Time frame: 24 months

07

Study locations

2 sites
  • Save Sight Institute
    Sydney, New South Wales 2001, Australia
  • Centre for Eye Research Australia
    Melbourne, Victoria 3002, Australia
08

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on May 31, 2022, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
09

Registry details

Key details

Study ID
NCT02432547
Lead sponsor
University of Sydney
Collaborators
Center for Eye Research Australia
Responsible party
Mark Gillies (Head of Macular Research Group, University of Sydney) — Principal investigator
First posted
May 4, 2015
Start date
Jun 15, 2017
Primary completion
May 24, 2022
Completion
May 24, 2022
Last update
May 31, 2022

Study contacts

Samantha Fraser-Bell, PhD FRANZCO
principal investigator · Save Sight Institute

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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