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

NCT02432547 | Completed Phase 4 DMC

• 1 other identifier: X14-0157
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 2

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.

Conditions

Diabetic Retinopathy

Keywords

Diabetic; Macular Oedema; Retinopathy

Outcome Measures

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

  24 months

Secondary Outcomes (19)

• Number of intravitreal aflibercept injections over 12 months

  12 months

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

  12 months

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

  12 months

• Mean change in best corrected visual acuity

  12 months

• Any change in best corrected visual acuity at 12 months

  12 months

Other Outcomes (7)

• Mean change in foveal avascular zone

  24 months

• Incidence of requirement for rescue macular laser treatment

  24 months

• Ocular adverse events

  24 months

Study Arms (2)

Aflibercept Monotherapy

ACTIVE COMPARATOR

Intravitreal aflibercept injections according to a treat and extend regimen.

Drug: Aflibercept

Targeted laser therapy with Aflibercept

EXPERIMENTAL

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

Aflibercept 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.

Also known as: Eylea

Aflibercept Monotherapy; Targeted laser therapy with Aflibercept

Targeted laser therapy 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.

Also known as: Laser

Targeted laser therapy with Aflibercept

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Sydney: lead
• Center for Eye Research Australia: collaborator

Study Sites (2)

Save Sight Institute

Sydney, New South Wales, 2001, Australia

Location

Centre for Eye Research Australia

Melbourne, Victoria, 3002, Australia

Location

MeSH Terms

Conditions

Diabetic Retinopathy; Macular Edema; Retinal Diseases

Interventions

aflibercept; Lasers

Condition Hierarchy (Ancestors)

Eye Diseases; Diabetic Angiopathies; Vascular Diseases; Cardiovascular Diseases; Diabetes Complications; Diabetes Mellitus; Endocrine System Diseases; Macular Degeneration; Retinal Degeneration

Intervention Hierarchy (Ancestors)

Optical Devices; Equipment and Supplies; Radiation Equipment and Supplies

Study Officials

• Samantha Fraser-Bell, PhD FRANZCO

  Save Sight Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head of Macular Research Group

Study Record Dates

• First Submitted: April 23, 2015
• First Posted: May 4, 2015
• Study Start: June 15, 2017
• Primary Completion: May 24, 2022
• Study Completion: May 24, 2022
• Last Updated: May 31, 2022

Record last verified: 2022-05

Locations

AU (2)