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

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ClinicalTrials.gov Identifier: NCT02432547
Recruitment Status : Unknown
Verified June 2015 by Mark Gillies, University of Sydney.
Recruitment status was:  Recruiting
First Posted : May 4, 2015
Last Update Posted : June 3, 2015
Sponsor:
Collaborator:
Center for Eye Research Australia
Information provided by (Responsible Party):
Mark Gillies, University of Sydney

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.


Condition or disease Intervention/treatment Phase
Diabetic Retinopathy Drug: Aflibercept Procedure: Targeted laser therapy Phase 4

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.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Outcomes Assessor)
Primary Purpose: Treatment
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 Start Date : June 2015
Estimated Primary Completion Date : December 2017
Estimated Study Completion Date : March 2018

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Aflibercept Monotherapy
Intravitreal aflibercept injections according to a treat and extend regimen.
Drug: 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.
Other Name: Eylea

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
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.
Other Name: Eylea

Procedure: 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.
Other Name: Laser




Primary Outcome Measures :
  1. Number of intravitreal aflibercept injections over 24 months [ Time Frame: 24 months ]
    Number of intravitreal aflibercept injections in each of the 2 groups required over 24 months


Secondary Outcome Measures :
  1. Number of intravitreal aflibercept injections over 12 months [ Time Frame: 12 months ]
    Number of intravitreal aflibercept injections in each of the 2 groups required over 12 months

  2. Central macular thickness at 12 months [ Time Frame: 12 months ]
    Proportion of eyes that have central macular thickness <300 microns at 12 months

  3. Central macular thickness at 12 months [ Time Frame: 12 months ]
    Mean change in central macular thickness (CMT) as measured by OCT at 12 months

  4. Mean change in best corrected visual acuity [ Time Frame: 12 months ]
    Mean change in best corrected visual acuity at 12 months

  5. Any change in best corrected visual acuity at 12 months [ Time Frame: 12 months ]
    Any change in best corrected visual acuity at 12 months

  6. Effect of peripheral retinal ischaemia on number of aflibercept injections [ Time Frame: 12 months ]
    Correlation between area of peripheral retinal ischaemia and number of intravitreal injections required at 12 months

  7. Disc vessel measurement [ Time Frame: 12 months ]
    Change in disc vessel diameter at 12 months

  8. Number of intravitreal aflibercept injections over 24 months [ Time Frame: 24 months ]
    Number of intravitreal aflibercept injections in each of the 2 groups required over 24 months

  9. Central macular thickness at 24 months [ Time Frame: 24 months ]
    Proportion of eyes that have central macular thickness <300 microns at 24 months

  10. Central macular thickness at 24 months [ Time Frame: 24 months ]
    Mean change in central macular thickness (CMT) as measured by OCT at 24 months

  11. Mean change in best corrected visual acuity [ Time Frame: 24 months ]
    Mean change in best corrected visual acuity at 24 months

  12. Any change in best corrected visual acuity at 24 months [ Time Frame: 24 months ]
    Any change in best corrected visual acuity at 24 months

  13. Effect of peripheral retinal ischaemia on number of aflibercept injections [ Time Frame: 24 months ]
    Correlation between area of peripheral retinal ischaemia and number of intravitreal injections required at 24 months

  14. Disc vessel measurement [ Time Frame: 24 months ]
    Change in disc vessel diameter at 24 months

  15. Time until vision stabilisation [ Time Frame: 24 months ]
    Length of time from baseline to vision stabilisation

  16. Quality of life assessment [ Time Frame: 24 months ]
    Quality of life assessment using IVI and NEI VFQ-25 forms at 24 months


Other Outcome Measures:
  1. Mean change in foveal avascular zone [ Time Frame: 24 months ]
    Mean change in maximum diameter of foveal avascular zone at 24 months

  2. Incidence of requirement for rescue macular laser treatment [ Time Frame: 24 months ]
    Incidence of requirement for rescue macular laser treatment

  3. Ocular adverse events [ Time Frame: 24 months ]
    Incidence and severity of ocular adverse events including severe (>15 letter) loss of vision

  4. Non-ocular adverse events [ Time Frame: 24 months ]
    Incidence and severity of non-ocular adverse events

  5. Change in visual field from baseline [ Time Frame: 24 months ]
    Incidence of new visual field defect that would fail to meet driving standard at 24 months. (Selected study sites only).



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02432547


Contacts
Contact: Samantha Fraser-Bell, PhD FRANZCO 61 2 9382 7309 sfraserbell@gmail.com
Contact: Maria D Williams, BA BN 61 2 9382 7309 maria.williams@sydney.edu.au

Locations
Australia, New South Wales
Save Sight Institute Recruiting
Sydney, New South Wales, Australia, 2001
Contact: Samantha Fraser-Bell, PhD FRANZCO    61 2 9382 7309    sfraserbell@gmail.com   
Contact: Maria D Williams, BA BN    +612 93827309    maria.williams@sydney.edu.au   
Principal Investigator: Mark C Gillies, Professor         
Principal Investigator: Samantha Fraser Bell, Dr         
Sub-Investigator: Hemal Mehta, Dr         
Sub-Investigator: Aaron Yeung, Dr         
Australia, Victoria
Centre for Eye Research Australia Recruiting
Melbourne, Victoria, Australia, 3002
Contact: Sanj Wickremasinghe, Dr    61 3 9929 8263    Sanj.Wickremasinghe@eyeandear.org.au   
Principal Investigator: Sanj Wickremasinghe, Dr         
Sub-Investigator: Lyndell L Lim, Dr         
Sub-Investigator: Sukpal Sandhu, Dr         
Sub-Investigator: Salmaan Qureshi, Dr         
Sponsors and Collaborators
University of Sydney
Center for Eye Research Australia
Investigators
Principal Investigator: Samantha Fraser-Bell, PhD FRANZCO Save Sight Institute

Responsible Party: Mark Gillies, Head of Macular Research Group, University of Sydney
ClinicalTrials.gov Identifier: NCT02432547     History of Changes
Other Study ID Numbers: X14-0157
First Posted: May 4, 2015    Key Record Dates
Last Update Posted: June 3, 2015
Last Verified: June 2015

Keywords provided by Mark Gillies, University of Sydney:
Diabetic
Macular Oedema
Retinopathy

Additional relevant MeSH terms:
Retinal Diseases
Diabetic Retinopathy
Eye Diseases
Diabetic Angiopathies
Vascular Diseases
Cardiovascular Diseases
Diabetes Complications
Diabetes Mellitus
Endocrine System Diseases