search
Back to results

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

Primary Purpose

Diabetic Retinopathy

Status
Completed
Phase
Phase 4
Locations
Australia
Study Type
Interventional
Intervention
Aflibercept
Targeted laser therapy
Sponsored by
University of Sydney
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Diabetic Retinopathy focused on measuring Diabetic, Macular Oedema, Retinopathy

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Save Sight Institute
  • Centre for Eye Research Australia

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Aflibercept Monotherapy

Targeted laser therapy with Aflibercept

Arm Description

Intravitreal aflibercept injections according to a treat and extend regimen.

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Number of intravitreal aflibercept injections over 12 months
Number of intravitreal aflibercept injections in each of the 2 groups required over 12 months
Proportion of eyes that have central macular thickness <300 microns at 12 months
Mean change in central macular thickness (CMT) as measured by OCT at 12 months
Mean change in best corrected visual acuity
Mean change in best corrected visual acuity at 12 months
Any change in best corrected visual acuity at 12 months
Any change in best corrected visual acuity at 12 months
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
Disc vessel measurement
Change in disc vessel diameter at 12 months
Number of intravitreal aflibercept injections in each of the 2 groups required over 24 months
Proportion of eyes that have central macular thickness <300 microns at 24 months
Mean change in central macular thickness (CMT) as measured by OCT at 24 months
Mean change in best corrected visual acuity
Mean change in best corrected visual acuity at 24 months
Any change in best corrected visual acuity at 24 months
Any change in best corrected visual acuity at 24 months
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
Disc vessel measurement
Change in disc vessel diameter at 24 months
Time until vision stabilisation
Length of time from baseline to vision stabilisation
Quality of life assessment
Quality of life assessment using IVI and NEI VFQ-25 forms at 24 months
Change in area of macular hard exudates
Change in area of macular hard exudates from baseline to 24 months
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
Mean change in treatment interval over time
Mean change in treatment interval between intravitreal aflibercept injections over time

Full Information

First Posted
April 23, 2015
Last Updated
May 27, 2022
Sponsor
University of Sydney
Collaborators
Center for Eye Research Australia
search

1. Study Identification

Unique Protocol Identification Number
NCT02432547
Brief Title
Laser Therapy Combined With Intravitreal Aflibercept vs Intravitreal Aflibercept Monotherapy (LADAMO)
Acronym
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

2. Study Status

Record Verification Date
May 2022
Overall Recruitment Status
Completed
Study Start Date
June 15, 2017 (Actual)
Primary Completion Date
May 24, 2022 (Actual)
Study Completion Date
May 24, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Sydney
Collaborators
Center for Eye Research Australia

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diabetic Retinopathy
Keywords
Diabetic, Macular Oedema, Retinopathy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderOutcomes Assessor
Allocation
Randomized
Enrollment
48 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Aflibercept Monotherapy
Arm Type
Active Comparator
Arm Description
Intravitreal aflibercept injections according to a treat and extend regimen.
Arm Title
Targeted laser therapy with Aflibercept
Arm Type
Experimental
Arm Description
Targeted laser photocoagulation therapy to areas of peripheral retinal ischaemia and intravitreal aflibercept injections using a treat and extend regimen.
Intervention Type
Drug
Intervention Name(s)
Aflibercept
Other Intervention Name(s)
Eylea
Intervention Description
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
Procedure
Intervention Name(s)
Targeted laser therapy
Other Intervention Name(s)
Laser
Intervention Description
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.
Primary Outcome Measure Information:
Title
Number of intravitreal aflibercept injections over 24 months
Description
Number of intravitreal aflibercept injections in each of the 2 groups required over 24 months
Time Frame
24 months
Secondary Outcome Measure Information:
Title
Number of intravitreal aflibercept injections over 12 months
Description
Number of intravitreal aflibercept injections in each of the 2 groups required over 12 months
Time Frame
12 months
Title
Proportion of eyes that have central macular thickness <300 microns at 12 months
Time Frame
12 months
Title
Mean change in central macular thickness (CMT) as measured by OCT at 12 months
Time Frame
12 months
Title
Mean change in best corrected visual acuity
Description
Mean change in best corrected visual acuity at 12 months
Time Frame
12 months
Title
Any change in best corrected visual acuity at 12 months
Description
Any change in best corrected visual acuity at 12 months
Time Frame
12 months
Title
Effect of peripheral retinal ischaemia on number of aflibercept injections
Description
Correlation between area of peripheral retinal ischaemia and number of intravitreal injections required at 12 months
Time Frame
12 months
Title
Disc vessel measurement
Description
Change in disc vessel diameter at 12 months
Time Frame
12 months
Title
Number of intravitreal aflibercept injections in each of the 2 groups required over 24 months
Time Frame
24 months
Title
Proportion of eyes that have central macular thickness <300 microns at 24 months
Time Frame
24 months
Title
Mean change in central macular thickness (CMT) as measured by OCT at 24 months
Time Frame
24 months
Title
Mean change in best corrected visual acuity
Description
Mean change in best corrected visual acuity at 24 months
Time Frame
24 months
Title
Any change in best corrected visual acuity at 24 months
Description
Any change in best corrected visual acuity at 24 months
Time Frame
24 months
Title
Effect of peripheral retinal ischaemia on number of aflibercept injections
Description
Correlation between area of peripheral retinal ischaemia and number of intravitreal injections required at 24 months
Time Frame
24 months
Title
Disc vessel measurement
Description
Change in disc vessel diameter at 24 months
Time Frame
24 months
Title
Time until vision stabilisation
Description
Length of time from baseline to vision stabilisation
Time Frame
24 months
Title
Quality of life assessment
Description
Quality of life assessment using IVI and NEI VFQ-25 forms at 24 months
Time Frame
24 months
Title
Change in area of macular hard exudates
Description
Change in area of macular hard exudates from baseline to 24 months
Time Frame
24 months
Title
Change in distance of closest hard exudate from the foveal centre
Description
Change in distance of closest hard exudate from the foveal centre between baseline and 24 months
Time Frame
24 months
Title
Mean change in treatment interval over time
Description
Mean change in treatment interval between intravitreal aflibercept injections over time
Time Frame
24 months
Other Pre-specified Outcome Measures:
Title
Mean change in foveal avascular zone
Description
Mean change in maximum diameter of foveal avascular zone at 24 months
Time Frame
24 months
Title
Incidence of requirement for rescue macular laser treatment
Description
Incidence of requirement for rescue macular laser treatment
Time Frame
24 months
Title
Ocular adverse events
Description
Incidence and severity of ocular adverse events including severe (>15 letter) loss of vision
Time Frame
24 months
Title
Non-ocular adverse events
Description
Incidence and severity of non-ocular adverse events
Time Frame
24 months
Title
Change in visual field from baseline
Description
Incidence of new visual field defect that would fail to meet driving standard at 24 months. (Selected study sites only).
Time Frame
24 months
Title
Development of new neovascular complexes on posterior pole OCT imaging
Description
Incidence of new neovascular complexes at 24 months
Time Frame
24 months
Title
Development of new proliferative diabetic retinopathy on wide-field fluorescein angiography
Description
Incidence of new proliferative diabetic retinopathy at 24 months
Time Frame
24 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Samantha Fraser-Bell, PhD FRANZCO
Organizational Affiliation
Save Sight Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
Save Sight Institute
City
Sydney
State/Province
New South Wales
ZIP/Postal Code
2001
Country
Australia
Facility Name
Centre for Eye Research Australia
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3002
Country
Australia

12. IPD Sharing Statement

Learn more about this trial

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

We'll reach out to this number within 24 hrs