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

NCT ID: NCT02432547

Last Updated: 2022-05-31

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 48 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-06-15
• Study Completion Date: 2022-05-24

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.

Conditions

Diabetic Retinopathy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Aflibercept Monotherapy

Intravitreal aflibercept injections according to a treat and extend regimen.

Group Type: ACTIVE_COMPARATOR

Aflibercept

Intervention Type: DRUG

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.

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.

Group Type: EXPERIMENTAL

Aflibercept

Intervention Type: DRUG

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.

Targeted laser therapy

Intervention Type: PROCEDURE

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.

Interventions

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.

Intervention Type: DRUG

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 Type: PROCEDURE

Other Intervention Names

Eylea; Laser

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Center for Eye Research Australia

OTHER

Sponsor Role: collaborator

University of Sydney

OTHER

Sponsor Role: lead

Responsible Party

Mark Gillies

Head of Macular Research Group

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Samantha Fraser-Bell, PhD FRANZCO

Role: PRINCIPAL_INVESTIGATOR

Save Sight Institute

Locations

Save Sight Institute

Sydney, New South Wales, Australia

Centre for Eye Research Australia

Melbourne, Victoria, Australia

Countries

Australia

Other Identifiers

X14-0157

Identifier Type: -

Identifier Source: org_study_id