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Intravitreal Bevacizumab (Avastin®) Versus Intravitreal Dexamethasone (Ozurdex™) for Persistent Diabetic Macular Oedema

Primary Purpose

Diabetic Retinopathy, Macular Edema

Status
Completed
Phase
Phase 2
Locations
Australia
Study Type
Interventional
Intervention
bevacizumab
dexamethasone
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 Diabetes, Retinopathy, Macular oedema, Laser, Photocoagulation, Fovea, Steroid, Bevacizumab, Intravitreal

Eligibility Criteria

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

Inclusion Criteria:

  • Age >= 18 years
  • Diagnosis of diabetes mellitus types 1 or 2
  • Diabetic macular oedema affecting the fovea in one or both eyes (phakic or pseudophakic) for which laser treatment is unlikely to be helpful in the opinion of the centre chief investigator
  • Best corrected visual acuity of 17-72 letters (6/12 -6/120)
  • Retinal thickness > 250 micron in central 1mm subfield on Stratus (time domain) OCT and 300 on Spectral domain OCT
  • Previous macular laser treatment, or the investigator believes laser treatment is unlikely to be helpful
  • Intraocular pressure <22mmHg
  • 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
  • Written informed consent has been obtained.

Exclusion Criteria:

  • Known allergy to Ozurdex, Avastin 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
  • Glaucoma which is uncontrolled or is controlled but with more than one medication or with only one medication and with glaucomatous field defects
  • Loss of vision due to other causes (e.g. age related macular degeneration, myopic macular degeneration, retinal vein occlusion)
  • Macular oedema due to other causes
  • An ocular condition that would prevent visual acuity improvement despite resolution of oedema (such as foveal atrophy or substantial premacular fibrosis)
  • Treatment with IVTA within the last 6 months or peribulbar TA within the last 3 months or bevacizumab within the last 2 months.
  • Cataract surgery within the last 6 months
  • Retinal laser treatment within the last 3 months
  • History of herpes virus infection in study eye
  • Media opacity including cataract that already precludes adequate macular photography and laser treatment, or cataract that is likely to require surgery within 2 years
  • Known allergies to dexamethasone or bevacizumab
  • Patient is already receiving systemic steroid treatment > 5mg prednisolone daily or equivalent)
  • Intercurrent severe disease such as septicemia, 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
  • South West Retina
  • Centre for Eye Research Australia
  • Lions Eye Institute

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Active Comparator

Arm Label

AVASTIN

OZURDEX

Arm Description

intravitreal bevacizumab

intravitreal dexamethasone

Outcomes

Primary Outcome Measures

Visual acuity gain
The comparison of the proportion of eyes gaining 10 letters of visual acuity between the bevacizumab (Avastin®) and dexamethasone (Ozurdex™) implant arms after 104 weeks.

Secondary Outcome Measures

Visual acuity change
Change in visual acuity compared with the pre-injection level
OCT change
Change in retinal thickness demonstrated on optical coherence tomography(OCT)
Laser requirement
Number of laser treatments required for the treatment of macular oedema
Patient satisfaction
Patient satisfaction with treatment
Safety
Mean change in maximum diameter of foveal avascular zone Incidence and severity of ocular adverse events Incidence and severity of non ocular adverse events

Full Information

First Posted
August 31, 2010
Last Updated
June 2, 2015
Sponsor
University of Sydney
Collaborators
National Health and Medical Research Council, Australia
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1. Study Identification

Unique Protocol Identification Number
NCT01298076
Brief Title
Intravitreal Bevacizumab (Avastin®) Versus Intravitreal Dexamethasone (Ozurdex™) for Persistent Diabetic Macular Oedema
Official Title
A Multicentre Randomised Clinical Trial of Intravitreal Bevacizumab (Avastin®) Versus Intravitreal Dexamethasone (Ozurdex™) for Persistent Diabetic Macular Oedema
Study Type
Interventional

2. Study Status

Record Verification Date
June 2015
Overall Recruitment Status
Completed
Study Start Date
October 2010 (undefined)
Primary Completion Date
September 2014 (Actual)
Study Completion Date
September 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Sydney
Collaborators
National Health and Medical Research Council, Australia

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
The specific aims of the study are to test the following hypotheses: That there is a difference in change in visual acuity resulting from treatment with intravitreal bevacizumab compared with dexamethasone implant in eyes with advanced macular oedema That there is a difference in degree of resolution of macular oedema resulting from treatment with intravitreal bevacizumab compared with dexamethasone implant in eyes with advanced macular oedema That both intravitreal bevacizumab and dexamethasone implants have a manageable and acceptable safety profile in eyes with diabetic macular oedema
Detailed Description
Diabetic retinopathy is a common cause of severe loss of vision and 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. Diabetic macular oedema (DMO) is treated with laser photocoagulation of areas of leak in the macula according to established guidelines which take into account the extent of the leak and its proximity to the centre of the macula, the "fovea". This treatment does not always work, however, and is inherently destructive. New drugs have become available which appear to reduce the risk of loss of vision in eyes with advanced diabetic macular oedema for which further laser treatment is unlikely to be beneficial. Intravitreal injection of slow-release steroid formulations such as Ozurdex™, a slow release formulation of dexamethasone, has been proposed as a new modality to treat clinically significant DMO. We have recently conducted randomised clinical trials which have demonstrated that treatment with intravitreal triamcinolone (IVTA) leads to reduction of DMO and improved vision in these eyes. Another class of drugs, inhibitors of Vascular Endothelial Growth Factor (VEGF) such as bevacizumab (Avastin®), also appear efficacious. While both drugs appear to reduce macular oedema and improve vision in the short term, they may have differences which could guide how they are best used. Around 1/3 of eyes that receive dexamethasone may develop elevated intraocular pressure and cataract, both of which are manageable but may complicate the picture. Anti-VEGF drugs do not have these local adverse events, however they must be given more frequently (4-6 weekly vs 4-6 monthly for Ozurdex™) and it is suspected they may have a neurotoxic effect on the retina. Some authorities suspect that anti-VEGF treatment may be associated with a small increased risk of having a stroke or heart attack during treatment, even when they are injected into the eye. This has not been proven with a related drug, ranibizumab, but it is still possible that it may occur with bevacizumab. This will be a, 2 year, phase II, prospective, multicentre, randomised, single-masked clinical trial of sustained release intravitreal dexamethasone (Ozurdex™) versus intravitreal injections of bevacizumab (Avastin®) for diabetic foveal oedema that persists or recurs despite previous laser treatment, or for which the investigator believes laser treatment is unlikely to be helpful.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diabetic Retinopathy, Macular Edema
Keywords
Diabetes, Retinopathy, Macular oedema, Laser, Photocoagulation, Fovea, Steroid, Bevacizumab, Intravitreal

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Allocation
Randomized
Enrollment
61 (Actual)

8. Arms, Groups, and Interventions

Arm Title
AVASTIN
Arm Type
Active Comparator
Arm Description
intravitreal bevacizumab
Arm Title
OZURDEX
Arm Type
Active Comparator
Arm Description
intravitreal dexamethasone
Intervention Type
Drug
Intervention Name(s)
bevacizumab
Intervention Description
Anti-VEGF drug for intravitreal injection
Intervention Type
Drug
Intervention Name(s)
dexamethasone
Intervention Description
Slow-release steroid formulation for intravitreal injection
Primary Outcome Measure Information:
Title
Visual acuity gain
Description
The comparison of the proportion of eyes gaining 10 letters of visual acuity between the bevacizumab (Avastin®) and dexamethasone (Ozurdex™) implant arms after 104 weeks.
Time Frame
2 years
Secondary Outcome Measure Information:
Title
Visual acuity change
Description
Change in visual acuity compared with the pre-injection level
Time Frame
2 years
Title
OCT change
Description
Change in retinal thickness demonstrated on optical coherence tomography(OCT)
Time Frame
2 years
Title
Laser requirement
Description
Number of laser treatments required for the treatment of macular oedema
Time Frame
2 years
Title
Patient satisfaction
Description
Patient satisfaction with treatment
Time Frame
2 years
Title
Safety
Description
Mean change in maximum diameter of foveal avascular zone Incidence and severity of ocular adverse events Incidence and severity of non ocular adverse events
Time Frame
2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age >= 18 years Diagnosis of diabetes mellitus types 1 or 2 Diabetic macular oedema affecting the fovea in one or both eyes (phakic or pseudophakic) for which laser treatment is unlikely to be helpful in the opinion of the centre chief investigator Best corrected visual acuity of 17-72 letters (6/12 -6/120) Retinal thickness > 250 micron in central 1mm subfield on Stratus (time domain) OCT and 300 on Spectral domain OCT Previous macular laser treatment, or the investigator believes laser treatment is unlikely to be helpful Intraocular pressure <22mmHg 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 Written informed consent has been obtained. Exclusion Criteria: Known allergy to Ozurdex, Avastin 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 Glaucoma which is uncontrolled or is controlled but with more than one medication or with only one medication and with glaucomatous field defects Loss of vision due to other causes (e.g. age related macular degeneration, myopic macular degeneration, retinal vein occlusion) Macular oedema due to other causes An ocular condition that would prevent visual acuity improvement despite resolution of oedema (such as foveal atrophy or substantial premacular fibrosis) Treatment with IVTA within the last 6 months or peribulbar TA within the last 3 months or bevacizumab within the last 2 months. Cataract surgery within the last 6 months Retinal laser treatment within the last 3 months History of herpes virus infection in study eye Media opacity including cataract that already precludes adequate macular photography and laser treatment, or cataract that is likely to require surgery within 2 years Known allergies to dexamethasone or bevacizumab Patient is already receiving systemic steroid treatment > 5mg prednisolone daily or equivalent) Intercurrent severe disease such as septicemia, 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
Mark C Gillies, Professor
Organizational Affiliation
University of Sydney
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
South West Retina
City
Sydney
State/Province
New South Wales
ZIP/Postal Code
2170
Country
Australia
Facility Name
Centre for Eye Research Australia
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3002
Country
Australia
Facility Name
Lions Eye Institute
City
Perth
State/Province
Western Australia
ZIP/Postal Code
6009
Country
Australia

12. IPD Sharing Statement

Citations:
PubMed Identifier
33206392
Citation
Rittiphairoj T, Mir TA, Li T, Virgili G. Intravitreal steroids for macular edema in diabetes. Cochrane Database Syst Rev. 2020 Nov 17;11(11):CD005656. doi: 10.1002/14651858.CD005656.pub3.
Results Reference
derived
PubMed Identifier
31047591
Citation
Mehta H, Fraser-Bell S, Nguyen V, Lim LL, Gillies MC. The Interval between Treatments of Bevacizumab and Dexamethasone Implants for Diabetic Macular Edema Increased over Time in the BEVORDEX Trial. Ophthalmol Retina. 2018 Mar;2(3):231-234. doi: 10.1016/j.oret.2017.06.010. Epub 2017 Aug 23.
Results Reference
derived
PubMed Identifier
28779007
Citation
Mehta H, Fraser-Bell S, Nguyen V, Lim LL, Gillies MC. Short-term vision gains at 12 weeks correlate with long-term vision gains at 2 years: results from the BEVORDEX randomised clinical trial of bevacizumab versus dexamethasone implants for diabetic macular oedema. Br J Ophthalmol. 2018 Apr;102(4):479-482. doi: 10.1136/bjophthalmol-2017-310737. Epub 2017 Aug 4.
Results Reference
derived
PubMed Identifier
28228411
Citation
Wickremasinghe SS, Fraser-Bell S, Alessandrello E, Mehta H, Gillies MC, Lim LL. Retinal vascular calibre changes after intravitreal bevacizumab or dexamethasone implant treatment for diabetic macular oedema. Br J Ophthalmol. 2017 Oct;101(10):1329-1333. doi: 10.1136/bjophthalmol-2016-309882. Epub 2017 Feb 22.
Results Reference
derived
PubMed Identifier
27768792
Citation
Aroney C, Fraser-Bell S, Lamoureux EL, Gillies MC, Lim LL, Fenwick EK. Vision-Related Quality of Life Outcomes in the BEVORDEX Study: A Clinical Trial Comparing Ozurdex Sustained Release Dexamethasone Intravitreal Implant and Bevacizumab Treatment for Diabetic Macular Edema. Invest Ophthalmol Vis Sci. 2016 Oct 1;57(13):5541-5546. doi: 10.1167/iovs.16-19729.
Results Reference
derived
PubMed Identifier
26537156
Citation
Mehta H, Fraser-Bell S, Yeung A, Campain A, Lim LL, Quin GJ, McAllister IL, Keane PA, Gillies MC. Efficacy of dexamethasone versus bevacizumab on regression of hard exudates in diabetic maculopathy: data from the BEVORDEX randomised clinical trial. Br J Ophthalmol. 2016 Jul;100(7):1000-1004. doi: 10.1136/bjophthalmol-2015-307797. Epub 2015 Nov 4.
Results Reference
derived
PubMed Identifier
25155371
Citation
Gillies MC, Lim LL, Campain A, Quin GJ, Salem W, Li J, Goodwin S, Aroney C, McAllister IL, Fraser-Bell S. A randomized clinical trial of intravitreal bevacizumab versus intravitreal dexamethasone for diabetic macular edema: the BEVORDEX study. Ophthalmology. 2014 Dec;121(12):2473-81. doi: 10.1016/j.ophtha.2014.07.002. Epub 2014 Aug 22.
Results Reference
derived

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Intravitreal Bevacizumab (Avastin®) Versus Intravitreal Dexamethasone (Ozurdex™) for Persistent Diabetic Macular Oedema

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