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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified October 2012 by University of Sydney.
Recruitment status was  Active, not recruiting
Sponsor:
Collaborator:
National Health and Medical Research Council, Australia
Information provided by (Responsible Party):
Mark Gillies, University of Sydney
ClinicalTrials.gov Identifier:
NCT01298076
First received: August 31, 2010
Last updated: October 28, 2012
Last verified: October 2012
  Purpose

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

Condition Intervention Phase
Diabetic Retinopathy
Macular Edema
Drug: bevacizumab
Drug: dexamethasone
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Multicentre Randomised Clinical Trial of Intravitreal Bevacizumab (Avastin®) Versus Intravitreal Dexamethasone (Ozurdex™) for Persistent Diabetic Macular Oedema

Resource links provided by NLM:


Further study details as provided by University of Sydney:

Primary Outcome Measures:
  • Visual acuity gain [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    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 [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Change in visual acuity compared with the pre-injection level

  • OCT change [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Change in retinal thickness demonstrated on optical coherence tomography(OCT)

  • Laser requirement [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Number of laser treatments required for the treatment of macular oedema

  • Patient satisfaction [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Patient satisfaction with treatment

  • Safety [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
    • Mean change in maximum diameter of foveal avascular zone
    • Incidence and severity of ocular adverse events
    • Incidence and severity of non ocular adverse events


Estimated Enrollment: 65
Study Start Date: October 2010
Estimated Study Completion Date: July 2014
Estimated Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: AVASTIN
intravitreal bevacizumab
Drug: bevacizumab
Anti-VEGF drug for intravitreal injection
Active Comparator: OZURDEX
intravitreal dexamethasone
Drug: dexamethasone
Slow-release steroid formulation for intravitreal injection

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01298076

Locations
Australia, New South Wales
Save Sight Institute
Sydney, New South Wales, Australia, 2001
South West Retina
Sydney, New South Wales, Australia, 2170
Australia, Victoria
Centre for Eye Research Australia
Melbourne, Victoria, Australia, 3002
Australia, Western Australia
Lions Eye Institute
Perth, Western Australia, Australia, 6009
Sponsors and Collaborators
University of Sydney
National Health and Medical Research Council, Australia
Investigators
Principal Investigator: Mark C Gillies, Professor University of Sydney
  More Information

No publications provided

Responsible Party: Mark Gillies, Professor, University of Sydney
ClinicalTrials.gov Identifier: NCT01298076     History of Changes
Other Study ID Numbers: NHMRC project 632667, 2009-01024
Study First Received: August 31, 2010
Last Updated: October 28, 2012
Health Authority: Australia: Human Research Ethics Committee

Keywords provided by University of Sydney:
Diabetes
Retinopathy
Macular oedema
Laser
Photocoagulation
Fovea
Steroid
Bevacizumab
Intravitreal

Additional relevant MeSH terms:
Edema
Macular Edema
Retinal Diseases
Diabetic Retinopathy
Signs and Symptoms
Macular Degeneration
Retinal Degeneration
Eye Diseases
Diabetic Angiopathies
Vascular Diseases
Cardiovascular Diseases
Diabetes Complications
Diabetes Mellitus
Endocrine System Diseases
Bevacizumab
Dexamethasone
Dexamethasone acetate
Dexamethasone 21-phosphate
BB 1101
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Growth Inhibitors
Antineoplastic Agents
Therapeutic Uses
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents

ClinicalTrials.gov processed this record on October 19, 2014